Ifeoma Onwubiko Gary Kaperek Philip Kuriakose Zaher K. Otrock
Henry Ford Health System
Context: Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation Factor VIII, is a rare and life-threatening bleeding disorder with a mortality rate of up to 25%. The clinic..
Context: Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation Factor VIII, is a rare and life-threatening bleeding disorder with a mortality rate of up to 25%. The clinical characteristics and outcomes of AHA remain difficult to establish due to disease rarity. We evaluated the clinical characteristics, predictors of response and outcome of patients with AHA.Design: We retrospectively evaluated 25 consecutive patients with AHA managed at our institution from February 2007 to January 2018. The study was approved by our Institutional Review Board. Result: The median age was 73.5 years (range: 55.1 - 91.7 years); 13 (52%) were male. Underlying conditions were identified as malignancy in 8 patients (2 gastrointestinal carcinoma, 2 prostate adenocarcinoma, 2 lung carcinoma, 1 cervical carcinoma, 1 follicular lymphoma, 1 small cell lymphoma/chronic lymphocytic leukemia, 1 squamous cell carcinoma of the face) with 2 patients having more than 1 underlying malignancy. Infection was identified as the underlying cause in 2 patients (1 patient with HIV and hepatitis B and 1 patient with multiple infections with arm cellulitis). The most frequent presenting symptoms were subcutaneous/intramuscular hemorrhage (soft tissue, skin or joints) and gastrointestinal bleeding with variable severity. Twenty (80%) patients required red blood cell transfusion during admission with a median of 7 units (range: 1- 40 units). On initial presentation, Factor VIII activity was decreased in all patients (median = 1.0%; range: 0.3 - 34%) by Factor VIII inhibitor (median 30.0 Bethesda units (BU); range: 0.8 - 702 BU). Nineteen (76%) patients achieved complete remission after initiation of immunosuppressive therapy with prednisone alone (3/3 patients), prednisone with cyclophosphamide (8/10 patients), prednisone with rituximab (3/5 patients), or prednisone/cyclophosphamide/rituximab (5/7 patients). The median time to complete remission was 50 days (range: 2 - 191 days). Complete remission was achieved early (within 1 month) in patients with low titers of Factor VIII inhibitors (20 BU) were likely to achieve complete remission after 30 days (odds ration = 4.33, CI: 1.61 - 11.69, p = 0.003). Patients with high Factor VIII inhibitor titers (>20 BU) received more than 5 units of packed red blood cells (RBCs) as compared to patients with low titers (odds ratio = 4.33, CI: 1.14 - 38.83, p = 0.047). Only 2 patients relapsed after 10 months and 2 years, respectively. None of the patients died of treatment; only one patient died of bleeding complications. Conclusion: Most of our patients achieved complete remission after immunosuppressive therapy. High titers of Factor VIII inhibitors were predictors of delayed response (more than 1 month from presentation) and increased need for packed RBCs transfusion, consistent with an aggressive disease. Studies with larger cohorts are warranted to better determine the predictors of response and outcome in AHA.