Journal of Blood Medicine (2010) 1: 9–12
Authors: Maristella D’Uva, Pierpaolo Di Micco, Ida Strina, Giuseppe De Placido
Affiliations:
- Department of Obstetrics and Gynecology and Human Reproduction, “Federico II” University of Naples, Italy
- Internal Medicine Division, Buonconsiglio Fatebenefratelli Hospital, Naples, Italy
Correspondence: Pierpaolo Di Micco (pdimicco@libero.it)
Abstract
In recent decades, the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL), has been studied extensively. Although the first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Thromboprophylaxis should be considered also for pregnant subjects carriers of molecular thrombophilia or that previously experienced VTE, in order to prevent VTE during pregnancy, while antithrombotic treatment for VTE should be performed during all pregnant periods.
Keywords: thrombophilia, venous thromboembolism, recurrent pregnancy loss, factor V Leiden
Hypercoagulable state during pregnancy
Recurrent pregnancy loss (RPL) represents a major health problem with two to three or more losses in up to 5% of women of reproductive age and is one of the most common causes of female sterility. Several reports identify inherited predisposition to thrombophilia as one of the main causes of RPL, particularly when other diseases such as endocrine disorders, uterine malformation, chromosomal aberrations, inflammatory or infectious diseases have been excluded.
From a pathological perspective, women affected by thrombophilia show a hypercoagulable state that may impair placental flow, its function, and fetal growth, predisposing to venous thrombosis. Pregnancy itself is a thrombophilic condition, associated with increased levels of clotting factors (VIII, von Willebrand, fibrinogen, VII) and markers such as D-dimer or prothrombin fragment 1+2. Thus, women carrying additional risk factors (e.g., inherited thrombophilia) have higher risk of thrombotic events and abortion.
Occurrence of VTE during pregnancy and its causes
VTE is a multifactorial disease involving acquired and inherited risk factors. Molecular thrombophilia is involved in the pathophysiology of juvenile VTE, whereas pregnancy is recognized as one of the acquired thrombotic risk factors. However, not all pregnant women develop VTE; therefore, an individual risk evaluation is required.
Data from the RIETE registry underline that VTE is more common in the first trimester, and 55% of affected women are carriers of molecular thrombophilia (mainly factor V Leiden and prothrombin A20210G variants). Once therapy is started, recurrences are rare, but bleeding complications are more frequent after delivery.
Treatment of acute VTE during pregnancy
Episodes of acute VTE during pregnancy should be treated as in nonpregnant women, with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), possibly monitored by anti-Xa levels. Due to metabolic changes in pregnancy, plasma concentration and bioavailability of heparins may vary.
RIETE data show that most cases were treated with LMWH (≈80%), UFH (≈10%), vena cava filters (≈4%), or thrombolysis (≈1%). Antivitamin K drugs were used for long-term therapy in 20% of cases. Anticoagulant therapy should be continued until delivery and restarted postpartum to prevent recurrence.
Thrombophilia and thromboprophylaxis during pregnancy
Thromboprophylaxis can be primary (no prior VTE) or secondary (previous VTE).
- Primary prophylaxis is recommended after Cesarean section and during puerperium.
- It is also suggested for asymptomatic pregnant women with conditions such as antithrombin deficiency, combined thrombophilic defects, or family history of severe juvenile VTE.
- Secondary prophylaxis is indicated for women with a prior VTE, using UFH or LMWH, especially if other risk factors (bed rest, surgery, obesity, autoimmune disease, infection, nephrotic syndrome, preeclampsia) are present.
Prophylaxis should continue for 6–8 weeks postpartum due to high risk of VTE in the first weeks after delivery.
Conclusion
VTE is a multifactorial disease that remains a significant cause of maternal morbidity and mortality. Despite the lack of large-scale trials including pregnant women, evidence supports a key role for molecular thrombophilia in VTE during pregnancy and confirms the efficacy and safety of anticoagulant therapy. Risk-based prophylaxis is recommended, especially for high-risk patients, pending further studies.
References
(1–23, complete as in the paper — from Sarig G. et al., Fertil Steril 2002; through Brill-Edwards P. et al., N Engl J Med 2000.)