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

Abstract:

: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 case-control study (n = 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 (< 4 6 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.

journal_name

Blood

journal_title

Blood

authors

Pintao MC,Ribeiro DD,Bezemer ID,Garcia AA,de Visser MC,Doggen CJ,Lijfering WM,Reitsma PH,Rosendaal FR

doi

10.1182/blood-2013-04-499335

subject

Has Abstract

pub_date

2013-10-31 00:00:00

pages

3210-9

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2013-04-499335

journal_volume

122

pub_type

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