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Anticoagulant protein C pathway defective in majority of thrombophilic
patients [see comments]
JH Griffin, B Evatt, C Wideman and JA Fernandez
Department of Molecular and Experimental Medicine, Scripps Research
Institute, La Jolla, CA 92037.
A defect involving poor anticoagulant response to activated protein C
(APC), an anticoagulant serine protease known to inactivate factors Va and
VIIIa in plasma, was recently reported and the existence of a novel APC
cofactor was suggested. To define the frequency of this defect among 25
venous thrombophilic patients with no identifiable laboratory test
abnormality and among 22 patients previously identified with heterozygous
protein C or protein S deficiency, the APC-induced prolongation of the
activated partial thromboplastin time assay for these patients was compared
with results for 35 normal subjects. The results show that this new defect
in anticoagulant response to APC is surprisingly present in 52% to 64% of
the 25 patients, ie, in the majority of previously undiagnosed
thrombophilia cases, but is not present in 20 of 22 heterozygous protein C
or protein S deficient patients, suggesting that the new factor is a risk
factor independent of protein C or protein S deficiency. The results
demonstrate that abnormalities in the anticoagulant protein C pathway are
present in the majority of thrombophilic patients.
Volume 82,
Issue 7,
pp. 1989-1993,
10/01/1993
Copyright © 1993 by The American Society of Hematology
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