OBJECTIVES The effects of ximelagatran, an oral direct thrombin inhibitor (DTI), recombinant hirudin (r-hirudin) and enoxaparin on thrombin generation and platelet activation were studied in humans. BACKGROUND Recombinant hirudin (parenteral DTI) and enoxaparin (low molecular weight heparin) have been demonstrated to be clinically effective in acute coronary syndromes. Ximelagatran is current...

The folding pathway of hirudin was analyzed by structural characterization and stop/go folding experiments of acid-trapped intermediates. The results show that the folding is initiated by a near-random packing, followed by the reorganization and fine adjustment of partially compact intermediates to attain the active molecule. The process of packing is observed as the unfolded hirudin flows sequ...

A new sensitive and precise method for quantitative determination of direct thrombin inhibitors is described, the ecarin chromogenic assay (ECA). Ecarin is used as the specific prothrombin-activating principle. The cleavage of a chromogenic substrate by meizothrombin is inhibited in a concentration-dependent fashion by direct thrombin inhibitors. For the ECA, the linear measuring range is about...

BACKGROUND The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. METHODS AND RESULTS This study evaluated the effect of intravenous r-hirudin, a selective inhibitor...

T he problem of heparin-induced thrombocytopenia (HIT) among patients undergoing cardiac surgery is increasingly being appreciated. However, no safe standard anticoagulation strategy has been established for the management of these patients during cardiopulmonary bypass (CPB). Recombinant hirudin (r-hirudin), a 65-amino acid polypeptide, is a direct thrombin inhibitor that has been used success...