The effect of salt on the boiling temperature of water research paper Essay

Project Design Plan Everyone knows that water boils at 212Â °F, but does adding salt to a pot of water make it boil at a higher temperature? Being a person that cooks frequently at home, I wanted to test the debated idea that adding salt to my water will make it boil faster. One of my friends says it does raise the temperature and therefore cooks it faster. My other friend says it only helps it taste better. Literature Review Table salt is often added to water before the boiling process in hopes that the water will boil faster. It has been argued that the boiling temperature difference is insignificant with a small pot of water. However, when adding salt to larger amounts of water, the change is more noticeable. Southwest Research Institute states that the heat capacity of salt water is less than that of pure water, which means that it takes less energy to raise the temperature of the salt water 1Â ° C. than pure water. The time it takes a pot of water to boil is controlled by three things, first is how much heat you put into the pot, second is how fast the temperature rises and third is the boiling point of the liquid (Southwest Research Institute, 2014). Salt elevates the boiling temperature of water using a process known as boiling point elevation. With water being a known solvent and salt a non-volatile solute, when you add salt to the water, it makes the water an impure solvent, and raises its boiling point above that of pure solvents (Effect of Salt on the Boiling Temperature of Water). Experimental Design Steps Water will be boiled four different times as follows: 1.2 cups of distilled water are added to a 2 quart cooking pot a. First run add NO salt – this is the control b. Second run add 1 Tablespoon of table salt – Trial #1 c. Third run add 1 Tablespoon of table salt – Trial #2 d.Fourth run add 1 Tablespoon of table salt – Trial #3 2. For each run, bring water to boil 3. For each run, record the highest temperature reading of the boiling water 4. After first through third runs, allow pot and burner to cool 5. Wash pot after each run to clean salt residue Reasoning A typical recipe will call for a dash of salt in the water. The articles I read made me believe that adding more salt would make the temperature difference more noticeable, I upped the salt to 1 tablespoon of salt to each pot of water per run, instead of a dash. Adding a dash of salt could skew the results, because when adding a dash, you will not have the same measurement of salt to each pot of water as you would when measuring the salt with a tablespoon. In order to reduce error, so I used three trials. Sequence of Events During each trial I will be measuring the temperature of the water with a thermometer. Once it reaches its highest temperature, I will record it in my data table. This will be the process for each trial. Tools, Technologies, and Measurement Units Table Salt Distilled Water 2 Quart Cooking Pot Pint measuring cup Teaspoon and tablespoon measuring spoons Thermometer (Degrees Fahrenheit) Stirring spoon Stove top burner (electric) Variables Independent Variable: Amount of salt added to the water Dependent Variable: Temperature at which the water boils Controlled Variables: Temperature of stove setting, pot, type of water, brand of salt, amount of water, thermometer Threat Reduction to Internal Validity By washing the pot and thermometer between each trial, I will reduce the amount of salt residue that is on the pot that could alter my results. I will use the same heating unit, pot, and thermometer each time to get more valid results. Hypothesis The hypothesis of this experiment is that adding table salt to water will raise the boiling temperature of the water. Process of Data Collection Boiling Point of Two Cups of Water Amount of salt added (IV) Temperature of boiling water in Fahrenheit (DV) No Salt (Control) 212.7Â °F 1 Tablespoon Salt Run #1 214.9Â °F 1 Tablespoon Salt Run #2 215.3Â °F 1 Tablespoon Salt Run #3 215.1Â °F As predicted, adding salt to water does raise the boiling temperature of the water, even if only minimally. Variations in the boiling temperature may be contributed to slight variations in the measurements of the salt added to the water. It is important to measure both the water and salt accurately to ensure accurate results. Appropriate Methods For each run, 2 cups of water were added to a 2 quart saucepan; 1 tablespoon of salt was then added to the water and stirred to mix the two ingredients together. The saucepan was then put on the stove and brought to a boil. Once the water reached a full boil the final temperature was recorded using a Go-Temp thermometer. The tools and methods used in this are appropriate to the experiment. Results The results were larger than anticipated. The average temperature of the water with the salt was 215.1 degrees Fahrenheit, while the temperature of the control was 212.7 degrees Fahrenheit. This was a difference of 2.4 degrees. Conclusion Confirmation of Hypothesis My hypothesis was confirmed. Adding table salt to water causes the water to boil at a higher temperature. The temperature readings were hard to make. Oven mitts had to be worn to keep my hands from getting burned. I had to be sure that the thermometer wasn’t too close to the stove or the temperature would be skewed. Experimental Design as a Key Factor How you design your experiment is key to helping you keep your results reliable and valid. You only need one independent variable. If you have more than one, you won’t know which one is actually affecting your results, it will also be harder to measure. Making as many variables as possible constant will help increase the reliability of the experiment. Replication By following this plan and report, you can replicate this experiment. One might try adding different amounts of salt to see if there is a point at which the amount of salt added stops increasing the boiling point. Evaluation of Validity Replicating this experiment will add to the validity of my results and others results. If the experiment is replicated numerous times this will add to the validity, resulting in a more accurate conclusion. It is important to measure both the water and salt accurately to ensure that the results collected are as accurate as possible. References Does water boil faster if you put salt in the water? (n.d.). Retrieved July 19, 2014, from http://www.swri.org/10light/water.htm EXPERIMENTAL SCIENCE PROJECTS: The Effect of Salt on the Boiling Temperature of Water. (n.d.). Retrieved July 19, 2014, from http://www.freesciencefairproject.com/projects/effect_salt_boiling_water.html Effect of Salt on the Boiling Temperature of Water. (n.d.). Retrieved July 19, 2014, from http://www.actiondonation.org/articles/effect-of-salt.html Post navigation. (n.d.). Retrieved July 19, 2014, from http://www.sciencebase.com/science-blog/how-does-salt-affect-the-boiling-point-of-water.html

2 Unit Religion – Aboriginal Spirituality.

What does Terra Nullius mean? From at least 60,000 B. C. , Australia was inhabited entirely by Aboriginal and Torres Strait Islander people with traditional, social and land rights. To the Aborigines the land was everything to them and is closely linked to their Dreaming stories. Dreaming is the belief system which explains how the ancestral beings moved across the land and created life and significant geographic features. In consideration, the Indigenous Australians are a people with a close relationship with the land, and through the land they maintain the spiritual links to the ancestral beings.The land is sacred, and for many thousand years, Aboriginal people lived in harmony on their land. After the arrival of the British colonies in 1788, Australia was declared â€Å"Terra Nullius†, which is a Latin term meaning land belongs to no one. As a result of this, Captain Cook, the British captain of the first fleet of ships to arrive at Australia’s shore, claimed that al l of the east coast of Australia belonged to Britain. The underlying argument was that Aboriginal people were so low on scale of human development that their needs were discounted.Because Aboriginal people did not farm the land, build permanent houses on it or use it in other familiar ways, the British decreed that they did not have rights over the land nor did they have any proof of land ownership. Another reason was that there was no identifiable hierarchy or political order which the British government could recognise or negotiate with. Once European settlement began, Aboriginal rights to traditional lands was disregarded and the Aboriginal people of the Sydney region were almost obliterated by introduced diseases and, to a lesser extent, armed force.First contacts were relatively peaceful but Aboriginal people and their culture was strange to the Europeans as well as their plants and animals. Consequently, Terra Nullius continued on for over 200 years. Figure 1: Eddie Mabo Figur e 1: Eddie Mabo Who was Eddie Mabo? Eddie ‘Koiki’ Mabo (seen in figure 1) was born on 29 June 1936, in the community of Las on Mer, known as Murray Island in the Torres Strait. His birth name was Eddie Koiki Sambo; however he was raised by his Uncle Benny Mabo through a customary ‘Island adoption’. During this time, the concept of â€Å"terra nullius† was legislation.When Eddie was growing up, life for the people of the Torres Strait Islands was strictly regulated with laws made by the Queensland Government. However, the Meriam people strived to maintain continuity with the past and continued to live a traditional lifestyle based on fishing, gardening and customary laws of inheritance. At the age of 16, Eddie was exiled from Murray Island for breaking customary Island law, and he set off for the mainland where a new life was waiting for him. Through university, Eddie read a speech in front of people about his people’s belief about the land own ership.A lawyer heard him and asked if he would like to argue with the Australian government about the right for Aboriginal and Torres Strait Islanders to have land rights. After this, Eddie Mabo was successful in addressing the concept of native title to the Australian government on behalf of Murray Island people. He is known for his role in campaigning for indigenous land rights and for his role in a landmark decision of the high court of Australia which neglected the legal doctrine of â€Å"terra nullius† land belong to nobody, which characterized Australian law with regards to land and title.Eddie died in 21 January 1992 and was unable to see the native title given to them. What were the Mabo case and the high court decisions? In the 1970’s, the Queensland Government took over Aboriginal land and was unsympathetic to the concept of land rights or any idea of native title to the land. On the 20th of May 1982, Eddie Koiki Mabo and four other Torres Strait Islanders c hallenged â€Å"terra Nullius† and began their legal claim for ownership to the Supreme Court of Queensland of heir lands on the island of Mer in the Torres Strait since their people had lived on the islands long before the arrival of the white settlement. Eventually, the supreme court of Queensland dismissed the case. Later, another challenge to the concept of â€Å"terra Nullius† was witnessed when Mabo and the four other islanders took the case to the High court of Australia. They requested that the court declare that their traditional land ownership and rights to the land and seas of the Mer Islands had not been extinguished. Furthermore, they claimed that the Crown’s authority over the islands was subject to the land rights of the Murray Islanders.It was not until 3 June 1992 that Mabo case No. 2 was decided. By then, 10 years after the case opened, Eddie Mabo had died. By a majority, six out of one of the judges agreed that the Meriam people did have tradi tional ownership of their land. The judges held that British possession had not eliminated their title and that the Meriam people are entitled as to possession, occupation, use and enjoyment of the lands of the Murray Islands. This decision has wiped the concept of â€Å"terra nullius† and awarded the indigenous Australians with the Native Title.Consequently, the term â€Å"Native title† is still in existence and contributed to allow the Indigenous Australians to maintain a continuous spiritual and cultural connection to the land. Therefore, this decision was important because it recognised that Australia was inhabited By the Indigenous Australians long before the White settlement and hold the native title. What is the Native title Act (1993) Commonwealth? Native title is a legal term which recognises the rights of Aboriginal and Torres Strait Islander people to the use and occupation of lands with which they have maintained a continuing, traditional connections.Eventu ally, in the 1970’s the Queensland government began to remove the land rights of people of Murray Island in the Torres Strait. One of the Meriam people, Eddie Mabo, took the Queensland Government to court to prevent this from happening. Sadly, this case failed. Moreover, Mabo and some other people took the case to the high court of Australia. The high court decided in favour of the Meriam people and recognised the principle of Native title. Ultimately, during this historical event, Eddie Mabo was dead. In 1993, The Keating Labor government passed the Native Title Act.This Act accepted the notion of Native title in law and also recognised the rights of owners of freehold property. Nevertheless, pastoralists and miners were still concerned, and many people leased land from the government. The legislation aimed to codify the Mabo decision and implemented strategies to facilitate the process of granting native title. However, it had not resolved the question of whether the granti ng of pastoral lease extinguished Native title. In this case, the High court argued that native title could co-exist with the rights of leaseholders.However, the pastoralists and the mining companies who lease lands were still concerned that the court was too much in favour of native title. In 1997, native title act passed by the Howard government. This act stated that Native title and leasehold rights could co-exist and in any conflict, the rights or the leaseholders would come first. What was the Wik Decision (1996) commonwealth? The Native title Act of 1993 had not resolved the question of whether the granting of a pastoral lease extinguished Native title.In 1993, the Wik people on Cape York in Queensland made a claim for land on Cape York Peninsula which included two large Pastoral leases. The federal court upheld the Native Title Act 1993 against the Wik people, with an argument that Aboriginal Australians had no control over land that has been leased. This case was further tak en to the High court of Australia. In December 1996, the high court ruled that the granting of a pastoral lease had not in fact extinguished native title. With reference to a letter from 1848 in which a British secretary of state for colonies wrote to governor ofNSW which stated that the leaseholders had to negotiate with the traditional owners to allow them access. Pastoralists viewed the Wik decision with great concerns, for they had always believed that they had full and sole rights to manage their leases. After the Wik decision, Pastoralists would have to negotiate with any group who could prove native title right. Unfortunately, the pastoralists and miners increased the pressure on government because they were not happy with the Wik decision and the idea that Indigenous Australians had rights to leased land.After a debate on this issue, the Howard government passed an amendment to the 1993 Native title Act. This change reduced the rights of indigenous Australians under the act and removed their right to negotiate with pastoralists and miners. This new law, made it difficult for Aboriginal Australians to make land rights claims Outline the importance of the Dreaming for the land rights movement? The Dreaming for Australian Indigenous people (sometimes referred to as the Dreamtime or Dreamtimes) refers to when the Ancestral Beings moved across the land and created life and significant geographic features.The land rights are of critical importance in relation to Aboriginal spirituality, because the dreaming is inextricably connected with the land. Since the Dreaming is closely connected to the land, the land rights movement is an important movement in helping Aboriginal people re-establish spiritual links with their sacred land which was lost as a result of the European settlement. The dreaming is essential to the land rights movement because of many reasons such as: To the Aborigines, the dreaming is the central role which land occupies in Aboriginal spirit uality, as land is the path through which the dreaming is experienced and communicated.Without the land, the dreaming cannot be communicated because it is from the land that the stories of ancestor spirits in the dreaming flow. It is through their intimate connection to the land that the foundational concept which lies at the heart of Aboriginal spirituality, that is, the dreaming can be accessed. The land therefore, acts as the mother for the Aboriginal people, and that since it is, the identity of every Aboriginal person is closely linked to the land. Therefore, the importance of the land rights movement for Aboriginal spirituality should not be underestimated.More importantly, the dreaming stories provide the entire ethical and moral basis by which Aboriginal people live on their land and relate to each other. It is known that the access to their land is fundamental to the putting into practice of Aboriginal law. This factor underlies the Aboriginal law is the knowledge and ritua l relating to sacred sites. These sites need to be cared for and this is done through ritual ceremony. Each person is linked to the spirit ancestor who created the land, and it is this which creates an Aboriginal person’s identity.Through the dreaming, Spirit connects each person with particular sacred sites, with the result that each person has a connection with specific places on the land. According to the Aboriginal belief system, individuals have clearly defined responsibilities in relation to the land, in particular the protection of sacred sites. Sacred sites may be desecrated through grazing, mining, or perhaps contact with site by people without knowledge of the necessary ritual. Access to these sites is critical for the performance of rituals and ceremonies so that the law can be taught to new generations.Another importance of the dreaming is that the dreaming connects each tribe to a totem. A totem is an emblem mainly a plant or an animal that has become a symbol fo r a group who is believed to be responsible for their existence. The totem unifies the Clan (group) under the leadership of the spirit ancestor and thereby also creates a metaphysical connection with other clans bearing the same totem. Without their access to their totems, the Aboriginal people would lose their identity and prevent the belief system to be passed on to the next generation. Also, being taken away from a totem can alienate the individual from their clan.The land rights movement can re-establish the access to the totems and belonging to the same clan under the sacred totem. Thus, the dreaming which explains the clan’s existence by their totem is essential to the land rights movement. For the purpose of land rights and spiritual fulfilment of the land, the Australian History has witnessed many land rights movement. Those include the Yolgnu people of Yirrkala in 1963 and the 1966 Gurindji people. In 1963, the Yolgnu people of Yirrkala sent a typed petition in both their own language and English to the federal parliament because the government had granted a mining company the right to mine auxite without consulting the traditional owners. The paper was fixed to a surrounding bark painting which depicted the people’s relationship with the land, and the Yirrkala people were seeking recognition of rights to their traditional lands on the Gove Peninsula. This however, was rejected in the court. To not underestimating this land rights movement, it was the first Aboriginal land rights movement and was an important step in the eventual recognition of indigenous land rights movement.Another Early land rights movement was in 1966, when the Gurindji people began a strike at the British-owned Wave Hill station in the Northern Territory to protest about intolerable working conditions and low wages. They set up a camp at Wattie Creek and demanded that some of their traditional lands to be restored to them. The protest eventually led to their being g ranted the rights to Wattie Creek by the Whitlam Government in 1975. The passing by the Fraser Government of the Commonwealth Land Rights Act northern territory, 1976, gave Aboriginal people freehold title to traditional lands in the northern territory.As shown, the land rights movements were based on the belief of the dreaming. This is because the land is closely linked to the dreaming and by restoring land rights again, the Aboriginal community could re-establish the dreaming which involves the land, sacred sites, totems and ancestral beings. How has dispossession affected Aboriginal spirituality? (seperatio Land, kinship, stolen generation). The Dispossession of the Indigenous Australians has had a major impact on their Spirituality and beliefs, including their connection to the land, kinship and explored a major effect which is the stolen Generation.When the White Settlement began in Australia in 1788, Australia was called â€Å"terra Nullius† meaning that the land belong s to no body. What was unknown to the British settlement is that the land is the home for the Aborigines and those Aborigines have been living in this land for more than 50,000 years. In the nineteenth century and much of the twentieth century the official policy towards Aboriginal Australians was called protectionism. Protectionism is the idea that Aboriginal Australians needed to be separated from the white society and be protected because they were unable to do so.As a result, they were removed from their traditional lands and placed in missions which at that time were controlled by Christian churches. This was a major factor in separating Aboriginal people from their own culture and religions. Since the Aboriginal religion is based on the dreaming which refers to the time where ancestors created the land, the dreaming is closely connected to the land because it is through the land that the stories of the dreaming emerge. Many of their rituals and ceremonies were inseparably link ed to the land and sacred sites.Consequently, many Aborigines were separated from their spiritualties and beliefs. Another major effect of dispossession from land is when separated people have later tried to gain access to their land but have no knowledge of the law and tradition and also no proof of their connection to the land. Therefore, dispossession from land has impacted on the Aborigines because the land plays a major role in their spiritual beliefs. Similarly, separation from Kinship groups has limited the Aboriginal people’s opportunity to express their religion in traditional songs and dances.The Kinship is a complex system of belonging, relationships and responsibilities within a tribe that are based on the dreaming. Due to the fact that most of Aboriginal tribes had their own language, separation from kinship made it impossible for Aboriginal people to preserve their own language and dreaming stories of their clan (tribe). It is known that each Aboriginal individu al has a responsibility within their clan. Many Aborigines as a result of dispossession lost the opportunity to participate in rituals that would gain them acceptance into the clan.Eventually, Kinship groups had the responsibility for raising and nurturing children even though they were not their biological children. When children were taken away from their clan by the white colonisation, the community lost the responsibility of taking care and nurturing the children and thus, lost the concept of kinship. Another effect of separation from Kinship groups is that the separation prevented individuals from inheriting the traditional parenting skills such as teaching the young their responsibilities and the dreaming stories.Separation from Kinship can also mean isolation from the ceremonial life. Ceremonies such as initiations or funerals are of a critical importance because they are a part of the Aboriginal life. Without these ceremonies, a person is disconnected to their kinship and th eir Aboriginal spirituality. This also limited the spread of their beliefs to the next generations. Hence, Kinship separation has led to the loss of spirituality. The so called â€Å"Stolen Generations† have also affected the Aboriginal spirituality.The term â€Å"Stolen Generation† refers to the children who were removed from their homes between 1900 and 1972 by the Government and Church missionaries in an attempt to assimilate these children into European society. Most of the children who were taken away lost contact with other Aboriginal people, their culture, beliefs and land. In addition, they also lost their own languages. As a result, the stolen generation found it difficult to restore the connection with their own people and culture. The children were only exposed to white culture, because they were told that their families had rejected them or they were dead.The contact between the children and families was rarely allowed. This lead to a lack of role models ta ught the Aboriginal beliefs. Some of the stolen Generation could not pass on the dreaming stories of the ancestral beings to their children, unlike how they were initially taught with their Aboriginal community. Many of the children were exposed to Christianity in its various forms. The children were taught the Christian religion in Christian missions, which undoubtedly contributed to the destruction of aboriginal culture and spirituality. Thus, the removing of the Aboriginal children had impacted on the Aboriginal spirituality.Therefore, the dispossession from the land, kinship and the stolen Generation has affected the Aboriginal Spirituality. ——————————————– [ 1 ]. http://www. aboriginalheritage. org/history/history/ [ 2 ]. http://www. parliament. nsw. gov. au/prod/web/common. nsf/key/HistoryBeforeEuropeanSettlement [ 3 ]. Religion and Belief system in Australia post-1945 [ 4 ]. http://en. wikipedia. org/wiki/Eddie_Mabo [ 5 ]. http://www. racismnoway. com. au/teaching-resources/factsheets/19. html [ 6 ]. http://www. racismnoway. com. au/teaching-resources/factsheets/19. tml [ 7 ]. http://en. wikipedia. org/wiki/Eddie_Mabo [ 8 ]. http://en. wikipedia. org/wiki/Eddie_Mabo [ 9 ]. Religion and Belief system in Australia post-1945 [ 10 ]. Religion and Belief system in Australia post-1945 [ 11 ]. http://www. aboriginalheritage. org/history/history/ [ 12 ]. Religion and Belief system in Australia post-1945 [ 13 ]. Religion and Belief system in Australia post-1945 [ 14 ]. www. atns. net. au/agreement. asp? EntityID=775 [ 15 ]. http://www. library. uq. edu. au/fryer/1967_referendum/labour. html [ 16 ]. http://www. library. uq. edu. u/fryer/1967_referendum/labour. html [ 17 ]. http://reconciliaction. org. au/nsw/education-kit/land-rights/ [ 18 ]. http://www. library. uq. edu. au/fryer/1967_referendum/labour. html [ 19 ]. :http://www. abs. gov. au/Ausstats/[email  protected] nsf/Previousproducts/1301. 0Feature%20Article21995? opendocument [ 20 ]. http://reconciliaction. org. au/nsw/education-kit/land-rights/ [ 21 ]. http://reconciliaction. org. au/nsw/education-kit/land-rights/ [ 22 ]. http://www. library. uq. edu. au/fryer/1967_referendum/labour. html [ 23 ]. http://www. library. uq. edu. au/fryer/1967_referendum/labour. html

Tell About the Time When You Gained Something Precious

It was cold that October morning in Elizabeth City, NC. I hardly slept at all the night before and 4a. m. had come very early. It didn’t matter; I had to be at the hospital at 6a. m. It was finally time for the world to meet baby Valarey and for baby Valarey to meet the world. It was time, time to have my precious baby. By 7a. m. I was hooked up to my IV. By 9a. m. the nurses had me hooked up to a fetal monitor that monitored my baby and my contractions. I was now stuck in this not so comfortable bed until after my baby was born. My labor had started on its own but my doctor decided to start a Pitocin drip to induce my labor and make it go a little faster. It was now 4p. m. and was time for the epidural. My husband almost passed out after watching the elongated needle go into the small of my back! It took everything in me to whisper â€Å"Something’s wrong† to the nurse. Everything went dark and I could hear a beeping noise that sounded like it was fading in the distance. I was dying, slowly slipping away from this world. When I finally regained consciousness I looked at my husband in dismay. The look on his face was complete trepidation. He told me that my blood pressure had plummeted and they had almost lost me. The nurse asked me how I was feeling and I told her I was ok. It seemed like I had been out for a very long time but my husband said it was only seconds. He said that the nurse had to inject me with some emergency medication to bring my blood pressure back to normal. It was now about 9p. m. and the nurse told me it was time to have my baby. It was pushing time! You could see the excitement is my husband’s face. I was just as excited! We were about to meet our second baby. To finally see what she looked like, to hear the sounds of here cries and to feel her soft skin. The pushing began but the doctor was not in the room yet. My knees were up to my ears and my chin was on my chest as I pushed with all my might, bearing down as hard as I could. After pushing really hard three times everyone in the room started to yell stop! Stop pushing! I thought something was wrong. The baby’s head was out. Her beautiful mystical blue eyes were fluttering like a butterflies wings. Soft, fine almost white, blonde hair and ivory fair skin was the first thing we saw of her. The doctor walked in the room all suited up and the pushing began again. After just a few more pushes our second baby girl was delivered. She was 8lbs even and 19 1/2in long. Valarey Joyce Hunter was born at 9:45p. m. on October 30th, 2001. She was the most beautiful and inestimable thing I had ever seen.

Marketing Communication and Branding Case Study

Marketing Communication and Branding - Case Study Example Consequently, the initial objectives that intend to be achieved with effectively implemented marketing plan are the following: Raising people’s awareness of the necessity to follow healthy and active lifestyle; Inducing of the community to benefit the society; Forming moral principles and awareness of own importance and consequence for the social problem-solving; Developing mutual assistance and intention to help other people; Providing full information about donorship centers, opportunities and conditions to become a donor and possible privileges for new donors; Showing benefits of donorship to public; Substantiating the safety and hygiene of the donorship procedures; Providing confidentiality of test results; Cutting number of drinkers and accordingly increasing number of donors by 50 per cent during a scheduled period; Proposing new effective methods of donors’ stimulating and attracting. Achieving of the defined objectives should give results in three main aspects. First of all people must understand the importance and necessity of the donorship for the society and particular individual. It is essential to develop mutual assistance and feelings of responsibility in peoples’ deeds. Secondly, population of United Kingdom has to realize that the procedure of donorship is totally safe and harmless, if donor complies with required regulations. And the last urgent direction that is defined by mentioned objectives will be elaborating of the effective methods, which are aimed to raise the number of volunteers due to the demand of the hospitals and clinics. Answer 2. Taking into account all stated goals, several areas of the future performance should be outlined. In this respect, it is recommended for the National Blood Service, first of all, to make an emphasis on safety of the blood donorship. For example, it could be essential to ensure future donors with preliminary consultations, accentuating the usage of sterile needles and gloves by medic al workers. It can help to convince people of a thought that they will not get infected with any disease during the procedure. The second crucial aspect of the strategy is to work out the most attracting motives for the future donors. With this aim it can be suggested to stimulate the rate of donors with financial support. The obligatory payment for each donor should be nominal, though easy money will be able to pull a lot of students and unemployed people into donorship. For the first time new donor will get minimal award, but for the following procedure organization may increase its payments. In addition, it can be important to reward each donor with a small bar of chocolate that helps to restore the haemoglobin level. From one side it is just a trifle, but on the other hand this sign of care will improve donors’ conditions and the process of rehabilitation. Moreover, to enhance number of volunteers for giving blood the NBS may guarantee them to be served in the local hospi tals fully or partly free of charge. Also people may become more available for donorship if, for example, one of the benefits of being a blood donor will be a privilege and right to make appointment with dentist or laryngologist out of turn. For those people who cherish their time this benefit is going to be influential. To attain mentioned goals it is urgent to use special marketing tools that form push and pull strategies. First strategy can be implemented by means of mass

Report on Financial and Economic issues around the EU and affects on Essay

Report on Financial and Economic issues around the EU and affects on Arcelor Mittal - Essay Example It is critical to note that the firm reports its operational performance across the whole Europe wide region and therefore country wide segregation of the relative performance of the firm is relatively not present. What is key to understanding is the fact that firm is facing strong macroeconomic risks in these countries as fiscal expansion has been curtailed by the relative governments in these countries. The weak demand is mostly due to the austerity measures taken by the governments. Since Governments are major users of steel and related products therefore a decline in the fiscal expansion is one of the key reasons for decline in the business of the firm in PIIGS and other European countries. Details of Staff Employed Firm has reported that 37% of its employees are located in EU27 countries. (Statista.com,2000).   These countries are 27 European countries where firm have operations of different nature including mining, steel production, construction and other related activities. The production sites are located in Madrid, Averio, Ireland and other smaller locations where firm operates its so called mini-steel mills. In Spain, firm has four different production locations where firm is engaged in different activities including steel production as well as mining activities. Since firm is located in Luxemburg therefore the number of employees working in the headquarters of the firm is also included in its workforce in Europe. Difficulties in PIIGS Markets In Spain, firm is facing severe problems of high energy prices and lack of alternative energy resources. The lack of these resources therefore has increased the overall level of operational cost for the firm and resultantly has an impact on its profitability. (Mitchell,2012).  In Ireland, Portugal, Italy and Greece, one of the key difficulties is the lack of demand being generated from the government and private sector. Since these countries are still under strict austerity measures. In Spain, firm is also f acing disputes with the employees and many of the Staff members have protested against the closure of factories in Madrid.( En.tengrinews.kz 2012)   In Greece, firm is specifically facing debt related issues and the major write down by the firm in Europe is appropriated towards the Greece debt. Most of the challenges faced by the firm in the EU region come from Greece as the country as a whole hardly avoided bankruptcy after due funding support from European Union member countries. Cost of borrowing is also on the rise especially in Greece due to heavy borrowing by the government and bond issues.( Eichengreen, 2012)   Apart from this, the global demand for Steel is slowing down causing overall decline in the business operations of the firms. It is critical to note that EU27 experienced a negative growth rate of Steel consumption during 2012 suggesting that the overall demand is on the decline in these markets. Expansion or Contraction Firm is already on its way to close some of its production facilities in Spain as it has closed its Madrid facilities and is also in process of redeploying some of its staff to other locations in Spain. This indicates that firm is curtailing back on its operations in Spain and same practice may also be adapted in other countries and markets also. It is also already in process of closing down its furnaces in

Helping teens grow emotionally Essay Example | Topics and Well Written Essays - 1000 words

Helping teens grow emotionally - Essay Example These two minds together shape our destiny. When we talk about the main theme of Emotional Intelligence in teens, as mentioned by Geoff Maslen in his article, we may see that several other writers also mentioned and explained the same concept. Daniel Goleman writes in his book â€Å"Emotional Intelligence† that the main idea or the concept of Emotional Intelligence, basically, argues the IQ. He further mentions that there are extensive areas of Emotional Intelligence that can further indicate that how successful a person is. Success desires something more than Intelligence Quotient. Intelligence Quotient is used to measure the intelligence only, and pays no heed to the essential behaviors and several other elements. There are many people who are rationally and academically brilliant and successful in their lives but they are socially inept. So it is not necessary fact having high IQ level directs to a totally successful and brilliant life. Teenagers mostly appear to be arousing, touching, unpredictable and sometimes violated as well. However, teenagers are always dependent on their teachers and parents. As far as teachers are concerned, they are responsible to supervise the students and to manage all the rising tensions and conflicts among them. So, teacher is always obliged to understand the emotional levels of the class. There is a need of proper consideration about emotional intelligence to manage the whole class. Robert Needlman, M.D, also mentioned in his article ‘Emotional Intelligence’ that the teachers should have the aptitude to forecast or predict and influence the student’s emotions. This is most significant and vital skill that a teacher can have. Actually teens always need inter personal intelligence to be established and accepted in the class, by their peers as well as teachers. Furthermore in this article, Karen Hansen says that it is a theory that teens with elevated levels of emotional intelligence can attain better than students

Internationa project finance law Essay Example | Topics and Well Written Essays - 5000 words

Internationa project finance law - Essay Example In 2010, the gross domestic product per capita of Malaysia was about US$14,700. In the year 2009, the nominal gross domestic product (GDP) was around $383.6 billion, and the nominal GDP per capita was about us$8,100. â€Å"The IMF, in its September 2011 World Economic Outlook Report, lowered its forecast for 2012 global growth to 4 per cent, down from 5.1 per cent it had forecasted earlier. By early January 2012, its chief economist had announced that the IMF would on 24 or 25 January 2012 makes a "fairly substantial" cut to its forecast for global economic growth this year†2 Power Purchase Agreements  in Malaysia: Power Purchase Agreements  are agreements between two parties, the one who creates electricity for the cause of sale and the one who is seeks to purchase electricity. There are different kinds of power purchase agreements. They include the source of energy harnessed from solar power, wind, etc. Financing the project is defined in the agreement, which also identi fies applicable dates of the project coming into consequence, when the project starts marketable operations, and an execution date for which the agreement can be abandoned or renewed. Every sale of electrical energy is metered, to provide the buyer and the seller with the exact data regarding the amount of electricity created and bought. The electricity charges are decided upon the agreement between the aforementioned two parties, to give an economic enticement of being a  Power Purchase Agreement. â€Å"In Malaysia, the power generation sector is principally dominated by three integrated power producer companies: Tenaga Nasional Berhad (TNB), Sabah Electricity Sdn Bhd (SESB) and Syarikat SESCO Berhad (SESCO). TNB and SESB fall under the jurisdiction of the Energy Commission (EC), whilst SESCO is under the jurisdiction of the Sarawak State Government. TNB is the main electricity supplier for Peninsular Malaysia while East Malaysia is covered by SESB (Sabah) and SESCO (Sarawak)â⠂¬ 3 In the year1992, Independent Power Producers (IPPs) were permitted to enter the national power generation division, to move the problem of power plant financing from government owned electricity principles to the private sector. The motivations for the IPP programme too came from the prevailing then set back in power generation capability. The openings of five IPP licences were awarded to huge business units. The tariffs for first generation IPPs were as well especially more than those for subsequent IPPs, which helped capital market financing for the initial waive of IPP savings, with the auspicious risk distribution of IPP connected risks. The enduring power purchase agreement (PPA) in which generation facility is sold to TNB insulates the IPP from fuel cost and demand cost risks. Subsequent PPAs have featured lesser tariffs, and an additional balanced distribution of risks with necessary availability targets, and various quantify of demand risk sharing. The strong credit pr ofiles of most of the issuers from this division carry on to be supported by their stable and predictable cash flow generation. â€Å"

Contemporary Issues in Strategic Management Assignment

Contemporary Issues in Strategic Management - Assignment Example There have also been many chief executives at the company but the latest expansion was under the stewardship of Mr. Sarin who was taken from the Coca-Cola Company. Its growth has been mostly of the acquisition type and this has seen it assume the level of operating on economies of scale. This case below, therefore, undertakes to analyze the value chain framework, unearth the key competencies and then lineate the strategic development of the company to the main goals and objectives.  Ã‚   Value Chain refers to the activities taking place in a business and related to the competitive strengths of the company. The value chain has two major branches; primary activities and support activities. Primary activities are the activities of a company that are concerned with the creation and delivery of a product. Support activities are all those activities that increase the efficiency of primary activities. One of the primary chain activities is the inbound logistics operations. These activities concern themselves with storage of materials that are sourced externally. Outbound logistics, on the other hand, are all the activities that are used to get the finished company products to the buyers. Marketing and sales services are activities that are concerned with giving the information to the consumers about the availability of the goods and services in a company.  Ã‚   Key competencies are the activities of strength that are used to create a positive advantage of the company above others by utilization of its key strengths. The core competencies may take the form of effective people management as well as investing in the strength of the brand of the company. Moreover, the company can decide to sell its wares at a lower price which would culminate into cost advantages.

Irish Immigrants and Scottish Society Essay Example | Topics and Well Written Essays - 1500 words

Irish Immigrants and Scottish Society - Essay Example The arrival of the large mass of Irish immigrants belonging to lower social classes and carrying no educational values, but only the desire to survive, made it difficult for both sides to coexist and found the basis of a new society. The immigrants brought with them the religious and ideological conflict between Catholics and Protestants and supplemented in this way a problem that haunted British history from early times. As Tom Devine discusses in his paper there is a major crisis that started with the first wave of immigrants who came from area belonging to what is nowadays the Republic of Ireland and who were mostly Catholics. In such conditions, generated by what should be interpreted as the fled from famine and not immigration per se, the identity of the Irish immigrants transformed itself in a very spectacular way. Their values that were founded on religious beliefs represented an impediment in the process of assimilation that was supposed to take place between the Scottish society and its values and the newly arrived. The differences between the Irish and the Scottish are not to be analyzed only in terms of religion, but also from a social perspective; the nineteenth century meant for Scotland industrialization, new means of work and production that were not present in the rural Ireland. Lack of systematization of work generated not only the difficulties related to food in Ireland, but it triggered problems such unemployment and lack of education and working skills. After the first wave of immigrants, in the years following 1800, the Irish who came to Scotland carried with them a different aspect of Irish identity and, as Tom Devine points out, the interaction with the Scots was starting to open new paths, and the relationship between the two waves of immigration unveiled the fact that there were significant differences of mentality between them and that in the first decades there has been an agrarian improvement in Ireland and that Protestants developed a different intellect and thus were able to cope better with the new social environment. Comparing the two movements, the first one, the Catholics, were driven to Scotland by famine, these people who formed in Ireland a crafting society changed their lives in a significant way, leaving behind their rural homelands and throwing them in the middle of a society that they could not cope with because they lacked industrial skills. However, their identity was not shattered immediately because of the pride they took as Catholics, without realizing that to be an Irish immigrant is not all about expressing a religious statement. The stubbornness and will to survive shaped both English and Irish identities and the experience generated even by these uneducated and ill people imposed new values in the British history. Nevertheless, their desire to permanently reinforce their beliefs and also to create the necessary institutions devoted to its practice helped them surpass their minimal organizational status and rise in time to that of the more evolved Scottish society. The Protestant Irish belonging to the second wave provided a change for the Scottish society and Irish

Science Assignment Example | Topics and Well Written Essays - 250 words - 2

Science - Assignment Example The research conducted revealed that medical conspiracy theories are known and endorsed predicting many health behaviors. Individuals endorsing these theories are normal thus conspiracies arise from common process of attribution. The medical conspiracies act as diagnostic tools for many health practitioners since conspiracies do not follow the traditional medical advice. There are numerous ways to categorize conspiracy theories. Individuals who tend to believe in conspiracy theories endorse a fictitious theory that is made up for experimental purposes. Personality and belief variables are significantly related to conspiracy theories. This results into the question the question of what factors account for variance in conspiracy theories? The psychologist in this study has been unable to come up with factors that account for more than 10% of the common variance (Furnham 5). Thus, individual difference variables explain little of variance in such beliefs. This is in consideration that beliefs in conspiracy theories are widespread across the

MGM330-0704A-04 Business Decision-Making - Phase 3 Discussion Board Essay

MGM330-0704A-04 Business Decision-Making - Phase 3 Discussion Board - Essay Example Hypothesis testing is a statistical method can be utilized in a variety of applications. The method basically allows a researcher to make a claim about a particular population (data) called the null hypothesis which is then tested by this method to determine if the claim was true or false (Levine & Stephan & Krehbel & Berenson, 2006, p.332). The test works by providing a null hypothesis and an alternative hypothesis. If the null hypothesis is either accepted or rejected. If the null hypothesis is rejected that means there is sufficient evidence to validate the alternative hypothesis is true. The normal curve and its corresponding normal distribution table which is associated with Z values is an important variable in the process of a hypothesis test. Hypothesis testing follow a particular algorithm or procedure that must be perform every time the test is perform. The key steps of a hypothesis test are: Another powerful and very useful statistical method is regression analysis. The regression analysis method is a predictive model that allows the statistician to determine the values of a variable within an equation based on the given data about the other variable. This method has very valuable application for forecasting. A common technique of this model is simple regression which can be applied utilizing the least square approach. This approach uses the formula Y = aX + b (McClave & Benson & Sinich, 2001, p.460). The two key variables are called the dependent and the independent variables. An example of an application of this model is a production problem. A company can used this equation to predict many sales it can generate in the future based on past sales totals of the past years. Software such as Microsoft Excel, Minitab or graphical calculators such as the Ti-89 Titanium created by Texas Instrument can be utilized to perform linear regression analysis. There is another type o f regression analysis called multiple

Ethnic Literature Essay Example for Free

Ethnic Literature Essay The term â€Å"ethnic† when in conjunction with the word â€Å"literature† in the academic discourse community of students, often brings out mixed feelings of excitement and dread. On the one hand, students understand that they will be getting away from the canonical American literature – which can equal boring in their eyes; on the other hand, students interpret the term â€Å"ethnic literature† to mean distinctive – which can equal confusing or ambiguous – and perhaps at times not relatable because it is outside their scope of experiences. Perhaps before jumping into why it matters, the term â€Å"ethnic literature† should be defined first and because I am still learning how to interpret this term myself, I searched for a suitable one I could agree with. I found one in an article entitled â€Å"Assessing Teachers’ Knowledge of Multi-Ethnic Literature†, and the article actually used another source themselves to come up with a workable, layman’s definition. Ethnic literature as defined by D. E. Norton (as the article’s source) is, â€Å"Literature about racial or ethnic minority groups that are culturally and socially different from the white Anglo-Saxon majority in the United States, whose largely middle-class values and customs are most represented in American literature† (qtd. in Hager Thompson 22). I think this definition works well to define what ethnic literature is on a surface level, but the more I dig in, I feel that this idea goes much deeper. I asked myself, who can write about ethnic literature? Can anyone just pick up a pen so to speak and tell a story about a young Japanese boy, or a Hispanic family? Can an African-American writer write about Hispanic or Chinese people and claim it is ethnic literature? And the answer to myself is no. Why? Because unless that African-American has been submersed in the Hispanic or Japanese culture from the time of childhood, how are they going to capture the very essence of being, thinking, and living day-to-day in that culture? And even if that African-American had, they would still most likely have a different perspective from the average Hispanic or Chinese person because of being different themselves (i. e black) and perhaps are treated different by the community at large which corrupts the â€Å"normal† cultural thinking. At this deeper level I am trying to get at, I find John M. Reilly’s article â€Å"Criticism of Ethnic Literature: Seeing the Whole Story† helpful in acquiring this. He states that, â€Å"the assertion of ethnicity in literature can be made only through a procedure by which the writer resolves formal problems what moves from recognition of identity to creation of a strategy for handling reality still is not literature until the individual author sustains her or his ethnic identity through a sequence of formal choices† (4). I am interpreting this to mean that as a reader of this literature, I should see and feel throughout the story (perhaps subtlety) that in some way, the characters mindset (and perhaps actions) in the story differ from my own specifically because of the culture they have grown up in in, which has shaped that character’s thinking. There are thoughts and feelings – ideas, I don’t understand without further explanation from the author, which is sometimes provided, and sometimes not. An example of this is in Brando Skyhorse’s novel The Madonnas of Echo Park, I find myself wondering what the significance of the jacaranda trees mentioned in different parts of the book. Looking up what they are, it becomes apparent to me as jacaranda trees are native to Central America – roots back to their homeland. The blossoms from the trees fall and are scattered everywhere. Felicia in chapter 2 states that â€Å"there’s no way getting away from them† (25). Basically meaning, you cannot escape who you are and where you come from. I would not have understood this had I not explored the history of that tree to uncover the significance in the book. Another example is in Seventeen Syllables in the story â€Å"Seventeen Syllables†. The story about a Japanese family is easy to read, but is hard to connect with as I don’t share the same philosophies about a woman’s place in the Japanese culture. A specific instance in the story was when Mrs. Hayashi, Rosie’s mother received her the first place prize for her stellar Haiku. When the man from the newspaper presented her with a package, Mrs. Hayashi, stating she knew it was unorthodox, asked if she might open it because she was very curious. (Yamamoto 17). At this point, I am thinking to myself, â€Å"I don’t get it – why wouldn’t she open it? † but upon reflection, I considered the patriarchal society that is dominant in this culture, and perhaps it is the wife’s obligation to consult or have the husband open the gift, even if it is not specifically for him. Yet another example is in Oscar Wao by Junot Diaz. To come specifically to the point, I do not understand this idea of why it is understood that Dominican men are supposed to be these â€Å"manly men† that women flock to and fall on their knees for. That the sexual appetite along with innate sense of charisma from Dominican men is expected, and when it’s lacking, it doesn’t go unnoticed. â€Å"Anywhere else his triple-zero batting average with the ladies might have passed without comment, but this is a Dominican kid we’re talking about, in a Dominican family: dude was supposed to have Atomic Level G, was supposed to be pulling in the bitches with both hands† (24). Why is this idea so indoctrinated in this culture according to the book? This is perhaps something I will never understand, except that it is a part of their culture. All of these examples are all good and well, but the important question is why is ethnic literature important? What can be gained from reading it? From a most basic viewpoint, it is a highly effective vehicle for helping people understand themselves and the world around them. Thompson and Hager in their article state that, â€Å"multi-ethnic literature mirrors and validates the experiences for minority groups and juxtaposes the familiar with the less familiar for mainstream children† (22). In other words, through reading ethnic literature, readers can find ways to connect with others around them that are different. The article also states that when readers are exposed to divergent thoughts, language patterns, value systems, and different ways of living, that it can open up awareness about others and create compassion and understanding towards them that might not have happened without the literary exposure (23). To sum it all up, I will never argue against the instruction of ethnic literature in the school setting. In fact, I think teaching it should begin right from the beginning in kindergarten, and perhaps one day we won’t need the designated term â€Å"ethnic literature† – perhaps one day it can just be â€Å"American Literature† and part of the regular American canon of literature. Works Cited Diaz, Junot. The Brief and Wondrous Life of Oscar Wao. New York: Penguin, 2007. Print. Reilly, John. M. â€Å"Criticism of Ethnic Literature: Seeing the Whole Story†. Critical Approaches to Ethnic Literature. 5. 1 (1978): 2-13. Web. 21 Apr. 2012. Skyhorse, Brando. The Madonnas of Echo Park. New York: Free Press, 2010. Print. Thompson, Deborah L. and Jane Meeks Hager. â€Å"Assessing Teachers’ Knowledge of Multi-Ethnic Literature†. Yearbook of the American Reading Forum. 1990. 21-29. Web. 21 Apr. 2012. Yamamoto, Hisaye. Seventeen Syllables. New Brunswick, NJ: Rutgers University Press, 2001. Print.

Haemoglobin-related Diseases Management Strategies

Haemoglobin-related Diseases Management Strategies Abstract Haemoglobinopathies or inherited disorders of haemoglobin are the most common monogenic disorders in humans. Red cell transfusion is a well accepted therapy for clinical management of the most severe form of haemoglobinopathies namely, sickle cell disease (SCD) and ÃŽ ²-thalassaemia major. Patients affected by SCD need red blood cell transfusions on a regular basis to reduce morbidity and mortality. The transfusions are administered intermittently to control or prevent a serious complication of SCD, and as a perioperative measure. Or, as a chronic procedure, transfusion strategy is applied to prevent the recurrence, or the first occurrence, of stroke which is a major crisis in SCD, and to manage pulmonary hypertension and other sources of morbidity and mortality. Exchange transfusions are used to reduce the sickle cell haemoglobin (HbS) levels during crisis. Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudic ious. Many side effects of transfusion have been identified and methods to overcome them have been developed. Iron overload (remedy: iron chelation), and alloimmunisation (remedy: phenotypical matching of transfused blood) are two notable examples. Association of haemoglobinopathies and neurologic sequelae after transfusion is also known. At the present time, bone marrow transplant is the only curative procedure available for both SCD and ÃŽ ²-thalassaemia major. Potential therapies involving stem cell transplantation and gene techniques are being vigorously researched. A detailed discussion of the current status of clinical management strategies as applied to inherited haemoglobin-related diseases in particular, sickle cell disease and the thalassaemias, is presented in this paper. 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (G TG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).   2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia. (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing haematopoietic cells, and can result in macrocytic anaemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is ACD (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anaemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weat herall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anaemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocytes, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (HbS) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of haemoglobin, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and del ivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characteristically impaired in A CD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cytokines causing impai rment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  SCD arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle mono cytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell disease including a critical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). 4.1 Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). 4.2 Red blood cell transfusion A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1. 4.3 Indications for intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1). Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACS accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recommended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). 4.4 Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). 4.5 Controversial and indeterminate indications for transfusion Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious in SCD management. Some examples are indicated in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion therapy currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs (Febrile Non-Haemolytic Transfusion Reaction i.e., fever resulting from a blood transfusion) and alloimmunisation to HLAs (Human Leucocyte Antigens),   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (E Haemoglobin-related Diseases Management Strategies Haemoglobin-related Diseases Management Strategies Abstract Haemoglobinopathies or inherited disorders of haemoglobin are the most common monogenic disorders in humans. Red cell transfusion is a well accepted therapy for clinical management of the most severe form of haemoglobinopathies namely, sickle cell disease (SCD) and ÃŽ ²-thalassaemia major. Patients affected by SCD need red blood cell transfusions on a regular basis to reduce morbidity and mortality. The transfusions are administered intermittently to control or prevent a serious complication of SCD, and as a perioperative measure. Or, as a chronic procedure, transfusion strategy is applied to prevent the recurrence, or the first occurrence, of stroke which is a major crisis in SCD, and to manage pulmonary hypertension and other sources of morbidity and mortality. Exchange transfusions are used to reduce the sickle cell haemoglobin (HbS) levels during crisis. Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudic ious. Many side effects of transfusion have been identified and methods to overcome them have been developed. Iron overload (remedy: iron chelation), and alloimmunisation (remedy: phenotypical matching of transfused blood) are two notable examples. Association of haemoglobinopathies and neurologic sequelae after transfusion is also known. At the present time, bone marrow transplant is the only curative procedure available for both SCD and ÃŽ ²-thalassaemia major. Potential therapies involving stem cell transplantation and gene techniques are being vigorously researched. A detailed discussion of the current status of clinical management strategies as applied to inherited haemoglobin-related diseases in particular, sickle cell disease and the thalassaemias, is presented in this paper. 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (G TG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).   2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia. (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing haematopoietic cells, and can result in macrocytic anaemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is ACD (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anaemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weat herall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anaemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocytes, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (HbS) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of haemoglobin, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and del ivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characteristically impaired in A CD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cytokines causing impai rment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  SCD arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle mono cytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell disease including a critical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). 4.1 Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). 4.2 Red blood cell transfusion A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1. 4.3 Indications for intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1). Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACS accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recommended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). 4.4 Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). 4.5 Controversial and indeterminate indications for transfusion Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious in SCD management. Some examples are indicated in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion therapy currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs (Febrile Non-Haemolytic Transfusion Reaction i.e., fever resulting from a blood transfusion) and alloimmunisation to HLAs (Human Leucocyte Antigens),   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (E