Value of family history in identifying women at risk of venous thromboembolism during oral contraception: observational study

Participants, methods, and results

We prospectively evaluated a cohort of women (age range 15–49 years) consecutively referred to our thrombophilia unit by gynaecologists at family planning clinics in Bologna, Italy, between 1998 and 2000. The gynaecologists had established that the women were eligible to take oral contraceptives and had no history of venous thromboembolism. Before the women were screened, experienced investigators administered a modified structured questionnaire3 that was designed and validated to evaluate both personal and family history (first degree=parents and siblings, second degree=grandparents, aunts, uncles, and cousins) of venous thromboembolism (see BMJ's website for details). We considered family history positive if a thromboembolism was reported in any first or second degree relatives.

Thrombophilia screening was conducted as previously described.4 Prothrombin activity was measured by chromogenic assay5 and lupus anticoagulant by LA-test and LA-check assays (Organon Teknika, Rome, Italy). If prothrombin activity was confirmed to be above 1.10 U/ml, we analysed the DNA for the G20120A mutation according to the method of Poort et al.5 The tests were performed by staff blind to the results of the questionnaire.

We calculated sensitivity and positive predictive values according to standard methods. The 95% confidence intervals for proportions were calculated by an approximate method, and we used the χ² test when appropriate. A two sided probability value <0.05 was considered significant. All data were analysed with the statistical package SOLO (BMDP, Los Angeles).

We evaluated 324 women (mean age 34 years) who had a negative personal history for venous thromboembolism confirmed by our questionnaire. Thirty four women reported a positive family history (10%, 95% confidence interval 7% to 14%), of whom two were heterozygous for factor V Leiden and one had protein S deficiency. Thrombophilic defects were identified in 19 women (6%, 3% to 8%), only three of whom had a positive family history. Among the 290 women with a negative family history, thrombophilic defects were detected in 16 (6%, 3% to 8%); eight were heterozygous for factor V Leiden and eight were heterozygous for the G20120A mutation.

The table shows the sensitivity and positive predictive value of family history for identifying thrombophilic defects. The proportion of women with thrombophilia was similar among those with a positive history and those with a negative history of venous thromboembolism when first and second degree family history was considered (9% (3/34) v 5% (16/290), P=0.44) and when only first degree family history was considered (8% (2/26) v 6% (17/298), P=0.68).

Comment

Family history of venous thromboembolism has unsatisfactory sensitivity and positive predictive value for identifying carriers of common thrombophilic defects before taking oral contraceptives. A policy of selective screening may therefore miss a substantial number of women at increased risk of thromboembolism when taking oral contraceptives.