Gallistl S, Muntean W, Leis H J
Department of Pediatrics, University of Graz, Austria.
Thromb Haemost. 1995 Oct;74(4):1163-8.
The effects of unfractionated heparin (UH) and recombinant hirudin (rH) on prothrombin activation, free thrombin generation, and platelet aggregation induced by endogenously generated thrombin after intrinsic activation of platelet rich plasma were compared. Free thrombin generation and platelet aggregation were assessed simultaneously by delaying fibrinogen polymerisation with GPRP. UH more effectively inhibited prothrombin activation and free thrombin generation than rH. Increasing concentrations of rH had hardly any effect on the peak amount of free thrombin, while in the presence of 400 nM UH only traces of free thrombin were detected. Comparison of TAT and THC (thrombin-hirudin complex) generated until the onset of platelet aggregation on a molar basis showed that much more thrombin was inactivated in the presence of rH than in plasma containing UH. The explosive generation of free thrombin in hirudinized plasmas was accompanied by a markedly steeper aggregation curve as compared to heparinized plasmas. The generation of thromboxane B2 was markedly delayed in the presence of UH but not influenced in the presence of rH. Our results suggest that UH is more effective than rH in inhibiting prothrombin activation after intrinsic activation of platelet rich plasma, while rH prevents clotting more by direct inactivation of already generated thrombin. The inability of even high concentrations of rH to prevent the explosive generation of free thrombin might contribute to the observed inefficiency of rH to inhibit platelet aggregation.
比较了普通肝素（UH）和重组水蛭素（rH）对富含血小板血浆内源性激活后凝血酶原激活、游离凝血酶生成以及内源性生成的凝血酶诱导的血小板聚集的影响。通过用GPRP延迟纤维蛋白原聚合同时评估游离凝血酶生成和血小板聚集。UH比rH更有效地抑制凝血酶原激活和游离凝血酶生成。rH浓度增加对游离凝血酶的峰值几乎没有影响，而在存在400 nM UH的情况下仅检测到微量游离凝血酶。在摩尔基础上比较血小板聚集开始前产生的凝血酶 - 抗凝血酶复合物（TAT）和凝血酶 - 水蛭素复合物（THC）表明，与含有UH的血浆相比，在rH存在下更多的凝血酶被灭活。与肝素化血浆相比，水蛭素化血浆中游离凝血酶的爆发性生成伴随着明显更陡的聚集曲线。在UH存在下血栓素B2的生成明显延迟，但在rH存在下不受影响。我们的结果表明，在富含血小板血浆内源性激活后，UH在抑制凝血酶原激活方面比rH更有效，而rH更多地通过直接灭活已生成的凝血酶来防止凝血。即使高浓度的rH也无法防止游离凝血酶的爆发性生成，这可能导致观察到rH抑制血小板聚集的效率低下。
