Epidemiology and Management of Acquired Hemophilia A in a Single Hospital System

Introduction: Acquired Hemophilia A (AHA) is an uncommon autoimmune disease that occurs when autoantibodies form against intrinsic factor VIII. Cases are typically identified due to isolated prolongation of the partial thromboplastin time (PTT) or unexplained bleeding diathesis, prompting further evaluation with PTT mixing studies and the Bethesda assay. AHA is historically associated with a high mortality rate; however, when appropriately diagnosed and treated, modern mortality from acute bleeding is approximately 4.5% (Knoebl et al Journal of Thrombosis and Haemostasis 2012). This study aims to explore the epidemiology, management, and outcomes in cases of AHA found within our hospital system to guide future care.

Methods: The study design involves identifying all diagnosed cases of AHA within our hospital system using diagnosis codes and use of specific laboratory tests. The study design was presented to the University of Illinois College of Medicine at Peoria Internal Review Board and granted exempt status. 1,931 patients were identified, of which 6 patients met criteria for diagnosis of AHA.

Results: The initial analysis reveals that the study population had a median age of 79.5 years old (high: 90; low: 61). All the patients presented with bleeding symptoms and 5 of 6 had major bleeding requiring transfusion. 5 of the 6 patients also developed soft tissue bleeding with hematoma or hemarthrosis. Underlying diagnosis of cancer was the suspected etiology in 4 of 6 cases. The median initial Bethesda assay value was 106.5 Bethesda units (high: 180; low: 33) and the median initial factor VIII activity assay result was less than 1%. The median PTT mixing study result was 51.5 seconds (high: 66.7; low: 44). In 3 of the 6 cases, patient survival was less than 1 year from onset of bleeding symptoms. 1 patient died prior to initiation of a bypassing agent. All the remaining patients were treated with the bypassing agent recombinant factor VIIA (NovoSeven ®). 2 of those 5 cases required management with a second line bypassing agent and in both cases porcine recombinant factor VIII (Obizur ®) was used and successfully achieved hemostasis. Remission with complete eradication of the acquired factor inhibitor was achieved in 4 of 5 cases receiving a bypassing agent with subsequent immunosuppressive therapy. Prednisone was used in all cases, with two using a second immunosuppressant (cyclophosphamide and rituximab). Of the 4 patients achieving remission, all eventually had recurrence of bleeding. Only 1 patient is still alive and none of the other patients survived to 5 years from initial presentation. 4 of those 5 patients died from direct complications of bleeding.

Conclusions: Despite having access to electronic patient data from one of the largest hospital systems in Illinois, only 6 diagnoses were confirmed. We suspect that AHA is significantly underdiagnosed and that many patients developing factor inhibitors die before a full workup can be performed. The EACH2 registry changed how we view AHA; however, that analysis of that database must continue to be supported by population data from centers not included in that study (Knoebl et al Journal of Thrombosis and Haemostasis 2012). Furthermore, analysis of outcomes with newer bypassing agents and more sophisticated use of these agents is ongoing. We plan to publish the full results of our study, including a cost-benefit analysis of these 6 cases. We hope that our patient data can be compounded with other recent studies to help to shape future management decisions and guidelines.