Recombinant desulfatohirudin retains largely the thrombin-inhibitory activity of natural hirudin from Hirudo medicinalis and causes at most minimal immune response in humans. With regard to potential pharmaceutical applications it is of interest to further investigate the structural basis of hirudin functions. In this paper transient hydrogen bonds between backbone amide protons and side-chain ...

The role of thrombin inhibition in platelet vessel wall interaction and thrombus growth was studied under controlled flow conditions. Natural hirudin and recombinant hirudin (r-hirudin), which are specific thrombin inhibitors, were compared with heparinized blood (1.8 +/- 0.2 U/mL) and Ca(2+)-chelated blood in their potential to inhibit platelet interaction and thrombus growth on two biologic v...

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...

BACKGROUND-Intravascular clotting has been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV). We previously identified the expression of tissue factor (TF), the primary cellular initiator of blood coagulation, within the coronary intima, which was associated with neointimal thickening. In the present study, the effect of recombinant hirudin on CAV was assessed in Lewis to F...

In this work, we hypothesize that a surface modified with both polyethylene glycol (PEG) and hirudin may provide a non-fouling, thrombin-neutralizing surface suitable for blood contacting applications. With gold as a model substrate we used two different approaches to the preparation of such a surface: (1) a "direct" method in which PEG was conjugated to hirudin and the conjugate was then immob...

Thrombus extension in patients with venous thromboembolism is due to the accretion of fibrin onto existing thrombi. Extension is promoted by both circulating and thrombus-bound thrombin, which convert fibrinogen to fibrin. Heparin is an effective antithrombotic agent, but it requires continuous administration to achieve persistent inhibition of thrombus extension. Heparin is highly effective in...

AIMS Although hirudin is superior to unfractionated heparin for prevention of death, myocardial infarction, or refractory ischaemia in patients with non-ST-elevation acute coronary syndrome, it is not clear whether hirudin is also of benefit in acute coronary syndrome patients undergoing early percutaneous coronary intervention. METHODS AND RESULTS In the OASIS 2 trial, 10 141 patients with n...

Hematophagous leeches express a broad variety of secretory factors in their salivary glands; among them are hirudins, inhibitors blood coagulation, and decorsins/ornatins, platelet aggregation. Here, we describe the identification molecular functional characterization putative hirudins decorsins/ornatins two leech species American origin, Limnobdella mexicana Haementeria vizottoi. The represent...

Thrombin bound to a fibrin clot remains active and poorly accessible to heparin-AT III complex. During fibrinolysis, thrombin is released as thrombin-FDP complex and is inactivated by heparin-AT III. However, as successive fibrin layers are removed, inaccessible molecules of thrombin are exposed at the surface of the residual clot, possibly contributing to the occurrence during thrombolytic the...