The three-dimensional structures of D-Phe-Pro-Arg-chloromethyl ketone-inhibited thrombin in complex with Tyr-63-sulfated hirudin (ternary complex) and of thrombin in complex with the bifunctional inhibitor D-Phe-Pro-Arg-Pro-(Gly)4-hirudin (CGP 50,856, binary complex) have been determined by X-ray crystallography in crystal forms different from those described by Skrzypczak-Jankun et al. (Skrzyp...

BACKGROUND Platelet reactivity assessment is an important tool in both the causal determination of bleeding diathesis as well as in the evaluation of the efficacy of anti-platelet therapy in patients at risk of thrombosis. Sodium citrate is the most widely used anticoagulant for hemostasis investigations. However, some doubt exists over the suitability of sodium citrate in platelet function tes...

Hirudin is a 65-amino acid polypeptide with three disulfide linkages. It is stable under extreme pH (1.4712.9), high temperature (95 “C), and in the presence of denaturants (6 M guanidinium chloride or 8 M urea). The thrombin inhibitory activity of hirudin remains unaffected even after cleavage of an internal peptide bond ( L y ~ ~ ‘ A s n ~ ~ ) . One condition which effectively and irreversibl...

Heparin-induced thrombocytopenia (HIT) is a severe complication following the application of heparin; antibodies against complexes of heparin and PDF4 initiate activation of platelets. This may lead to massive thrombembolism, which is associated with a slight and transient drop of platelets in HIT I or a drop below 50% after approximately 5 days in HIT II. Further administration of heparin has ...

Hirudin, a thrombin-specific inhibitor, comprises a compact amino-terminal core domain (residues 1-52) and a disordered acidic carboxyl-terminal tail (residues 53-65). An array of core fragments were prepared from intact recombinant hirudin by deletion of various lengths of its carboxyl-terminal tail on selective enzymatic cleavage. Hir1-56 and Hir1-53 were produced by pepsin digestion at Phe56...

To determine the role of thrombin in high blood flow, platelet-dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin. Thrombus formation was determined in vivo using three relevant mo...

In former experiments we found that various substances, among them hirudin, injected intravenously into mice inhibited the growth of mouse tumors.’ We found, furthermore, that in the course of the injections of the solutions of colIoida1 copper and of hirudin, immunity was produced against the effect of these substances, the rate of growth of the tumors serving as an indicator of the degree of ...

Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quant...