Eichinger S, Wolz M, Nieszpaur-Los M, Schneider B, Lechner K, Eichler H G, Kyrle P A
Department of Medicine I, Vienna University Hospital, Austria.
Thromb Haemost. 1994 Dec;72(6):831-5.
The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, ld), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both ldLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to ldLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable.(ABSTRACT TRUNCATED AT 250 WORDS)
普通肝素（UFH）和低分子量肝素（LMWH）的临床益处已在许多试验中得到证实。然而，肝素的作用方式尚未完全阐明。因此，我们想通过测量直接从血管损伤部位获取的血液中的凝血激活标志物来研究UFH和LMWH在体内的作用。在一项双盲、随机、三因素、交叉研究中，18名健康志愿者接受了UFH（150 U/kg皮下注射）和两剂LMWH[35 U/kg皮下注射（低剂量，ld），75 U/kg皮下注射（高剂量，hd）]。在给药前后，测量出血时间血液和静脉血中的凝血酶原片段1+2（F1+2）、凝血酶-抗凝血酶复合物（TAT）和纤维蛋白肽A（FPA）。此外，还研究了UFH和LMWH对体外凝血试验的影响。与基线相比，UFH以及ldLMWH和hdLMWH在2小时时均导致出血时间血液中的F1+2、TAT和FPA显著降低。在5小时时也观察到UFH和hdLMWH的显著作用。与ldLMWH相比，hdLMWH后FPA生成的抑制作用更明显。在静脉血中，UFH和LMWH导致F1+2降低，但TAT和FPA未降低。在体外，UFH主要影响抗IIa检测（活化部分凝血活酶时间、凝血酶时间），而LMWH主要影响抗Xa检测系统。使用一种研究体内活化凝血系统的技术，可检测到肝素对凝血激活的时间和剂量依赖性抑制作用。（摘要截短至250字）
