Protein S type III deficiency is no risk factor for venous and arterial thromboembolism in 168 thrombophilic families: a retrospective study.

Abstract

Free protein S rather than total protein S levels are currently measured to detect inherited protein S deficiency. Because type III (free protein S) deficiency is still not established as risk factor for thrombosis, we assessed the absolute risk of venous and arterial thromboembolism in a family cohort study. Annual incidences in first-degree relatives with and without protein S deficiency type III were compared. Probands had experienced thrombosis and had either the prothrombin G20210A mutation, increased factor VIII:C levels or hyperhomocysteinemia. Relatives were tested for these thrombophilic disorders and factor V Leiden. Levels of antithrombin, protein C, total and free protein S, and factor XI:C were additionally measured. Of 500 relatives enrolled, 105 were excluded from analysis because they could not be classified, due to acquired conditions. Protein S deficiency type III was demonstrated in 60/395 remaining relatives (15%). Other thrombophilic defects were equally distributed among deficient and non-deficient relatives. Annual incidences of venous thromboembolism were 0.28 per 100 person-years [95% confidence interval (CI), 0.09-0.66] in deficient relatives versus 0.20 per 100 person-years (95% CI, 0.12-0.30) in non-deficient relatives [hazard ratio, 1.4 (95% CI, 0.4-4.0)]. For arterial thromboembolism these values were 0.16 per 100 person-years (95% CI, 0.03-0.46) versus 0.10 per 100 person-years (95% CI, 0.05-0.19) [hazard ratio, 1.5 (95% CI, 0.3-6.0)]. These results suggest that protein S deficiency type III is not associated with an increased risk of either venous or arterial thromboembolism.

• Authors: Eduard J Libourel, Ivan Bank, Nic J G M Veeger, Karly Hamulyàk, Saskia Middeldorp, Martin H Prins, Harry R Büller, Jan van der Meer
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 16 Issue 2 Pg. 135-40 (Mar 2005) ISSN: 0957-5235 [Print] England
• PMID: 15741801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein C
• Prothrombin
• Factor VIII

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Factor VIII (analysis)
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Mutation
• Protein C (analysis)
• Protein S Deficiency (blood, complications, genetics)
• Prothrombin (analysis, genetics)
• Retrospective Studies
• Risk Factors
• Thromboembolism (blood, etiology, genetics)