TY - JOUR
T1 - Selective testing for thrombophilia in patients with first venous thrombosis
T2 - results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives
AU - Lijfering, Willem M.
AU - Brouwer, Jan-Leendert P.
AU - Veeger, Nic J. G. M.
AU - Bank, Ivan
AU - Coppens, Michiel
AU - Middeldorp, Saskia
AU - Hamulyak, Karly
AU - Prins, Martin H.
AU - Bueller, Harry R.
AU - van der Meer, Jan
PY - 2009/5/21
Y1 - 2009/5/21
N2 - Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis. (Blood. 2009; 113: 5314-5322)
AB - Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis. (Blood. 2009; 113: 5314-5322)
KW - DEEP-VEIN THROMBOSIS
KW - FACTOR-V-LEIDEN
KW - ACTIVATED PROTEIN-C
KW - ARTERIAL THROMBOSIS
KW - PULMONARY-EMBOLISM
KW - FACTOR-VIII
KW - THROMBOEMBOLISM
KW - MUTATION
KW - DEFICIENCY
KW - CARRIERS
U2 - 10.1182/blood-2008-10-184879
DO - 10.1182/blood-2008-10-184879
M3 - Article
VL - 113
SP - 5314
EP - 5322
JO - Blood
JF - Blood
SN - 0006-4971
IS - 21
ER -