Practice Based Learning: How does IVIG cause hemolytic anemia and can you have a negative DAT in autoimmune hemolytic anemia?

Adrienne DePorre, MD

Presented by Adrienne DePorre, MD
Resident, Department of Pediatrics
Emory University

Key Points:

  • Antibodies to blood group antigens (anti-A/anti-B) are found in all preparations of IVIG as a result of pooling from O donors. Average antiblood titers are 1:16 for A and 1:8 for B. Those that developed hemolysis often had antiblood group titers of greater than 1:32. This combined with higher affinity antibodies can cause hemolysis.
  • There is an increased risk with higher doses of IVIG in those who receive greater amounts of pathogenic antibodies.
  • It is standard practice now to monitor the patient’s hemoglobin 24 to 48 hours after completing IVIG and one week after discharge, and to be concerned if the hemoglobin drops after 1 dose of IVIG.
  • DAT negative autoimmune hemolytic anemia (AIHA) represents 3-10% of all AIHA, most commonly because RBC-bound IgA/IgM is not detectable by routine reagents, and because low affinity IgG is washed off the RBCs during the washing phase of the DAT.
  • If strongly suspecting AIHA, it may be helpful to find a reference lab where special reagents (such as a LISS test or a direct polybrene test) are available.


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Garratty G, Leger RM, Hunt P, Co A. Serological investigation of a large series of direct antiglobulin test negative hemolytic anemias (SP313). Transfusion. 2004; 44 (Suppl 1): 121A-122A.

Gordon JM, Cohen P, Finlayson JS. Levels of anti-A and anti-B in commercial immune globulins. Transfusion. 1980 Jan-Feb; 20(1): 90-2. PMID: 6986683.

Wilson JR, Bhoopalam H, Fisher M. Hemolytic anemia associated with intravenous immunoglobulin. Muscle Nerve. 1997 Sep; 20(9):1142-5. PMID: 9270670.

Savage N, Georgi D, Kutlar A, Cook L. Coombs’-negative autoimmune hemolytic anemia in a patient with small lymphocytic lymphoma involving the bone marrow. LabMedicine 2008; 39 (8): 465-466.

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