What are the steps in managing delayed transfusion reactions?

Management of Delayed Transfusion Reactions

Stop any ongoing transfusion immediately, maintain IV access with normal saline, notify the blood bank urgently, and initiate supportive care while investigating for alloantibodies and hemolysis. 1

Immediate Recognition and Initial Actions

Stop the transfusion immediately at the first suspicion of a delayed transfusion reaction—this is the single most critical intervention to prevent progression to severe morbidity or mortality. 1 Maintain IV access with normal saline for medication administration and potential fluid resuscitation. 1

Vital Sign Monitoring and Assessment

• Monitor vital signs every 5-15 minutes, including heart rate, blood pressure, temperature, respiratory rate, and oxygen saturation. 1
• Double-check all documentation for administration errors, particularly patient identification and blood component compatibility. 1
• Assess for signs of hemolysis: fever, jaundice, dark urine, unexplained anemia worsening, and back/flank pain. 2, 3

Laboratory Investigation

Contact the transfusion laboratory immediately to report the reaction and initiate investigation. 1 The blood bank will perform:

• Direct antiglobulin test (DAT) to detect antibody-coated red cells 2
• Antibody screen and identification to detect new alloantibodies 3, 4
• Hemolysis markers: lactate dehydrogenase (LDH), indirect bilirubin, haptoglobin, plasma-free hemoglobin 2
• Complete blood count to assess hemoglobin drop and reticulocyte response 3

Critical caveat: In sickle cell disease patients, delayed hemolytic transfusion reactions (DHTR) may present as painful crises within 6 days of transfusion, with selective disappearance of transfused cells. 4 These reactions are often more severe than in other populations and may progress to life-threatening hyperhemolysis syndrome. 5, 6

Supportive Management

Mild to Moderate Reactions

For patients with laboratory evidence of hemolysis but stable hemodynamics:

• Avoid further transfusion unless absolutely life-threatening anemia exists, as additional transfusions may worsen hemolysis. 5, 3
• Maintain adequate hydration with IV fluids to support renal perfusion and prevent acute kidney injury. 2
• Monitor renal function closely (creatinine, urine output). 2
• Provide symptomatic treatment for fever and pain with NSAIDs or acetaminophen. 5

Severe Reactions and Hyperhemolysis Syndrome

In patients with life-threatening anemia requiring transfusion despite high risk of acute hemolytic reaction (particularly in sickle cell disease with history of multiple or severe DHTR):

• Consider immunosuppressive therapy: IVIg, corticosteroids (hydrocortisone 200 mg IV or equivalent to 1-2 mg/kg methylprednisolone every 6 hours), or rituximab. 5
• This represents a conditional recommendation based on very low certainty evidence, reserved for rare situations where compatible blood cannot be found or patients have history of repeated severe hemolytic reactions. 5
• Engage in shared decision-making with hematology and transfusion medicine specialists, weighing potential benefits against harms of ongoing life-threatening anemia. 5

Warning: Corticosteroids are not routinely effective once hypersensitivity reactions occur, and premedication with oral corticosteroids is usually unsuccessful in preventing recurrent reactions. 5

Reporting and Documentation

• Notify the blood bank immediately—delayed transfusion reactions are underdiagnosed and underreported despite significant morbidity risk. 1
• Report to the patient's primary care provider to update transfusion records. 1
• Document all symptoms, timing relative to transfusion, laboratory findings, and management interventions. 5
• Ensure the reaction is recorded in the patient's permanent transfusion record to guide future transfusion decisions. 2

Prevention of Future Reactions

For Sickle Cell Disease Patients

• Perform extended red cell phenotyping (Rh, Kell, Duffy, Kidd systems) before first transfusion. 3, 4
• Provide extended phenotypic matching of transfused cells to minimize alloimmunization risk. 3, 4
• Use blood that is nonimmunogenic in antigen systems frequently associated with DHTR, especially in patients who have previously formed alloantibodies. 4
• Consider prophylactic immunosuppression (rituximab) in patients with history of multiple life-threatening DHTR requiring ongoing transfusion support, though evidence is limited. 5

For All Patients

• Maintain centralized transfusion records accessible across healthcare facilities to prevent exposure to incompatible antigens. 3
• Minimize unnecessary transfusions—transfuse single units in non-hemorrhaging patients and reassess before additional units. 1
• Use electronic transfusion management systems rather than manual checking when available. 1

Special Considerations for Delayed Reactions

Delayed reactions typically occur 3-14 days post-transfusion and may present with flu-like symptoms, arthralgias, myalgias, and fever lasting up to 24 hours. 5 In sickle cell disease, reactions may occur within 6 days and mimic painful crises with fever, arthritis, and serum sickness-like illness. 4

Patients should be informed before discharge about possible delayed symptoms and instructed to seek medical evaluation if symptoms persist beyond a few days, as this may indicate hemolysis or other pathology requiring provider assessment. 5