IVIG-Induced Coombs-Positive Hemolytic Anemia in a Critically Ill Adolescent Male

BACKGROUND: A well-described but not universally appreciated side effect of IVIG administration is clinically apparent, sometimes severe hemolysis. We describe a severe case of Coombs-positive hemolytic anemia secondary to IVIG. IVIG is a blood derivative manufactured from pools of 5,000 to 10,000 individual plasma donations. IVIG is not ABO-type restricted, so anti-A, anti-B and anti-A,B isoagglutinins are measureable in IVIG. A number of other RBC alloantibodies to minor blood group antigens have also been detected. CASE REPORT: A 16-year-old male with PMH of OSA and obesity was admitted for adenoviral pneumonia leading to respiratory failure requiring mechanical ventilation. A complicated PICU course included severe ARDS, septic-shock, AKI and Coombs-positive hemolytic anemia. The patient was treated with IVIG, 400 mg/Kg daily for five days, after which severe hemolysis occurred, associated with elevated LDH and total bilirubin. The hemolytic process dropped the hemoglobin from 13.8 g/dL to a nadir of 6.6 g/dL, requiring transfusion of four units of Red Blood Cells. The pre-transfusion peripheral blood smear showed spherocytosis with rouleaux formation and large clumped rbc aggregates. The patient’s blood type was Blood Group A-negative and all transfusions were type specific. The Coombs test was positive with polyspecific and anti-IgG typing antisera, and acid eluate prepared from the Coombs-positive rbc's revealed anti-A. The patient’s antibody screen (against Group O reagent cells) was negative ruling out both allo- and autoantibodies. However, Anti-A was also detected in his plasma. The patient’s hemolysis was associated with the anti-A passively transmitted from the IVIG. RBC transfusion support was changed to use of Group O-negative RBCs and the hemolytic process resolved. The patient later died due to complications of ARDS. DISCUSSION: Before this severe hemolytic event, the patient was already in multi-system organ failure due to adenoviral pneumonia (severe ARDS, leading to pulmonary hypertension and pulmonary hemorrhage, septic shock, AKI, adrenal insufficiency). He was not eligible for ECMO due to his progressive pulmonary hemorrhage, was ultimately made DNR, and died due to progressive hypoxia despite maximal ventilator support. In this critically-ill patient given IVIG in an attempt to treat a viral infection associated ARDS, an unexpected and harmful comorbidity developed. The empirical use of IVIG in this setting is not yet an evidence-based indication for its use. CONCLUSION: Although immune hemolysis is a recognized adverse effect of IVIG, it is seldom considered when deciding to administer IVIG and has rarely been described in the pediatric population. IVIG is used to treat a growing number of medical conditions. In the setting of managing critically-ill patients, unexpected iatrogenic hemolysis adds unnecessary co-morbidity. Such events also require supplemental blood transfusions, the risks of which are better avoided. Severe immune hemolytic events such as this require transfusion support with compatible RBCs.

• Copyright © 2018 by the American Academy of Pediatrics