Therapeutic choices for patients with hemophilia and high-titer inhibitors.

Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis.

Characterization of mutations within the factor VIII gene of 73 unrelated mild and moderate haemophiliacs.

To screen for mutations within the factor VIII gene of 101 patients (85 unrelated), we used denaturing gradient gel electrophoresis (DGGE) after DNA amplification of target regions, including all coding regions except for the middle part (amino acid 757 to amino acid 1649) of the B domain. With this method, missense mutations were identified in 86% of unrelated patients. 41 different mutations were identified: 25 of them have not been described previously.

Clinical safety of recombinant factor VIII. The rFactor VIII Clinical Trial Group.

The safety of rFVIII has been studied in patients with severe or moderate hemophilia A in a noncontrolled observation study. A total of 40 patients participated in the study. Thirteen patients were included in stage I and 40 patients in stage II.