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Acute Hemolytic Transfusion Reaction

Approximately 1 in 38,000 red cell units is transfused to the wrong patient. When the wrong unit of blood is given, it is ABO-incompatible 1 in 3 times. Two thirds of these erroneous transfusions are caused by a clerical or management error in identifying the patient, blood sample or blood component and one third are due to an error in the transfusion service. Of these ABO-incompatible transfusions, about 10% are associated with a fatal hemolytic transfusion reaction. Occasionally, a non-ABO antibody may also trigger acute intravascular hemolysis. Very rarely, an antibody from transfused donor plasma may be implicated in an acute hemolytic reaction.

The pathophysiology of acute hemolytic transfusion reactions (AHTR) involves 3 phases.

  • In the first phase, IgM or IgG antibody binds to the transfused red blood cell membranes. If these antibodies are capable of activating complement (C1 to C9), hemolysis occurs.
  • In phase 2, the red cells that are not hemolyzed can bind to phagocytic cells through IgG or C3b receptors, stimulating the production of cytokines such as IL-8 and TNF alpha. Bound red cells are destroyed by phagocytosis.
  • In phase 3, the systemic effects of anaphylotoxins, C3a and C5a, and cytokines produce the clinical signs and symptoms of an acute hemolytic reaction.

The National Healthcare Safety Network (NHSN) hemovigilance protocol has published the following case definition of AHTR. Hemolysis occurs during or within 24 hours of cessation of transfusion and causes new onset of any of the following signs or symptoms:

  • Back or flank pain
  • Chills and/or rigors
  • Disseminated intravascular coagulation (DIC)
  • Epistaxis
  • Fever
  • Hematuria
  • Hypotension
  • Oliguria or anuria
  • Renal failure
  • Pain and or oozing at IV site


2 or more of the following:

  • Decreased fibrinogen
  • Decreased haptoglobin
  • Elevated bilirubin
  • Elevated LDH
  • Hemoglobinemia
  • Hemoglobinuria
  • Plasma discoloration compatible with hemolysis
  • Spherocytes on peripheral smear


Positive direct antiglobulin test (DAT) for anti-IgG or anti-C3 AND positive elution test with alloantibody present on transfused red blood cells


Negative serologic testing and confirmed physical cause of hemolysis such as thermal, osmotic, mechanical or chemical.

 Initial symptoms of hemolysis may include fever, chills, a burning sensation at the IV site, flank pain, anxiety, and tightness in the chest. Clinical signs include tachycardia, fever and hypotension. Anesthesized patients may exhibit only hemoglobinuria, hemoglobinemia or oozing of blood from cut surfaces.  Renal failure and DIC may subsequently occur. 

The morbidity and mortality of hemolytic reactions is proportional to the amount of incompatible blood transfused.  Symptoms and signs may occur after transfusion of as little as 1 mL of incompatible blood. Pronounced signs and symptoms are common after 5 to 20 mL. Life-threatening consequences include acute renal failure, shock and DIC. The risk of a fatal reaction is much higher after transfusion of more than 200 mL of incompatible blood. 

When a hemolytic reaction is suspected, immediate action must be taken to determine its etiology and minimize its consequences.

  • Lavender top tube of blood should be centrifuged and the plasma examined for hemoglobin.  A pre-reaction specimen should be used for comparison. Pink or red discoloration in the post-reaction, but not the pre-reaction specimen, may indicate a hemolytic reaction.
  • Transfusion Service performs testing for an immune mediated AHTR.

If no free hemoglobin is detected in the plasma and the patients' RBCs are not coated with antibody, a hemolytic reaction is highly unlikely. If either test is positive, a hemolytic reaction probably occurred. The hemoglobin or hematocrit should also be checked to see if the expected rise per unit of 1 g/dL for hemoglobin or 3% for hematocrit was achieved.  If not, transfused red cells may have been hemolyzed.

A plasma haptoglobin should be performed on both pre and post-transfusion serum specimens.  After transfusion of several units of stored blood, the post-transfusion haptoglobin level may be decreased to 50% of the pre-transfusion level, even though the units were compatible. After hemolysis, the pre-transfusion level will be within the reference range of 100 to 150 mg/dL and the post-transfusion level will be zero.

If hemolysis has occurred coagulation tests including PT, aPTT, fibrinogen, platelet count and D-Dimer should be ordered to determine if DIC is occurring.  BUN and creatinine should be monitored to assess renal function. 

The transfusion should be stopped immediately, but the IV line should be kept open with Normal Saline infusion since hypotension, acute renal failure and shock may occur.  Vital signs and urine output should be monitored. Medical consultation may be necessary for management of severe complications.

Acute hemolytic reactions are prevented by meticulous attention to patient identification protocols and the introduction of technological advances such as bar coded wristbands. All blood samples drawn for testing must be positively identified. An additional safety measure in the transfusion service is to require that a patient have two blood types on file before ABO specific blood components are issued. Two persons should always verify the identification of the patient and the blood component at the bedside prior to transfusion.

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