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Blood and itsproducts are dangerous therapeutic agents.

Blood has many roles within thebody and therefore consists of many components in order to execute all of itsfunctions. In turn each of these components produces molecules and substancesto complete their tasks. However when these functions are harnessed throughtransfusion in an attempt to improve another's condition the shortcomings inthe understanding of just how taylor made these components are become exposed.The consequences of new medical techniques and advancements sometimes remaindormant until it is too late to reverse the effects and only measures can betaken in prevention of a reoccurrence.

Blood consists of 55% plasma and45% cells by volume and each section has a different function within the body(Waugh and Grant 2001). Plasma is the fluid fraction of centrifugated bloodand is a water solution containing 8 - 10% by volume mixture of plasmaproteins, such as albumins, globulins, fibrinogen and clotting factors, inorganicsalts, nutrients, waste materials, such as urea, as well as enzymes andhormones (Waugh and Grant 2001). The cellular fraction of the centrifugatedblood contains three main types of cells; erythrocytes (red blood cells),thrombocytes (platelets) and leukocytes (white blood cells) which are allsubdivided again into varies cell types summarised in the table one.

Table One: White blood cells and their roles (informationfrom Waugh and Grant 2001 and Alberts et al 2002)

The cellular components of theblood produce many substances to accomplish their individual roles and thesesometimes have opposing and diverse effects, with the main results being toprevent infection, destroy any foreign bodies that may cause infection and totransport the nutrients required by the tissue of the body efficiently whileremoving the waste products. However, as important as these roles are therecan be detrimental effects.

Erythrocytes contain a type ofrecognition code, in the form of antigens, on their external surface to allowthem to be recognised by their own immune system as 'self' and therefore avoiddestruction. However, in the event of blood transfusion, if the antigenmolecules on the newly introduced erythrocytes are not of the same type theywill be destroyed in a transfusion reaction, where the body creates antibodiesto the unrecognised antigen and thus destroys all the cells that contain thisantigen (Waugh and Grant 2001). The ability of the blood to transport oxygenand other products around the body will be significantly reduced, thusadversely affecting the health of the person concerned and haemolysis can occurin the cardiovascular system where the resulting by-products of the reactioncollect in the nephrons in the kidneys causing shock, lumbar pain, fever andeven death (Waugh and Grant 2001).

Many infections are known toremain in the blood and there may be more that we are as yet unaware of. TheHuman Immunodeficiency Virus (HIV) is one of the more recent and mostpublicised viruses that can be transmitted through the blood and use of bloodproducts. In the mid nineteen eighties the retrovirus (now known as HIV) wasconfirmed as the mediator for the Adult Immunodeficiency disease (Levy et al1984). Decades of research have resulted in the increased understanding of howthe virus replicates, infects and survives to the point where the virus can berecreated in a laboratory using the latest biotechnology resources to predictpotential genetic alterations and therapies against the virus. But perhaps themost important finding was that the virus actually infects the immune system inplace to defend the host against it. The virus infects white cells via a surfacerecognition glycoprotein on the virus (Allan JS et al 1985) that attaches toCD4 receptors on T-cells (Dalgleish et al 1984 and Klatzmann et al 1984) andfrom here it can remain dormant or reproduce and further infect more T-cells,in the same or a new host. This disease highlighted the need for screening ofall donated blood in order to prevent the transfusion therapy causing fatalconsequences.

FigureOne: Totalincidence rates of AIDS cases associated with blood and blood products per millionby countryand transmission category in the years1985-93 (Taken from Franceschi et al 1995).

The same problem is againhighlighted with the disease of Creutzfeldt-Jakob disease (CJD) in 2003 when itwas determined that a person whose received a blood transfusion in 1996 dieddue to likely infection from variant CJD harboured in the blood of the donor(Bird 2004) . In CJD infectious protein particles (prions), rather than avirus that requires the host cell machinery to replicate, appear to be presentin the blood of the infected person, or animal, which can be passed on throughsurgical procedures via instruments (Glatzel et al 2003), although far littleis known in comparison with HIV as to how these prions spread and replicate.

The steps that can be taken toreduce the risk of the spread of CJD and therefore other unknown viruses areaddressed by Bird in 2004 and include using surveillance units for the knownblood borne infections or particles to cross check donors and recipients,immediate withdrawal of tissue or blood donated by said individuals, recipientsof potentially contaminated products or transfusions should be immediatelyinformed even before a definitive diagnosis to prevent further spread, checkextended network of potentially infected patients that have undergone surgeryaround the time of the infected and above all educate individuals to helpprevent further transmission.

Transfusion infection from bloodand blood products have been reduced through increased virulence by the blooddonors and improved diagnostic tests preformed on all donations, however therisk now appears to have shifted to the spread through surgical procedures andinstruments where standard sterilisation may not be effective enough (CJDprions are not destroyed after sterilisation at 121 degrees Celsius (www.cjdsupport.org)).However, infection with blood and its products does not stop there as bloodalso carries other useful products such as hormones which can be used to treatvarious conditions for example insulin dependent diabetes can be treated usingsystematic injection of the insulin to control the blood glucose levels andcause the conversion of excess glucose to glycogen for storage in the liver.The insulin for intravenous use can be purified from the blood of animals, butagain as demonstrate by the infectious proteins of CJD, there is no tellingwhat else may be contained in the concentrate. The alternative is the modernday use of genetic engineering to produce massive amounts of the hormone usingbacteria modified to secrete the required protein and thus making the processmore efficient and safe.

Blood produced products can alsobe fatal even with out infective surgery. Individuals with high levels ofImmunoglobulin E (IgE) can suffer from Type I hypersensitivity or anaphylactichypersensitivity, when exposed to an allergen like dust or pet hair. Theallergen activates the mast and basophil cells causing tehm to releasehistamine which usually increases vascular permeability to allow the bloodfluid and proteins to reach the tissue where required. However it can causethe contraction of the smooth muscle leading to broncho-constriction and thusrestricted breathing (Waugh and Grant 2001).

In conclusion, the use of bloodin transfusion and during surgery has with no doubt increased the success ratesof the actual surgery and improved the quality of life for many of therecipients whom with out the procedure would probably not have survived, aswell as improving the everyday lives of people receiving hormone treatment forproblems regarding growth defects to menopause. However, the success of thesetreatments must be weighed up against the potential risks that the diagnostictest have failed to pick up on or those that have not even as yet beendiscovered. We are working on a minute scale where it can only take a fewmolecules to fall through the detection net to cause infection. The greaterimplication of this would be that even if the treatment you received was safeit may well not be and then you could be transmitting that infection on toothers without even knowing.

References

Alberts B, Johnson A, Lewis J, Raff M, Roberts K and WalterP (2002). Molecular Biology of the Cell, Fourth Edition. Published by GarlandScience, a member of the Taylor Francis Group.

Allan JS, Coligan JE, Barin F,McLane MF, Sodroski JG, Rosen CA, Haseltine WA, Lee TH, Essex M (1985). Majorglycoprotein antigens that induce antibodies in AIDS patients are encoded byHTLV-III. Science 228:1091-4.Kulstad R, Ed., AIDS: Papers from Science, 1982-1985 (AAAS, WashingtonDC, 1986).

Bird M (2004). Recipientsof blood or blood products at vCJD risk. British Medical Journal328:118-9

DalgleishAG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1985). The CD4(T4) antigen is an essential component of the receptor for the AIDS retrovirus.Nature 312: 763-7.

Franceschi S, Dal Maso L and La Vecchia C (1995). Trendsin incidence of AIDS associated with transfusion of blood and blood products in Europe and the United States, 1985-93. British Medical Journal 311:1534-1536

Glatzel MG, Abela E, Maissen M& Aguzzi A (2003). Extraneural pathologic prion protein in sporadicCreutzfeldt-Jakob disease. The New England Journal of Medicine, 349: 1812 - 1820.

Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, GluckmanJC, Montagnier L (1984). T-lymphocyte T4 molecule behaves as the receptor forhuman retrovirus LAV. Nature 312:767-8.

Levy JA, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oshiro LS (1984)Isolation of lymphocytopathic retroviruses from San Francisco patients withAIDS. Science 225, 840 - 2.

Waugh A and Grant A (2001). Ross and Wilson Anatomy andPhysiology in Health and Illness, Ninth Edition. Published by ChurchhillLivingstone

Websites

"WHO Infection Control Guidelines for Transmissible SpongiformEncephalopathies." World Health Organization - Department of CommunicableDisease Surveillance and Response.

http://www.cjdsupport.org.au/who_infection_control_guidelines.htm.March 1999. Heaphy, S. "Prion Disease." http:// www. micro.msb.le.ac.uk/335/Prions.html. July 2002.

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