Gandossi E, Lunven C, Gauffeny C, Roome N O, Berry C N
Thrombosis and Haematology Department, Cardiovascular Research, Synthélabo Recherche, Chilly Mazarin, France.
Thromb Haemost. 1998 Nov;80(5):840-4.
The 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.
研究了兔血浆凝块对兔血小板的激活作用，以及肝素-抗凝血酶III、重组水蛭素（rHV2Lys47）和低分子量凝血酶抑制剂阿加曲班对凝块相关凝血酶的抑制作用。通过单血小板计数和扫描电子显微镜（凝块表面存在血小板聚集体）评估，血浆凝块导致悬浮在无血浆培养基中的血小板聚集。与用人凝血酶溶液滴定以产生与血浆凝块相同程度的血小板计数降低时的IC50为12±2 nM相比，阿加曲班抑制凝块相关凝血酶诱导的血小板聚集，IC50为14±3 nM。rHV2Lys47也抑制凝块相关凝血酶诱导的聚集，IC50为1.6±0.4 nM，而凝血酶溶液的IC50为1.6±0.5 nM。肝素对凝块相关凝血酶的活性（IC50 = 69±9 mU/ml）低于对溶液中凝血酶的活性（IC50 = 15±5 mU/ml）。本研究表明，血浆凝块结合的凝血酶激活血小板，并且直接作用的凝血酶抑制剂如阿加曲班和rHV2Lys47在抑制这种现象方面比肝素-抗凝血酶III更有效。
