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Protein C deficiency in a controlled series of unselected outpatients: an
infrequent but clear risk factor for venous thrombosis (Leiden
Thrombophilia Study) [see comments]
T Koster, FR Rosendaal, E Briet, FJ van der Meer, LP Colly, PH Trienekens, SR Poort, PH Reitsma and JP Vandenbroucke
Department of Clinical Epidemiology, University Hospital Leiden, The
Netherlands.
A deficiency of protein C (PC), antithrombin, or protein S is strongly
associated with deep-vein thrombosis in selected patients and their
families. However, the strength of the association with venous thrombosis
in the general population is unknown. This study was a population-based,
patient-control study of 474 consecutive outpatients, aged less than 70
years, with a first, objectively diagnosed, episode of venous thrombosis
and without an underlying malignant disease, and 474 healthy controls who
matched for age and sex. Relative risks were estimated as matched odds
ratios. Based on a single measurement, there were 22 (4.6%) patients with a
PC deficiency (PC activity, less than 0.67 U/mL or PC antigen, less than
0.33 U/mL when using coumarins). Among the controls, the frequency was 1.5%
(seven subjects). Thus, there is a threefold increase in risk of thrombosis
in subjects with PC levels below 0.67 or 0.33 U/mL [matched odds ratio,
3.1; 95% confidence interval (CI), 1.4 to 7.0]. When a PC deficiency was
based on two repeated measurements, the relative risk for thrombosis
increased to 3.8 (95% CI, 1.3 to 10); when it was based on
DNA-confirmation, the relative risk increased further to 6.5 (95% CI, 1.8
to 24). In addition, there was a gradient in thrombosis risk, according to
PC levels. The results for antithrombin are similar to those for PC,
although less pronounced (relative risk, 2.2; 95% CI, 1.0 to 4.7). We could
not find an association between reduced total protein S (relative risk,
0.7; 95% CI, 0.3 to 1.8) or free protein S levels (relative risk, 1.6; 95%
CI, 0.6 to 4.0) and thrombosis risk. Although not very frequent, PC and
antithrombin deficiency are clearly associated with an increase in
thrombosis risk.
Volume 85,
Issue 10,
pp. 2756-2761,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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