Why are blood transfusions from strangers not rejected, like transplanted organs can be?















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Blood banks perform pretransfusion compatibility testing to avoid hemolytic reactions. Routine pretransfusion testing consists of analyzing the patient¿s red cells for A and B antigens, testing for the presence of anti-A and anti-B in the plasma, testing for the Rh(D) antigen on red cells and screening for other red cell antibodies in the plasma. Because ABO incompatibility can be so serious, doctors need to be sure that a patient¿s ABO type is correct. That is why hospitals test for both the antigens and the antibodies and require agreement between the tests in order to conclude the blood type. Out of hundreds of other blood group antigens (including dozens in the Rh system), testing is routinely performed for only one other: the Rh(D) antigen, which is the most likely to cause an immune response. If it is present, the patient is Rh-positive. There is about an 85 percent chance that an Rh-negative person will make antibodies if transfused with Rh-positive blood, whereas other blood group antigens are not such strong immune stimulators. The screening test for unexpected (not A or B) antibodies covers about 25 that patients are most likely to make and can detect red cell antibodies that were generated in response to previous transfusions or pregnancies. If the screen is positive, further testing is performed to identify the specificity of the antibody and select blood from a donor that lacks the corresponding antigen. More commonly, the antibody screen is negative and we can safely transfuse ABO compatible red cells despite other blood group differences between the donor and recipient that may be present.

The situation is a little different for transfusions of platelets rather than red cells, which occur with patients undergoing chemotherapy. Because A and B antigens are weakly expressed on platelets, they are less important in this case. Although there are antigens that are specific to platelets, it is rare for people to make antibodies against them even after repeated transfusions. But HLA antigens, which are critically important in transplantation, are strongly expressed on platelets (but only very weakly expressed on red cells). It is common for patients to make antibodies to HLA antigens in response to transfusions or pregnancy. When platelets are transfused to a patient with corresponding HLA antibodies they are very rapidly cleared from circulation, which is essentially immediate rejection of the transfusion. Usually there is not a clinically evident reaction, as in case of incompatible red cell transfusion, but the platelet transfusion is ineffective. Such a patient can become refractory to platelet transfusion (meaning that the platelet count does not rise and the patient experiences no benefit) and may be at risk for serious bleeding. Refractoriness to platelet transfusion is a serious problem in cancer chemotherapy and bone marrow transplantation. Unfortunately, it is much more difficult to test for HLA and platelet antibodies than it is to test for red cell antibodies. Platelet compatibility testing is done for patients who do not have a successful response after several platelet transfusions.

Things get even more complicated when white cells (such as lymphocytes) are transfused. Normally, there are very small numbers of viable white cells in most units of blood transfused today. People with normal immune systems can reject transfused donor lymphocytes, which is a good thing. If transfused lymphocytes are not rejected there can be problems. Very sensitive tests for donor white cells have shown that they may persist in the recipient¿s blood for one or two weeks after transfusion before they are rejected. It is possible for transfused lymphocytes to survive and proliferate, however. Small numbers of donor lymphocytes have been found in some patients months or years after transfusion. This results in a state of microchimerism, in which a little of the patient¿s immune system is genetically foreign. We do not know the full implications of microchimerism, but it most likely causes some abnormalities in immune responses. In the most severe case, transfused lymphocytes can not only survive, but also react against the patient¿s tissues. This causes graft-versus-host disease, which is usually fatal. Patients with markedly impaired cellular immunity are at risk of transfusion-associated graft-versus-host disease. Blood for such patients is routinely gamma irradiated to prevent this rare but very serious reaction.



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Why are blood transfusions from strangers not rejected, like transplanted organs can be?

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