Factor XI activation by thrombin and Factor XIa

D. Gailani, G. J. Broze

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

The clinical observation that individuals deficient in Factor XII, HMWK, or prekallikrein do not have a bleeding diathesis indicates that a Factor XII-independent mechanism for the activation of Factor XI must exist in vivo. In current models of hemostasis, coagulation is induced when Factor VII or VIIa in plasma comes into contact with its cofactor, tissue factor, at sites beneath the blood vessel endothelium. The Factor VIIa-tissue factor complex activates a small amount of Factors X and IX before it is rapidly inhibited by the tissue factor pathway inhibitor. The severe bleeding seen in patients with hemophilia lacking Factor VIII or IX indicates that additional Factor X must be activated by Factor IXa/VIIIa for adequate hemostasis to occur. Factor XI would function in this model by activating additional Factor IX to sustain Factor X activation after the inhibition of the Factor VIIa-tissue factor complex. The results reviewed in this article suggest that thrombin produced through the initial activity of the Factor VIIa-tissue factor complex may activate Factor XI, which, in turn, would sustain the hemostatic process by activating Factor IX. This process may be further augmented by Factor XI autoactivation after thrombin has produced the initial Factor XIa. The kinetic parameters of Factor XI activation by thrombin indicate that one or more cofactors would be necessary to produce sufficient Factor XIa. Although sulfatides are found in the plasma membranes of numerous cell types, the form and concentrations used in the experiments just described are not likely to be physiologic. GAG or proteoglycan components of the blood vessel subendothelium appear to be candidates for such a cofactor.

Original languageEnglish
Pages (from-to)396-404
Number of pages9
JournalSeminars in Thrombosis and Hemostasis
Volume19
Issue number4
DOIs
StatePublished - Jan 1 1993

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