Advertisement

Management of Venous Thromboembolism in Pregnancy

  • Annemarie E. Fogerty
Pregnancy and Cardiovascular Disease (N Scott, Section Editor)
  • 426 Downloads
Part of the following topical collections:
  1. Topical Collection on Pregnancy and Cardiovascular Disease

Abstract

Purpose of review

This manuscript addresses the risks for venous thromboembolism (VTE) during pregnancy and the associated challenges of both diagnosis and treatment.

Recent findings

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.

Summary

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.

Keywords

Pregnancy Thrombosis Anticoagulation Pulmonary embolism Deep venous thrombosis Diagnosis 

Notes

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

  1. 1.
    Fogerty AE. Challenges of anticoagulation therapy in pregnancy. Curr Treat Options Cardiovasc Med. 2017;19(1D):76.CrossRefPubMedGoogle Scholar
  2. 2.
    Chan WS, Spencer FA, Ginsberg JS. Anatomic distribution of deep vein thrombosis in pregnancy. CMAJ. 2010;182:657–60.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wan T, Skeith L, Karovitch A, Rodger M, Le Gal G. Guidance for the diagnosis of pulmonary embolism during pregnancy: consensus and controversies. Thromb Res. 2017;157:23–8.CrossRefPubMedGoogle Scholar
  4. 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
  5. 5.
    Touhami O, Marzouk SB, Bennasr L, Touaibia M, Souli I, Felfel MA, et al. Are the wells score and the revised Geneva score valuable for the diagnosis of pulmonary embolism in pregnancy? Eur J Obstet Gynecol Reprod Biol. 2018;221:166–71.CrossRefPubMedGoogle Scholar
  6. 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. 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
  8. 8.
    Salim R, Nachum Z, Gavish I, Romano S, Braverman M, Garmi G. Adjusting enoxaparin dosage according to anti-Xa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial. Thromb Haemost. 2016;116(4):687–95.PubMedGoogle Scholar
  9. 9.
    Petrie S, Barras M, Lust K, Fagermo N, Allen J, Martin JH. Evaluation of therapeutic enoxaparin in a pregnant population at a tertiary hospital. Inter Med J. 2016;46(7):826–33.CrossRefGoogle Scholar
  10. 10.
    Rodger MA, Kahn SR, Cranney A, Hodsman A, Kovacs MJ, Clement AM, et al. TIPPS investigators. Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: a substudy of a randomized controlled trial. J Thromb Haemost. 2007;5(8):1600–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Patil AS, Clapp T, Gaston PK, Kuhl D, Rinehart E, Meyer NL. Increased unfractionated heparin requirements with decreasing body mass index in pregnancy. Obstet Med. 2016;9(4):156–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Dahlman T, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum. Br J Obstet Gynaecol. 1990;97(3):221–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Dahlman TC. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin. Am J Obstet Gynecol. 1993;168(4):1265–70.CrossRefPubMedGoogle Scholar
  14. 14.
    Pettila V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost. 2002;87(2):182–6.CrossRefPubMedGoogle Scholar
  15. 15.
    De Carolis S, di Pasquo E, Rossi E, Del Sordo G, Buonomo A, Schiavino D, et al. Fondaparinux in pregnancy: could it be a safe option? A review of the literature. Thromb Res. 2015;135(6):1049–51.CrossRefPubMedGoogle Scholar
  16. 16.
    Dempfle CE. Minor transplacental passage of fondaparinux in vivo. N Engl J Med. 2004;350:1914–5. (Letter)CrossRefPubMedGoogle Scholar
  17. 17.
    Chaudhary RK, Nepal C, Khanal N, et al. Management and outcome of heparin-induced thrombocytopenia in pregnancy: a systematic review. Cardiovasc Hematol Agents Med Chem. 2015;13:92–7.CrossRefPubMedGoogle Scholar
  18. 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. 19.
    Bivalirudin [package insert]. The Medicines Company Parsippany, NJ.Google Scholar
  20. 20.
    Argatroban [package insert]. Pfizer. New York, NY.Google Scholar
  21. 21.
    Beyer-Westendorf J, Michalski F, Tittl L, Middeldorp S, Cohen H, Abdul Kadir R, et al. Pregnancy outcome in patients exposed to direct oral anticoagulants – and the challenge of event reporting. Thromb Haemost. 2016;116(4):651–8.PubMedGoogle Scholar
  22. 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. 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
  24. 24.
    Leonhardt G, Gaul C, Nietsch HH, Buerke M, Schleussner E. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis. 2006;21(3):271–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Gomes S, Guimaraes M, Montenegro N. Thrombolysis in pregnancy: a literature review. J Matern Fetal Neonatal Med. 2018.Google Scholar
  26. 26.
    Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv. 1995;50(7):534–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Pfeifer GW. Distribution studies and placental transfer of 131 I streptokinase. Australas Ann Med. 1970;19(Suppl 1):17–8.CrossRefPubMedGoogle Scholar
  28. 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
  29. 29.
    Rheaume M, Weber F, Durand M, Mahone M. Pregnancy-related venous thromboembolism risk in asymptomatic women with antithrombin deficiency: a systemic review. Obstet Gynecol. 2016;127(4):649–56.CrossRefPubMedGoogle Scholar
  30. 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
  31. 31.
    Paidas MJ, Triche EW, James AH, DeSancho M, Robinson C, Lazarchick J, et al. Recombinant human antithrombin in pregnant patients with hereditary antithrombin deficiency: integrated analaysis of clinical data. Am J Perinatol. 2016;33(4):343–9.PubMedGoogle Scholar
  32. 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
  33. 33.
    Crosby DA, Ryan K, McEniff N, Dicker P, Regan C, Lynch C, et al. Retrievable inferior vena cava filters in pregnancy: risk versus benefit? Eur J Obstet Gynecol Reprod Biol. 2018;222:25–30.CrossRefPubMedGoogle Scholar
  34. 34.
    Harris SA, Velineni R, Davies AH. Inferior Vena Cava Filters in Pregnancy: a Systemic Review. J Vasc Interv Radiol. 2016;27:354–60.CrossRefPubMedGoogle Scholar
  35. 35.
    Vedantham S, ATTRACT Trial Investigators, et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. NEJM. 2017;377:2240–52.CrossRefPubMedGoogle Scholar
  36. 36.
    Boilot T, Raia-Barjat T, Ollier E, Chapelle C, Laporte S, Chauleur C. Influence of anticoagulant therapy during pregnancy on the peripartum and anesthesia delivery terms. Gynec Obstet Fertil. 2015;43(7-8):502–8.CrossRefGoogle Scholar
  37. 37.
    Wang EHZ, Marnoch CA, Khurana R, Sia W, Yuksel N. Haemorrhagic complications of peripartum anticoagulation: a retrospective chart review. Obstet Med. 2014;7(2):77–83.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    James A, Committee on Practice Bulletins – Obstetrics. Practice Bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol. 2011;118(3):718–29.CrossRefPubMedGoogle Scholar
  39. 39.
    Branch DW, Holmgren C, Goldberg JD, Committee on Practice Bulletins – Obstetrics. Practice Bulletin no. 132: antiphospholipid antibody syndrome. Obstet Gynecol. 2012;120(6):1514–21.CrossRefGoogle Scholar
  40. 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
  41. 41.
    Chan WS, Rey E, Kent NE, VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36(6):527–53.CrossRefPubMedGoogle Scholar
  42. 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. 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. 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

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Massachusetts General HospitalBostonUSA

Personalised recommendations