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Several adverse reactions to blood transfusion can occur despite checking, inspecting and testing at several levels. Fortunately, the common adverse reactions to blood transfusion are minor and serious reactions occur very rarely if ever. If any adverse reaction is suspected, the blood transfusion should be stopped immediately and reported to blood bank for investigation.

Commonly two types of adverse reactions to blood transfusion are seen, (1) immune mediated adverse reactions and (2) non immunologic adverse reactions. Complications due to infectious organisms may also occur in blood transfusion.

What are the immune mediated adverse reactions to blood transfusion?

The immune mediated adverse reactions to blood transfusion are FNHTR or febrile non hemolytic transfusion reaction (occurs 1-4 out of 100 units of blood transfusions or 1-4:100), allergic reactions (1-4:100), delayed hemolytic reaction (1:1,000), TRALI or Transfusion Related Acute Lung Injury (1:5,000), acute hemolytic transfusion reaction (1:12,000), fatal hemolytic reaction (1:100,000), anaphylactic reaction (1:150,000), HLA (human leukocyte antigen) allosensitization (1:10), RBC allosensitization (1:100), graft-versus-host disease (occurs very rarely due to cross matching of blood), post transfusion purpura etc.

Febrile non hemolytic transfusion reaction (FNHTR):

This is the commonest transfusion reaction that occurs in transfusion of blood involving cellular components. The clinical features of febrile non hemolytic transfusion reaction are rise in temperature of more than or equal to 1°C with chills and rigors. The diagnosis of FNHTR in transfused patient is generally made if no other cause of fever can be found or ruled out.

The cause of FNHTR may be presence of antibodies in recipient’s blood against donor WBCs and HLA antigens, which is why women with many children (multiparous) and recipients of repeated blood transfusion are at higher risk of FNHTR. Antibodies can be detected in recipient’s serum, but detection is not done routinely because the FNHTR is a mild reaction.

FNHTR can be reduced, delayed or prevented by reducing or removing WBCs from blood. The incidence of FNHTR can also be reduced by giving acetaminophen (paracetamol) or other antipyretic agents, which is more practicable and cost effective.

Allergic reactions to transfused blood:

Allergic reactions (commonly urticaria) in blood transfusions are due to the presence of plasma proteins in transfused blood.

Treatment of allergic reaction is generally done symptomatically by use of antihistamines and temporary stoppage of transfusion. Transfusion can be restarted once symptoms subside. If patient (recipient of blood) gives previous allergic reaction, he/she should receive antihistamines before starting blood transfusion.

Delayed hemolytic reaction:

The delayed hemolytic reaction occurs due to previous sensitization to RBC alloantigens, but showed negative result in screening due to low antibody level. When the previously sensitized patients are transfused with antigen positive blood, it can result in early production of alloantibody which binds to the donor RBCs and result in delayed hemolytic reaction. The RBCs which are coated with alloantibody are cleared by the host’s reticuloendothelial system. Due to mild nature of delayed hemolytic reaction, it is mostly detected in blood banks when a blood sample shows alloantibody.

The delayed hemolytic reactions are generally mild in nature and need no specific treatment in most cases. Rarely additional RBCs may be required.

Transfusion Related Acute Lung Injury:

This is an uncommon reaction that results due to presence of high-titer anti-HLA antibodies in donor’s plasma, which binds to the WBCs of the recipient. The antibody coated WBCs aggregate in the blood vessels of the lung and increases the permeability of blood vessels (capillaries) by releasing mediators. The patient develops pulmonary edema, breathlessness and bilateral interstitial infiltrates on chest x-ray.

The treatment of transfusion related acute lung injury is symptomatic and generally gives excellent result. The presence of anti-HLA antibody in donor’s plasma can support diagnosis in case of doubt.

This complication is generally seen if the donor is a multiparous woman and transfusion of plasma products from multiparous women should be avoided to prevent transfusion related acute lung injury.

Acute hemolytic transfusion reaction:

Hemolysis (immune mediated) can occur if the recipient has preformed antibodies that can break the RBCs of donor blood. Generally ABO agglutinins are responsible for hemolysis, but alloantibodies can also cause hemolysis, especially the ones that are directed against Rh, Kell, and Duffy RBC antigens.

Signs and symptoms of acute hemolytic transfusion reaction are low blood pressure, high pulse rate, fever and chills, high respiratory rate, pain in the infusion site, chest and flanks. Hemoglobin may be detectable in urine. To detect acute hemolytic reaction promptly, the vital signs (pulse, blood pressure, respiratory rate etc.) should be monitored before starting transfusion as well as during transfusion. If acute hemolytic reaction is suspected, transfusion should be stopped immediately and donor blood sample as well as recipient’s blood sample should be sent to blood bank for analysis, meanwhile intravenous line maintained.

The acute hemolytic transfusion reaction can cause kidney dysfunction and kidney failure, due to immune complexes that are responsible for lysis of RBCs. To prevent renal failure diuresis should be maintained by IV (intravenous) fluids and use of diuretics (furosemide, mannitol etc.). The chemicals released from lysed RBCs can cause disseminated intravascular coagulation and should be monitored by prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and platelet count.

But the commonest causes of acute hemolytic transfusion reaction are not due to immune mediated reactions, but are due to human errors such as transfusing the wrong patient and mislabeling of blood/plasma units.

Anaphylactic reaction:

This is a serious form of transfusion reaction and occurs immediately after starting transfusion (only few milliliter of blood is required), although fortunately rare.

The signs and symptoms of anaphylactic reaction are low blood pressure, bronchospasm, difficulty in breathing, nausea, vomiting, and cough, loss of consciousness, respiratory arrest and shock.

Treatment of anaphylactic reaction is immediate stoppage of transfusion, prompt administration of 0.5 to 1 ml of adrenalin (1:1000 dilution) subcutaneously and maintenance of intravenous line. Rarely glucocorticoids may be required in severe cases.

HLA (human leukocyte antigen) allosensitization:

Allosensitization may occur in a recipient due to number of antigens in plasma (mainly plasma proteins) as well as in cellular components of donor blood. Before doing blood transfusion to women of childbearing age, it should be properly tested for D antigen and cross matched to prevent hemolytic disease of newborn.

Graft-versus-host disease:

The blood transfusion related graft-versus-host disease is due to the donor T-lymphocytes, which consider the HLA antigen of the recipient as foreign.

The symptoms and signs of transfusion related graft-versus-host disease are fever, diarrhea, cutaneous eruption, liver function problems, bone marrow aplasia and pancytopenia. Symptoms of graft-versus-host disease generally appear in 8-10 days and death can occur in 3-4 weeks after blood transfusion.

The treatment of transfusion related graft-versus-host disease is difficult to treat and generally treated with glucocorticoids, cyclosporine, antithymocyte globulin. In most of the cases bone marrow transplantation is required.

Post transfusion purpura:

This reaction usually occurs 7-10 days after transfusion of platelets and mostly in women, due to presence of platelet specific antigen (common antigen is HPA-1a) in recipient’s serum. The antiplatelet antibody is directed against donor as well as recipient’s platelets.

The treatment is administration of intravenous immunoglobulin to neutralize the antibodies. Plasmapheresis can be used to remove the antibodies. Additional transfusion of platelet must be avoided as it will worsen the thrombocytopenia.

Is it possible to prevent or reduce adverse reactions to blood transfusion?

Yes, it is possible to prevent or at least reduce some adverse reactions of blood transfusion. Use of blood components after modification by filtration, irradiation or washing can prevent or reduce some blood transfusion reaction.

How to prevent or reduce adverse reactions to blood transfusion?

Acute hemolytic transfusion reactions are most commonly due to clerical error and mislabeling and this can be prevented with proper guidelines and strict implementation of the guidelines.

Febrile non hemolytic transfusion reaction (FNHTR) can be reduced by prior (before transfusion of blood) administration of acetaminophen (commonly known as paracetamol).

Allergic transfusion related reactions can be minimized by prior administration of antihistamines, if recipient has history of allergic transfusion reactions. In case of extreme sensitized recipient cellular components such as packed red cells, concentrated platelets can be washed to remove plasma.

Transfusion related acute lung injury is most commonly seen if the donor is a multiparous woman and to prevent this, multiparous woman should not be selected for blood donation.

Acute hemolytic transfusion reaction occurs most commonly due to mislabeling and clerical errors and to prevent this there should be proper guidelines and followed strictly.

Recipients who are deficient in IgA (immunoglobulin A) are at higher risk of anaphylactic reactions, may be due to sensitization to IgA. To prevent anaphylactic reaction in IgA deficient recipient, only IgA deficient donor blood and washed cellular components should be used.

If there is development of alloimmunization, the best is to find HLA-compatible platelets from donors who share similar antigens with the recipient, but it may be difficult to find such donor. Due to difficulty in finding compatible donor, in transfusion practice the WBC reduced cellular components are transfused.

Transfusion related graft-versus-host disease can be prevented by irradiating cellular components with a minimum of 2500 cGy, before transfusion to recipients at high risk, such as person undergone bone marrow transplantation, donor is a blood relative, lymphoma patients, fetus receiving intrauterine transfusion etc.