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Chapter: Biology of Disease: Transfusion and Transplantation

Hazards of Transfusion

Transfusion Related Acute Lung Injury , Iron Overload , Alloimmunization, Graft versus Host Disease, Infections.

HAZARDS OF TRANSFUSION

One hazard of transfusion is a hemolytic transfusion reaction (HTR) if preex-isting antibodies are present in the recipient. This may result in acute intra-vascular hemolysis, as in ABO incompatibility, or in delayed extravascular hemolysis, as with several of the other blood group systems. Acute intravas-cular hemolysis has serious clinical consequences and, indeed, may be fatal. With delayed extravascular hemolysis the patient may suffer fever and general malaise as the donated erythrocytes are destroyed and the hemoglobin levels fall. To prevent either occurrence, the recipient should be screened before the transfusion for the presence of anti-erythrocyte antibodies.

The transfusion of leukocytes may also lead to adverse reactions, such as nonhemolytic febrile transfusion reactions. Such patients exhibit flushing,fever, rigors and hypotension. These may be caused by the reaction between antibodies and leukocyte antigens in the recipient, resulting in the lysis of donated leukocytes and release of cytokines from them. In addition, activated complement proteins cause the release of histamine from basophils, trigger-ing inflammatory reactions. As all blood is leukodepleted before transfusion, such reactions are rare.

TRANSFUSION RELATED ACUTE LUNG INJURY

Transfusion related acute lung injury (TRALI) is a life-threatening complica-tion of transfusion. It presents as a rapidly progressing and severe respiratory failure with diffuse damage to alveolar cells and the filling of alveolar spaces with fluid. Histological examinations reveal an infiltration of the alveoli with neutrophils and monocytes, indicative of an acute inflammatory reaction.

The symptoms of TRALI include dyspnea, cyanosis, hypotension, fever and pulmonary edema, which usually occur within 6 h of transfusion. The con-dition is thought to arise from the interaction of leukocytes and specific antileukocyte antibodies, usually in the donor plasma, though occasionally in that of the recipient. The most likely antibodies are those to the Major Histocompatibility (MHC) antigens, which are commonest in women who have had multiple pregnancies  and in males and females who have received multiple transfusions. In addition, antibodies to neutrophil antigens have also been implicated.

TRALI has been reported to occur after transfusion of fresh frozen plasma, platelets, whole blood and concentrated erythrocytes. In the UK in 2003, 36 cases of suspected TRALI were reported to SHOT. Nine patients died, seven possibly, and one definitely due to transfusion. Plasma-rich components were implicated in 20/21 cases in which there was proven leukocyte incompat-ibility between the patients and the donor. In 2004, however, 23 suspected cases were reported in the UK. Of these, 13 were highly likely to be TRALI and were linked to fresh frozen plasma, in six cases, platelets in four, erythrocytes in two and whole blood in one. The incidence of TRALI has since decreased in the UK, due to the processing of fresh frozen plasma from untransfused male donors who have tested negative for antileukocyte antibodies.

IRON OVERLOAD

Patients who receive many transfusions over a long period of time may develop iron overload. The excess of iron, for which there is no excretory route, from transfused blood may cause tissue damage, especially to the liver, heart and endocrine glands. Signs of iron overload can be detected after 10–20 transfusions and the condition may be fatal if left untreated. Patients should be treated with a chelating agent such as deferrioxamine mesylate to remove unwanted iron .

ALLOIMMUNIZATION

Patients who receive regular erythrocyte transfusions may become immu-nized to other blood group antigens present on the ABO compatible cells. This may have consequences for future transfusions. If patients receive whole blood, rather than leukodepleted blood, they may become immunized to the MHC antigens on the foreign leukocytes. This may become clinically signifi-cant if in the future they require an organ transplant. However, the increasing use of leukodepleted blood, in which the leukocytes have been removed prior to transfusion, prevents the immunization of recipient to these antigens.

GRAFT VERSUS HOST DISEASE

Graft versus host disease (GVHD) is a potentially fatal condition which is associated with the transfusion of whole blood or blood products, such as packed erythrocytes or platelets, which contain residual lymphocytes. It usually results from the transfusion of leukocytes into an immunodeficient patient or when blood is transfused into neonates or premature babies. The small lymphocytes present in the donated blood recognize the anti-gens of the recipient as foreign and mount an immune response against them. The donor lymphocytes proliferate in the patient and attack tissues, causing enlargement of the spleen and liver, diarrhea and an extensive skin rash. Acute GVHD may be fatal and for this reason it is recommended that products such as packed erythrocytes be irradiated prior to use to pre-vent residual small lymphocytes from reacting to the host antigens. Graft versus host reaction can also be a consequence of bone marrow transplan-tation. Frozen plasma is safe in this respect, since freezing destroys leukocytes. Transfusion associated GVHD is not usually linked to AIDS.

INFECTIONS

One potential hazard of transfusion is infection with microorganisms present in the donor. In the past, blood transfusions have spread infections such as HIV and hepatitis C  to the patient. For this reason there is now extensive screening of blood donors.

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