Platelet aggregation induced in vitro by rabbit plasma clot-associated thrombin, and its inhibition by thrombin inhibitors
| Autor: | Nigel O. Roome, Eric Gandossi, Christopher N. Berry, Catherine Lunven, Christiane Gauffeny |
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| Rok vydání: | 1998 |
| Předmět: |
Blood Platelets
Male Platelet Aggregation Antithrombin III Hirudin Arginine Argatroban Thromboplastin Thrombin Medicine Animals Humans Blood Coagulation Sulfonamides business.industry Heparin Antithrombin Hematology Hirudins Recombinant Proteins Biochemistry Pipecolic Acids Biophysics Microscopy Electron Scanning Platelet aggregation inhibitor Rabbits business Platelet Aggregation Inhibitors circulatory and respiratory physiology medicine.drug Discovery and development of direct thrombin inhibitors |
| Zdroj: | Thrombosis and haemostasis. 80(5) |
| ISSN: | 0340-6245 |
| Popis: | SummaryThe activation of rabbit platelets by rabbit plasma clots, and the inhibition of clot-associated thrombin by heparin:antithrombin III, recombinant hirudin (rHV2Lys47) and argatroban, a low molecular weight thrombin inhibitor, was studied.Plasma clots caused the aggregation of platelets suspended in a plasma-free medium as assessed by single platelet counting, and by scanning electron microscopy (platelet aggregates present on the clot surface). Platelet aggregation, induced by clot-associated thrombin, was inhibited by argatroban with an IC50 of 14 ± 3 nM compared to an IC50 of 12 ± 2 nM when human thrombin in solution titrated to give the same decrease in the platelet count as plasma clots was used. rHV2Lys47 also inhibited aggregation induced by clot-associated thrombin with an IC50 of 1.6 ± 0.4 nM compared to 1.6 ± 0.5 nM with thrombin in solution. Heparin was less active against clot-associated thrombin (IC50 = 69 ± 9 mU/ml) than against thrombin in solution (IC50 = 15 ± 5 mU/ml).This study shows that plasma clot-bound thrombin activates platelets and that direct-acting thrombin inhibitors such as argatroban and rHV2Lys47 are more effective than heparin:antithrombin III in inhibiting this phenomenon. |
| Databáze: | OpenAIRE |
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