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Transfusion Transmitted
Injuries Section Acute Hemolytic Transfusion Reaction (AHTR) The acute hemolytic transfusion reaction (AHTR) refers to an accelerated destruction of red blood cells in a transfused recipient occurring during or within 24 hours after a blood transfusion. The destruction of red blood cells results from an interaction between existing antibodies in the recipient and antigens in transfused red cells1-2. AHTR is characterized by a sudden onset of fever, chills, facial flushing, chest pain or low back pain, hypotension, and dyspnea and may result in severe complications such as renal failure and disseminated intravascular coagulation (DIC)1. AHTR is the leading cause of death associated with transfusion. It has been estimated that AHTR occurs approximately 1 in 12,000 to 1 in 33,000 red cell units transfused3. Fatal AHTR, on the other hand, occurs 1 in 600,000 to 1 in 800,000 units transfused4. The majority of AHTR occurs as a result of erroneous administration of ABO-incompatible red cells to recipients who have corresponding preformed antibodies4. Commonly reported errors include improper specimen identification and improper patient identification. Measures aimed to detect and prevent these errors are essential to reduce the occurrence of ABO-incompatible transfusion and its associated AHTR. Early diagnosis and treatment are also important in reducing AHTR-related fatalities. Febrile Nonhemolytic Transfusion Reaction (FNHTR)Febrile nonhemolytic transfusion reaction (FNHTR) is the most common, non life-threatening transfusion reaction associated with a transfusion of red cells and platelets5. FNHTR is characterized by an isolated temperature increase, of at least one degree Celsius within 24 hours after completion of transfusion, which is not explained by the patient's clinical condition. The fever is usually accompanied by chills, rigors, and discomfort6. Transfusion of platelets is associated with a higher risk of FNHTR than transfusion of red blood cells. It has been estimated that the risk of red cell associated FNHTR is about 1% of all transfusions, with a range of 0.5% to 6.8%3,6-7; however, the risk of platelet associated FNHTR occurs in 4% to 37.5% of transfusions7-8. Recipients who have had a history of blood transfusion and pregnancy are at increased risk of red blood cell associated FNHTR, however, no specific profiles of recipients have been identified as being associated with an increased risk of platelet associated FNHTR7-8.Red cell associated FNHTR is caused by the reaction between leukocyte antibodies present in the plasma of a recipient and leukocytes present in transfused red cells6. However, platelet associated FNHTR seems to be related to the presence of pyrogenic cytokines released from leukocytes during the platelet storage. Leukoreduction of the cellular blood components may effectively reduce the occurrence of FNHTR5. Urticarial (or allergic) reaction is a common and usually non life-threatening adverse reaction associated with transfusion of plasma, platelets, or red cells8. In general, urticarial reactions manifest mild symptoms such as localized erythema, hives, and pruritus and are usually not accompanied by fever or any other severe symptoms9. The definitive etiology of urticarial reactions remains unknown; however, it may result from the presence of soluble allergen in donors' plasma9. Approximately 1% to 3% of all transfusions result in urticarial reactions3,10. Although no specific profiles of recipients at risk have been identified, a history of allergic predisposition may be associated with increased risk8. Anaphylactic ReactionAnaphylactic reaction is a rare but severe complication following a blood transfusion. Signs and symptoms associated with anaphylactic reactions usually begin within 1 to 45 minutes after the start of a transfusion when only a few millimetres of blood has been transfused10. This reaction can be characterized by a severe allergic hypersensitivity in the absence of fever. Patients often present with mild symptoms such as cough and bronchospasm at the beginning, which then progress rapidly and may result in severe consequences such as shock, loss of consciousness, and death3.
The incidence of anaphylactic reactions has been estimated to be 1 in 20,000 to 1 in 47,000 units of blood transfused9. Many anaphylactic reactions result primarily from a reaction between donors' IgA and anti-IgA antibodies produced by IgA-deficient recipients, even though other possible antigens have been reported in the literature9. To prevent anaphylactic reactions, it is recommended that IgA-deficient patients with evidence of anti-IgA antibodies in their serum receive IgA-deficient blood components9. Transfusion-Related Acute Lung Injury (TRALI) Transfusion-related acute lung injury (TRALI) is a rare and life-threatening complication associated with transfusion of blood components containing plasma such as red cells, platelets, granulocytes, and cryoprecipitates11. TRALI usually occurs within 1 to 2 hours after the start of a transfusion and is characterized by acute respiratory distress. The symptoms of TRALI include severe bilateral pulmonary edema, severe hypoxemia, tachycardia, cyanosis, hypotension, and fever12. The incidence of TRALI has varied considerably among different studies, with a range of 1 in 5,000 to 1 in 10,000 units transfused, or 4 to 16 per 10,000 recipients11. Although no specific profiles are available to identify recipients who may be at increased risk of TRALI, clinical conditions among recipients such as active infection or massive transfusion may be associated with increased risk7. TRALI has been reported to be the third leading cause of death associated with transfusion, with a case fatality rate ranging from 5% to 14%12.
The precise mechanism of TRALI is unknown, but increasing evidence has indicated that it is an immune mediated event initiated by pathological antibodies from donors11-13. The presence of human leukocyte antigen (HLA)-specific antibodies in the plasma of donors has been strongly associated with the occurrence of TRALI12. To reduce the occurrence of TRALI, some investigators have recommended that donors who have been previously implicated in TRALI in a recipient be permanently deferred and that multiparous donors be screened for HLA antibodies13. On the other hand, prevention of TRALI-related fatalities involves careful bedside observation during and after transfusion for any respiratory distress and provision of respiratory support as early as possible. Transfusion-Associated Circulatory Overload (TACO)Transfusion Associated Circulatory Overload (TACO) is a common reaction resulting from a rapid or massive transfusion of blood12. TACO usually occurs within several hours after the start of a transfusion and is manifest in signs and symptoms that include dyspnea, orthopnea, peripheral edema, and rapid increase of blood pressure. The incidence of TACO is difficult to determine because of underreporting. It has been estimated that TACO occurs approximately 1 in 100 to 1 in 10,000 transfusions3. Certain groups of patients are at increased risk for TACO. These include infants, elderly patients over 60 years of age, patients with cardiac, pulmonary or renal failure, and patients with chronic anemia9,12. Identification of patients who may be at risk of TACO and administration of small volumes of required blood components at a well-controlled rate may effectively prevent TACO9. Transfusion-associated metabolic reactions are associated with massive or rapid transfusion and include citrate toxicity, hypothermia and hyperkalemia. Citrate toxicitySodium citrate is the substance used to prevent blood coagulation during blood collection. The liver, under normal conditions, can rapidly metabolize sodium citrate; however, the metabolic capacity of the liver can be exceeded when large volumes of blood are transfused. This may result in an increased level of citrate and may induce hypocalcemia and hypomagnesemia with clinical symptoms such as paresthesia, tetany, and arrhytmia3. In addition, metabolic alkalosis may result from the accumulation of bicarbonate -- the metabolic derivative of citrate14. The incidence of citrate toxicity is unknown. Patients who are undertaking prolonged apheresis procedures and infants who have already suffered underlying diseases may be at increased risk14. HypothermiaHypothermia is also associated with rapid transfusion of large amounts of cold blood, which may result in cardiac arrhythmias3. Hypothermia can be prevented by careful control of the transfusion rate or by the use of ultra-efficient blood warmers to rapidly warm large volumes of blood before transfusion9. HyperkalemiaAlthough the potassium level in the plasma increases during blood storage, this rarely causes hyperkalemia among recipients because potassium can be rapidly diluted, redistributed and excreted after the transfusion. However, a massive or rapid transfusion in a short period of time may cause hyperkalemia, particularly among premature infants and acidotic patients, and result in significant morbidities and even death15-16.
Transfusion Associated Air Embolism Air embolism is a rare complication of blood transfusion. It may result from transfusion of blood under pressure using an open system. Small amounts of air may enter into the circulation during transfusion and result in clinical symptoms such as cough, dyspnea, chest pain and shock, and occasionally deaths3,9. The incidence of transfusion associated air embolism is unknown. Intraoperatively or postoperatively recovered blood has been associated with the occurrence of air embolism if it is not properly performed17. Delayed Hemolytic Transfusion Reaction (DHTR)Delayed hemolytic transfusion reaction (DHTR) is an accelerated destruction of transfused red blood cells that usually occurs days to weeks (usually within 2 weeks) after a transfusion2,18. Unlike AHTR, most patients with DHTR are either asymptomatic or present with mild symptoms such as low-grade fever, decreased hemoglobin level, and jaundice. Occasionally, patients may present with hemoglobinemia and hemglobinuria1. The estimated risk of DHTR ranges from 1 in 5,000 to 1 in 11,000 transfusions19-21. The majority of DHTR cases result from a secondary immune response in patients previously sensitized by a transfusion or pregnancy. Thus, patients who have a history of transfusions and pregnancy are at increased risk of DHTR. To prevent DHTR, it has been recommended that red cells that do not carry the associated antigens be provided to patients who have a history of DHTR1. Posttransfusion Purpura (PTP)Posttransfusion purpura (PTP) is a rare complication associated with transfusion of blood components that contain platelets antigens such as whole blood, packed red blood cells, plasma, and platelet concentrates22. PTP can be characterized by a sudden diminution of the platelet count to less than 10,000/µL, which usually occurs 5 to 10 days after a blood transfusion. Clinical signs and symptoms associated with PTP include wet purpura with mucous membrane hemorrhage, epistaxis, gastrointestinal bleeding, and bleeding from the urinary tract3,8,22. The incidence of PTP is unknown, but it has been estimated to be 1 in 200,000 transfusions7. The most severe complication following PTP is intracranial hemorrhage. The case fatality rate of PTP ranges from 0% to 13%22. Individuals who have a history of transfusion or pregnancy are at increased risk of PTP. Thus women, in particular middle aged or elderly women, are at the risk7. To prevent PTP, it is recommended that patients who have a documented history of PTP receive antigen-negative blood components22. Transfusion Associated Graft-Versus-Host Disease (TA-GVHD)Transfusion associated graft-versus-host disease (TA-GVHD) is a rare but often fatal complication following a blood transfusion. TA-GVHD is an acute syndrome that occurs usually 2 to 30 days after a transfusion and can be characterized by fever, liver dysfunction, skin rash, diarrhea, and severe pancytopenia8. The incidence of TA-GVHD is currently unknown; however, some patients have been identified as being at increased risk: patients with congenital immunodeficiency syndromes, Hodgkin's disease, chronic lymphocytic leukemia, and recipients of blood donated by relatives23. It has been estimated that TA-GVHD occurs at a rate of approximately 0.1% to 1% among these high-risk patients. About 90% of patients with TA-GVHD eventually die as a result of the reaction8. TA-GVHD occurs when donors' lymphocytes are not recognized as foreigners by recipients' lymphocytes and therefore are not destroyed. Consequently, donor lymphocytes multiply and initiate an immune attack against the recipient's cells, resulting in TA-GVHD24-25. There is no effective treatment once TA-GVHD has occurred. Prevention of its occurrence among high-risk patients is critical to reducing TA-GVHD related fatalities. Gamma-irradiated blood components are highly recommended for use among high-risk recipients24. Iron OverloadIron overload is a transfusion-induced reaction that can damage organs and result in dysfunction of the liver, heart, and kidneys. Iron overload occurs primarily among patients who receive repeated red blood cell transfusions over a long period and, therefore, accumulate a high level of iron that the body cannot physiologically excrete7. The incidence of iron overload is currently unknown3. However, certain individuals such as patients with thalassemia, sickle cell anemia, and myelodysplasia have been identified as being at increased risk of iron overload7. Prevention involves several approaches, including minimization of red cell transfusions, the use of pharmacological therapy or iron-chelating agents to reduce the need for red cell transfusions, and the use of red blood cell exchange procedures9. References
[Blood Safety Surveillance and Health Care Acquired Infections Division]
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Last Updated: 2004-07-15 | ![]() |