Basic Study of Combination Therapy Based on APCC-induced FVllI Activation in Hemophilia A Patients With Inhibitors

Basic Study of Combination Therapy Based on APCC-induced FVllI Activation in Hemophilia A Patients With Inhibitors

Basic Study on Novel Therapeutic Strategy With Bypassing Agent Therapy in Hemophilia A Patients With Inhibitors

Using whole blood samples and plasma samples obtained from some hemophilia A patients with inhibitors, the investigators will perform the coagulation assessment in the co-presence of aPCC and factor VIII by comprehensive coagulation assays and flow chamber analysis under blood flow conditions.

Comprehensive coagulation assays using recently popular rotational thromboelastometry (ROTEM), factor Xa/thrombin/plasmin generation test, and coagulation wave analysis and recently developed flow chamber system under blood flow conditions (T-TAS®) will be used. A bypassing agent, aPCC (Feiba®) and recombinant factor VIII (Advate®) will be added ex vivo to whole blood and plasma samples from patients with hemophilia A with inhibitors to compare with the coagulation effects of aPCC in the presence of factor VIII and those of aPCC in its absence under the conditions close to the physiological condition. Furthermore, the difference in the coagulation effects by the difference in inhibitor epitopes will be examined.

Evaluation of coagulation effects using patients' plasmas by FXa/thrombin/plasmin generation tests and clot waveform analysis

Inclusion Criteria: Patients with hemophilia A with inhibitors (Inhibitor titer; >0.5 Bethesda U/ml) Patients with agreement consents with the patients signatures Exclusion Criteria: Patients that do not fill the conditions described above

We guess that there are approximately 200-300 hemophilia A patients with inhibitors in our country. We have approximately 20 out-patients in our hospital. Based on this information, we set up the patients subjects (n=10).