Background Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinan...

Hirudin, the first specific thrombin inhibitor, which was used clinically, stems from medicinal leeches and is produced today by recombinant technology. R-hirudins have been studied in many clinical trials. R-hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In acute coronary syndromes hirudin a...

BACKGROUND The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND RESULTS Eighty-two patients in this prospective, multicenter study received 1 of 4 intraven...

The solution structure of recombinant wild-type hirudin and of the putative active site mutant Lys-47----Glu has been investigated by nuclear magnetic resonance (NMR) spectroscopy at 600 MHz. The 1H NMR spectra of the two hirudin variants are assigned in a sequential manner with a combination of two-dimensional NMR techniques. Some assignments made in our previous paper [Sukumaran, D. K., Clore...

BACKGROUND Circadian variations have been described for a number of haemostatic and physiological factors, all of which might predispose towards clotting in the late morning. The anticoagulation effect of heparin has been shown to respond in a circadian manner, resulting in minimal prolongation of the activated partial thromboplastin time (aPTT) in the morning. METHODS Recombinant hirudin (HB...

This study aimed to investigate the effects of thrombin released in hematoma after intracerebral hemorrhage (ICH) on the cerebral injury of perihematomal tissues and to evaluate the protection effect of hirudin on the cerebral injury after ICH. We used the autologous uncoagulated blood injection method to prepare the ICH rat model, and all rats were randomly divided into a normal group, an ICH ...

Hirudin and hirulog-1 [D-Phe-Pro-Arg-Pro-[Gly]4-desulphohirudin-(54-65)] abrogate the enzyme activities of alpha-thrombin by binding the enzyme simultaneously at its catalytic centre and fibrin(ogen)-recognition exosite. In contrast, hirugen [hirudin-(54-65)] binds alpha-thrombin solely at the fibrin(ogen)-recognition exosite, and competitively inhibits fibrinopeptide A release. To investigate ...

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after...

hirudin is an anticoagulant agent of the salivary glands of the medicinal leech. recombinant hirudin (r-hir) displays certain drawbacks including bleeding and immunogenicity. to solve these problems, cysteine-specific pegylation has been proposed as a successful technique. however, proper selection of the appropriate cysteine residue for substitution is a critical step. this study has, for the ...

BACKGROUND Recombinant technology was used to produce a new anticoagulant that is preferentially localized and active at the site of the clot. METHODS AND RESULTS The variable regions of the heavy and light chains of a fibrin-specific antibody were amplified by polymerase chain reaction (PCR) with hybridoma cDNA. To obtain a functional single-chain antibody (scFv), a linker region consisting ...