Professor Dr Jan van der Meer recently passed away following a sudden illness.
A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin
Article first published online: 4 MAR 2010
© 2010 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 8, Issue 6, pages 1193–1200, June 2010
How to Cite
MAHMOODI, B. K., BROUWER, J.-L. P., TEN KATE, M. K., LIJFERING, W. M., VEEGER, N. J. G. M., MULDER, A. B., KLUIN-NELEMANS, H. C. and VAN DER MEER, J. (2010), A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. Journal of Thrombosis and Haemostasis, 8: 1193–1200. doi: 10.1111/j.1538-7836.2010.03840.x
Presented as an oral communication at the session of ‘Genetic Thrombophilia: Clinical Applications’ on 13 July 2009 at the ISTH congress in Boston, MA, USA.
- Issue published online: 7 JUN 2010
- Article first published online: 4 MAR 2010
- Received 8 December 2009, accepted 19 February 2010
- thrombosis risk factors;
- venous thrombosis
See also Keeling D. Thrombophilia screening or screaming. This issue, pp 1191–2.
Summary. Background: Absolute risks of venous thromboembolism (VTE) in protein S-, protein C-, or antithrombin-deficient subjects are mainly based on retrospective data. Screening asymptomatic relatives of these patients is disputed, though studies addressing this issue have yet to be conducted. Methods: We prospectively followed 382 relatives of 84 probands. Participants were assessed for other thrombophilic defects and occurrence of exogenous risk factors (i.e. surgery/trauma/immobilization, malignancies, use of systemic estrogens, and pregnancy/puerperium). After screening, deficient subjects were advised to use thromboprophylaxis during exogenous risk factors; use of oral contraceptives was discouraged. Results: Overall annual incidence of VTE was 1.53% (95% CI, 1.00–2.34) in deficient vs. 0.29% (0.13–0.64) in non-deficient relatives; adjusted hazard ratio, 7.0 (95% CI, 2.7–18.0). Annual incidence of unprovoked VTE was 0.95% in deficient vs. 0.05% in non-deficient subjects; age-adjusted hazard ratio, 22.3 (P = 0.003). In contrast, annual incidence of provoked VTE was 0.58% vs. 0.24%; age-adjusted hazard ratio, 2.8 (P = 0.08). Fifty-five (37%) deficient and 80 (34%) non-deficient subjects experienced 91 and 143 exogenous risk factors, respectively, during which six vs. five VTEs (6.6% vs 3.5% per risk-period) occurred, despite the higher compliance with recommended thromboprophylaxis use in deficient (51%) vs. non-deficient (22%) subjects. In deficient subjects all provoked VTEs occurred when thromboprophylaxis was not used. Conclusions: Protein S, protein C or antithrombin deficiencies confer high absolute risk of VTE. Screening and subsequent augmentation of thromboprophylaxis use may result in reduction of provoked VTE, whereas risk of unprovoked VTE could not be affected by screening.