TFPI ANTIGEN LEVELS IN NORMAL HUMAN VOLUNTEERS AFTER INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATION OF UNFRACTIONATED HEPARIN AND A LOW-MOLECULAR-WEIGHT HEPARIN
TFPI ANTIGEN LEVELS IN NORMAL HUMAN VOLUNTEERS AFTER INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATION OF UNFRACTIONATED HEPARIN AND A LOW-MOLECULAR-WEIGHT HEPARIN
复制标题
DOI：
10.1016/0049-3848(95)91623-s
复制
发表时间：
1995-01-15
影响因子：
7.5
通讯作者：
FAREED, J
中科院分区：
文献类型：
--
作者：
HOPPENSTEADT, DA;WALENGA, JM;FAREED, J
组织因子途径抑制物（TFPI）是普通肝素（UFH）和低分子量肝素（LMWH）体内抗凝/抗血栓作用的重要介质。静脉和皮下注射UFH和LMWH后，TFPI的血管池释放到循环中。我们已经以剂量依赖性方式将LMWH（Ardeparin（R））和UFH给予正常人类志愿者。我们的结果表明，TFPI抗原水平在静脉内和皮下施用UFH和Ardeparin（R）后增加。由于LMWH在等重量剂量下通过皮下途径的生物利用度更好，Ardeparin（R）比UFH释放更多的TFPI。然而，当静脉内给予时，已经观察到TFPI从脉管系统的相同释放。当皮下施用UFH或Ardeparin（R）时，TFPI的血浆浓度增加0.5 - 2倍，当静脉内施用时，TFPI的血浆浓度高3倍。TFPI抗原水平的这种显著增加取决于所施用的Ardeparin（R）的剂量。TFPI中的这种释放与Heptest（R）凝血测定的延长相关。然而，从该研究中可以看出，TFPI的释放先于Heptest（R）凝血时间的升高。
Tissue factor pathway inhibitor (TFPI) is an important mediator of the in vivo anticoagulant/antithrombotic properties of unfractionated heparin (UFH) and low molecular weight heparin (LMWH). The vascular pool of TFPI is released into the circulation after intravenous and subcutaneous administration of both UFH and LMWH. We have administered LMWH (Ardeparin(R)) and UFH to normal human volunteers in a dose dependent manner. Our results demonstrate that the TFPI antigen levels increase upon the intravenous and subcutaneous administration of UFH and Ardeparin(R). Because of the better bioavailability of LMWH by the subcutaneous route at equigravimetric dosages, Ardeparin(R) released more TFPI than UFH. However, when given intravenously an identical release of TFPI from the vasculature has been observed. The plasma concentration of TFPI was increased 0.5 - 2 fold when UFH or Ardeparin(R) was administered subcutaneously and was 3 fold higher when administered intravenously. This profound increase in TFPI antigen levels was dependent on the dosage of Ardeparin(R) administered. This release in TFPI correlates with prologation of the Heptest(R) clotting assay. However, it appears from this study that TFPI release precedes the elevation of the Heptest(R) clotting time.