当前位置： SCI文献检索 > JOURNAL OF THROMBOSIS AND THROMBOLYSIS期刊下所有文献 > Enoxaparin, a low molecular weight heparin, inhibits platelet-dependent prothrombinase assembly and activity by factor-Xa neutralization.

Enoxaparin, a low molecular weight heparin, inhibits platelet-dependent prothrombinase assembly and activity by factor-Xa neutralization.

Abstract：

BACKGROUND:The available evidence suggests strongly that intravascular thrombosis is mediated predominantly by tissue-factor and its activation of factor X, which in the presence of factor Va, calcium, and phospholipid (prothrombinase complex) effectively converts prothrombin to thrombin. In vitro experiments have shown that low molecular weight heparins (LMWHs) have greater anti-Xa activity than unfractionated heparin; however, it remains unclear as to whether their antithrombotic effects in vivo are determined by a similar mechanism. We determined the ability of plasma obtained from patients with either unstable angina or non-ST segment elevation myocardial infarction (MI) receiving the LMWH enoxaparin (anti Xa:IIa ratio 3:1) to inhibit tissue factor-mediated thrombin generation and to inactivate platelet prothrombinase. METHODS:Platelet rich plasma was prepared by suspending washed donor platelets in the plasma of 7 patients participating in the TIMI 11A study. Samples were obtained before, 1 hour after a 30-mg IV bolus of enoxaparin and 6 hours after the third subcutaneous injection (1. 0-1.25 mg/kg given subcutaneously every 12 hrs). Tissue factor (0.1 ng/ml) and 10 mM CaCl(2) were added to initiate extrinsic coagulation. At timed intervals prothrombin activation fragment 1.2 (F1.2) levels (thrombin generation) were measured using an ELISA technique. Inactivation of reformed platelet prothrombinase by samples obtained at the same time points was also determined. RESULTS:Patient plasma obtained 1 hr after treatment initiation and 6 hours after the third subcutaneous injection inhibited tissue factor mediated prothrombinase assembly by 31% and 11%, respectively and platelet prothrombinase activity by 27% and 22%, respectively. CONCLUSION:We conclude that enoxaparin in plasma concentrations achieved routinely in clinical practice is able to: (1) inhibit tissue factor mediated extrinsic coagulation by preventing platelet surface prothrombinase assembly, and (2) inactivate platelet prothrombinase activity and resulting thrombin generation. These observations suggest that a LMWH's anti-Xa activity (and anti-Xa:IIa profile) is important in determining its overall antithrombotic potential. Clinical trials comparing agents with differing anti-Xa:IIa properties will be required, however, to provide proof of concept.

journal_name

J Thromb Thrombolysis

journal_title

Journal of thrombosis and thrombolysis

authors

Spencer FA,Ball SP,Zhang Q,Liu L,Benoit S,Becker RC

doi

10.1023/a:1018710526772

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

223-8

issue

eissn

0929-5305

issn

1573-742X

journal_volume

pub_type

杂志文章,多中心研究

在线工具

Enoxaparin, a low molecular weight heparin, inhibits platelet-dependent prothrombinase assembly and activity by factor-Xa neutralization.