In this review, we consider the contribution of antithrombin deficiency to venous thrombosis, highlighting some recent work from our laboratory on mutations within the antithrombin signal peptide. In addition, we place antithrombin deficiency in the context of a contributor to the complex genetic basis for the phenotype of venous thrombosis. Recent reviews provide coverage of other aspects of antithrombin and venous thrombosis.

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Appropriate replacement therapy in patients with hemophilia A depends on the amount of factor VIII administered. The dose of factor VIII is calculated according to the manufacturer's stated value labeled on each vial of factor VIII concentrate. To verify correlation between the labeled value and the actual factor VIII potency, we assayed factor VIII activity in two recombinant factor VIII concentrates, a monoclonal antibody-purified factor VIII concentrate, and a factor VIII/von Willebrand factor complex concentrate. The measured factor VIII contents in 40 lots of factor VIII concentrates varied from 70% to 196% of the labeled value. Inter-lot values of each factor VIII concentrate showed percent coefficient of variation from 7.7% to 23.5%, depending on the manufacturer. The data suggest that standardization of factor VIII unitage is required and that labeling of actual potency in each lot of factor VIII product is needed for optimal treatment of patients with hemophilia A.

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Ifenprodil tartrate, a cerebral vasodilator used for patients with a chronic cerebral infarction, is known to inhibit platelet aggregation. We have studied the mechanism of its inhibition of platelet aggregation by utilizing the particle-counting method using light scattering and a shear-induced platelet aggregometer.
Ifenprodil was found to inhibit both epinephrine-induced platelet aggregation, and shear-induced and epinephrine-enhanced platelet aggregation. When epinephrine was replaced with brimonidine, a selective platelet α₂ adrenoceptor agonist, similar inhibition by ifenprodil was observed. As the inhibition profiles were similar to those by yohimbine, our results altogether seem to indicate that ifenprodil may inhibit platelet aggregation via inhibition of the platelet α₂ adrenoceptor.

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The diagnostic guideline for the disseminated intravascular coagulation (DIC) proposed by the DIC Study Group under the Ministry of Health and Welfare, the Government of Japan (1980) has been widely used in clinical practice for these 20 years. However, there exists an opinion that the guideline should be revised, since it is thought to be too strict to allow starting early therapy for DIC. We have put a questionnaire to over 1, 000 doctors to survey the present status of usage of the guideline. Although 98% of the doctors acknowledged the presence of the guideline and about 50% of the doctors answered that they use it for the diagnosis of DIC, 57% of them replied that they do not always follow this guideline but rather make the diagnosis of DIC based on their own criteria. Moreover, there was a trend to give more weight on the abnormal increase or decrease of individual coagulation parameters than on a single point analysis as indicated in the guideline. As a summary of the present study, it is indicated that the guideline should be revised in order to overcome the problems revealed by this study and to match the status quo.

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We have compared the effect of two thrombolytic agents, i. e., single chain urokinase-type plasminogen activator (scu-PA) and tissue type plasminogen activator (t-PA), on the stenosis rate of PTCA catheter-induced injury of the coronary artery in dogs. The stenosis rate of the injured vessel as observed by coronary artery angiography four weeks after the injury was found to be reduced in the scu-PA-treated animals, but increased in the t-PA-treated animals, as compared with the control animals given physiological saline alone. These results were confirmed histologically and by assessment of the intima/media ratio, as well, and the difference in the stenosis ratios between the two drug-treated groups was statistically significant. Interestingly, scu-PA was found to promote proliferation of endothelial cells but not that of smooth muscle cells, whereas t-PA promoted proliferation of smooth muscle cells but not that of endothelial cells. These results seem to imply that scu-PA may be engaged in an early stage of repair of blood vessel injuries through endothelial cell proliferation. Furthermore, lack of smooth muscle cell proliferation at loci in the scu-PA-treated animals seems to be relevant to the low stenosis rate in this group as compared with the t-PA-treated group.

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