Management of Venous Thromboembolism in Pregnancy
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Purpose of review
This manuscript addresses the risks for venous thromboembolism (VTE) during pregnancy and the associated challenges of both diagnosis and treatment.
The obstacles to diagnosis given lack of specificity of typical biomarkers to predict VTE in pregnancy, as well as the unique fetal and bleeding risks introduced by managing massive pulmonary embolism (PE) with thrombolytics or thrombectomy are highlighted.
VTE during pregnancy and the postpartum window occurs at a 6–10-fold higher rate compared with age-matched peers and is a major cause of morbidity and mortality. Hypercoagulability persists for 6–8 weeks after delivery with the highest risk of PE being postpartum. The lack of randomized trials in pregnant women leads to variability in practice, which are largely based on expert consensus or extrapolation from non-pregnant cohorts. The standard treatment of VTE in pregnancy is anticoagulation with low molecular weight heparin (LMWH), which like unfractionated heparin does not cross the placenta and is not teratogenic. LMWH is preferred given the negligible risk for heparin-induced thrombocytopenia and osteoporosis, better bioavailability, and a predictive dose response. Depending on the severity of the VTE, additional treatments including thrombolysis, thrombectomy, inferior vena cava filter placement, or venous stenting may be used. Management requires balancing the competing bleeding and thrombotic risks during labor and delivery and factoring the impact of treatment on the fetus. A multidisciplinary team involving hematology, obstetrics, anesthesia, vascular medicine, and cardiology is critical for safe and timely management. The design and execution of prospective, randomized trials to specifically address optimal diagnosis and management are a top priority in obstetric hematology.
KeywordsPregnancy Thrombosis Anticoagulation Pulmonary embolism Deep venous thrombosis Diagnosis
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 4.• Hunt BJ, Parmar K, Horspool K, Shepard N, Nelson-Piercy C, Goodacre S. DiPEP research group. The DiPEP (diagnosis of PE in pregnancy) biomarker study: an observational cohort study augmented with additional cases to determine the diagnostic utility of biomarkers for suspected venous thromboembolism during pregnancy and puerperium. Br J Haematol. 2018;180(5):694–704. Recent publication demonstrating the difficulty in diagnosing PE in pregnancy due to significant overlap of traditional biomarkers in normal pregnancies and cases of PE in pregnancy.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Leung AN, Bull TN, Jaeschke R, Lockwood CJ, Boiselle PM, Hurwitz LM, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med. 2011;184:1200–8.CrossRefPubMedGoogle Scholar
- 7.• McDonnell BP, Glennon K, McTiernan A, O’Connor HD, Kirkham C, Kevane B, et al. Adjustment of therapeutic LMWH to achieve specific target anti-Xa activity does not affect outcomes in pregnant patients with venous thromboembolism. J Thromb Thrombolysis. 2017;43(1):105–11. Recent publication showing that routine monitoring of the anti-Xa activity in pregnant women managed with LMWH does not affect clinical outcomes.CrossRefPubMedGoogle Scholar
- 18.Syme MR, Paxton JW, Keelan HA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004;43(8):487–514.Google Scholar
- 19.Bivalirudin [package insert]. The Medicines Company Parsippany, NJ.Google Scholar
- 20.Argatroban [package insert]. Pfizer. New York, NY.Google Scholar
- 22.Hoeltzenbein M, Beck E, Meixner K, Schaefer C, Kreutz R. Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in women at suspected risk for thromboembolic events: a case series from the German Embryotox Pharmacovigilance Centre. Clin Res Cardiol. 2016;105(2):117–26.CrossRefPubMedGoogle Scholar
- 23.Wiessen MH, Blaich C, Muller C, Streichert T, Pfister R, Michels G. The direct factor Xa inhibitor rivaroxaban passes into human breast milk. Chest. 2016;150(1):e1–4.Google Scholar
- 25.Gomes S, Guimaraes M, Montenegro N. Thrombolysis in pregnancy: a literature review. J Matern Fetal Neonatal Med. 2018.Google Scholar
- 28.• Martillotti G, Boehlen F, Robert-Edabi H, Jastrow N, Righini M, Blondon M. Treatment options for severe pulmonary embolism during pregnancy and the postpartum period: a systemic review. J Thromb Haemost. 2017;15(10):1942–50. Recent review comparing outcomes of thrombolysis and thrombectomy in pregnant women with massive PE demonstrating slight improvement in maternal and fetal mortality with thrombolysis, but more postpartum hemorrhage.CrossRefPubMedGoogle Scholar
- 30.Refaei M, Xing L, Lim W, Crowther M, Boonyawat K. Management of venous thromboembolism in patients with hereditary antithrombin deficiency and pregnancy: case report and review of the literature. Case Rep Hematol. 2017. Article ID 9261351.Google Scholar
- 32.Rottenstreich A, Kalish Y, Elchalal U, Klimov A, Bloom A. Retrievable inferior vena cava filter utilization in obstetric patients. J Matern Fetal Neonatal Med. 2018.Google Scholar
- 40.Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S–736S.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/. Accessed 10 June 2015.
- 43.Royal College of Obstetricians and Gynaecologists (2015) Green-top Guideline No. 37b. Thrombotic disease in pregnancy and the puerperium: acute management. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37b/. Accessed 10 June 2015.
- 44.McIntock C, Brighton T, Chunilal S, Dekker G, McDonnell N, McRae S, et al. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. ANZJOG. 2012;52:14–22.Google Scholar