S3509 Aplastic Anemia Following Autoimmune Hepatitis Treated With Azathioprine

Abstract

INTRODUCTION: Aplastic anemia is a serious and potentially fatal disease where bone marrow suppression leads to pancytopenia. Azathioprine, an immunosuppressive drug used to treat various autoimmune disorders, can cause aplastic anemia. Here we present a case of aplastic anemia following azathioprine treatment of autoimmune hepatitis. CASE DESCRIPTION/METHODS: A 24 Y.O. Male presented with no significant past medical history presented with elevated liver enzymes and bilirubin. Ultrasound and CT confirmed mild hepatomegaly and diagnosis of acute hepatitis was given. A liver biopsy was performed and was noted for necrotic tissue. Acute hepatitis resolved spontaneously but relapsed 6 months later. Upon relapse, Anti Smooth Muscle Antibodies were found suggesting autoimmune hepatitis. The patient was treated with prednisone and 4 weeks later, azathioprine was started. 2 months after beginning azathioprine, labs revealed low hematocrit and platelet count, so the dose was lowered. By 4 months labs revealed pancytopenia and azathioprine treatment was stopped. The patient had a bone marrow biopsy done and was diagnosed with aplastic anemia. The patient began treatment to receive a bone marrow transplant but died of a systemic fungal infection. DISCUSSION: It is well documented that aplastic anemia, as a side effect of azathioprine treatment, is highly correlated to polymorphisms in the Thiopurine methyltransferase (TPMT) gene which occurs in 0.3%–0.5% of the population. Current treatment guidelines call for consideration of screening TPMT levels but considering the potential severity of the side effect and ease of testing, screening TPMT levels should be more common practice. However, it is also noted that the patient had low hematocrit levels starting about 1 month before the second episode of hepatitis. This suggests that the azathioprine may not have been the causative factor leading to pancytopenia, and it may have been a progression of Hepatitis Associated Aplastic Anemia (HAAA). HAAA is characterized by auto-immune hepatitis followed by aplastic anemia 2–3 months later. Testing for TPMT levels before starting azathioprine treatment for autoimmune hepatitis can help identify patients at risk for developing aplastic anemia as well as help rule out azathioprine as the causative agent for the aplastic anemia.