Subscribe to RSS
DOI: 10.1055/s-0041-1736188
Approach to the Evaluation and Treatment of Venous Thromboembolism in Pregnancy
Abstract
Thrombosis in pregnancy is a major cause of maternal and fetal morbidity and mortality. Risk stratification of venous thromboembolism (VTE) during pregnancy is complex. The hypercoagulability observed in pregnant women can reduce bleeding during childbirth, but may cause thrombosis especially in the presence of additional prothrombotic risk factors such as antiphospholipid antibodies or genetic thrombophilic defects. The availability of large datasets allows for the identification of additional independent risk factors, including assisted reproductive technologies (ARTs), endometriosis, and recurrent pregnancy loss. Data on the risk of VTE linked to COVID-19 in pregnant women are very limited, but suggest that infected pregnant women have an increased risk of VTE. Current guidelines on the prevention and treatment of VTE in pregnancy are based on available, albeit limited, data and mainly present expert opinion. Low-molecular-weight heparins (LMWHs) are the mainstay of anticoagulation to be employed during pregnancy. Administration of LMWH for VTE treatment in pregnancy should be based on the personalized approach, taking into account a weight-based adjusted scheme. During gestation, due to physiological changes, in women at high risk of VTE, monitoring of anti-Xa activity is performed to ensure adequate LMWH dosing. As for the treatment duration for pregnant women with acute VTE, guidelines suggest that anticoagulation should be continued for at least 6 weeks postpartum for a minimum total duration of therapy of 3 months.
Publication History
Article published online:
24 September 2021
© 2021. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev 2021; 3: CD001689
- 2 Sarig G, Klil-Drori AJ, Chap-Marshak D, Brenner B, Drugan A. Activation of coagulation in amniotic fluid during normal human pregnancy. Thromb Res 2011; 128 (05) 490-495
- 3 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium–a register-based case-control study. Am J Obstet Gynecol 2008; 198: 233 , e231–237
- 4 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
- 5 Aharon A, Brenner B, Katz T, Miyagi Y, Lanir N. Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis. Thromb Haemost 2004; 92 (04) 776-786
- 6 Boer K, den Hollander IA, Meijers JC, Levi M. Tissue factor-dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery. J Thromb Haemost 2007; 5 (12) 2415-2420
- 7 Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014; 370 (14) 1307-1315
- 8 Wik HS, Jacobsen AF, Fagerland MW, Sandvik L, Sandset PM. Long-term mortality and incidence of cancer after pregnancy-related venous thrombosis: results of a population-based cohort study. Thromb Res 2013; 131 (06) 497-501
- 9 Wik HS, Jacobsen AF, Mowinckel MC, Sandset PM. The role of inflammation in post-thrombotic syndrome after pregnancy-related deep vein thrombosis: a population-based, cross-sectional study. Thromb Res 2016; 138: 16-21
- 10 Robertson L, Greer I. Thromboembolism in pregnancy. Curr Opin Obstet Gynecol 2005; 17 (02) 113-116
- 11 Robertson L, Wu O, Langhorne P. et al; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132 (02) 171-196
- 12 Gerhardt A, Scharf RE, Greer IA, Zotz RB. Hereditary risk factors for thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium. Blood 2016; 128 (19) 2343-2349
- 13 Sennström M, Rova K, Hellgren M. et al. Thromboembolism and in vitro fertilization - a systematic review. Acta Obstet Gynecol Scand 2017; 96 (09) 1045-1052
- 14 Henriksson P, Westerlund E, Wallén H, Brandt L, Hovatta O, Ekbom A. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study. BMJ 2013; 346: e8632
- 15 [Anonymous] National Institute for Health and Care Excellence (2021). Risk factors for venous thromboembolism in pregnancy (NICE guideline tbc. Evidence reviews underpinning recommendations 1.2.16 and 1.2.17). Accessed July 2021 at: https://www.nice.org.uk/guidance/GID-NG10096/documents/evidence-review-7
- 16 Kane EV, Calderwood C, Dobbie R, Morris C, Roman E, Greer IA. A population-based study of venous thrombosis in pregnancy in Scotland 1980-2005. Eur J Obstet Gynecol Reprod Biol 2013; 169 (02) 223-229
- 17 Lindqvist P, Dahlbäck B, Marŝál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94 (04) 595-599
- 18 Sultan AA, Tata LJ, West J. et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood 2013; 121 (19) 3953-3961
- 19 Sugiura-Ogasawara M, Ebara T, Matsuki T. et al; The Japan Environment & Children's Study (JECS) Group. Endometriosis and recurrent pregnancy loss as new risk factors for venous thromboembolism during pregnancy and post-partum: the JECS birth cohort. Thromb Haemost 2019; 119 (04) 606-617
- 20 Wu Q, Ding D, Liu X, Guo SW. Evidence for a hypercoagulable state in women with ovarian endometriomas. Reprod Sci 2015; 22 (09) 1107-1114
- 21 Brenner B. Haemostatic changes in pregnancy. Thromb Res 2004; 114 (5-6): 409-414
- 22 Sciascia S, Bertolaccini ML. Thrombotic risk assessment in APS: the Global APS Score (GAPSS). Lupus 2014; 23 (12) 1286-1287
- 23 Grandone E, Di Micco PP, Villani M. et al; RIETE Investigators. Venous thromboembolism in women undergoing assisted reproductive technologies: data from the RIETE registry. Thromb Haemost 2018; 118 (11) 1962-1968
- 24 Chan WS, Spencer FA, Ginsberg JS. Anatomic distribution of deep vein thrombosis in pregnancy. CMAJ 2010; 182 (07) 657-660
- 25 Barillari G, Londero AP, Brenner B. et al; RIETE Investigators. Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: findings from the RIETE registry. Eur J Intern Med 2016; 32: 53-59
- 26 Sarig G, Vidergor G, Brenner B. Assessment and management of high-risk pregnancies in women with thrombophilia. Blood Rev 2009; 23 (04) 143-147
- 27 Chauleur C, Quenet S, Varlet MN. et al. Feasibility of an easy-to-use risk score in the prevention of venous thromboembolism and placental vascular complications in pregnant women: a prospective cohort of 2736 women. Thromb Res 2008; 122 (04) 478-484
- 28 Chauleur C, Gris JC, Laporte S. et al; STRATHEGE Investigators and The STRATHEGE Group. Benefit of risk score-guided prophylaxis in pregnant women at risk of thrombotic events: a controlled before-and-after implementation study. Thromb Haemost 2018; 118 (09) 1564-1571
- 29 Sultan AA, West J, Grainge MJ. et al. Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study. BMJ 2016; 355: i6253
- 30 Bauersachs RM, Dudenhausen J, Faridi A. et al; EThIG Investigators. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost 2007; 98 (06) 1237-1245
- 31 Gutiérrez García I, Pérez Cañadas P, Martínez Uriarte J, García Izquierdo O, Angeles Jódar Pérez M, García de Guadiana Romualdo L. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest 2018; 78 (06) 439-442
- 32 Ercan Ş, Özkan S, Yücel N, Orçun A. Establishing reference intervals for D-dimer to trimesters. J Matern Fetal Neonatal Med 2015; 28 (08) 983-987
- 33 Refaai MA, Riley P, Mardovina T, Bell PD. The clinical significance of fibrin monomers. Thromb Haemost 2018; 118 (11) 1856-1866
- 34 Hunt BJ, Parmar K, Horspool K, Shephard 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 (05) 694-704
- 35 de Haan HG, van Hylckama Vlieg A, Lotta LA. et al; INVENT Consortium. Targeted sequencing to identify novel genetic risk factors for deep vein thrombosis: a study of 734 genes. J Thromb Haemost 2018; 16 (12) 2432-2441
- 36 Righini M, Robert-Ebadi H, Elias A. et al; CT-PE-Pregnancy Group. Diagnosis of pulmonary embolism during pregnancy: a multicenter prospective management outcome study. Ann Intern Med 2018; 169 (11) 766-773
- 37 van der Pol LM, Tromeur C, Bistervels IM. et al; Artemis Study Investigators. Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. N Engl J Med 2019; 380 (12) 1139-1149
- 38 Cohen SL, Feizullayeva C, McCandlish JA. et al. Comparison of international societal guidelines for the diagnosis of suspected pulmonary embolism during pregnancy. Lancet Haematol 2020; 7 (03) e247-e258
- 39 Palmerola KL, D'Alton ME, Brock CO, Friedman AM. A comparison of recommendations for pharmacologic thromboembolism prophylaxis after caesarean delivery from three major guidelines. BJOG 2016; 123 (13) 2157-2162
- 40 Gassmann N, Viviano M, Righini M, Fontana P, Martinez de Tejada B, Blondon M. Estimating the risk thresholds used by guidelines to recommend postpartum thromboprophylaxis. J Thromb Haemost 2021; 19 (02) 452-459
- 41 Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 92-128
- 42 Omunakwe HE, Roberts LN, Patel JP, Subramanian D, Arya R. Re: A comparison of the recommendations for pharmacologic thromboembolism prophylaxis after caesarean delivery from the major guidelines: impact on thromboprophylaxis rates of implementing Royal College of Obstetricians and Gynaecologists' guidance for reducing the risk of ante- and postnatal venous thromboembolism. BJOG 2017; 124 (05) 831-832
- 43 [Anonymous] Royal College of Obstetricians & Gynaecologists. Thrombosis and Embolism during Pregnancy and the Puerperium, Reducing the Risk. 2015 . Accessed December 2018 at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/
- 44 [Anonymous] MBRACE-UK: saving lives, improving mothers' care. Accessed May 2019 at: https://www.npeu.ox.ac.uk/downloads/files/mbrrace-uk/reports/MBRRACE-UK%20Maternal%20Report%202017%20-%20Web.pdf
- 45 Greer IA, Aharon A, Brenner B, Gris JC. Coagulation and placenta-mediated complications. Rambam Maimonides Med J 2014; 5 (04) e0034
- 46 Bates SM, Rajasekhar A, Middeldorp S. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22) 3317-3359
- 47 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (08) 1673-1676
- 48 Beyer-Westendorf J, Michalski F, Tittl L. et al. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost 2016; 116 (04) 651-658
- 49 Cox S, Eslick R, McLintock C. Effectiveness and safety of thromboprophylaxis with enoxaparin for prevention of pregnancy-associated venous thromboembolism. J Thromb Haemost 2019; 17 (07) 1160-1170
- 50 Rajaratnam N, Patel JP, Roberts LN, Czuprynska J, Patel RK, Arya R. More on enoxaparin thromboprophylaxis in pregnancy: a review of 10 years' experience from King's College Hospital. J Thromb Haemost 2021; 19 (01) 304-308
- 51 Bleker SM, Buchmüller A, Chauleur C. et al. Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: rationale and design of the Highlow study, a randomised trial of two doses. Thromb Res 2016; 144: 62-68
- 52 Knight M. UKOSS. Antenatal pulmonary embolism: risk factors, management and outcomes. BJOG 2008; 115 (04) 453-461
- 53 Ismail SK, Norris L, Muttukrishna S, Higgins JR. Thrombin generation post elective caesarean section: effect of low molecular weight heparin. Thromb Res 2012; 130 (05) 799-803
- 54 Goland S, Schwartzenberg S, Fan J, Kozak N, Khatri N, Elkayam U. Monitoring of anti-Xa in pregnant patients with mechanical prosthetic valves receiving low-molecular-weight heparin: peak or trough levels?. J Cardiovasc Pharmacol Ther 2014; 19 (05) 451-456
- 55 Patel JP, Hunt BJ. Where do we go now with low molecular weight heparin use in obstetric care?. J Thromb Haemost 2008; 6 (09) 1461-1467
- 56 Arya R. How I manage venous thromboembolism in pregnancy. Br J Haematol 2011; 153 (06) 698-708
- 57 Lang IM. What is new in the 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy?. Wien Klin Wochenschr 2020; 132 (3-4): 69-72
- 58 Bates SM, Greer IA, Middeldorp S. 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: e691S-e736S
- 59 Siah TH, Chapman A. Should catheter-directed thrombolysis be the standard of care for pregnancy-related iliofemoral deep vein thrombosis?. BMJ Case Rep 2018; 2018
- 60 Wik HS, Enden TR, Jacobsen AF, Sandset PM. Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity. J Thromb Haemost 2011; 9 (10) 1931-1936
- 61 Wik HS, Jacobsen AF, Sandvik L, Sandset PM. Prevalence and predictors for post-thrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study. J Thromb Haemost 2012; 10 (05) 840-847
- 62 Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev 2016; 11: CD002783
- 63 Rodriguez D, Jerjes-Sanchez C, Fonseca S. et al. Thrombolysis in massive and submassive pulmonary embolism during pregnancy and the puerperium: a systematic review. J Thromb Thrombolysis 2020; 50 (04) 929-941
- 64 Harris SA, Velineni R, Davies AH. Inferior vena cava filters in pregnancy: a systematic review. J Vasc Interv Radiol 2016; 27 (03) 354-60.e8
- 65 Jering KS, Claggett BL, Cunningham JW. et al. Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19. JAMA Intern Med 2021; 181 (05) 714-717
- 66 Servante J, Swallow G, Thornton JG. et al. Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: a systematic review and critical analysis. BMC Pregnancy Childbirth 2021; 21 (01) 108
- 67 Lou-Mercadé AC, Gavín O, Oros D. et al. Prevention of thrombosis in pregnant women with suspected SARS-CoV-2 infection: clinical management algorithm. Ultrasound Obstet Gynecol 2020; 56 (01) 111-112