Transfusion medicine developed during the 1950's and 60's, understanding the basics of blood groups and red cell antigens. Scientists accelerated their development and understanding of blood transfusion via the plastic bag system and plasma fractionation. As years went on, different complications occurred with immunomodulation effects of transfusion. Blood transfusion medicine has now developed into very complex and sophisticated techniques which accounts for the success of modern day medical therapies (Campbell N, A,. Reece J, B,. 2005)
Like other medical procedures, blood can produce benefit or harm to the patient but from blood donation to post blood transfusion, complications can occur. It has been estimated that almost 20% of transfusion procedures result in a dangerous effect, with 0.5% of these being classed as serious (Walker R, H,. 1987).
Overview of 366 patients from Williamson, L, M,. (1999) study
These complications of blood transfusion can be divided into two categories, immune and non-immune or immediate and delayed. One complication that's immunologic is a haemolytic transfusion reaction (HTR). This is sometimes referred to as the most dangerous immunologic complication as it accounts to 41% of ABO incompatible transfusion fatalities in the USA which is a type of acute haemolytic transfusion reactions (AHTR). Linden et al (1987) suggested that on average 16 patients die per year from a fatal HTR in the USA.
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A haemolytic transfusion reaction is when lysis or increased clearance occurs on red cells in a transfusion recipient. These reactions are caused by incompatibility between blood donor and the recipient. HTR's can occur when a little incompatible blood has been transfused and some patients tolerate a whole unit with no effects. If a reaction occurs within 24 hours of the transfusion it is classed as acute but if its 5-7 days, then it's classed as delayed. Pineda et al (1978) studied 47 patients HTR's and reported fever with chills (40%), Chest pain (12%) and hypotension (12%). There are many other signs including vomiting, diarrhoea and unexpected bleeding.
ABO incompatible transfusion results in an acute HTR, which is mainly down to the incorrect blood given to the incorrect patient. The majority of these errors are due to administrative issues.
Haemolytic transfusion reactions can also result in oliguria and renal failure. The mechanism involved in these complications is disseminated intravascular coagulopathy (DIC) which causes a decrease in endothelial expression of thrombomodulin. Also the activation of Hageman factor (XIII) which induces vasoconstriction and hypotension.
The other type of haemolytic reactions is a delayed response (DHTR), where incompatibility was not detected at the stage of incompatibility testing. These reactions are due to secondary immune responses which involve the destruction of red blood cells and can occur after 24 hours of the transfusion or even up to 1 week. DHTR occurs when weak alloantibodies, that are undetected in antibody screening tests, increase in strength after a secondary antibody response. These antibodies can be found in sensitized patients who have been exposed to RBC's via previous transfusions. Delayed haemolytic reactions are not as severe as acute haemolytic reactions which are shown by the mild symptoms. Destruction of the transfused RBC's results in a decrease of haematocrit (HCT) and a rise in bilirubin. This is why it is sometimes undetectable post transfusion but is accelerated sometime after. It can sometimes be detected with the decreasing number of haemoglobin (McCullough, J,. 2005).
Another complication is a non-febrile haemolytic transfusion (FNHTR) reaction which occurs in 0.5% to 1% of transfusions. An FNHTR is normally associated with excess leukocyte antibodies in the patient which reacts with the leukocytes in transfused blood. The number of leukocytes in the transfused blood will determine how severe the reaction will be. This reaction could be caused by antileukocyte antibodies present in the recipient's plasma which are directed against the antigens. A non-febrile transfusion reaction can be associated with a slight increase in temperature of around 1oC, assuming there is no other medical reason. An FNHTR has to be closely monitored as the reaction could be a symptom of a more serious haemolytic transfusion (Geiger TL,. Howard SC,. 2008).
One serious complication with an FNHTR is transfusion related acute lung injury (TRALI). This can be detected if the patient experiences acute respiratory difficulties or even pulmonary edema following x-ray scans. With TRALI, the patients granulocytes reacts with transfused antileukocyte antibodies which results in capillary damage and fills the alveolar spaces with fluid. Therefore gases cannot be exchanged in the lungs which could lead to hypoxia and respiratory problems (Mcclellend DBL,. 2001).
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An Allergic reaction is a frequent complication to occur, with signs of mild hives, itching and redness. In previous studies, it shows that this reaction can result from foreign allergens in the donor plasma or when recipient allergens combine with transfused donor antibodies. If allergic reactions occur during transfusion, the procedure can be stopped and antihistamine will be used to reduce symptoms. Once local symptoms have been reduced, transfusion can continue. The patient could have previously had the same symptoms undergoing transfusion, which will enable the transfusionist to provide antihistamine prior to transfusion. Other potential risks are tachycardia, shock and cardiac arrest. A previous study showed that this is more prominent to patients who are IgA deficient (Murphey MF, Pamphilon DH,. 2005).
An exclusive disease called Graft versus Host disease can be seen in immune-compromised patient's following a blood product transfusion. It is a rare complication but one that has a high mortality rate. It's caused by transfused T lymphocytes from blood components, which engraft, multiply and attacks the host's tissues. Patients with B-cell malignancies appear to be especially at risk (Anwar B, Bhatti FA,. 2003).
Massive transfusion can be defined as a volume of blood greater than or equal to one blood volume in 24 hours (McCullough J,. 2005). This could result in hypothermia because of the large amount of cold blood being transfused, which cause's arrhythmia's. Many doctors will warm the patient up at this stage with a heating device to stabilize the temperature. Another complication with massive transfusion is jaundice which is caused by large volumes of damaged red blood cells fuse with dysfunctional liver. Walker RH (1987) explained that coagulation factors and platelet levels have to be observed as depletion sometimes occurs. Coagulopathy is a common symptom of massive transfusion which is caused by the host's platelets and clotting factors being diluted, as well as the abundance of them in red blood cells. Hyperkalaemia is due to the rapid transfusion of older RBC's which take up potassium. A rare complication with massive transfusion is hypocalcaemia, where calcium is chelated by citrate. These influxes of potassium or citrate could be due to hypothermia as they are increased in its presence.
Air embolism is a concern as it allows an air bubble to enter the system which leads to the right side of the heart. Here it can be fatal as it blocks the pulmonary system and causes circulatory collapse.
If a rapid transfusion is taken place, a high flow of blood products in intravascular space enters which could lead to volume overload. This might result in heart failure or pulmonary edema. Appropriate diuretics should be given to patient to help stabilize volume.
Alloimmune transfusion reactions occur when patients receive donor blood that contains leukocytes. Severity depends on how much the antibodies attach to the red blood cells which results in the patient becoming refractory making the transfusion pointless. Therefore at pre-transfusion, leukocytes need to be removed which reduce the risk of alloimmunization.
Post transfusion purpura (PTP) is rare but lethal and occurs mostly in women. Around 7 days after transfusion the patient can develop a very low platelet count. Platelet transfusions in large quantities have to be administered to control severe bleeding.
Blood is collected at very high standards and undergoes rigorous testing before being used. Braude AI et al (1954) proved that even at refridgerated temperatuees, there is still a chance of old growing bacteria. They tested their own bottles for contamination and found that 2.27% were positive. One problem that is not always eliminated is bacterial contamination. This can be caused by not aseptically cleaning the venepuncture site which contaminates the blood with staphylococci. These contaminants are quite rare due to a closed collection system following tight standards but can be fatal resulting in septic shock, muscle pain and DIC. Blood components can be stored at around 4oC and keeping the bags sterile are the best prevention methods. Both grams positive and negative can very rarely contaminate blood but to avoid this, blood should be administered in no longer than 4 hours.
A number of infectious agents could have been transmitted via transfusion which is another risk involved. This is a delayed reaction where patients will develop risks for example HIV and hepatitis infection. A component that's regularly tested for is syphilis, which has to be removed before transfusion otherwise potential secondary rashes can occur. Until recently hepatitis was a large problem at around 10% incidence, with the majority of these infections caused by hepatitis C. Buseri et al (2009) showed that his testing IN Nigeria with 1410 healthy patients resulted in 28.8% of individuals with some sought of infectious agent. They also related the sexually active to be more prone to agents and so is still a high risk, especially in third world countires. Another infectious agent is HIV, where it's classed as dangerous but does have low risks with anti-HIV-1 antibody being the component for infectivity. When red blood cells are infected, they can easily carry a parasitic disease called malaria in a transfusion. A patient could have malaria but not be aware of it after a considerable amount of time. If detected then appropriate procedures to reject all future blood donations are carried out, for at least 3 years.
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There are many complications involved in the transfusion of blood, some being more serious than others. They could involve immune or non-immune mechanisms and can occur within minutes or even after days.