Effect of heparin on the inactivation rate of human activated factor XII by antithrombin III

Détails

ID Serval
serval:BIB_A381580FC5D7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of heparin on the inactivation rate of human activated factor XII by antithrombin III
Périodique
Blood
Auteur⸱e⸱s
Pixley  R. A., Schapira  M., Colman  R. W.
ISSN
0006-4971 (Print)
Statut éditorial
Publié
Date de publication
07/1985
Volume
66
Numéro
1
Pages
198-203
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul
Résumé
Human antithrombin III (ATIII) is a plasma inhibitor of several serine proteases of the blood coagulation system. Previous investigations have reported that the presence of heparin has a multifold accelerating effect on the inhibition of factor XIIa and XIIf, the active species derived from factor XII. Recent studies from our laboratories have confirmed that ATIII inactivates factor XIIa and factor XIIf, but only contributes 2% to 3% to the inhibition of activated factor XII species in plasma. The major inhibitor is C1 inhibitor. Therefore, we have reexamined the heparin effect on the rate of inhibition of factor XIIa and factor XIIf in purified systems. We also have studied the effect of heparin on the inactivation of both factor XII-derived active species by various plasmas. Using purified factor XIIa and ATIII, we found that heparin (0.7 to 34.0 U/mL) increased the rate of inhibition of Factor XIIa. However, at heparin concentrations usually achieved during anticoagulant therapy (0.7 U/mL), the inhibition was accelerated only fourfold. This implies only a 6% contribution to the inhibitory effect of plasma. This suggestion was confirmed by the observation that heparin (1.5 U/mL) added to factor XII-deficient plasma and reconstituted with factor XIIa did not produce a detectable enhancement of the rate of inhibition of factor XIIa. Furthermore, using purified factor XIIf and antithrombin III, heparin (3.6 to 57.2 U/mL) increased the inactivation rate constant of factor XIIf by 1.6 to 14.0 times. This small effect was confirmed by the observation that heparin at a concentration greater than that sufficient for anticoagulation (1.4 U/mL) did not modify the inactivation rate of factor XIIf by prekallikrein-deficient plasma, and thus C1 inhibitor remains the major inhibitor even in the presence of heparin. From this study and our previous investigations on the effect of heparin on the inhibition of kallikrein and factor XIa, we conclude that heparin does not significantly affect the protease activity of purified contact activation factors or the activities expressed by these proteases in plasma.
Mots-clé
Antithrombin III/*metabolism Blood Coagulation/drug effects Factor XII/*antagonists & inhibitors Factor XIIa Heparin/*pharmacology Hexadimethrine/pharmacology Humans Kinetics Peptide Fragments/antagonists & inhibitors
Pubmed
Web of science
Création de la notice
25/01/2008 15:27
Dernière modification de la notice
20/08/2019 15:09
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