Allogeneic Blood Transfusions - Assignment Example

Allogeneic Blood Transfusions Introduction Allogeneic blood transfusion is the transfusion of blood from a donor with the same blood group to a recipient in need of blood. This occurs quite frequently in hospitals, with particular emphasis on the intensive care units in the hospital. There is concern in the use of allogeneic blood transfusion, because of the risk factors associated with exposure to allogeneic blood transfusions. These risks include the potential for infectious diseases, immunomodulation and transfusion reactions (Weiniger & Matot, 2006). Infectious Risks of Allogeneic Blood Transfusion There are two main contributory factors in the risk of allogeneic blood transfusion-transmitted infection. The first factor is the failure to identify the transmissible infectious pathogens that are present in the donor population and for which there is the need for screening of the donor blood. The second factor is the failure to detect donor blood containing these infectious agents, even when screening of the donor blood is done (Kitchen & Barbara, 2008). The first factor is based on the fundamental need in allogeneic blood transfusion to make sure that the appropriate infectious pathogens are screened for in the donor blood. Universal screening is uses the thumb rule that all donations be screened for the viral agents hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and the bacterial agent responsible for syphilis (Treponema pallidum). This raises the issue of the remaining infectious agents like those responsible for Chagas disease and human T-cell lymphotropic virus. Many of such infectious agents are not geographically widespread and are restricted to certain continents, regions or countries in the world. Thus their presence is not universal restricting the need for universal screening of these infectious agents. The additional screening policy for infectious should be based on the relevant prevalence of these infectious agents narrowed down to the donor population in the country or region (Kitchen & Barbara, 2008). The second factor is an even more critical issue in infectious risks of allogeneic blood transfusion. The failure to detect an infectious blood donation in the screening program may arise from several reasons of human error to biological variability. While failure to detect infectious blood donation due to scientific or biological variability is difficult to remove, failure to detect infectious blood donation from human error is manageable through well-developed and managed blood transfusions, as demonstrated by the healthcare systems of most of the developed world (Kitchen & Barbara, 2008). The list of infectious agents that can be transmitted through allogeneic blood transfusion is long for there are several viral, bacterial and protozoa infectious agents that can be transmitted through infected donor blood. The key to reducing the failure in screening for appropriate infectious agents in donor blood is to ensure that the additional screening of the donor blood for these pathogens that are endemic to the country. Table – 1 provides the list of infectious agents that can be transmitted through allogeneic blood transfusion Table – 1 List of Infectious Agents Viruses Bacteria Protozoa Hepatitis Viruses – Hepatitis A Virus, Hepatitis B Virus, Hepatitis C Virus, Hepatitis D Virus, Hepatitis E Virus Treponema pallidum, Borrelia burgdorferi, Brucella melitensis, Yersinia enterocolitica, Salmonella spp. Staphylococcal spp. Pseudomonades, Serratia spp. Coxiella burnettii Plasmodium spp. Trypanosoma cruzi, Toxoplasma gondii, Babesia microti/divergens, Leishmania spp. Prions, Variant Creutzfeldt-Jakob disease Retroviruses - Human immunodeficiency virus, Human T-cell leukaemia virus, Herpes virus, Human cytomegalovirus, Epstein-Barr virus, Human herpes virus 8 Parvoviruses – Parvovirus B19, GBV-C, TTV, West Nile virus (Kitchen & Barbara, 2008). Table – 2 Estimate of the risk that a donation that is positive for HIV, hepatitis B or hepatitis C may enter the blood supply In UK 2002-2003 Donations by HIV HCV HBV   Per million donations Per million donations Per million donations All donors 0.22 0.05 2.20 New donors 0.50 0.19 6.7 Repeat donors 0.19 0.03 1.7 (Transfusion Handbook, 2005) Immunomodulation by Transfusion Transfusion-related immunomodulation (TRIM) occurs as a result of the several foreign antigens that are present in donor blood that can cause immunologic changes in the patients receiving allogeneic transfusions. Stimulation of humoral immunity with the consequence of alloantibody production and down regulation of cellular responses with the consequence of altered host defences is possible immunological changes. These immunological changes happen in patients already facing the challenge of an illness or surgery and lead to added issues for these patients. The issues of concern associated with the TRIM effect include increase in the rates of infection, ventilator support times, need for intensive care, length of stay in the hospital and mortality rates (Boucher & Hannon, 2007). In spite of the general acceptance of immunomodulation effects of allogeneic blood transfusion, arising from blood being a heterogeneous mixture of diverse cellular and plasma constituents that is transfused from one immunologically different individual to another, the mechanisms involved in the TRIM effect still lack clarity. One of the possible causes of the TRIM effect is the allogeneic blood transfusion-associated iron overload of the reticuloendothelial system. In vitro studies have shown that an increase in serum iron leads to decrease in lymphocyte response to antigens. In addition, endocytosis of damaged red blood cells can hinder the normal mono-nuclear phagocytic function (Singal, 1994). Another possible mechanism is that in the storage of blood, the contents of blood are minutely altered. Stored blood contains microaggregates of fibrin strands, degenerating platelets and leukocytes, as a result of which transfusion of stored blood causes a significant decrease in concentration of plasma fibronectin that can influence the efficiency of macrophage function and the clearance of nonbacterial particulate matter. Fibronectin also plays the role of ligand for some of the cell surface molecules of the leukocyte integrin family of receptors and its concentration may influence immunomodulation by impacting on T cell adhesion, activation and migration. In the event of frequent blood transfusion the consequence of fibronectin cleavage products could stimulate neutrophil degeneration. Platelet-derived growth factor is known to increase on storage of blood and this growth factor can stimulate tumour growth, which could cause recurrence of cancer in patients receiving allogeneic blood transfusions (Singal, 1994). There is evidence to support the understanding that Prostaglandin E (PGE) has several immunosuppressive properties, which include the inhibitory aspects on lymphocyte blastogenesis, interleukin 2 (IL2) productions, NK cell activity and DR antigen expression by macrophages and endothelial cells. Furthermore PGE plays a role in activation of suppressor cells. PGE release from the human peripheral blood lymphocytes is observed to increase subsequent to blood transfusion for a period of up to seven days after the transfusion, thereby influencing immunomodulation. IL2 plays a vital role in immune response. IL2 is a growth factor and in addition stimulates the secretion of biologically active T cell-derived lymphokines that are responsible for the activation of T and B cells and macrophages. It also is responsible for the T helper cells release of factors that are essential to the development of cytotoxic capacity of cytotoxic T cells and the release of IFN for activation of the cytodestructive capacity of the macrophages and NK cell precursors. IL2 production in the spleen is observed to decrease subsequent to blood transfusion for a period of up to seven days after the transfusion, thereby influencing immunomodulation (Singal, 1994). Acute Transfusion Reactions Transfusion reactions can be classified into acute or delayed, immunological or non-immunological. Acute transfusion reactions make up a large portion of the serious acute complications associated with allogeneic blood transfusion (Gottschall & Menitove, 1995). Acute transfusion reactions are seen as adverse signs or symptoms during the blood transfusion or within a period of 24 hours after the blood transfusion. Acute transfusion reactions can be typically broken up into transfusion-related acute lung injury (TRAI), circulatory volume overload, bacterial contamination and endotoxemia, acute haemolytic transfusion reactions, non-haemolytic transfusion reactions, non-haemolytic febrile transfusion reactions and allergic reactions (Sandler & Johnson, 2009). There are several causes attributed to acute transfusion reactions. Acute haemolytic reactions occur from accidental wrong blood type transfusions that result from misidentification of the patient or the blood component at the time of blood collection for compatibility testing or from failure to realize that patient may have similar names bit different blood types. Febrile non-haemolytic reactions occur from the accumulation of cytokines and other normal blood constituents of leukocytes, platelets or plasma during the storage of the blood, which causes some recipients of blood transfusion to react. Allergic reactions occur due to the presence of allergens in the blood to which the recipient of blood transfusion is sensitized. This exposure causes allergic reactions. The pathophysiology of TRALI is as follows. Neutrophils are effector cells found adhering to the pulmonary endothelium for the function of increased permeability and can cause pulmonary oedema. Factors that lead to the activation of neutrophils consist of transfused HLA and HNA antibodies and transfused bioactive substances including lipids or cytokines. In clinical conditions like inflammation, surgery and infection, patients have neutrophils that are prone to activation of transfused bioactive substances. Since pregnancy can cause alloimmunization to HLAs and HNAs, another common cause of TRALI is the transfusion of blood from female blood donors. Circulatory volume overload can occur in patients with compromised cardiovascular functions, the elderly and small children causing pulmonary oedema. Bacterial contamination is one of the causes of acute transfusion reactions. Bacteria can enter container at any time during the collection of blood to the time of transfusion to the recipient. The blood in some donors may contain very low concentrations of bacteria. When such blood is stored bacteria can grow and elaborate endotoxin, resulting in adverse transfusion reaction, when the blood is transfused to a recipient (Sandler & Johnson, 2009). Table – 3 shows the frequency of reported serious hazards of blood transfusion in the United Kingdom Table – 3 Frequency of Reported Serious Hazards of Blood Transfusion in the United Kingdom Event type Events reported 1996−2004 Events reported per 100,000 components issued 1996−2004 Events reported 2003−2004 Events reported per 100,000 components issued 2003−2004 Incorrect blood component transfused (IBCT) 1832 7 787 12 ABO incompatible transfusions (all components − included in IBCT) 249 1 56 0.8 Death as a result of IBCT 20 0.07 3 0.04 Transfusion-related acute-lung injury (TRALI) 162 0.6 59 0.9 Fatal TRALI 36 0.1 9 0.1 Acute transfusion reaction (ATR) 267 1 73 1 Transfusion-transmitted infection (including bacterial) 49 0.2 6 0.1 Total adverse reactions/events 2628 10 994 14 Total transfusion-related deaths 100 0.4 21 0.3 (Transfusion Handbook, 2005) Literary References Boucher, B. A. & Hannon, T. J. 2007, ‘Blood Management: A Primer for Clinicians, ‘Pharmacotherapy, vol.27, no.10, pp.1394-1411. Gottschall, J. L. & Menitove, 1995, ‘J. E. ‘Transfusion: Blood and Blood Components’, in Manual of Clinical Hematology, Second Edition, Lippincott Williams & Wilkins, Philadelphia, PA, pp.369-387. Kitchen, A. D. & Barbara, J. A. J. 2008, ‘Current Information on the Infectious Risks of Allogeneic Blood Transfusion’, Transfusion Alternatives in Transfusion Medicine, vol.10, no.3, pp.102-111. Sandler, G. S. & Johnson, V. V. 2009, ‘Transfusion Reactions’, emedicine from WebMD [Online] Available at: http://emedicine.medscape.com/article/206885-overview Singal, D. P. 1994, ‘Mechanisms and Blood Transfusion Effect’, in Immunological Effects of Blood Transfusion, ed. Dharam P. Singal, CRC Press, Boca Raton, pp.155-186. Transfusion Handbook. 2005, ‘Number of Adverse Transfusion Events and Reactions’, UK Blood Transfusion & Tissue Transplantation Services [Online] Available at: http://www.transfusionguidelines.org/Index.aspx?Publication=HTM&Section=9&pageid=1148 Weiniger, C. F. & Matot, I. 2006, ‘Acute Normovolemic Hemodilution: Its Role as a Blood Conserving Technique’, in New Developments in Blood Transfusion Research, ed. Brian R. Peterson, Nova Science Publishers New York, pp.121-140. Read More