Direct thrombin inhibitors are not equally effective in vivo against arterial thrombosis: in vivo evaluation of DuP714 and argatroban in a porcine angioplasty model and comparison to r-hirudin.

Background: Qualitative differences in antithrombotic efficacy between thrombin inhibitors may be explained by the affinity for which they bind thrombin. This affinity is inversely proportional to the inhibitory constant for the agent (Ki). Thrombin inhibitors, DuP714 (Ki=10(-11)) and argatroban (Ki=10(-8)), were compared to our previous studies with r-hirudin (Ki=10(-13)).

The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich thrombosis after deep arterial injury.

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10).

Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction.

Objectives: The purpose of this study was to examine the impact of sulfonylurea drug use on outcome in diabetic patients undergoing direct coronary angioplasty for acute myocardial infarction.

Background: Sulfonylurea drugs impair ischemic preconditioning. Whether sulfonylurea drugs affect outcome adversely in diabetic patients undergoing direct angioplasty for acute myocardial infarction is unknown.

Tissue prothrombin. Universal distribution in smooth muscle.

Immunohistochemical analysis of surgically obtained porcine tissue samples reveals ubiquitous staining for prothrombin in organs rich in smooth muscle content and universal staining of smooth muscle in tissue vasculature. The native character of tissue prothrombin is verified first by chromogenic substrate hydrolysis and hirudin inhibition after incubation of tissue extracts with taipan snake venom and phospholipid. Western analysis of tissue extracts confirms the native zymogen molecular weight.

Genetic analysis and functional characterization of prothrombins Corpus Christi (Arg382-Cys), Dhahran (Arg271-His), and hypoprothrombinemia.

The structural abnormalities and functional characteristics of dysfunctional prothrombin variants in two new kindreds have been determined. Prothrombin Corpus Christi (family 1) was purified and found to have markedly reduced fibrinogen clotting activity, yet normal amidolytic and near-normal platelet aggregating activity. A transition (C to T) at nucleotide position 8885, present in the heterozygous form in affected family members, resulted in the substitution of Cys for Arg 382.

Acute Myocardial Infarction and the Role of Aspirin, Heparin, and Warfarin.

Acute myocardial infarction is initiated by plaque disruption of a fatty plaque with a thin fibrous cap which has been infiltrated by macrophages. The macrophages are attracted and stimulated by oxidized lipids to secrete metalloproteinases which dissolve collagen and arterial wall matrix and to synthesize tissue factor which accumulates in the fatty gruel, and initiates the thrombotic process when exposed to flowing blood after plaque disruption. This initiates thrombin generation which is greatly amplified by the coagulation cascade.