Blood transfusion is a critical medical procedure often employed to save lives, particularly in acute clinical settings. While most transfusions are safe, complications and risks are inherent. Even in cases where the procedure is performed under optimal conditions, adverse outcomes can still occur. Therefore, blood transfusion should only be administered when there is a definitive clinical need, as infections or other complications remain possible, even with stringent blood banking standards.
The potential complications associated with blood transfusions can be classified as either immediate or delayed reactions (as outlined in Table 1).
Immediate | Delayed |
---|---|
Acute hemolytic transfusion reaction | Delayed hemolytic transfusion reaction |
Febrile non-hemolytic transfusion reaction | Transmission of infections |
Allergic reactions | ron overload |
Anaphylactic reactions | Graft vs. host disease |
Transfusion-associated lung injury | Post-transfusion purpura |
Volume overload | - |
Bacterial contamination of the donor unit | - |
Common Causes of Transfusion-Related Mortality
The most frequent causes of transfusion-related deaths include:
- Acute hemolytic transfusion reaction (often due to ABO incompatibility)
- Pulmonary edema and heart failure from circulatory overload
- Bacterial contamination of blood units
- Transfusion of physically damaged red blood cells (e.g., by extreme temperatures)
- Transfusion-associated graft-versus-host disease
Acute Hemolytic Transfusion Reaction
This severe and potentially fatal condition occurs when donor red blood cells are destroyed by recipient antibodies, primarily resulting from ABO mismatch. Clerical errors during blood typing or transfusion can lead to the infusion of incompatible blood, such as transfusing group A blood into a group O recipient. This antigen-antibody interaction activates the complement system, triggering intravascular hemolysis, which manifests as hypotension, shock, acute renal failure, and disseminated intravascular coagulation (DIC). Common symptoms include fever, loin pain, and tachycardia. In anesthetized patients, bleeding and hypotension may be the only indicators.
- Antigen-antibody reaction
- Activation of complement
- C5b-9
- Intravascular hemolysis
- Hemoglobinemia, Hemoglobinuria, Raised serum bilirubin, Methemalbumin
- Disseminated intravascular coagulation
- Intravascular hemolysis
- C3a,C5a
- Hypotension, Shock
- C5b-9
- Activation of complement
Laboratory features are:
- Hemoglobinemia (pink coloration of plasma after centrifugation of post-transfusion sample)
- Positive direct antiglobulin test
- Hemoglobinuria
- Schistocytes (fragmented red cells) and spherocytes on blood smear
- Elevated indirect serum bilirubin
Febrile Non-Hemolytic Transfusion Reaction
This is the most frequent reaction, affecting approximately 1% of transfusion recipients. It is characterized by a rise in temperature of at least 1°C during or shortly after transfusion. This reaction often occurs in patients who have received multiple transfusions and is caused by the release of pyrogenic cytokines from white blood cells. Symptoms include fever, chills, and tachycardia. Diagnosis depends on the exclusion of other causes of febrile transfusion reaction.
Transfusion reactions presenting with fever are shown in Flowchart 2.
- Febrile Transfusion Reaction
- Acute hemolytic transfusion reaction
- Febrile nonhemolytic transfusion reaction
- Bacterial contamination of donor units
- Transfusion-associated lung injury
- Delayed hemolytic transfusion reactions
Bacterial Contamination of Blood Units
Bacterial contamination is more common in platelet transfusions because platelets are stored at room temperature, which fosters bacterial growth. Gram-positive cocci typically contaminate platelets, while red blood cells are more often contaminated by Yersinia enterocolitica, Escherichia coli, or Pseudomonas species. Signs of contamination include high-grade fever, rigors, and hypotension.
Laboratory investigations involve examining the blood bag for any discoloration, performing Gram staining, and culturing blood samples from both the blood bag and the recipient. The direct antiglobulin test results are negative.
Transfusion-Associated Lung Injury (TRALI)
TRALI is an acute respiratory condition that occurs following blood transfusion. It presents with fever, chills, dyspnea, and non-productive cough. Chest X-rays show diffuse pulmonary infiltrates. TRALI likely arises from a reaction between donor HLA or neutrophil antibodies and the recipient's leukocytes, causing the formation of leukocyte aggregates that obstruct the pulmonary vasculature.
Delayed Hemolytic Transfusion Reaction
This reaction can occur days or even weeks after a transfusion and is typically associated with previously sensitized individuals, such as those with past transfusions or pregnancies. It involves a secondary immune response, primarily against Kidd antibodies, leading to extravascular hemolysis. Symptoms include mild jaundice and anemia, with laboratory findings revealing elevated indirect bilirubin and a positive direct antiglobulin test.
Table 2 provides a comparison between acute and delayed hemolytic transfusion reactions.
Parameter | Acute | Delayed |
---|---|---|
Type of antibody | Anti-ABO | Anti-Kidd |
Nature of antibody | Naturally-occurring | Immune |
Time of appearance of clinical features after transfusion | Within minutes | After several days or weeks |
Site of hemolysis | Intravascular | Extravascular |
Clinical features | Fever, chills, back pain, acute renal failure, DIC | Fever, mild jaundice, anemia |
Anaphylactic Reaction
This rare and severe reaction occurs in IgA-deficient recipients, where anti-IgA antibodies interact with donor plasma IgA, triggering complement activation and the release of anaphylatoxins (C3a and C5a). Symptoms typically include acute hypotension, shock, and shortness of breath after the transfusion of just a few drops of blood.
Allergic Reaction
This is the second most common transfusion reaction, caused by type I hypersensitivity to plasma proteins in donor blood. Mild symptoms include urticaria, rash, and pruritus (itching).
Volume Overload
Transfusing blood too quickly or in large amounts, especially in patients with compromised cardiac or renal function, can result in volume overload, leading to heart failure and pulmonary edema.
Iron Overload
Patients who receive regular transfusions, such as those with thalassemia, are at risk of iron overload, as each blood unit contains approximately 200 mg of iron. Over time, iron can accumulate and damage vital organs.
Transmission of Infections
Although modern screening has greatly reduced the risk, certain infections can still be transmitted via blood transfusions, including hepatitis B and C, and HIV. Screening protocols have been developed to detect these infections early and exclude affected donors from the blood supply.
- Hepatitis A Virus: Although hepatitis A is infrequently transmitted through transfusion due to the brief duration of viremia, donors diagnosed with hepatitis A or in close contact with an infected individual are deferred from donation for one year.
- Hepatitis B Virus: In India, the prevalence of hepatitis B virus ranges from 1.5% to 4%, with approximately 43 million carriers. This DNA virus can be transmitted through both cellular and plasma components, with an incubation period of 2 to 6 months. Blood donations undergo testing for HBsAg using sensitive methods, significantly reducing transmission risks. During the early stages of infection, HBsAg may not be detectable; in this "window period," antibodies to hepatitis B core antigen (anti-HBc) may be the only markers of infection. Donors testing positive for HBsAg are permanently barred from donating. Hepatitis B can lead to several liver diseases, including subclinical hepatitis, acute icteric hepatitis, fulminant hepatitis, chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
- Hepatitis C Virus: The reported prevalence of hepatitis C in India is approximately 1.66%, with 15 million carriers. This RNA virus is the leading cause of transfusion-transmitted hepatitis and can be passed through both cellular and plasma components. Its incubation period is about 8 weeks, and persistent infection is common, with chronic hepatitis typically presenting mild symptoms. While cirrhosis may develop in a minority of cases, hepatocellular carcinoma occurs in approximately 10% of patients with cirrhosis. The primary screening test for donors is the anti-HCV antibody test, but HCV RNA can be detected via PCR testing from infection onset until the appearance of anti-HCV antibodies (70-80 days later).
- Human Immunodeficiency Virus (HIV): In India, the adult prevalence of HIV is 0.7%. The two closely related viruses recognized are HIV-1 and HIV-2, both of which are RNA retroviruses. The progression of HIV infection includes an initial acute phase characterized by flu-like symptoms occurring 3 to 6 weeks post-infection, followed by a prolonged chronic phase that may remain asymptomatic or feature persistent lymphadenopathy, and culminating in a final stage marked by opportunistic infections and malignancies. HIV can be transmitted through both cellular and plasma components. Detection is primarily achieved through anti-HIV-1/2 antibody testing via enzyme immunoassay, though nucleic acid testing (NAT) for HIV RNA is recommended to reduce the window period from 22 days to 10 days.
- Treponema Pallidum: Although transfusion-related transmission of syphilis is rare due to the inability of T. pallidum to survive in refrigerated conditions (inactivated at 4°C after four days), fresh blood and platelet concentrates can still harbor the organism. The principal role of screening tests in this context is to identify high-risk behaviors.
- Malaria Parasites: Malaria parasites can be readily transmitted through transfusion. In endemic regions, it is often impractical to exclude all potential donors with a history of malaria. Consequently, the most effective preventive measure is administering prophylactic antimalarial drugs to all transfusion recipients.
Complications Associated with Massive Transfusion
Massive transfusion is defined as the administration of stored blood equal to a patient’s total blood volume within a 24-hour period. The associated morbidity and mortality often arise from rapid blood loss compounded by the transfusion of stored blood.
The storage of blood leads to the depletion of 2,3-diphosphoglycerate, a decrease in pH, loss of ATP, impaired platelet function, and depletion of coagulation factors. Furthermore, microaggregates formed from leukocytes and platelets gradually develop in stored blood. The rapid transfusion of significant volumes of stored blood may result in:
- Dilution of platelets and coagulation factors
- Hyperkalemia (due to potassium release from stored red blood cells)
- Hypocalcemia (resulting from calcium binding by citrate)
- Hypothermia (caused by the rapid infusion of cold blood)
- Adult respiratory distress syndrome due to the migration of microaggregates to the lungs.
Recognition and Investigation of a Transfusion Reaction
All reactions following blood transfusion should be considered hemolytic in nature and investigated accordingly (See Flowchart 3).
- Immediate Action: The transfusion should be halted immediately, with an intravenous line left open and normal saline infused.
- Error Verification: Review all documentation and the blood bag for clerical errors, as over 90% of hemolytic transfusions occur due to such mistakes (e.g., incorrect blood unit given to an inappropriate recipient).
- Notify Blood Bank: The blood bank must be informed immediately, and the blood bag, administration set, as well as post-transfusion blood and urine samples should be sent for further analysis.
- Evidence of Hemolysis: A post-transfusion blood sample should be obtained from the recipient and centrifuged. A pink discoloration in the overlying plasma (hemoglobinemia) is the most rapid indication of intravascular hemolysis if the pre-transfusion sample is normal. Additionally, the patient's urine should be visually inspected for hemoglobinuria. Blood smear examination will reveal fragmented red cells and spherocytes, while indirect serum bilirubin levels may be elevated.
- Detection of Blood Group Incompatibility: Conduct a direct antiglobulin test (DAT) on both post- and pre-transfusion blood samples. A positive DAT on the post-transfusion sample (with a negative test on the pre-transfusion sample) indicates an immunological hemolytic transfusion reaction. Blood group incompatibility will also be identified through (i) repeated ABO grouping of the recipient’s pre- and post-transfusion samples and the donor unit, and (ii) repeated crossmatching of donor blood against recipient samples collected pre- and post-transfusion.
- Investigative Tests for Complications:
- For suspected disseminated intravascular coagulation: conduct a blood smear, coagulation screen, and tests for fibrin degradation products.
- For acute renal failure: assess blood urea, serum creatinine, and serum electrolyte levels.
- Bacteriological Cultures: If the cause of the acute transfusion reaction remains unclear, bacteriological cultures should be obtained for further investigation.
- Fever, chills, pain at infusion site, loin pain, hypotension, dark urine, bleeding
- Stop transfusion. Maintain intravenous line in place with normal saline
- Emergency management
- Check blood bag and paperwork for clerical error
Notify blood bank
Send
(1) Transfusion reaction report form
(2) Blood bag with attached IV set
(3) Post-transfusion blood and urine sample
Document reaction on patient chart
- Stop transfusion. Maintain intravenous line in place with normal saline