The oral antiplatelet agent clopidogrel sulfate (SR25990C), an ADP receptor antagonist, showed an antiplatelet effect comparable to that of ticlopidine hydrochloride at a lower dose. Clopidogrel is therefore expected to be a safer antiplatelet drug than ticlopidine. The present clinical pharmacology study was performed on 124 Japanese patients with cerebral infarction, who were all given either 10, 37.5, or 75mg/day of clopidogrel or 200mg/day of ticlopidine for 2 weeks in order to evaluate the dose-response relationship in terms of the precisely measured inhibition of platelet aggregation. Sex, age, smoking and diabetes mellitus have been reported as factors affecting platelet aggregation. The effects of sex and age on the baseline platelet aggregation were confirmed, whereas no effect was observed on the post-treatment platelet aggregation in the present study. In contrast, the platelet count and the baseline platelet aggregation appeared to affect the post-treatment platelet aggregation.

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We report successfully controlled severe bleeding in two hemophiliacs with a high responding titer. This was accomplished by neutralizing the inhibitors with a bolus infusion of a sufficient amount of the relevant blood coagulation factor concentrate, which was followed by a continuous infusion of the concentrate to maintain the titers of the factors in plasma at required levels.
The first patient, a 38-year-old man with severe hemophilia A, suffered from an intracerebellar hemorrhage. The inhibitor titer on his admission was 2.1 Bethesda units (BU)/ml. An initial bolus dose of 5,000 U of recombinant factor VIII (FVIII) concentrate was administered, followed by a continuous infusion of the concentrate at 3.8 U/kg/hr. Plasma FVIII : C level was maintained at 0.9-1.44U/ml over a period of 4 days, resulting in the reduction of the size of hematoma. At the age of 40, he suffered from a parietal lobe intracerebral hemorrhage. Despite the use of prothrombin complex concentrate (PCC) as a bypassing agent, the brain CT revealed a new hemorrhage in the subdural space. The inhibitor titer at this episode was 10 BU/ml. An initial bolus dose of 12, 000U of recombinant FVIII concentrate, followed by a continuous infusion of the concentrate at 4-6U/kg/hr raised the plasma FVIII : C level to 0.54-2.04U/ml over 5 days and resulted in the reduction the size of hematoma.
The second patient was a 4-year-old boy with severe hemophilia B. He was hurt on the right foot, having developed a large subcutaneous hematoma. The bypassing therapy with the prothrombin complex concentrate over a period of 6 days did not reduce the hematoma size. The inhibitor titer at the time of his admission was 2.1BU/ml. He was given an initial bolus dose of 2,000U of factor IX (FIX) concentrate, followed by a continuous infusion of the concentrate at 13U/kg/hr that yielded the FIX : C level at 1.3U/ml, and reduction in the size of the hematoma.

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