Successful elimination of factor VIII inhibitor using cyclosporin A.

Acquired Factor VIII (FVIII) deficiency is an uncommon but sometimes catastrophic autoimmune condition for which standard immune suppression, such as steroid or immunoglobulin infusion, is often insufficient to induce long-term remission (Dykes et al, 2001). A number of second-line therapies, such as cyclophosphamide, azathioprine and vincristine, have been used with varying success (Morrison & Ludlam, 1995). Here, we describe the use of cyclosporin A in a patient in whom conventional treatments failed to eradicate the inhibitor. At present, only limited experience exists of its use in this setting (Pfliegler et al, 1989). A 68-year-old woman with a 4-month history of easy bruising presented with life-threatening retropharyngeal haemorrhage. She had no significant past medical history, and medication consisted of aspirin and naproxen. Coagulation studies at presentation demonstrated a normal prothrombin time and fibrinogen activity but a prolonged activated partial thromboplastin time of 65 s (normal range 32–48 s). Factor assays confirmed a reduced FVIII coagulant activity (FVIII:C) at 1 il ⁄ dl. An inhibitor was detected and quantified at 54 Bethesda units (BU). von Willebrand factor activity and antigen were both within the normal range excluding acquired von Willebrand’s disease. Her initial treatment was with high-purity plasmaderived FVIII (Liberate, Scottish National Blood Transfusion Service), commencing at 20 000 units twice daily, with prednisolone 60 mg and high-dose intravenous immunoglobulin (2 g ⁄ kg). Clinical response to treatment was excellent with no further haemorrhage. The patient’s inhibitor titre remained detectable at 10–20 BU with FVIII:C remaining below 20 il ⁄ dl over the succeeding months. The introduction of cyclophosphamide 50 mg daily, 9 months after presentation, initially in conjunction with further prednisolone (1 mg ⁄ kg), rendered the inhibitor transiently undetectable, with FVIII:C peaking at 40 il ⁄ dl. However, with reduction of the prednisolone dose, the inhibitor returned, and the FVIII:C fell. After 9 months of treatment with cyclophosphamide, it was discontinued because of lack of a sustained response. Approximately 28 months after presentation, cyclosporin A (CyA) was introduced at 100 mg twice daily (3 mg ⁄ kg ⁄ d), initially with prednisolone (1 mg ⁄ kg). A target trough plasma CyA concentration of 200–250 mg ⁄ l was achieved over 3 months with a dose of 175 mg twice daily ( 5 mg ⁄ kg ⁄ d), during which time the prednisolone was discontinued. The inhibitor titre fell and was undetectable 3 months after the commencement of CyA. The FVIII:C rose to within the normal range following disappearance of the inhibitor (Fig 1). After 14 months of therapy with CyA, and with FVIII:C levels remaining in the normal range, cyclosporine was reduced and stopped over a 4-month period. Ten months after cessation of all immunosuppressive therapy, the FVIII:C remains in the normal range with no detectable inhibitor. Permanent eradication of inhibitor without the need for continued therapy is the ultimate aim of immunosuppressive treatment for acquired haemophilia. Initial reduction in inhibitor titre may be achieved with high-dose intravenous immunoglobulin and steroids; however, long-term clearance may not be achieved with this approach alone (Hay et al, 1996). Further options include cytotoxic regimens or immunosuppressant agents such as cyclosporine. As no