A High Purity Factor VIII/vWF Complex Concentrate Is Effective in the Management of Mild Hemophillia A with Inhibitors: A Case Report.

Introduction: Inhibitor development in Mild Haemophilia A (MHA) is an uncommon complication, occurring in approximately 15% of MHA patients. Risk factors associated with the development of inhibitors in MHA include change in recombinant factor VIII (rFVIII), intensive replacement therapy, immunological challenges and missense mutations in the FVIII gene, including Tyr2105Cys mutation on exon 22. Only few reports have addressed the therapeutic options to eradicate these inhibitors, either by immune tolerance or immunosuppressive protocols.

Patient: We present a case report of a 36-year-old MHA patient (original factor VIII activity of 17.5% (10–20%) with a Tyr2105Cys mutation. He developed a low titre inhibitor after intensive exposure to rFVIII to cover for spinal epidural steroid injection, switch of recombinant product (full length rFVIII to B-domain deleted rFVIII) and intensive antiviral treatment (pegylated interferon and ribavarin) for Hepatitis C. His quality of life was very poor due to recurrent spontaneous bleeds - ecchymoses, haematomas and haemarthroses. His baseline factor VIII activity dropped to 1% with an initial inhibitor titre of 2.6 BU and factor VIII recovery of less than 25%.

Results: The patient responded positively when started on an immune tolerance protocol with a low dose of high purity FVIII/vWF complex concentrate. All clinical parameters improved two weeks after commencing 50 IU/kg on alternate days of the high purity FVIII/vWF product. FVIII recovery levels improved to 50% and he was asymptomatic in terms of bleeding manifestations for the following 17 weeks. Inhibitor titres stabilised at 3.5 BU. Recently, the recovery levels dropped to 26% and the frequency of bleeds increased, necessitating treatment with additional doses. The immune tolerance dose of the high purity FVIII/vWF was increased to 100IU/kg/day. Haemostatic and clinical parameters again recovered (factor VIII recovery levels of 43%) with no further spontaneous bleeds.

Conclusions: The use of recombinant factor VIII, especially high intensity replacement may pose a risk of inhibitor development and bleeding complications during the management of MHA patients with Tyr2105Cys mutation. An immune tolerance protocol with FVIII/vWF concentrate is effective in the management of MHA patients with inhibitors and can improve the quality of life soon after the start of the treatment. There is no anamnestic response observed. Though low dose immune-tolerance protocol may be effective, the benefits may be short-lasting, necessitating treatment with high daily dose protocol.