Problem: Inherited thrombophilia has been shown to be a risk factor for cardiovascular disease including deep venous thrombosis as well as reproductive disorders including recurrent pregnancy loss. We have previously reported three out of the 10 thrombophilic mutations studied, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, factor XIII V34L, and homozygous MTHFR C667T, correlated significantly with recurrent pregnancy loss compared with controls. This study was undertaken to compare the frequencies of nine inherited thrombophilias among women with a history of recurrent pregnancy loss with individuals experiencing deep venous thrombosis and fertile controls.
Method of study: Six hundred thirty-four participants including 550 women with a history of recurrent pregnancy loss, 43 individuals with deep vein thrombosis and 41 fertile women without a history of recurrent miscarriage. All participants had buccal swabs taken for DNA analyses of nine gene polymorphisms including factor V G1691A, factor V H1299R (R2), factor II Prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, human platelet antigen 1 a/b (L33P), MTHFR C677T, MTHFR A1298C. Frequencies of thrombophilic gene polymorphisms were compared among the three populations studied.
Results: Individuals with a history of DVT had a significantly higher frequency of all of the polymorphisms studied compared with women experiencing a history of recurrent pregnancy loss and the fertile controls. The frequencies of mutations for V34L and PAI-1 4G/5G were significantly increased among women experiencing recurrent pregnancy loss compared with controls. The most prevalent polymorphisms were factor XIII V34L and PAI-1 4G/4G for both individuals with a history of deep vein thrombosis and recurrent pregnancy loss compared with controls.
Conclusion: Screening for risk factors for inherited thrombophilia with only polymorphisms for factor V von Leiden, factor II prothrombin and MTHFR may be missing the more prevalent identifiers of jeopardy.