Hemolytic Reaction Following Intravenous Immunoglobulin (IVIg) for Platelet Alloimmunization During Pregnancy

Abstract Abstract 4409 IVIg has become standard therapy for the prevention of severe neonatal thrombocytopenia in women with platelet alloimmunization (Bussel et al. Blood Reviews 2008). A regimen of IVIg 1g/kg twice weekly is increasingly being given for this indication. Although the benefits of this regimen outweigh its risks, clinically significant hemolysis can occur. We report here the case of a 36 year old woman who experienced hemolysis requiring red blood cell transfusions after administration of high dose IVIg for platelet alloimmunization during her second pregnancy. Her first pregnancy was terminated at 24 weeks gestation for a progressive asymmetrical ventriculomegaly first identified at 17 weeks and attributed to in utero intracerebral hemorrhage. The fetal platelet count was 5 ×109/L. Platelet antibody testing in the patient demonstrated the presence of anti-HPA-1a antibodies. The patient's genotype was HPA-1b1b and her partner's, HPA-1a1b. During the subsequent pregnancy, IVIg (Gammagard Liquid®) was started at 9 weeks gestation at a dose of 1g/kg twice weekly. Fetal genotyping was done at 15 weeks and found to be HPA-1a1b. The patient's blood group was AB+. Blood tests prior to each infusion included hemoglobin level, reticulocyte count, bilirubin, LDH, creatinine, urea, glucose and IgG as per our institutional protocol. IVIg was initially well tolerated. Between the fourth and fifth treatments, the patient complained of headache and fatigue. Her physical exam was normal. The laboratory investigation demonstrated hemolytic anemia with a hemoglobin of 74 g/L (Table). Anti-A et anti-B were present in her serum. In retrospect, her reticulocyte count and LDH had started to increase before the previous IVIg infusion (Table). She received 2 packed red cell transfusions as well as prednisone 1mg/kg/d for one week, followed by 0.5 mg/kg/d as planned in the context of her platelet alloimmunization. She improved and her hemoglobin stabilized. Therapy was resumed with a different preparation of IVIg (Gammagard S/D®) 1g/kg twice weekly for the remainder of pregnancy, without untoward effects. Acute hemolysis has been reported with IVIg. Hemolysis in these cases is generally due to passive sensitization with antibodies to the patient's red blood cells found in commercial IVIg. Risk factors are non O blood type, female sex and high dose IVIg (Daw Z et al. Transfusion 2008). Our patient had all three risk factors. Although anti-A and anti-B antibodies are found in all commercial preparations of IVIg, no recurrence was noted in our patient. In patients with alloimmune thrombocytopenia and hemolysis secondary to IVIg, treatment options include changing the commercial preparation of IVIg and giving a lower dose of IVIg with or without prednisone. In conclusion, this case demonstrates an infrequent reaction due to IVIg administration, to which clinicians and patients need to be aware. We now routinely monitor hemoglobin level, reticulocyte count, bilirubin and LDH prior to each IVIg infusion in all patients receiving high dose therapy and if signs of hemolysis appear consider treatment adjustments. Disclosures: No relevant conflicts of interest to declare.

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