Thrombophilia is a disorder involving the genetic predisposition to form a blood clot (deep venous or arterial thrombosis) potentially leading to stroke, heart attack or pulmonary embolus. Thrombophilia may also lead to clotting of the arterial or venous blood supply to an organ such as the kidney or in cases involving pregnancy, the placenta. The growth of a successful pregnancy depends on an adequate blood supply from the mother through her baby’s placenta. Therefore if the blood vessels on the maternal side of the placenta become clotted termed thrombosed, then the baby is unlikely to get an adequate blood supply leading to being small for gestational age, growth restricted, or in severe cases could cause fetal death. Thombophilia is not a cause of infertility and women with thrombophilic defects can have normal pregnancies. Thrombophilia, however, is considered a significant risk factor for recurrent pregnancy loss especially after the first trimester. Timing of fetal demise among women with pregnancy loss provides diagnostic clues since thormbophilias are not likely to be involved in miscarriages before 10 weeks of gestation and are most commonly associated with pregnancy complications later during the second trimester and early third trimester of pregnancy.
The inherited thrombophilias most often associated with recurrent pregnancy loss include hyperhomocyteinemia, activated protein C resistance associated with mutations in factor V, deficiencies in proteins C and S, mutations in the prothrombin gene promoter, mutations in prothrombin, and mutations in antithrombin III. These inherited disorders are mainly autosomal dominant and display a wide variation of how they may manifest a particular disorder in the person carrying these genes. These genes are also widely present in the general healthy population, between 2% to 15% depending on the study; so the mere presence of one of these mutations in women with recurrent pregnancy loss does not necessarily mean that it is the reason for their losses. Thrombotic events not surprisingly are more common in individuals having combinations of two or more of these inherited genes. Up to 50% of women who have a pulmonary embolus during pregnancy due to deep venous thrombosis have genetically acquired thrombophila as represented by having one or more of these thrombophilic mutations.