Interferon-α-Associated Acquired Factor VIII Inhibitor.

Introduction: Development of an acquired inhibitor to factor VIII (acquired hemophilia) is a rare autoimmune phenomenon that has been associated with a variety of medical conditions such as autoimmune diseases, malignancies, drugs like penicillin and postpartum state. It often presents with acute, life-threatening hemorrhage. Interferon alpha (IFN) is an immune system modulator that is widely used for the treatment of hepatitis C and various malignancies. It is known to stimulate or exacerbate autoimmune diseases and has been described in four separate reports to be associated with the development of inhibitors to factor VIII. All but one of these four cases represented patients with underlying malignancy or congenital hemophilia A.

Case Report: Our patient is a 55-year old non-hemophiliac with no prior diagnosis of cancer who developed new-onset bruising while on IFN therapy for hepatitis C. This was not evaluated or treated further at that time. Six months after completing IFN therapy, he presented to the emergency room with respiratory distress. On examination, he was found to have a large supraglottic hematoma and underwent an urgent tracheostomy for impending respiratory failure. This was followed by severe postoperative bleeding which the otolaryngologists were unable to control surgically. Laboratory testing showed a prolonged activated prothrombin time and infusion of fresh frozen plasma failed to achieve hemostasis. A hematology consultation was obtained and the patient was treated with activated recombinant factor VII (rVIIa) which resulted in prompt cessation of bleeding. Existence of factor VIII inhibitor was confirmed by abnormal mixing studies (no correction), low factor VIII activity (2.1%) and high inhibitor titer (42 Bethesda Units/ml [BU]). Following hospital discharge, inhibitor titers slowly declined to less than 1 BU after immunosuppressive therapy with steroids, alkylating agents and rituximab given sequentially over a period of nine months. The factor VIII activity has also increased to 15%. The patient has since had occasional mild to moderate soft tissue bleeding which responded well to rVIIa.

Conclusion: One previous report has described a patient without a history of hemophilia or cancer who developed factor VIII inhibitor while being treated with pegylated IFN for hepatitis C. Our patient represents only the second such report and adds to the slowly growing body of literature pointing to this association. Although this data is anecdotal, we believe that the potential for such inhibitors to produce serious and even life threatening hemorrhage warrants awareness of and attention to this possibility by clinicians treating patients with IFN. Simple clinical vigilance along these lines may help identify and address this condition in a timely fashion before it has a chance to produce catastrophic bleeding.