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Influence of low molecular weight heparin and low molecular weight dextran sulfate on the inhibition of coagulation factor XIa by serpins.

Abstract：

:We investigated the influence of low molecular weight dextran sulfate (LMWdxs) and low molecular weight heparins (LMWH: dalteparin, enoxaparin and nadroparin) on the inhibition of FXIa by C1-inhibitor, alpha1-antitrypsin, alpha2-antiplasmin and antithrombin in a purified system and in plasma. The second order rate constant for inactivation of FXIa by C1-inhibitor, alpha1-antitrypsin, alpha2-antiplasmin, and antithrombin was 1.23, 0.056, 0.33 and 0.59 x 10(3) M(-1) s(-1), respectively. LMWdxs and LMWH dose-dependently increased the second order rate constant of the inactivation of FXIa by C1-inhibitor up to 39-fold. The second order rate constant of the inactivation of FXIa by antithrombin was increased up to 6-fold by LMWH, whereas LMWdxs had no effect. In plasma, FXIa was inactivated to about 50% by C1-inhibitor, while the other serpins contributed together to the remaining 50% of plasma's inhibitory capacity towards FXIa. In the presence of LMWdxs or LMWH, FXIa was inactivated in plasma to more than 90% by C1-inhibitor. LMWH at maximal therapeutic plasma levels enhanced the contribution of antithrombin to the inactivation of FXIa in plasma up to 5-fold. In conclusion, we found that the tested low molecular weight glycosaminoglycans dalteparin, enoxaparin and nadroparin and LMWdxs stimulate inactivation of FXIa by C1-inhibitor in a system using purified proteins as well as in plasma. Furthermore, LMWH but not LMWdxs slightly enhanced FXIa inhibition by antithrombin.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Mauron T,Lämmle B,Wuillemin WA

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

82-6

issue

1

eissn

0340-6245

issn

2567-689X

pii

98070082

journal_volume

80

pub_type

杂志文章

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