Pegylated Interferon Induced Auto Immune Hemolytic Anemia (AIHA) During Hepatitis C Treatment

Abstract

Introduction: Auto Immune Hemolytic anemia (AIHA) is characterized by the presence of auto antibodies to red blood cells. Causes of AIHA include hematologic malignancies, infections or rheumatologic disorders. We present a case of pegylated interferon (peg-INF) induced AIHA in a patient with orthotopic liver transplant (OLT), on treatment with Ribavirin and peg-INF therapy for recurrence of hepatitis C. Case Report: 53-year-old woman with history of Hepatitis C cirrhosis who underwent OLT, developed Hepatitis C relapse in the transplanted liver. She was being treated with Ribavarin and pegylated-interferon (peg-IFN). After 28 weeks of treatment, patient developed severe anemia with hemoglobin of 5 gm/dL. Ribavarin was held and she was given blood transfusions, however, her hemoglobin continued to drop. Subsequently, peg -IFN was also held. Despite holding both the drugs, her hemoglobin continued to trend down. Labs were consistent with AIHA with low haptoglobin, elevated lactate dehydrogenase (LDH) and peripheral smear showing spherocytes. Direct Coomb's test was positive with IgG and C 3 indicating warm antibody AIHA. Bone marrow biopsy showed hypercellularity of all three cell lines. She was on mono therapy immunosuppression with Tacrolimus at the time with the level being sub therapeutic throughout the admission. She was also thrombocytopenic. Patient was started on steroids but it did not improve her anemia or thrombocytopenia. She was subsequently treated with rituximab and responded dramatically with marked improvement in both. Discussion: Patients with Hepatitis C (HCV) cirrhosis who have undergone OLT can have anemia and thrombocytopenia because of bone marrow suppression due to drugs or recurrence of HCV, infectious causes like parvovirus due to immunosuppression or hypersplenism due to portal hypertension. AIHA due to peg - IFN should be suspected when the anemia does not respond to stopping of ribavarin. It can occur during the treatment as in our case, or after treatment. There are two types of AIHA, warm antibody (IgG) and cold antibody (IgM) types. Warm antibody AIHA usually responds to steroids, but rarely as in our case, steroids may not be effective in warm antibody AIHA and the patients may need treatment with drugs like rituximab. Splenectomy is indicated for AIHA refractory to medical therapy. Severe anemia in patients on anti-HCV therapy should raise the suspicion of drug induced AIHA. Steroids are usually effective, however, in some cases, drugs like rituximab or Danazol may be needed. Splenectomy is indicated in refractory cases. At this point, we are unsure if immunosuppression with anti rejection therapy plays any role in the development of peg-INF induced AIHA.