Hellstern P, Kiehl R, von Blohn G, Köhler M, Meierhenrich U, Wenzel E
Thromb Haemost. 1986 Oct 21;56(2):225-8.
This study was performed to estimate appropriate dosages of two low molecular weight heparins (LMWH) for clinical trials on subcutaneous perioperative thrombosis prophylaxis. Anticoagulatory activities and platelet function were investigated after single doses of two LMWH and of unfractionated sodium heparin (UFH) in 24 healthy individuals. Twelve subjects received subcutaneous injections of 1000, 1500, and 2500 i.u. (aPTT) of LMHW 1, and the other 12 received LMWH 2 at same dosages. The following parameters were determined before 30 min, 1 h, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h after either LMWH or 5000 i.u. (aPTT) UFH: aPTT, thrombin time, anti-Xa activity (S 2222, Coatest heparin), and anti-IIa activity (Chromozym TH). Bleeding time, platelet count, and adrenalin-, collagen-, and ADP-induced platelet aggregation were assessed before and 3 h after administration. After application of 1500 i.u. LMWH 1 and LMWH 2, the anti-Xa and anti-IIa levels were already significantly higher than after 5000 i.u. UFH. 2500 i.u. LMWH 1 and LMWH 2 evoked significantly greater prolongations of aPTT and thrombin time values than did 5000 i.u. UFH. This was not the case after 1000 and 1500 i.u. LMWH. The half-lives of anticoagulatory effects after LMWH were markedly longer than after UFH. Platelet function was not altered by any of the heparins tested. Our results indicate that LMWH cause anticoagulatory effects in vivo that cannot be predicted by in vitro studies and that the appropriate single dosages of LMWH in subcutaneous perioperative thrombosis prophylaxis have to be estimated by dosage determinations in healthy subjects.
本研究旨在估算两种低分子量肝素(LMWH)在皮下围手术期血栓预防临床试验中的合适剂量。对24名健康个体单次给予两种LMWH及普通肝素钠(UFH)后,研究其抗凝活性和血小板功能。12名受试者皮下注射1000、1500和2500国际单位(aPTT)的LMWH 1,另外12名受试者接受相同剂量的LMWH 2。在给予LMWH或5000国际单位(aPTT)UFH后的30分钟、1小时、90分钟、2小时、3小时、4小时、6小时、8小时和10小时前,测定以下参数:活化部分凝血活酶时间(aPTT)、凝血酶时间、抗Xa活性(S 2222,Coatest肝素)和抗IIa活性(Chromozym TH)。在给药前及给药后3小时评估出血时间、血小板计数以及肾上腺素、胶原和二磷酸腺苷诱导的血小板聚集。给予1500国际单位的LMWH 1和LMWH 2后,抗Xa和抗IIa水平已显著高于给予5000国际单位UFH后。2500国际单位的LMWH 1和LMWH 2引起的aPTT和凝血酶时间值延长显著大于5000国际单位UFH。1000和1500国际单位LMWH给药后情况并非如此。LMWH后的抗凝作用半衰期明显长于UFH后。所测试的任何一种肝素均未改变血小板功能。我们的结果表明,LMWH在体内产生的抗凝作用无法通过体外研究预测,皮下围手术期血栓预防中LMWH的合适单次剂量必须通过在健康受试者中进行剂量测定来估算。