Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Screening for identified and unidentified protein C pathway defects by the Agkistrodon contortrix venom test in consecutive patients.

To determine the real performance of the Agkistrodon contortrix venom (ACV) screening test for protein C (PC) pathway defects, we studied 400 consecutive patients referred for the study of personal venous thrombosis or for family study. All 82 patients with factor V Arg 506 Gln (FV R506Q) (n = 82), 6 patients with activated PC resistance without FV R506Q, 17 patients with PC deficiencies, and 9 patients with combined defects were identified by an abnormal ACV result. Three of 6 protein S deficiencies overlapped the normal range. Among the 280 patients without a PC pathway defect, 63 of 193 with thrombosis and 18 of 87 asymptomatic subjects (relatives of patients with thrombosis) had an abnormal ACV result. A significant linear inverse relationship was observed between the ACV results and factor VIII. However, 31 of 63 patients (49%) with thrombosis and 15 of 18 (83%) asymptomatic subjects with an abnormal ACV had a normal factor VIII level. This test, with a 100% negative predictive value, is reliable for screening for PC deficiencies and for FV R506Q and can be used safely as an exclusion test. Moreover, the test may be useful to indicate, in the PC pathway, unidentified risk factors for venous thrombosis.