[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

Factor VIII : C (FVIII : C) inhibitor expressed by Bethesda unit had been widely assayed by Bethesda method. In recent years, Nijmengen method has been recommended by International Society on Thrombosis and Haemostasis because Bethesda method showed less specificity in the low levels of FVIII:C inhibitors. However, some kinds of modified Bethesda methods also exist in Japan, which have been afraid that their sensitivities are different. In this report, we compared four FVIII : C inhibitor assays of Bethesda (B), Nijmengen (N), and two (S and M) of modified Bethesda methods, using the samples obtained from Haemophilia A patients without inhibitor. The two modified methods utilize the pre-treated plasma with inactivation of coagulation factors at 56°C in testing samples, i.e. S method is using FVIII deficient plasma with a treatment of 56°C, and M method is using normal plasma with a treatment of 56°C, as a control.
In the results of pH values and FVIII : C activities obtained from the four methods, all of the reaction mixtures after 2hrs at 37°C incubation had changed into higher pH value, the pH values of those in S and M methods were high before the testing incubation. Especially in B methods, the pH discrepancy between tests and controls was the largest of >0.5, though their pH levels hardly changed between before and after the incubation. On the other hand, the FVIII:C activities were similar among the four methods, however, the remaining FVIII:C in the control of B method showed a remarkable high level of 90.4%. And the both of pH values and FVIII:C activities obtained from the four methods showed a negative relationship (correlation r=0.878).
In the comparison of the four methods using plasma samples from 13 patients of Haemophilia A without inhibitor, only B method showed a high false positive rate of 61.5%. Moreover, in the plasma samples with FVIII:C activity of >10%, N method showed higher levels of residual FVIII:C, the sensitivity for the inhibitor in that range was lesser than that of S and M methods with the inactivation.
These results have suggest that understanding the characteristics of FVIII:C inhibitor assays is important to evaluate the patients with FVIII:C inhibitor.

View full abstract

Recombinant activated factor VII (rFVIIa: NovoSeven^®) is a recombinant bypassing agent developed for the use of bleeding episodes in patients with hemophilia A or B with inhibitors. Some clinical studies of single/high dose with rFVIIa were conducted in foreign courtiers, and a single dose regimen with 270μg/kg was approved in the EU in 2007. We performed an investigator led clinical trial for the single dose regimen of 270μg/kg with rFVIIa. The phase I of this trial evaluated the safety and pharmacological effects of the 270 μg/kg single dose regimen. The phase II of this trial compared the efficacy and safety of the 270μg/kg single dose regimen with a 90μg/kg×3 regimen by a multi-center, randomized, open, cross-over trial. The single dose regimen with 270μg/kg tended to have an equal to or higher efficacy than the conventional regimen of 90μg/kg×3. No safety issues were identified regarding the single dose regimen with 270μg/kg. To ease the burden of haemophilia patients with inhibitor and their families, and to improve their quality of life, we expect that the single dose regimen with 270μg/kg should be widely used in Japan like foreign countries.

View full abstract

We developed an anti-thrombotic catheter, whose surface was coated with both urokinase and heparin, and evaluated its anti-thrombotic potential. A modified Chandler loop test revealed that the catheter kept high anti-thrombotic capacity even after 25 days'rinsing with human citrated whole blood. Activities of urokinase and heparin measured by synthetic substrate for plasmin and thrombin respectively were reserved even after 25 days'rinsing. Both TAT and D-dimer in blood in the modified Chandler loop increased gradually in a time dependent manner, which suggests that anti-thrombotic function of the catheter were reserved for the evaluated period by two distinct mechanisms of anticoagulation by heparin and of fibrinolysis by urokinase. These ex-vivo studies confirmed the long-lasting anti-thrombotic efficacy of anti-thrombotic catheter coated with both urokinase and heparin, and suggest promising usefulness of its clinical application.

View full abstract