High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin

Jan-Leendert P. Brouwer; Willem M. Lijfering; Min Ki ten Kate; Hanneke C. Kluin-Nelemans; Nic J. G. M. Veeger; Jan van der Meer

doi:10.1160/TH08-06-0364

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(01): 93-99
DOI: 10.1160/TH08-06-0364

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin

Jan-Leendert P. Brouwer

¹Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

,

Willem M. Lijfering

¹Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

,

Min Ki ten Kate

¹Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

,

Hanneke C. Kluin-Nelemans

¹Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

,

Nic J. G. M. Veeger

²Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands

,

Jan van der Meer

¹Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands

› Author Affiliations

Abstract

Summary

Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8–11.7) for protein S deficiency, 6.0% (3.9–8.7) for protein C deficiency, 10.0% (6.1–15.4) for antithrombin deficiency, and overall 7.7% (6.1–9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95–2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%, 38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7–2.6) (1 defect) and 1.4 (0.8–2.7) (≥2 defects). Annual incidence was 1.0% (0.03–5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2–1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects.

Keywords

Epidemiology - recurrent venous thromboembolism - thrombophilia

Full Text

References

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