Role of Plasmapheresis In Management of Acquired Factor VIII Inhibitor

Abstract 4656

A 91-year-old woman with past medical history of hypertension presented with hematuria. There were no ecchymosis, Petechiae or other obvious active bleeding. Her hemoglobin was 11.4 g/dl on presentation hematuria got worse and her hemoglobin drops to 7.6 g/dl over next 48 hours and she was hemodynamically unstable. She was transferred to the Medical Intensive Care Unit for resuscitation with IV fluids and PRBCs. Coagulation tests revealed a prolongation of activated partial thromboplastin time of more than 100 seconds (control 33 seconds) which could not be corrected with mixing normal plasma. Diagnosis of acquired factor VIII inhibitor was considered and recombinant activated factor VII (rFVIIa) was initiated. The factor VIII activity level was reduced to less than 1%. Bethesda assay demonstrated the presence of a factor VIII inhibitor at 103.8 Bethesda units per ml (BU/ml), other coagulation studies were with in normal range. CT scan of her abdomen showed retroperitoneal hematoma. rFVIIa was started at 50 units/kg body weight every 3 hours and subsequently increased to 200 units/kg. She was simultaneously started on steroids. Her hematuria did not improve in spite of high dose rFVIIa. On day 4 rFVIIa was tapered and switched to 50 units/kg FEIBA (Factor eight inhibitor bypass agent). She also received Rituximab 375 mg/m2. We continued FEIBA until day 7 but her hematuria did not improve, she required more than 10 units of Packed Red Blood Cells PRBCs during this period. On day 7 we decided to start plasmapheresis as there were some case reports of using plasmapheresis with or without immunoadsorption columns (which are currently not available in US). We started plasmapheresis and gave her 2 doses of IVIG (Immunoglobulin). Her pre and post plasmapheresis inhibitor levels were 104 BU/ml and 54 BU/ml respectively. Her urine turned pink and her Prbc demand decreased. A second plasmapheresis was done 2 days later showed significant decrease of inhibitor level from 80 BU/ml to 14.5 BU/ml. Her hematuria resolved by next day. We continued her on FEIBA for three more days she did not have hematuria and she did not require any PRBCs. CT scan of abdomen showed decrease in size of retroperitoneal hematoma. Cyclophosphamide 1000 mg was given for induction of immune tolerance followed by high dose factor VIII (100 IU/KG) as per Bonn protocol. Her factor VIII levels and factor VIII inhibitor levels were checked every day before and after Factor VIII infusion. Her inhibitor level is ranging between 14–16 BU/ml she is not bleeding any more and her abdominal hematoma is resolved. Her pre and post transfusion factor VIII levels ranges between 30–40% and 120–140%. respectively. Patient is still getting factor VIII everyday.

Role of plasmapheresis is not very well defined in acquired Factor VIII inhibitor patients. Acquired hemophilia is a rare autoimmune disorder in which the patient develop an autoantibody directed against coagulation factor VIII leading to a clinically bleeding diathesis. There are few case reports in literature showing efficacy of Plasmapheresis in this disorder. This is a rare condition and it is very difficult to find large randomized trial to establish a standard of care. Patient mentioned above did not respond to rFVIIa or FEIBA. In our observation plasmapheresis with IVIG proved to be an effective method of rapidly reducing the inhibitor level. In case of life threatening bleeding we need to reduce the inhibitor level quickly. We also observed that once inhibitor level was low bleeding stopped. Immune induction therapy with cyclophosphamide followed by high dose factor VIII was successful in maintaining low inhibitor level.