Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study

Abstract

Key Points• Low free protein S and low total protein S levels could not identify subjects at risk for venous thrombosis in a population-based study.• Protein S testing and subsequent testing on PROS1 mutations should not be considered in unselected patients with venous thrombosis.In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based casecontrol study (n 5 5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free and total protein S deficiency was not associated with venous thrombosis: free protein S < 53 U/dL, odds ratio [OR] 0.82 (95% confidence interval [CI], 0.56-1.21) and total protein S < 68 U/dL, OR 0.90 (95% CI, 0.62-1.31). When lower cutoff values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in 5 patients and 5 controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis. (Blood. 2013;122(18):3210-3219)

Racial differences in primary cytogenetic abnormalities in multiple myeloma: a multi-center study

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Diagnosis and management of heritable thrombophilias

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