Complications after hemotransfusion

The most common transfusion complications are shivering reactions and febrile nonhemolytic reactions. The most serious complication is acute hemolytic reaction due to ABO-incompatible transfusion and acute transfusion-associated lung injury, which is associated with a high mortality rate.

Early recognition of transfusion complications and notification of the blood bank is important. The most common symptoms are chills, fever, shortness of breath, dizziness, rash, itching and pain. If these symptoms occur (except localized rash and itching), the transfusion should be stopped immediately and intravenous administration should be continued with normal saline. The remaining blood component and a sample of the recipient's blood with anticoagulant should be sent to the blood bank for appropriate testing. Further transfusions should be postponed until the cause of the reaction is determined; if transfusion is necessary, group O Rh-negative red blood cell mass is used.

Hemolysis of donor or recipient red blood cells during or after transfusion may be caused by ABO/Rh incompatibility, plasma antibodies, hemolyzed or fragile red blood cells (e.g. from blood overheating, contact with hypotonic solutions). The most common and severe hemolysis is when incompatible donor red blood cells are hemolyzed by recipient plasma antibodies. The hemolytic reaction may be acute (within 24 hours) or delayed (1 to 14 days).

Acute hemolytic transfusion reaction (AHTR)

About 20 people die each year in the United States from acute hemolytic transfusion reactions. Acute hemolytic transfusion reactions usually result from the interaction of recipient plasma antibodies with donor red cell antigens. ABO incompatibility is the most common cause of acute hemolytic transfusion reactions. Antibodies to blood group antigens other than ABO can also cause acute hemolytic transfusion reactions. The most common cause of acute hemolytic transfusion reactions is not a laboratory error in blood selection but rather mislabeling or mixing up of the blood product immediately before transfusion.

Hemolysis is intravascular, causing hemoglobinuria with varying degrees of acute renal failure and possible development of disseminated intravascular coagulation (DIC). The severity of acute hemolytic transfusion reaction depends on the degree of incompatibility, the amount of transfused blood, the rate of administration, and the preservation of renal, hepatic, and cardiac function. The acute phase usually develops within 1 hour of the start of transfusion, but may occur later in the transfusion or immediately after its completion. The onset is usually sudden. The patient may complain of discomfort or anxiety. Dyspnea, fever, chills, facial flushing, and severe lumbar pain may occur. Shock may develop, which is manifested by a weak, rapid pulse, cold, clammy skin, decreased blood pressure, nausea, and vomiting. Jaundice is a consequence of hemolysis.

If an acute hemolytic transfusion reaction develops under general anesthesia, the only symptoms that may be present are hypotension, uncontrolled bleeding from the incision site and mucous membranes caused by the development of DIC, and dark urine due to hemoglobinuria.

If acute hemolytic transfusion reaction is suspected, one of the first steps is to check the transfusion medium labeling and the patient's personal data. The diagnosis is confirmed by measuring urinary hemoglobin, serum LDH, bilirubin, and haptoglobin. Intravascular hemolysis produces free hemoglobin in plasma and urine; haptoglobin levels are very low. Hyperbilirubinemia may develop later.

After completion of the acute phase, the prognosis depends on the degree of renal failure that has developed. The presence of diuresis and a decrease in the urea level usually heralds recovery. The outcome in chronic renal failure is rare. Prolonged oliguria and shock are poor prognostic signs.

If acute hemolytic transfusion reaction is suspected, the transfusion should be stopped and supportive care initiated. The goal of initial treatment is to maintain arterial pressure and renal blood flow, which is achieved by intravenous infusion of 0.9% sodium chloride solution with furosemide. A urine output of 100 ml/h for 24 h should be achieved. The initial dose of furosemide is 40-80 mg (1-2 mg/kg in children), with the dose increased to maintain a urine output of 100 ml/h on the first day.

Antihypertensive drugs are administered with caution. Pressor drugs that reduce renal blood flow (e.g., adrenaline, noradrenaline, high doses of dopamine) are contraindicated. If pressor drugs are necessary, dopamine is used at a dose of 2-5 mcg/(kg x min).

Urgent examination of the patient by a nephrologist is necessary, especially if there is no diuresis within 2-3 hours after the start of therapy, which may indicate the development of acute tubular necrosis. In such cases, hydration and diuretics may be contraindicated and dialysis is necessary.

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Delayed hemolytic transfusion reaction

Occasionally, a patient sensitized to a red cell antigen has very low antibody levels and a negative pretransfusion test. After transfusion of red cells bearing the antigen, a primary or anamnestic response may develop, causing a delayed hemolytic transfusion reaction, which does not have the dramatic manifestations of an acute hemolytic transfusion reaction. It may be asymptomatic or cause a mild fever. Severe symptoms are rare. Usually, there is destruction of the transfused red cells (bearing the antigen), resulting in a decrease in hematocrit and a slight increase in LDH and bilirubin concentrations. Because the delayed hemolytic transfusion reaction is usually mild and self-limited, it often goes undetected and presents clinically with an unexplained decrease in hemoglobin concentration. Treatment of severe reactions is similar to that of an acute hemolytic transfusion reaction.

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Febrile non-hemolytic transfusion reactions

Febrile reactions may develop in the absence of hemolysis. One possible cause of a febrile reaction is antibodies directed against leukocyte antigens of the HLA system with all other compatible parameters of the donor blood. This cause is most typical in patients receiving frequent blood transfusions. The second possible cause is cytokines released from leukocytes during storage, especially in platelet concentrate.

Clinically, a febrile reaction is characterized by a temperature increase of more than 1°C, chills, and sometimes headache and back pain. Symptoms of an allergic reaction often develop simultaneously. Since fever and chills also accompany severe hemolytic transfusion reactions, all patients with febrile reactions should be evaluated as described above.

Most febrile reactions are successfully treated with acetaminophen and, if necessary, diphenhydramine. Patients can be given acetaminophen before other transfusions. If a patient has had more than one febrile reaction, special anti-leukocyte filters can be used before subsequent transfusions. Many hospitals use pre-prepared blood components with a low white blood cell count.

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Allergic reactions

An allergic reaction to an unknown component of donor blood is common and is caused by allergens in the donor plasma or, less commonly, antibodies from the allergic donor. These reactions are usually mild, with urticaria, swelling, and sometimes dizziness and headache during or immediately after the transfusion. Fever is common. Less common are dyspnea, noisy breathing, and urinary and fecal incontinence, indicating generalized smooth muscle spasm. Anaphylaxis is rare, especially in IgA-deficient recipients.

In patients with a history of allergy or post-transfusion allergic reaction, prophylactic administration of antihistamines before the transfusion (eg, diphenhydramine 50 mg orally or intravenously) may be used. Note: drugs are never mixed with blood. If an allergic reaction occurs, the transfusion is stopped. Antihistamines (eg, diphenhydramine 50 mg intravenously) usually control mild urticaria and itching, and the transfusion can be resumed. However, moderate reactions (generalized urticaria or mild bronchospasm) require hydrocortisone (100-200 mg intravenously), and a severe anaphylactic reaction requires additional administration of adrenaline 0.5 ml diluted 1:1000 subcutaneously, as well as investigation of the cause of the reaction in cooperation with the blood bank. Further transfusions are not performed until the cause is fully clarified. Patients with severe IgA deficiency require transfusions of washed red blood cells, washed platelets, and plasma from IgA-deficient donors.

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Volume overload

The high osmotic pressure of blood products, especially whole blood, increases the volume of intravascular fluid, which can lead to volume overload, especially in patients sensitive to this factor (e.g., in cardiac or renal failure). Whole blood transfusions are contraindicated in such patients. Red blood cells should be transfused slowly. The patient should be monitored, and if signs of cardiac failure (shortness of breath, wheezing) occur, the transfusion should be stopped and treatment for cardiac failure should be initiated.

Diuretics are usually prescribed (furosemide 20-40 mg intravenously). If large volumes of plasma need to be transfused, such as in case of warfarin overdose, furosemide can be used simultaneously with the start of the blood transfusion. In patients with a high risk of volume overload (in case of cardiac or renal failure), prophylactic treatment with diuretics (furosemide 20-40 mg intravenously) is carried out.

Acute lung injury

Transfusion-associated acute lung injury is a rare complication caused by anti-HLA or antigranulocyte antibodies in donor plasma that agglutinate and degranulate recipient granulocytes in the lungs. Acute respiratory syndrome develops and chest radiographs show characteristic features of noncardiogenic pulmonary edema. After ABO incompatibility, it is the second most common cause of transfusion-associated mortality. The incidence is 1:5000-10,000, but mild to moderate acute lung injury usually goes unnoticed. Supportive care usually results in recovery without long-term sequelae. Diuretics should be avoided. Cases of acute lung injury have been reported.

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Increased affinity for oxygen

In blood stored for more than 7 days, the content of erythrocyte 2,3-diphosphoglycerate (DPG) decreases, which leads to an increase in the affinity for O ₂ and hinders its release into tissues. There is inconclusive evidence that 2,3-DPG deficiency is clinically significant, except in cases of exchange transfusion performed in children, in patients with sickle cell anemia with acute coronary syndrome and stroke, in individual patients with severe heart failure. After transfusion of red blood cells, regeneration of 2,3-DPG occurs within 12-24 hours.

Graft-versus-host disease (GVHD)

Transfusion-associated graft-versus-host disease is usually caused by transfusion of blood products containing immunocompetent lymphocytes into immunocompromised patients. The donor lymphocytes attack the host tissues. Graft-versus-host disease occasionally occurs in immunocompetent patients who receive blood from donors who are homozygous for an HLA haplotype (usually close relatives) for which the patient is heterozygous. Symptoms and signs include fever, rash, nausea, bloody watery diarrhea, lymphadenopathy, and pancytopenia due to bone marrow aplasia. Jaundice and elevated liver enzymes may also occur. Graft-versus-host disease occurs within 4-30 days after transfusions and is diagnosed based on clinical signs and skin and bone marrow biopsy. Mortality from graft-versus-host disease exceeds 90%, as there is no specific treatment.

Pre-irradiation of all transfused blood products prevents the development of graft-versus-host disease (damaging the DNA of donor lymphocytes). This is done in recipients with an immunodeficiency state (hereditary immunodeficiency syndromes, hematological diseases, hematopoietic stem cell transplantation, newborns), and also if the donor is a 1st degree relative or when transfusing HLA-compatible components other than hematopoietic stem cells.

Complications of massive transfusions

Massive transfusions are transfusions of more than or equal to one volume of blood given in 24 hours (e.g. 10 units for a 70 kg adult). When a patient receives such a large volume of banked blood, the patient's own blood may only make up about 1/3 of the original volume.

In situations not complicated by prolonged hypotension or DIC, the most common complication of massive transfusions is dilutional thrombocytopenia. Platelets in stored blood are not fully functional. The content of coagulation factors (except factor VIII) usually remains adequate. Microvascular bleeding (bleeding from skin cuts, injuries) may occur. Transfusions of 5-8 units (1 unit/10 kg) of platelet concentrate are usually sufficient to correct this type of bleeding in adult patients. Additional administration of fresh frozen plasma and cryoprecipitate may be necessary.

Hypothermia due to rapid transfusion of large amounts of cold blood may cause arrhythmia or acute heart failure. Hypothermia can be prevented by using equipment to gently warm the blood. Other methods of warming (eg, microwave) are contraindicated due to the potential for red blood cell damage and hemolysis.

Citrate and potassium toxicity usually do not develop even with massive transfusions, but this type of toxicity may be enhanced by hypothermia. In patients with liver failure, citrate metabolism may be impaired. Hypocalcemia occurs but rarely requires treatment (10 ml of 10% calcium gluconate solution is administered intravenously no faster than 10 minutes). In patients with renal failure, potassium levels may increase if blood stored for more than 1 week is transfused (in blood stored for less than 1 week, potassium usually accumulates insignificantly). Mechanical hemolysis during transfusion may lead to an increase in potassium levels. Hypokalemia may occur 24 hours after transfusion of old red blood cells (more than 3 weeks of storage), which accumulate potassium.

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Infectious complications

Bacterial contamination of red cell packs is rare and may be due to poor aseptic technique during collection or transient asymptomatic donor bacteremia. Refrigeration of packed red cells generally limits bacterial growth, with the exception of cryophilic organisms such as Yersinia sp, which can produce harmful levels of endotoxin. All units of packed red cells should be inspected daily for possible bacterial growth, as indicated by a change in colour of the preparation. Because platelet concentrate is stored at room temperature, it has an increased risk of bacterial growth and endotoxin production if contaminated. To minimise bacterial growth, the shelf life is limited to five days. The risk of bacterial contamination of platelets is 1:2500. Therefore, platelet concentrate is routinely tested for bacteria.

Syphilis is rarely transmitted through fresh blood or platelets. Storing blood for more than 96 hours at 4-10°C destroys the spirochetes. Although federal regulations require serologic testing of donated blood for syphilis, infected donors are seronegative in the early stages of the disease. Recipients of infected blood may develop a characteristic secondary rash.

Hepatitis may occur after transfusion of any blood component. The risk is reduced by viral inactivation with heating of serum albumin and plasma proteins and by using recombinant concentrates of coagulation factors. Hepatitis testing is required for all donated blood. The risk of hepatitis B is 1:200,000, and for hepatitis C 1:1.5 million. Because of the short viremic phase and associated clinical manifestations that prevent blood donation, hepatitis A (infectious hepatitis) is not a common cause of transfusion-associated hepatitis.

HIV infection in the United States is almost entirely HIV-1, although there are cases of HIV-2. Testing for antibodies to both viruses is mandatory. DNA testing for HIV-1 antigen is also required, as is HIV-1 p24 antigen. Additionally, blood donors are questioned about their lifestyle, based on which they can be classified as high-risk for HIV infection. HIV-0 has not been identified among blood donors. The estimated risk of HIV transmission through transfusion is 1 in 2 million.

Cytomegalovirus (CMV) can be transmitted through white blood cells in transfused blood. The virus is not transmitted through fresh frozen plasma. Because the virus does not cause disease in immunocompetent recipients, routine antibody testing of donor blood is not required. However, CMV can cause severe or fatal disease in immunosuppressed patients who must receive CMV-negative blood products from donors who do not have antibodies to CMV or who must have white blood cells removed from the blood using filters.

Human T-cell lymphotropic virus type I (HTLV-I) can cause adult T-cell lymphoma/leukemia, HTLV-1-associated myelopathy, tropical spastic paraparesis, and post-transfusion seroconversion in some patients. All blood donors are tested for antibodies to HTLV-I and HTLV-II. The estimated risk of a false negative result when testing donor blood is 1:641,000.

There have been no reports of transfusion transmission of Creutzfeldt-Jakob disease, and current practice discourages donations by individuals who have received human growth hormone, a dura mater transplant, or family members of individuals with Creutzfeldt-Jakob disease. The new variant of Creutzfeldt-Jakob disease (mad cow disease) is not transmissible. However, donors who have spent significant time in the UK and parts of Europe are discouraged from donating blood.

Malaria is easily transmitted through infected blood. Many donors are unaware that they have malaria, which can be latent and transmissible for 10-15 years. Storing blood does not prevent transmission of malaria. Potential donors should be questioned about malaria and whether they have visited areas where infection may occur. Donors who have had malaria or who are immigrants or citizens from endemic countries are not allowed to donate blood for 3 years, and travelers to endemic countries are not allowed to donate blood for 1 year. Babesiosis is rarely transmitted by transfusion.