Leadership Values To Individuals And Society General Studies Essay

Leadership Values To Individuals And participation General Studies EssayLeadership is the art of making people to do what you want them to do. It is a process of influencing otherwises working for the coarse satisfactory and common goals while offering purpose and paths to achieve that. The army defines leadership as influencing people by providing purpose, direction, and motivation, while operating to accomplish the mission and ameliorate the knead-up (Army Leadership, Personnel General, Army Regulation 600-100). on that point argon disparate approaches to leadership as transactional leadership, transformational leadership, propertyal leadership, and contingency leadership. Even that each these leadership approaches bear similarities and differences they afford all incorporated into them fear and/or honor as a mean to achieve goals. Looking at the leaders billet this is his/her face-to-face behavior and the environment that they surrounded with or they faced at the beginning of the c atomic number 18r what real shape their future style of leading. If integrity leader dealt with fear and pressure from his/her supervisors, it is very belike that they pull up stakes likewise treat their subordinates the same way. In the other hand, if the leader was treated with reward and this was what build and shaped his or her base of leadership it is very likely that he go away treat his/her subordinates the same way.Even that there are different theories in the practice there always has been in suspense whether it is better to be feared or consider. And both of these are used in army leadership and in leadership in non-military organizations. It is very plain that to some leaders simply fear exists as a unprompted force toward achieving goals. They do non prefer to use other manner as motivation for pushing their subordinates. In the other hand, seems that subordinates do not prefer fear to be their driving force. Instead they would like to piddle such a relationship that would push them to work tirelessly to match their leader, further not fear.In this account I am overtaking to explore what does it mean for a leader to be feared or complianceed and what final result has it in his/her subordinates in particular or to the society in general based on personal experience as a cadet and what I learned and read near leadership. This paper actually is going to come across military leadership and leadership in non-military organizations.Respect by definition is esteem for or a sense impression of the value or excellence of a person, a personal property or great power, or something considered as a manifestation of a personal quality or ability (www.dictionary.com) heed is acknowledged to be a positive value that people posses. But people are not very conscious of what observe really means and of what markificance it is. In or so cases paying attention is perceived to as a judgment or opinion of some unmatchabl e not as a value. Based on my personal experience I can say that for observe to be durable it should be earned. It is important that a person should show respect to himself, to others (people that surround us), and try to earn the deserved respect. Since respect is viewed as a perspective for relationship, people decide whether it is achieved as a commitment for a successful relationship between people or whether it is part of our culture.For creating a world with collaboration and mutual respect we study to build a culture with worldwide respect and transmit our commitments toward others as respectable mankind beings. The basis for achieving respect in the leader-subordinate aspect is having satisfactory interactions with others. If there is a respectful environment there are possibilities for sharing vision, trust, mission, and there will be stronger teams within the organization to achieve common goals. A abduce by Mark Clement says that leaders who lucre the respect of othe rs are the ones who deliver more than they promise, not the ones who premise more that they can deliver. This shows that the ferment of a leader is largely increased when he or she has the respect of the subordinates and done this they can achieve what is thought to be unachievable pave the road to success.But expecting to reach all the goals with only the respect of the subordinates strength have shortcomings as well(p). Subordinates can be of a level not mature enough to understand what mutual respect means and this whitethorn turn against the leader. Also the leader might not induct a realistic evaluation of the subordinates and as a result the reliance on the respect might end in catastrophe. Machiavelli in his book Prince gives some(prenominal) reasons why a leader should not rely on peoples respect because they are ungrateful, fickle, false, cowardly, covetous, and as long as you succeed they are yours all in all they will offer you their blood, property, life and child ren. As is said above, when the read is faraway distant unless when it approaches they turn against you (Prince, 79). This actually tells that a leader moldiness much more rely in his/her own forces and make a proper evaluation of the readiness of his/her subordinates in order to not have a catastrophic end.Among the very first things taught in military academies is respect. This is overly taught to all soldiers. The very difference is that leaders have to know to win respect for themselves and for the others with whom they work and to create a respectful environment. Even that in militaries a straight chain of command exists there is an apparent need for respect. It is subjective having respect for one another because that is actually what makes the military to operate. Having respect means also having trust between each other which essential for performing daily activities and during crisis. Without respect subordinates would always look for ways to lean from their leaders a nd things would hardly ever be done on time.There are several ways to earn respect in military. On and the most important one is by living with army determine and becoming a role model for people that surround you. Moreover, the higher(prenominal) you go in ranks gives you a higher respect since earning higher ranks is not easily attained. In military when you have the respect of your subordinates it is much easier to empower them and delegate tasks without being reluctant that they will not perform well. Thus, it is worth quoting KPC (Kosovo Protection Corps) Officers Manual 103, which states that mutual respect will create a bond between officers and soldiers and it will always be there when hood times appear.There are certain ways to show that you respect someone. If you always tell the truth in good or lousy times it is a home run of respect, if you make promises and keep them it is a sign of respect, and if you treat all your subordinates at the same level it is a sign of respect.There are many cases in which leaders were respect. This was actually the chief(prenominal) driving force of peoples belief on their leaders and their decisions to be implied. Sir Winston Churchill was one of the most respected leaders in history. He led linked Kingdom during the most difficult times. He had many cases when he had to make tough decisions that were not very popular but were very well accepted. These decisions were accepted only for a reason, the respect that people had for him.In the other hand, the other component of federal agency is fear. This derives mainly from the capacity of the leader to r eveningge his/her subordinates. Some leaders have coercive power and use as the main tool in achieving their goals. These types of leaders tend to believe that through coercion you can achieve much more because you get the most from subordinate since they fear you. This derives from the belief that if someone fears you he or she will do anything just to not put into question your authority. Fearing the leader is a process that starts when subordinates come to contact for any sort information about this particular leader. They might hear that from the other fellow employees or other soldiers if military organization, that the leader is really a person who punishes in hardest way. In the book Prince, Machiavelli believes that it is impossible to achieve both respect and fear but when you have to choose between them fear is much more productive. He states that since you cannot trust people in tough times and it is better to be feared because fear preserves you by a dread of punishment which never fails you (Prince, 80).The coercive power mentioned above is based on fear and is the ability to punish someone for any noncompliance. One way that leaders nip their subordinates is by showing them that they are not complying with the process enforced by leader. However, also by fear and coercion can be achieved a lot of results.In the military fea r of leader exists in all levels, from the newly recruits up to the senior officers. In the beginning of the military go soldiers fear from the leader because he can use his power and authority to punish them, which can have a negative result in their career. Interesting is the fact that these new soldiers have their utmost respect for their commanding officer but yet fear has more influence than respect. This is much related to the stages of individual development and to the environment they perform in. There are a lot of cases that soldiers do things only regarding to the fear they have from their leader. There are also a lot of leaders that use fear upon their subordinates even that they complained when their former leaders used coercion on them. A good example of a leader who used fear could be Enver Hoxha, the communistic leader of Albania. He was considered to be the best man to lead Albania later World War II. He had graduated from a prominent cut University and fought h eroically during the war. But Albanian people turned to be wrong. As he came to power he started eliminating his opponents and anyone who could come on his way. The most know eliminations were deportation, imprisonment, family punishments and not excluding killing people. These eliminations had a very high psychological effect on the population. During this time Albania became a country where the continuous repression had affected everyone.This paper has been an overview of two sides of conceptualization of leadership by subordinates, respect and fear. Fear has the course to make employees or soldiers perform better and achieve results but they incur unworthy as individuals. Respect is much more welcomed because it makes employees or soldiers to belief more confident and to feel themselves as part of team. At the military point of view much respect is assigned to certain positions and ranks but only the real respect is the everlasting one.In conclusion I think that in order to be a properly respected leader you must at first show respect. If you earn to the respect of the employees is much easier to accomplish goals, also the job performed by the subordinates will be of a higher level. The point is that if you earn the respect of the employees or the soldiers in a military organization, they will perform accordingly whatever the situation or when not under direct supervision. Promoting respect to any organization gives a dose of authority through influencing people.We should always try to make respect the core of our relationship with others. Having a mutual respect with subordinates only brings us success and continuous improvements. This kind of relationship will have sincerity at the top of it something that will create an everlasting proneness and willingness to help each other. Only the true respect will juice up the subordinates to perform their best, and their best means the best for leader.

Successful Asian Businesses

fortunate Asian Businesses1. IntroductionThe aim of this report was to show the association of the orbiculate moving in st directgy in the C.P. convention industry betwixt of Thai grease substantial outline and Multinational firm strategy. The C.P. convention is the unmatchable of Asia leading successfully occupationes and affiliates within the tillage business retail, real estate and telecommunication industries. closely of well-k at present nutriment harvest-homes to an Asia and European countries (Asian Institute of engine room cc9). This information is as well linked in to the business oerview of C.P. group industries, goal of business and through effectual global follow strategies. Moreover, this report has showed some most fundamental relevant of functional of the global business strategy has come into effect in the C.P. group industry system.2. ships corporation BackgroundThe C.P. group industry is now become to the one of the extremum of the fast growing industry in Asia (Best Industry congregation 2009). on that point argon selling farm products, horticulture products, operating retail super commercializes (TESCO sacred lotus, Seven-Eleven), world-wide trading, telecommunications (True corporation), plastics, pet foods, automotive, industrial products, real estates and land maturation (Charoen Pokphand Group 2009). The C.P. Group was founded in 1921 by the two Chearavanont brothers named Ek Chor and Chorncharoen in the heart centre of capital of Thailands mainland mainland china town in Thailand. The two brothers began by moing seed and vegetables from China and exportinging pigs and orchis to Hong Kong. In 1951, they were earn to fly high into other related line of businesses, reasoning quite justly that the seeds they were selling to the sodbusters would produce to the raw material crops for fleshly run through and to a greater extent importantly. China tailers would become their customers. In 1954, the Charoen Po kphand Feed mill was posit up for the C.P. Group later. The development was lead blowup along vertical consolidation line, beginning with poultry, followed by swine. Moreover, in 1990 the C.P. Group has become totally feed mill corporations in Thailand and region it has become to the joust of the fifth largest merchandise mill producer in the world (C.P food oecumenical 2009). Nowadays, tour retaining strong links to its native country the group also trades and drops internationally with more than than 100,000 employees worldwide.Applying to The Cultural Iceberg model (2004), (see in appendix 1) the C.P. Group has parts as organizational cultural thusSurface farming the C.P. Group corporation is a well know as proud profile food industries and other related line of businesses in Asia mystical Culture The CP Groups organization structure is vertical structure. In experimental condition of pecuniary investment the CP Group investing at least(prenominal)(prenominal) THB 123.6 billion (2.5 billion) between 2008 to 2013, in a wide range of businesses including telecoms, property, confideing and retail (Business mass in Asia 2009)3. Situation synopsis3.1 Business Environmentmacro Environment AnalysisIt is very significant for CP Group industry to analyse Macro environment. Macro environment consist of Political, Economic, Social-cultural and technology factor. It exit make a motion for CP Group business in Thailand.Political Thailand has unstable semipolitical environment effect from the political problem people are divided in two groups, one group brook to the previous government a nonher group support to the present government. Moreover, the 2009 group protests are also happening in Thailand. Thailand has a parliamentary democracy. Thai legal is follow by civil fair play concepts, which accept compulsory ICJ jurisdiction with reservation. Thailand enjoys international trade and investment, which has signed bleak trade agreements with sev eral countries, including Thailand (FTA) and also a member of organizations much(prenominal)(prenominal) as WTO (Economist 2009).Economic In terminal figures of its economy Thailand has low GDP rate (see appendix 3) effect from political problem. Thais economy is dominated by the gardening product and travels (Thai Export Products 2009). Thais economy is anticipate to slow down in 2009 due to the political problem, global financial market issues and decrease in municipal demand. Moreover, the consumer p sift inflation seems to be a big problem. However, in term of trading it is still one of the great economic countries in South East Asia (Popline 2009)Socio-Culture Thailand is an unstable society that effect from political problem. Buddhistic has become to the main religion follow by Islamic and Christian. There are roughly 64 million people are liveliness in Thailand in 2009. The official national language is Thai. In term of developing countries, Thai people rich person a normal gauge of physical environment, lifestyle and learning (Thailand senesce of investment 2009).Technology Technology and cornerstone play a vital role in the Thailand economy. Its infrastructure is very good tho the pollution problem seem to be the big issues in Thailand because leave out of technology to control the pollution such as the water pollution from industrial areas. However, Thailand is the one of leader in term of communication and IT proceedss.4. Core radical of strategyNowadays, Charoen Pokphand Group is the biggest food familiarity in Thailand which has invested and managed in numerous industries in both domestic and international. Agribusiness is mainly rooted of fraternity to penetrate directly to international market. There are three returns philosophy of confederacy to do business including benefit to the Country, People and corporation. ( CP confederation 2009)The company believes in half-dozen guiding principle as they make the company dif ferent from rivalry and they also useful for company to corporate in culture. The guiding principles consist of Professionalism, Product innovation, Customer satisfaction, Versatility and adaptability, Quality products at lowest worths and Dedication and inscription of the workforce. The mission of company is to energize the soundbox and mind of communities to which we serve. Energizing the body consist of cultivating and treat crop products for animal feed, production and further processing of livestock and aquaculture products , providing channel of food consumption thought food service and retail outlets. Energizing the mind comprise of providing integrated communication and nitty-gritty service through fixed, wireless and cable networks. ( CP company 2009)4.1 Global schemeCP has promoted as the first truly Thai global company which is cooking to expand business slowly but confidently. (capital of Thailand brook 2003) CP focus to do RD to analysis the target market forw ards doing business in fact countries. (Umesh 2006) In addition, the company has more focus on logistic and dissemination to be an important component for future growth. (capital of Thailand run 2003) The company has apt(p) franchise of 7-11 Inc in US to operate in Thailand. Nowadays, CP 7-11 network is the by largest retails business in the worlds which there are more than 4,000 retails in Thailand. Moreover, the company has expanded their 7-11 networks to China and has the plan to get the license to set up 7-Eleven in Vietnam and Cambodia. (Jitpleecheep 2002) In terms of Tesco genus white lily, it is a jointventure between CP Company and Tesco from the UK, it was the hypermarket of CP Company in both Thailand and China. Since 2003, CP Company had sold the donation of Tesco Lotus in Thailand to Tesco because the Company want to focus on 7-11. However, the company has kept the share of Tesco Lotus in China by operating under Lotus trademark. (CP company 2003)The Company also is planning to be a protagonist in Premier League team which can represent CP punctuate in the global market and hit brand awareness before its competitors. (About CP company 2009)The company is planning to expand 7-11 convenience storage and Lotus in particular country as it can help company to develop in logistics sector and also help the company to dish their products. (Bangkok Post 2003) The company expects to expand 7-Eleven convenience stores by setting up more than 1000 outlets at PTT service station which is the largest fuel product retailer in Thailand. (Jitpleecheep 2002) Moreover, the company has used the strategic to make the release in the retails by purporting a new service to customers. In addition, CP bugger off managed 500 shops of CP Fresh Mart shops worldwide and planning to expand to 700 shops within 2011.( (Bangkok Post 2002)In terms of cps food industry, the company has integrated as a agro-business operator which provides production technology, aquacul ture practices and also have product traceability system. (Charoen 2005) The company has promoted cycles/second food resort standard to growth consumers confident and to complete in global market. CP expects to increase fresh eggs export business to support raising demand of consumers in Hong Kong, Africa and the pith East.(Bangkok Post 2009) CP also expects to increase rice export from Thailand to many destinations. Thus, the company has to expand their rices supplier (millers) as the company does not mill rice by itself, the Company buys the rice and repack under Royal Umbrella brand.(Walailak 2008)4.2 round strategy in ChinaSince 1979, CP had established in China which current the first business registration certificate from Chinese government to set up the shop in specific economic zone primed(p) in Shenzhen. (CP company 2009) The company used Agribusiness as a concept to expand their business and to increase living standard. Moreover, CP Company also provided motorcycles , telecommunication, beer brewing, petrochemical and retail in China which employed more than 15,000 peoples. The company had the strategy to make a joint ventures with topical anesthetic company and farmer in every province to expand their business. In terms of, motorcycles sector, the company own 70 percent of EK Chor China bike and was the first company in China on Wall Street since 1993.(Louise 1996) In 1994, the company produced more than 900,000 motorcycles. Moreover, CP had opened the first lotus Super centers in 1996 and also had the bank in ingrain to cooperate with 4,000 SME which supplied the goods for Lotus.Nowadays, the company has more confident to increase an investment since China had joint with WTO. CP Company has invested in China more than 30 years which more than 40 percent of revenue came from China market.(Bangkok Post 2009) The Company has invested to increase the retails and its property development in particular in Shanghai (Pudong), the company built up Super Brand nitty-gritty which is the biggest Asia entertainment 0complex to support high purchasing power of 160,000 shoppers.(Walailak 2007) Moreover, CP company is expected to raise in bargain volume in both Lotus and Shopping mall about 13 percent within 2009. (Bangkok Post 2009) In terms of motorcycles sectors, the company focus to increase their market in Chinas provinces in stead of focusing in big city such as Beijig and Shanghai that motorcycles are not permitted to drive inner the city. As high competitive of manufacture in this sector, CP Company decided to trim to footing from 10,000 to 4,500 yuan per unit to stay in the market. (Thapanachai 2002)4.3 rhythm swot analysisStrengthsHigh product qualityThe Charoen Pokphand Group (CP) has high news report in marketplace in Thailand by using Agribusiness to be a concept for business. CP products have high quality and reliable which are be classified in high class products and they are satisfactory in market.Strong poli cies to maintain organization growingThe company focuses on theirs human resource management to maintain their company standard by promoting staff aged between 20-30 years and to give the chance for them to create idea and to run departments. The company also has job evaluations from psychometric interrogation and training program. Moreover, the company had set the long-term goal to be a guild line for employee to prepare themselves to achieve to objective.( (Bangkok Post 2003)Understanding the motif of major market to raise living standardThailand is land of tillage which farmer is a majority occupation in the country. Company focuses on horticulture to be the core business by offering the seeds to farmer and provides retailer to buy the crop after harvesting. The company has integrated industrial farming. the six major steps carried out by CP were seed production, animal husbandry, animal production, food processing and marketing. All activities make the company to monopolies the agriculture market.Diversity of CP businessCP has diversified the business to more than one business area that can help the company to reduce the risk. The company is not only to deal business in food industry but also to manage in telecommunications industry and to provide the retail such as 7-Eleven and Lotus to expand their food products.(Charoen 2006)Competitive priceThe company has used mass products to reduce the cost and to expand the market for the products. (Umseh 2007)Weaknesses low breadabilityIn the recent years, CPF profitability has been decreased against the change magnitude of revenues to over 7.9% in 2006 to 2007. Moreover, both operating profit margin and the net profit margin declined from 3.9% to 2.9% and 2% to 0.9% from 2006 to 2007 respectively. Profitability decreasing represent that the company lack of control over an operating and it can make the company to perform its growth plans. (Business Source do 2008)Over dependence on Thailand marketMore than 86% of CP products had been sold in Thailand in the recently year, it represents that the company have more concern with Thais economy. Therefore, the fluctuation in Thailand might pose negative to companys revenues.(Walailak 2007)OpportunitiesIncreasing exports of value added meat productsAfter the spread of darn Flu, some countries such as Europe and Japan have banned the import of raw meat from Thailand thus CP company has improved theirs uncooked meat products by adding value to be cooked meat products including egg turn in herbs, grilled chicken, duck and sauced duck. On 2006, the cooked meat export worldwide had raised by 20-30% and the demand is expected to increase globally.(Charoen 2006)Free Trade Agreement between Thailand, Australia and New ZealandThe Agreement have changed the company to be more competitive in Australian and New Zealand market. It brings the great benefit for company to improve the assessment to agriculture product such as mangosteen, longan, lychee and coconut.(Walailak 2007)ThreatsIncreasing of vegetarianism dilute.The increasing health awareness of consumers drive the increasing demand to consume low carbohydrate and low calorie foods which affect to the increasing demand of vegetarian foods worldwide. The vegetarian food market worldwide is estimated to growth around $1,700 million within 2010 and Asia people are changing to become vegetarian. The vegetarianism trend might effect the sale volume of poultry and meat. ((Business Source Complete 2008)Bird and swine fluFlues become the important factor that affect the sale volume of company in both domestic and global market. In Thailand, Bird flue has hit domestic sales of chicken which chickens price went down 31 percent to approximately 24 baht per kg. In terms of global market, both European and Japan had ban the import of fresh meat from Thailand.(Charoen 2005)5. Issues5.1 Global Financial CrisisThe financial and economic crisis in the US impacts other export markets, es pecially Europe and Japan. Thailand mainly export to the US, Europe and Japan. Overall Thailands exports are expected to drop at least 10 percent. This situation also impact on Thailands food exports. Thus, CP would invest in new market such as Africa, the Middle East, India and easterly Europe, especially Russia and Ukraine. However, CP would face difficulty in expanding their business (Thai News Service, 2008).5.2 EU quota changesCP will face pressure because EU wants to modify tariff quota for neat poultry in 2009. Currently, EU had given Thailand a export quota parceling of 252,643 tonnes. It consists of 160,033 tonnes for processed chicken and 92,610 tonnes for salted poultry. Under the quota, the tariff is 8% of the price per tonne. For chicken exported above the quota, the tariff is 53% (Thai News Service, 2009). CP was closely supervise this problem because it might impact the companys poultry export. For this situation, Thai government is talk with the EU for maintainin g or increasing the countrys export quota of processed poultry. CP will offer other trade benefits in exchange. Nevertheless, if Thai government cannot achieve the constructive result in the negotiation, CPs current sales will not be affected much but it may reduce CPs chance to increase export volumes to the EU in the long term (Bangkok Post, 2009).5.3 Bird fluAfter the bird flu outbreak, many countries, especially Europe and Japan, have banned the uncooked meat from Thailand. It impacts on the CPs uncooked meat exports. However, the growing global concerns the bird flu will increase the focus on cooked food and seafood products. CP is expected to sell these products 200 billion baht in 2010. Currently, cooked food, especially Thai ready-to-eat meals, gain a good response from consumers in the US, Europe and Australia. Moreover, CP will increase its tip and shrimp products in the domestic and international markets. Due to many consumers have more awareness of quality and food saf ety. Thus, CP should increase branding campaigns and consumer education in order to emphasize the firms food safety standards (Kittikanya, 2005).5.4 Lack of managerial staff in ChinaCP launched the first Lotus Supercenter in China in 1998. Now, CP has 79 Lotus outlets in China. Currently, CP stops expanding of Lotus because of a lack of managerial staff. Moreover, CP changes strategy to improve the operational efficiency. CP plans to allow local staff to make the product that is suitable for customer in from each one province because China is huge (Keeratipipatpong, 2007).6. ConclusionCharoen Pokphand Group (CP) expands their business worldwide. in particular in China, CP is the largest food foreign company and also provides many kinds of product. Moreover, the development was lead expansion along vertical lines such as agriculture products, retail supermarkets (7-11 and Lotus), telecommunication, real -estate development and automotive products. CP expands their business slowly a nd confidently by using logistics and distribution as a key for hypermarket, it normally makes a joint venture with a local company to do the business in particular countries. CP also uses RD to analysis the target market. In addition, the company focuses on logistics and distribution. Nowadays, China is big international market for CPs products because there is high consumption from future increasing of Chinese population. Thus, this is an probability for CP company to increase the sale volume, brand awareness and this is a significant challenge for the next step of companys growing.BibliographiesAbout Charoen Pokphand Group 2009, Charoen Pokphand Group, viewed 12 kinfolk 2009, http//www.cpthailand.com/Charoen, K 2005, CPF shifts to cooked and seafood produce, eyes higher(prenominal) sales, Bangkok Post(Thailand), 10 Nov, Australia/New Zealand persona Centre, EBSCO host, AN2W60773310804, viewed 3 Sep 2009.Charoen, K 2006, CPF to tap rising Russian demand, Bangkok Post(Thailand), 7 July, Australia/New Zealand fictional character Centre, EBSCO host, AN2W62W6736640724, viewed 3 Sep 2009.Charoen Pokphand Foods Public Company Limited 2008, Charoen Pokphand Foods Public Company Limited SWOT Analysis, p1-8,8p, Business Source Complete, EBSCOhost, AN34307048, viewed 1 Sep 2009.Charoen Pokphand Group 2009, About CP, viewed 1 Sep 2009, http//www.cpthailand.com/AboutCP/tabid/216/Default.aspxCharoen Pokphand Group 2009, Charoen Pokphand in China viewed 12 kinfolk 2009, http//www.cpthailand.com/CorporateCommunications/pageNewsroom/tabid/107/articleType/ArticleView/articleId/163/Default.aspxCP food worldwide 2009, inner CP Group, viewed 12 September 2009, http//www.cpfworldwide.com/CP revamps Lotus network in China 2009, Bangkok Post, 25 July, Australia/New Zealand role Centre, EBSCO host, AN2W6519933027, viewed 4 Sep 2009.Economist 2009, Thailands political crisis Dousing the flames, view 12 September 2009, http//www.economist.com/world/asia/displayStory.cfm?story_ id=13496330Food safety allows CP to expand egg enterise 2009, Bangkok Post(Thailand), 18 Nov, Australia/New Zealand Reference Centre, EBSCO host, AN2W62W63112895133, viewed 3 Sep 2009.Head of Thai Agri-Product Maker Aims to Go Fully Global, 2003, Bangkok Post(Thailand), 21 Jan, Australia/New Zealand Reference Centre, EBSCO host, AN2W63013363186, viewed 3 Sep 2009.Jitpleecheep, S 2002, Thai Group Seeks Licences to Open 7-Eleven Stores in Cambodia, Vietnam, Bangkok Post(Thailand), 28 Sep, Australia/New Zealand Reference Centre, EBSCO host, AN2W61784931632, viewed 3 Sep 2009.Keeratipipatpong, W 2007, CP to list mall on Shanghai bourse IPO proceeds to fund expansion in China, Bangkok Post (Thailand), Australia/New Zealand Reference Centre, EBSCOhost, AN 2W64141647244, viewed 16 September 2009.Kittikanya, C 2005, CPF shifts to cooked and seafood produce, eyes higher sales, Bangkok Post (Thailand), Australia/New Zealand Reference Centre, EBSCOhost, AN 2W60773310804, viewed 11 September 20 09.Louise, L 1996, Thai company putting more chihens on Chinas tables, Chinatown News, issued 10, p20, 2p, Academic try Complete, EBSCOhost, AN9606155618, viewed 5 Sep 2009.Popline organization 2009, Country watch Thailand, view 11 September 2009, http//www.popline.org/docs/1346/148699.htmlPoultry firms eye EU quota changes 2009, Bangkok Post, 10 August, Factiva, register BKPOST0020090809e58a000k9, viewed 10 September 2009.Thai Food Company Announces New China Strategy, 2002, Bangkok Post(Thailand), 23 May, Australia/New Zealand Reference Centre, EBSCO host, AN2W60495805783, viewed 3 Sep 2009.Thailand board of investment 2009, Social and Culture inside Thailand, view 12 September 2009, http//www.boi.go.th/english/how/social_and_culture.aspThailand Charoen Pokphand executive predicts economic downturn to last at least 2 years 2008, Thai News Service, 1 October, Factiva, Document THAINS0020081001e4a10005q, viewed 16 September 2009.Thailands Charoen Pokphand Foods (CPF) Updates on 2 key issues 2009, Thai News Service, 12 August, Factiva, Document THAINS0020090811e58c000ad, viewed 10 September 2009.Thailands CP Group Investment 2009, Business Trends Asia, viewed 12 September 2009, http//www.cpfworldwide.com/cpd/en/page/ir/financial_information.aspxThapanachai, S 2002, Thai Motorcycle Output to Rise Six-Fold, Bangkok Post(Thailand), 16 July, Australia/New Zealand Reference Centre, EBSCO host, AN2W62415351361, viewed 4Sep 2009.The top of the fast growing industry in Asia 2007, Best Industry Group Co.,Ltd, view 10 September 2009, http//www.best-industry.com/Umesh, P 2006, CP leads the way overseas, Bangkok Post(Thailand), 18 Nov, Australia/New Zealand Reference Centre, EBSCO host, AN2W62W62277444032, viewed 3 Sep 2009.Umesh, P 2007, CP executive says inquisitive move to China nearly 30 years ago has salaried off, Bangkok Post(Thailand), 20 Jan, Australia/New Zealand Reference Centre, EBSCO host, AN2W61968696986, viewed 3 Sep 2009. scream of CP Group 2009, Asian I nstitute of Technology, viewed 10 September 2009, http//www.careercenter.ait.ac.th/Walailak, K 2007, CP to list mall on Shanghai bourse IPO proceeds to fund expansion in China, 29 Oct, Australia/New Zealand Reference Centre, EBSCO host, AN2W64141647244, viewed 4 Sep 2009.Walailak, K 2007, CP unit taps demand overseas hybrid corn projects in China also Bangkok Post(Thailand), 5 Mar, Australia/New Zealand Reference Centre, EBSCO host, 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Causes, Symptoms and Treatments of Anaemia

Causes, Symptoms and Treatments of genus Anemia1. Introduction genus Anemia is a syndrome characterised by a lack of healthy goingnessdened crease cubicles or protohemeoglobin wishing in the business- redness slant carrells, end pointing in inadequate oxygen bring out to the tissues. The control give the bounce be temporary, semi stable or continuing, and of mild to flagitious intensity. There be m some(prenominal) arrive ats and drivings of genus Anemia. normal product line consists of three characters of origin mobile ph ones snowy cable kiosks (leucocytes), platelets and red assembly line kiosks ( red pipeline carrelphoneular phoneular telephones). The first cistronration of erythrocyte harbingers in the develop foetus atomic gist 18 produced in the yolk sac. They ar carried to the developing liver by the billet where they form mature red brook cells that be demand to en itemizeer the metabolous needs of the foetus. Until the eighteenth week of gestation, erythrocytes be produced merely by liver after which the doing shifts to the spleen and the wad totality. The life of a red blood cell is about 127 sidereal daytimetimes or 4 months (Shemin and Rittenberg, 1946 Kohgo et al., 2008). The briny set outs of genus Anemia ar blood issue, output of too fewer red blood cells by the study eye or a rapid destruction of cells.Haemoglobin, a protein, en collectible in the red blood cells is composite in the post of oxygen from the lungs to solely(a) the another(prenominal) variety meat and tissues of the personate. constrict is an strategic lot of the haemoglobin protein structure which is intimately mired in the transport of oxygen. anemia is ordinaryly de first-rated as a bring low than normal haemoglobin density. The normal blood haemoglobin concentration is dependent on maturate and sex, and, according to the World Health placement (WHO) Expert Committee Report, anemia res ults when the blood concentration of haemoglobin go 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 start depending on the ethnicity, senesce, sex, env compressmental conditions and f atomic number 18 habits of the population analysed. According to Beutler and warren (2006), more than reasonable benchmarks for anaemia argon 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The none value for women of alin concert ages would be 122 g/L. Also, the bring down limit of normal of haemoglobin concentrations of Afri mass Americans atomic number 18 appreciably lower than that of Caucasians (Beutler and Warren, 2006).Besides the well accepted branding campaign privation anaemia, several genetical anaemias argon in like manner knget. These ar for the close to part haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of genu s Beta-chain or alpha-chain produce the respective(a) medically significant haemoglobinopathies. The variations in amino blistery composition induced heritableally impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes become bothers that be qualitative abnormalities in the entailment of haemoglobin (e.g., reaping hook cell infirmity) and some(a) that be valued abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In element cx, the missense magnetic declination in the -globin gene causes the dis ramble. The mutation causing reap hook cell anemia is a single nucleotide surrogate (A to T) in the codon for amino blistering 6. The substitution converts a glutamic superman codon (GAG) to a valine codon (GTG). The form of haemoglobin in persons with reaping hook cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the h aemoglobin tetramers to sum total into arrays upon deoxygenation in the tissues. This aggregation take ins to deformation of the red blood cell making it relatively inflexible and restrict its exploit in the capillary vessel beds. perennial cycles of oxygenation and deoxygenation top off to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds footings the kidneys, amount and lungs plot the unceasing destruction of the sickled red blood cells triggers inveterate anaemia and episodes of hyperbilirubinaemia.Fanconi anaemia (FA) is an autosomal recessive condition, and the close prevalent type of inherited bone burden failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and lancinating myeloid leukaemia (AML) world change magnitudely present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet other disorder caused by a dent in haemoglob in synthesis.Auto repellent hemolytic 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 life spoil (Sokol et al., 1992).megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in surface than normal. The disorder is usually associated with a neediness of vitamin B12 or folic acid . It can in addition be caused by intoxicant abuse, drugs that impact DNA much(prenominal) as anti-cancer drugs, leukaemia, and trusted inherited disorders among others (Dugdale, 2008).Malaria causes increase deformability of vivax-infected red blood cells (Anstey et al., 2009). malarial anaemia occurs payable to lysis of sponge-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).Large standards of agitate ar e needed for haemoglobin synthesis by erythroblasts in the bone effect. beta globulin receptor 1 (TfR1) uttered mellowly in erythroblasts plays an important place in extracellular adjure uptake (Kohgo et al., 2008). Inside the erythroblasts, atomic number 26 transported into the mitochondria gets corporate 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 shopping mall disorders, characterised by mitochondrial straighten out choke in developing red blood cells. These conditions are diagnosed by the presence of pathologic push out deposits in erythroblast mitochondria (Bottomley, 2006). 2. Classification of anaemiaAnaemia can be generally class based on the syllable structure of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The geomorphologic classification is based on sloshed corpuscular saturation (MCV) and comprises of microcytic, macrocytic and normocytic anaemia.(a) Microcytic anaemia refers to the presence of red blood cells smaller than normal volume, the trim MCV ( 15 would probably signalise IDA (Chulilla et al., 2009).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 haematogenic cells, and can result in macrocytic anemia. Drugs that intermeddle with nucleic acid transfiguration, such(prenominal) as.hydroxyurea increases MCV ( 110 fL) while alcohol induces a reticent macrocytosis (100-110 fL). In the initial stage, intimately anaemias are normocytic. The causes of normocytic anaemia are nutritionary deficiency, renal failure and hemolytic anemia (Tefferi, 2003). The just about common normocytic anaemia in adults is anaemia of continuing ailment (ACD) (Krantz, 1994). Com mon childhood normocytic anaemias are, prodigally weight-lift deficiency anaemia, those delinquent to stabbing bleeding, sickle cell anemia, red blood cell membrane disorders and current or recent contagious diseases in particular in the very puppylike (Bessman et al., 1983). Homozygous sickle cell distemper is the most common cause of haemolytic normocytic anemias in children (Weatherall DJ, 1997a).In practice, the morphological classification is quicker and therefore, more useful as a characteristic tool. Besides, MCV is also closely connect to lowly corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte denotative in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anemia and increase together in macrocytic, hyperchromic anemia.Pathogenic classification of anaemia is based on the business pattern of red blood cell whether anaemia is due to inadequate production or handout of erythroc ytes caused by bleeding or haemolysis. This tone-beginning is useful in those contingencys where MCV is normal. Pathogenic classification is also congenital for proper recognition of the chemical mechanisms confused in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is moreover divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is fall because of damage function, rock-bottom number of precursor cells, trim bone marrow infiltration, or lack of nutrients and (ii) regenerative when bone marrow upregulates the production of erythrocytes in answer to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increase 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 high.Sickle cell ailment is characterised by sickled red cells. The first tale of atomic number 110 was published a century ago noting the presence of unmated elongated cells in blood by James Herrick, an American doc (1910). Pauling et al. (1949) described it as a molecular(a) disease. The molecular character of sickle haemoglobin (Hb S) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of Hb, 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, blend deoxygenated (Bunn, 1997). The abnormal red cells hear down, tip to anaemia, and clog blood vessels with aggregates, leaders to recurrent episodes of disgustful disorder and multiorgan ischaemic damage (Creary et al., 2007). The high levels of seditious cytokines in atomic number 110 whitethorn promote retention of entreat by macroph age/reticuloendothelial cells and/or renal cells. atomic number 110 shell out usually depends on blood blood transfusion that results in weight-lift surcharge (Walter et al., 2009).3. Pathogenesis of anaemiaAnaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia collect been recognised, the pathogenesis of each cosmos unique. compact 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 period the causes of adjure deficiency vary significantly depending on chronological age and gender, IDA can reduce puddle capacity in adults (Haas Brownlie, 2001) and affect force and mental development in children (Halterman et al., 2001). The transfiguration of press is uniquely controlled by assiduousness rather than excreta (Siah et al., 2006). Iron absorption typ ically 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 straighten out overload, and increases up to fivefold under conditions of campaign depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) make in plant and dairy farm products. In the absence of a regulated excretion of iron by means of with(predicate) the liver or kidneys, the only way iron is lost from the body is through bleeding and desquamation 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 fooling production of 300 billion erythrocytes (20-3 0 mg) is provided broadly by recycling iron by macrophages (Andrews, 1999).Iron deficiency occurs when the metabolic demand for iron exceeds the amount uncommitted for absorption through consumption. want 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 normally attri neverthelessed to blood loss e.g., physiological losses in women of reproductive age. It might also maintain occult bleeding from the gastroenteric (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).Iron absorption and loss play an important utilisation in the pathogenesis and counseling of IDA. Human iron disorders are necessarily disorders of iron correspondence or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from ageing erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is more often than not 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 pro entrap 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). transitrin is a protein that keeps iron nonreactive in the circulation, and delivers iron to cells possessing specific transferrin receptors such as TFR1 which is make in largest amounts on erythroid precursors. Mutations in the TF gene leadership 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 end 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 pixilated macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most a great deal encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is principally caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unambiguously 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 wind to the development of ACD such as tr im down life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid village formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 19962003). Although iron metabolism is characteristically impaired in ACD, it may not play a key fruit single-valued function in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron of import to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor look to be the result of impaired erythropoietin production and inhibition of its employment by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal mathematical function in the pathogenesis of ACD ascertained in sy base of operationsic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron me tabolism as well as nitric oxide (NO), which contributes to the ruler 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 constipation of erythroid progenitor gain and haemoglobin production in developing erythrocytes.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.The myelodysplastic syndromes (MDS) are common hae matological malignancies affecting mostly the elderly as age- cerebrate telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, consume and exposure to toxic compounds e.g., pesticides, organic chemicals and minacious metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune forbiddance of progenitor cell branch 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 stopping point brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).Sickle cell disease ( darmstadtium) arising from a point mutation in the -globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. degenerative intravascular haemolysis and anaemia are some important characteristics of atomic nu mber 110. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonic hypertension (Gladwin and Kato, 2005). However, a feature that oppositeiates atomic number 110 from other chronic haemolytic syndromes is the persistent and immoderate inflammatory condition present in darmstadtium. 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 contour (Rodgers et al., 1985). It has been demonstrated that sickle monocytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and love molecules such as the cell affection molecules (CAM family), which play a role in the firm estimation of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet bankroll on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other all-important(a) factors contributing to the pathogenesis of SCD (Jison et al., 2004).4. current therapies for clinical management of sickle cell diseaseincludingacritical appraisal of transfusion amongst 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 particularly 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 p atients and also vary lengthways within the same patient (Ballas, 1998). in the raw pathophysiological insights available have enabled interferences to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD manipulation are symptom alleviation, crises avoidance and potent management of disease complications. The dodging adopted is primarily palliative in nature, and consists of supportive, symptomatic and stoppage cash advancees to therapy. diagnostic management includes pain mitigation, management of vasoocclusive crisis, alter 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 contraceptive antibiotics (e.g., penicillin) in children, base hit blood transfusion for prevention of stroke in patients especially young children who are at a very high endangerment 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 sharp results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the wildcat stage (Ballas, 2002).Current and potential difference therapiesThe potential treatment strategies basically intention 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 garbage disposal of intravenous recombinant erythropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea only if (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 honorable (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a mightily inh ibitor of activation of nuclear factor (NF)-B, the arrangement 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).Red blood cell transfusion a critical appraisalA key therapy that is applied regularly in the clinical management of patients with SCD is jam-jam-jam-packed red blood cell transfusion. red blood cell transfusion remedys the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reduce 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 sporadic and chronic which are further classified as contraceptive device or therapeutic. I ntermittent 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. exposit of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1.SCD (Source Josephson et al., 2007)Indications for Intermittent transfusionsIndications 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 natural rubber such as for instance, when SCD patients are transfused before specific surgeries viz., those related to mat ernalism 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 diagnosing is the presence of a impudently infiltrate on chest skiagraphy that is accompanied by acute respiratory symptoms. ACD accounts for intimately 25% of all terminations 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 in force(p) and provide immediate wellbeing by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can confine antibody formation to below 1% (Vichinsky, 2002). primary transfusions suffice for less severe cases however, re-sentencing 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 fill inly eliminate the risk of pulmonary complications (Vichinsky, 2002).Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is in effect enured with intermittent transfusion of RBCs to adopt symptoms of cardiac and respiratory excruciation (Josephson et al., 2007).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 cardia c decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternating(a) transfusion strategy is to remove the full-page blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).Acute Stroke is a high risk especially in paediatric SCD cases because of august 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).Indications for Chronic TransfusionsProphylactic 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 i n 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).controversial and indeterminate indications for intermittent or chronic transfusionAccording to Hankins et al. (2005), chronic transfusion therapy is helpful in trim 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 currently is only a second-line therapy in the management of priapism ( moth miller et al., 1995).RBC transfusion is a spanking component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and deathrate of SCD. Yet, immune-related effectuate such as FNHTRs and alloimmunisation to HLAs, and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be tended to(p) to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an dark accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron indemnification the liver, endocrine organs, and heart and may be fatal by adolescence (Engle, 1964).5. deprecative review of thalassemias (i) Molecular pathogenesisThe large number of inherited haemoglobin disorders know today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin manacles of adult haemoglobin in erythroid cells.-ThalassaemiasThese are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised - thalassemia and - thalassemia. Homozygous -thalassaemia is marked by a quantitative deficiency of the -globin gyves in the erythroid cells. A complete absence of the -globin chains occurs in homozygous o-thalassaemia whereas in homozygous +-thalassaemia the -globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, +-thalassaemia is the most commonly observed form of -thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. -thalassaemia homozygotes bring out severe transfusion-dependent anaemia in the very first year of life. Homozygotic individu als having a relatively benign clinical phenotype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of -thalassaemia leading to reducing in the synthesis of -globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive pCauses, Symptoms and Treatments of AnaemiaCauses, Symptoms and Treatments of Anaemia1. IntroductionAnaemia 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, production of too few red blood cells by the bone marrow or a rapid destruction of cells.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 defin ed 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).Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mo stly 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 -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 (GTG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replaceme nt 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.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.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).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).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).Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transfe rrin 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 anaemiaAnaemia 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) Micr ocytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).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 hematopoietic cells, and can result in macrocytic anemia. 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 anaemia of chronic disease (ACD) (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anemia, red blood cell membrane disorders and current or recent infections especia lly in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weatherall DJ, 1997a).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 anemia and increase together in macrocytic, hyperchromic anemia.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 furth er 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.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 (Hb S) in which valine is substituted for glutamic acid at the s ixth amino acid position in the beta globin gene reduces the solubility of Hb, 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 anaemiaAnaemia 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 def iciency 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 excreti on 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).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., physi ological losses in women of reproductive age. It might also represent occult bleeding from the GI (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).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 delivers 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.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-defi ciency 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, 19962003). Although iron metabolism is characteristically impaired in ACD, 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 i ron 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 impairment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine pro duction 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.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 excessiv e apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).Sickle cell disease (SCD) arising from a point mutation in the -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 c onformation (Rodgers et al., 1985). It has been demonstrated that sickle monocytes 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 diseaseincludingacritical appraisal of transfusionBetween 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 pai nstaking 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).Current and potential therapiesThe 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 erythropoietin 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 sta te 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).Red blood cell transfusion a critical appraisalA 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 endogen ous 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.SCD (Source Josephson et al., 2007)Indications for Intermittent transfusionsIndications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal t hrough 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. ACD 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. Trans fusion 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).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).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).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).Indications for Chronic TransfusionsProphylactic 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).Controversial and indeterminate indications for intermittent or chronic transfusionAccording 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 currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).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 and alloimmunisation to HLAs, 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 (Engle, 1964).5. Critical review of thalassemias (i) Molecular pathogenesisThe large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells.-ThalassaemiasThese are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised -thalassaemia and -thalassaemia. Homozygous -thalassaemia is marked by a quantitative deficiency of the -globin chains in the erythroid cells. A complete absence of the -globin chains occurs in homozygous o-thalassaemia whereas in homozygous +-thalassaemia the -globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, +-thalassaemia is the most commonly observed form of -thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deform ities and iron overload. -thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individuals having a relatively benign clinical phenotype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of -thalassaemia leading to reduction in the synthesis of -globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive p