Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives.
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.
Lijfering
Willem M
WM
Department of Hematology, University Medical Center Groningen, The Netherlands. w.lijfering@int.umcg.nl
Brouwer
Jan-Leendert P
JL
Veeger
Nic J G M
NJ
Bank
Ivan
I
Coppens
Michiel
M
Middeldorp
Saskia
S
Hamulyák
Karly
K
Prins
Martin H
MH
Büller
Harry R
HR
van der Meer
Jan
J
D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics; D020147:Coagulation Protein Disorders / Q000235:genetics; D015331:Cohort Studies; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D012306:Risk; D019851:Thrombophilia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000453:epidemiology* / Q000209:etiology*
D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors