PROTEIN-C DEFICIENCY IN A CONTROLLED SERIES OF UNSELECTED OUTPATIENTS- AN INFREQUENT BUT CLEAR RISK FACTOR FOR VENOUS THROMBOSIS (LEIDEN THROMBOPHILIA STUDY)

A deficiency of protein C (PC), antithrombin, or protein S is strongly associated with deep-vein thrombosis in selected patients and their f amilies. However, the strength of the association with venous thrombos is in the general population is unknown. This study was a population-b ased, 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 health y 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 co ntrols, the frequency was 1.5% (seven subjects). Thus, there is a thre efold 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 (C I), 1.4 to 7.0]. When a PC deficiency was based on two repeated measur ements, 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 incr eased further to 6.5 (95% CI, 1.8 to 24). In addition, there was a gra dient in thrombosis risk, according to PC levels. The results for anti thrombin are similar to those for PC, although less pronounced (relati ve risk, 2.2; 95% CI, 1.0 to 4.7). We could not find an association be tween 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 defi ciency are clearly associated with an increase in thrombosis risk. (C) 1995 by The American Society of Hematology.