Lormeau J C, Herault J P
Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
Thromb Haemost. 1995 Dec;74(6):1474-7.
The inhibition of thrombin generation (TG) was studied in plasma from human volunteers after single subcutaneous administrations of 4000, 8000 or 12,000 anti-Xa units (i.e., 6, 12 or 18 mg) of the synthetic pentasaccharide (SR 90107/ORG 31540) (SP). SP impaired TG in plasma for up to 18 h after injection, and the time-courses of TG and factor Xa inhibitions were similar. In untreated plasma supplemented in vitro with SP to obtain the same anti-Xa activity as in ex vivo samples, equivalent TG inhibitions were observed thus showing that no transformed SP molecules were involved in the TG inhibition ex vivo. Functional as well as immunological assay of TFPI indicated that subcutaneous injection of 12,000 anti-Xa units of SP did not induce any TFPI release, whereas under the same conditions, 13,000 IU of Fraxiparine produced a significant rise of TFPI in plasma. The plotting of TG inhibition versus SP concentration could be fitted with a good correlation (r = 0.94) to the graphical representation linking [ATIII-SP] to [SP]. These results demonstrate that following subcutaneous administration to man, SP inhibits TG ex vivo and likely in vivo exclusively through the same selective ATIII-mediated inhibition of factor Xa as the one elicited in vitro.
在健康志愿者单次皮下注射4000、8000或12000抗Xa单位（即6、12或18毫克）的合成五糖（SR 90107/ORG 31540）（SP）后，研究了血浆中凝血酶生成（TG）的抑制情况。注射后长达18小时，SP均能抑制血浆中的TG，且TG和因子Xa抑制的时间进程相似。在体外补充SP的未处理血浆中，获得与体内样本相同的抗Xa活性，观察到了等效的TG抑制作用，这表明在体内抑制TG的过程中不涉及转化的SP分子。组织因子途径抑制物（TFPI）的功能及免疫分析表明，皮下注射12000抗Xa单位的SP不会诱导TFPI释放，而在相同条件下，13000国际单位的速避凝可使血浆中TFPI显著升高。TG抑制与SP浓度的关系图与将[抗凝血酶III-SP]与[SP]联系起来的图形表示具有良好的相关性（r = 0.94）。这些结果表明，在人体皮下给药后，SP在体外和可能在体内均通过与体外引发的相同的选择性抗凝血酶III介导的因子Xa抑制作用来抑制TG。
