Gestational Vascular Complications Research Articles

Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications – Yes

Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications – Yes

Gestational vascular complications

Severe pregnancy complications, primarily severe pre-eclampsia, placental abruption, intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) occur in about 1–5% of gestations. This rate is even higher in special medical situations. These pregnancy complications have been shown to increase maternal and fetal morbidity and mortality considerably. Severe pregnancy complications have also been shown to be associated with deficient uteroplacental circulation and are linked with intervillous and spiral vessel thrombosis. Moreover, it has been suggested that these complications could have their basis in a deficient trophoblast invasion in the uterine spiral arteries at a stage much earlier than the clinical manifestations become evident. In the last few years, evidence has accumulated to suggest that severe pregnancy complications could have a common thrombogenic basis associated with inherited and acquired thrombophilia. In this chapter we present a comprehensive update of the aetiology, pathophysiology, clinical manifestations, diagnosis and treatment of these severe pregnancy complications.

Inherited thrombophilia and poor pregnancy outcome

Gestational vascular complications are a major cause of maternal and fetal morbidity. A growing body of evidence suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. While the majority of women with thrombophilia will have an uneventful gestation, case–control studies demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss and early-onset pre-eclampsia. Placental abruption and severe intrauterine growth restriction (IUGR) may also be associated with thrombophilia. Placental pathological findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition potentially to a greater degree than in normal pregnancy. Preliminary non-randomized studies suggest a benefit for prophylaxis with unfractionated and low-molecular-weight heparin (LMWH), and prospective randomized trials are in progress to define whether LMWH is effective in preventing pregnancy loss and other gestational vascular complications in women with thrombophilia and previous fetal wastage.

Inherited Thrombophilia and Gestational Vascular Complications

Severe obstetric complications, including preeclampsia, intrauterine growth retardation, abruptio placentae, and stillbirth, constitute a major cause of maternal and perinatal morbidity and death. The etiology of these severe obstetric complications is still unknown. However, the frequent finding of structural and thrombotic changes in placental capillaries, which lead to inadequate fetomaternal circulation and decreased placental perfusion, and the high prevalence of heritable or acquired risk factors for thrombosis found in women with these complications strongly suggest a cause-and-effect relationship. This review describes the recent findings on the association between these obstetric complications and the various thrombophilias, and recent therapeutic approaches. Aspirin, which was regarded as the drug of choice for the prevention of such obstetric complications, has proved to be ineffective in a large clinical trial. The encouraging observations on the efficacy of low-molecular-weight heparins, which are also included in the recently published guidelines of The American College of Chest Physicians, are summarized in this review. However, controlled clinical trials are still necessary to allow the development of better clinical standards.

Thrombophilia and fetal loss.

A large body of evidence obtained during the last 6 years suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. Case-control studies demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss. Other complications such as preeclampsia, placental abruption, and intrauterine growth retardation may also be associated with thrombophilia. Placental pathologic findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition. Preliminary case-control studies suggest that low-molecular-weight heparins are effective in preventing pregnancy loss in women with thrombophilia and previous fetal wastage.

Inherited thrombophilia and fetal loss.

Acquired thrombophilia is a well-established cause of pregnancy loss. Increasing numbers of recent observations suggest that inherited thrombophilia is not only associated with gestational thromboembolism but is also a major cause of fetal loss. This review focuses on association of fetal loss with inherited thrombophilias, including dysfibrinogenemia and protein C, protein S, and antithrombin III deficiencies. Activated protein C resistance and factor V Leiden mutation are frequent causes of pregnancy loss. Thrombophilic states such as factor V Leiden and hyperhomocysteinemia may also play a role in other gestational vascular complications, including intrauterine growth restriction, preeclampsia, and placental abruption. Preliminary reports suggest that antithrombotic therapy may be of value in this setting. The potential application of antithrombotic modalities to prevent fetal loss in women with thrombophilia is discussed.