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Keywords:

  • Protein S deficiency;
  • venous thrombosis;
  • arterial thrombosis;
  • absolute risk;
  • thrombophilia

Summary

Hereditary protein S (PS) deficiency type I is an established risk factor for venous thromboembolism. Contradictionary data on type III deficiency suggests a difference in risk between both types. We studied 156 first degree relatives (90% of eligible relatives) from type I deficient probands (cohort 1) and 268 (88%) from type III deficient probands (cohort 2) to determine the absolute risk of venous and arterial thromboembolism. Annual incidences of venous thromboembolism were 1·47 and 0·17 per 100 person-years in deficient and non-deficient relatives in cohort 1 [relative risk (RR) 8·9; 95% confidence interval (CI) 2·6–30·0], and 0·27 vs. 0·24 in cohort 2 (RR 0·9; 95% CI 0·4–2·2). Type III deficiency was demonstrated in 20% of non-deficient relatives in cohort 1 and the annual incidence in this subgroup was 0·70 (RR 4·3;0·95–19·0). The cut-off level of free PS to identify subjects at risk was 30%, the lower limit of its normal range (65%). PS deficiency was not a risk factor for arterial thromboembolism. In conclusion, type I deficiency was found to be a strong risk factor for venous thromboembolism, in contrast with type III deficiency. This was because of lower free PS levels in type I deficient subjects and a free PS cut-off level far below the lower limit of its normal range.