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Activation of factor XI in plasma is dependent on factor XII [see comments]
T Brunnee, C La Porta, SR Reddigari, VM Salerno, AP Kaplan and M Silverberg
Department of Medicine, State University of New York, Stony Brook 11794-
8161.
The activation of factor XI initiates the intrinsic coagulation pathway.
Until recently it was believed that the main activator of factor XI is
factor XIIa in conjunction with the cofactor high molecular weight
kininogen on a negatively charged surface. Two recent reports have
presented evidence that in a purified system factor XI is activatable by
thrombin together with the soluble polyanion dextran sulfate. To assess the
physiological relevance of these findings we studied the activation of
factor XI in normal and factor XII-deficient plasma. We used either
kaolin/cephalin or dextran sulfate as a surface for the intrinsic
coagulation pathway, tissue factor to generate thrombin via the extrinsic
pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added
to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is
rapidly cleaved on incubation with kaolin. The kinetics appear to be
exponential with half the maximum cleavage at 5 minutes. Similar kinetics
of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of
factor XII activation) is added to factor XII-deficient plasma if an
activating surface is provided. Tissue factor (1:500) added to plasma did
not induce cleavage of factor XI during a 90-minute incubation, although
fibrin formation within 30 seconds indicated that thrombin was generated
via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to
50% prothrombin activation) directly to factor XII deficient or normal
plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to
instantaneous fibrinogen cleavage, but again no cleavage of factor XI was
observable. We conclude that in plasma surroundings factor XI is not
activated by thrombin, and that proposals of thrombin initiation of the
intrinsic coagulation cascade are not supportable.
Volume 81,
Issue 3,
pp. 580-586,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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