Anticoagulant use to treat VTE (venous thromboembolism) in pregnancy: a review
Keywords:
Venous thromboembolism (VTE), anticoagulant, low molecule weight heparin (LMWH), unfractionated heparin (UFH), direct oral anticoagulants (DOACs)
Abstract
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a medical condition that occurs when a blood clot forms in a deep vein that major cause of pregnancy-related maternal death. As pregnancy progresses, the risk of hypercoagulability increases, fibrinogen, factors VII, VIII, X and VWF (Von Willebrand Factor), plasminogen activator inhibitor-1, plasminogen activator inhibitor-2 are increases and 40-60% protein S decreases. Therefore, anticoagulant drugs are the mainstay of therapy for patients with VTE. The review aimed to select the best anticoagulant for pregnancy women with VTE. A scoping review was used. The type of articles reviewed were original articles obtained from four electronic journal databases published within 2012-2021. The main therapeutic agent recommended for use in the prevention and treatment of VTE in pregnancy is low molecular weight heparin (LMWH). LMWH has better bioavailability than other anticoagulants, has a lower risk of maternal bleeding, thromboembolic, thrombocytopenia and osteoporosis. The use of LMWH is actually better, more comfortable and safety for patients.
References
REFERENCES
1.Creanga AA, Syverson C, Seed K, Callaghan WM. Pregnancy-related Mortality in the United States, 2011-2013. Obstet Gynecol. 2017; 130: 366–373.
2.Pregnancy Mortality Surveillance System. Center for Disease Control and Prevention. Available at: http://www.cdc.org/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm. Accessed October 22, 2021.
3.Abbasi N, Balayla J, Denny P, Laporta, Kezouh A, Abenhaim HA. Trends, Risk Factor, and Mortality among Women with Venous Thromboembolism during Labour and Delivery: a Population-based Study of 8 Million Births. Arch Gynecol Obstet. 2013.
4.Parunov LA, Soshitova NP, Ovanesov MV,Panteleev MA, Serebriyskiy II. Epidemiology of Venous Thromboembolism (VTE) Associated with Pregnancy. Birth Defects Res C Embryo Today. 2015; 105:167–184
5.Katherine M, Stanislav H, Mark A. 2020. Venous Thromboembolism Associated With Pregnancy : JACC Focus Seminar. Venous Thromboembolism Associated With Pregnancy: JACC Focus Seminar - PubMed (nih.gov) . Accessed on date October 21 2021.
6.Carlos J, David R, et al. Pregnancy-Associated Venous Thromboembolism : Insights From GARFIELD-VTE. Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE (nih.gov) . Accesed on date October 21 2021.
7.Karl E, Fionnuala. VTE Risk Assessment in Pregnancy. 2019. VTE risk assessment in pregnancy (nih.gov) . Accessed on date October 21 2021.
8.Nichols KM, Henkin S, and Creager MA. Venous thromboembolism associated with pregnancy: JACC Focus Seminar. Journal of the American College of Cardiology. 2020; 76(18): 2128-2141.
9.Lim, Annabel, Anusika Samarage, and Boon H Lim. Venous Thromboembolism in Pregnancy. 2016; 1-7.
10.ACOG. Thromboembolism in Pregnancy. 2018; 132(1): 1-17.
11.Ro A, Norimasa K, and Toshiji M. Pathophysiology of Venous Thromboembolism with Respect to the anatomical Features of the Deep Veins of Lower Limbs : A Review. Ann Vasc Dis. 2017; 10(2): 99–106.
12.Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, and Rodger M, Pulmonary embolism in pregnancy. The Lancet. 2013; 375(9713): 500-512.
13.Nutescu EA, Burnett A, Fanikos J, Spinler S, and Wittkowsky A. Pharmacology of anticoagulants used in the treatment of venous thromboembolism. Journal of thrombosis and thrombolysis. 2016; 41(1): 15-31.
14.De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, and Lip GY. General mechanisms of coagulation and targets of anticoagulants (Section I). Thrombosis and haemostasis. 2013; 109(04): 569-579.
15.Harter, Katherine et al. Anticoagulation Drug Therapy: A Review. Western Journal of Emergency Medicine. 2015; 16 (1): 11-17.
16.Ferreira JL, Wipf JE. Pharmacologic Therapies in Anticoagulants. Med Clin N Am. 2016; 695-718.
17.Yarrington CD, Valente AM, Economy KE. Cardiovascular Management in Pregnancy : Antithrombotic Agents and Antiplatelet Agents. Circulation. 2015; 132: 1354-1364.
18.Mandernach MW, Beyth RJ, Rajasekhar A. Apixaban for the Prophylaxis and Treatment of Deep Vein Thrombosis and Pulmonary Embolism: an Evidence-based Review. Therapeutics and Clinical Risk Management. 2015; 11: 1273-1282.
19.Komori M, Hayata E, Nakata M, Yuzawa H, Oji A, Morita M. Apixaban Therapy in a Pregnant Woman with Heparin-induced Thrombocytopenia and Venous Thromboembolic Events caused by Congenital Antithrombin Deficiency: a Case Report. Case Report in Women’s Health. 2020; 27.
20.Zachary A. Stacy, William B. Call, Aaron P. Hartmann, Golden L., Peters, Sara K. Richter. Edoxaban : A Comprehensive Review of The Pharmacology and Clinical Data for The Management of Atrial Fibrillation and Venous Thromboembolism.
2016; 5: 1-18.
21.James, AH. Pregnancy, Contraception and Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism). 2017; 22(2): 166-169.
22.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 and ISTH: reply. J Thromb Haemost 2016; 14: 195-197.
23.Beyer-Westendorf J, Michalski F, Tittl L, Middeldorf S, Cohen H, Abdul-Kadir R. Pregnancy Outcome in Patients Exposed to Direct Oral Anticoagulants and the Challenge of Event Reporting. Coagulation and Fibrinolysis. J Thromb Haemost 2016; 116: 651-658.
24.Sessa M, Mascolo A, Callerus T, Capuano A, Rossi F & Andersen M. Direct-Acting Oral Anticoagulants (DOACs) in Pregnancy: New Insight from Vigibase. Scientific reports. 2019; 9(7236).
25.Quinlan DJ, McQuillan A, and Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Annals of internal medicine. 2014; 140(3): 175-183.
26.Mclintock C, Brighton T, Chunilal S, Dekker G, Mcdonnell N, Mcrae S, Muller P, Tran H, Walters BN and Young L, Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Australian and New Zealand Journal of Obstetrics and Gynecology. 2012; 52(1): 14-22.
27.Sanches, Suzanna MV, et al. Thromboprophylaxis during the Pregnancy-Puerperal Cycle - Literature Review. Rev Bras Ginecol Obstet. 2020; 42(4): 218–227.
28.Galambosi P, Hiilesmaa V, Ulander VM, Laitinen L, Tiitinen A, and Kaaja R. Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density. Thrombosis research, 2016; 143: 122-126.
29.Fogerty, Annemarie MD. Challenges of Anticoagulation Therapy in Pregnancy. Curr Treat Options Cardio Med. 2017; 19(76): 1-13.
30.Sucker, Christoph, Rainer B. Zotz. Prophylaxis and treatment of venous thrombosis and pulmonary embolism in pregnancy. Reviews in Vascular Medicine 3. 2015; 24–30.
31.Jiang F, Hu X, Jiang K, Pi H, He Q, and Chen X. The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta- analysis. Taiwanese Journal of Obstetrics and Gynecology. 2021; 60(1): 1-8.
32.Goto M, Yoshizato T, Tatsumura M, Takashima T, Ogawa M, Nakahara H, Satoh S, Sanui A, Eguchi F, and Miyamoto S. Safety and efficacy of thromboprophylaxis using enoxaparin sodium after cesarean section: A multi-center study in Japan. Taiwanese Journal of Obstetrics and Gynecology, 2015; 54(3): 248-252.
33.Tang, Ai Wei, and Ian Greer. A systematic review on the use of new anticoagulants in pregnancy. Obstetric Medicine. 2013; 6: 64-71.
34.Dempfle C, et al. Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism. Thrombosis/Hemostasis. 2021; 27: 1-8.
35.Bapat P, et al. Transfer of dabigatran and dabigatran etexilate mesylate across the dually perfused human placenta. Obstet Gynecol. 2014; 123(6).
36.Carolis SD, et al. Fondaparinux in pregnancy: Could it be a safe option ? A review of the literature. Thrombosis Research. 2015; 135: 1049–1051.
37.Witt, Daniel M, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016; 41: 187–205.
38.Gibson P, Powrie R. Anticoagulants and pregnancy: when are they safe ?. Clev Clin J Med. 2009; 76(2): 113-127.
39.DeWald TA, Washam JB, Becker RC. Anticoagulants: Pharmacokinetics, Mechanisms of Action, and Indications. Neurosurg Clin N Am. 2018; 29(4): 503-515.
40.Alshawabkeh L, Economy KE, Valente AM. Anticoagulation During Pregnancy. American College of Cardiology Foundation : A Review. JACC. 2016; 68(16): 1804-1811.
1.Creanga AA, Syverson C, Seed K, Callaghan WM. Pregnancy-related Mortality in the United States, 2011-2013. Obstet Gynecol. 2017; 130: 366–373.
2.Pregnancy Mortality Surveillance System. Center for Disease Control and Prevention. Available at: http://www.cdc.org/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm. Accessed October 22, 2021.
3.Abbasi N, Balayla J, Denny P, Laporta, Kezouh A, Abenhaim HA. Trends, Risk Factor, and Mortality among Women with Venous Thromboembolism during Labour and Delivery: a Population-based Study of 8 Million Births. Arch Gynecol Obstet. 2013.
4.Parunov LA, Soshitova NP, Ovanesov MV,Panteleev MA, Serebriyskiy II. Epidemiology of Venous Thromboembolism (VTE) Associated with Pregnancy. Birth Defects Res C Embryo Today. 2015; 105:167–184
5.Katherine M, Stanislav H, Mark A. 2020. Venous Thromboembolism Associated With Pregnancy : JACC Focus Seminar. Venous Thromboembolism Associated With Pregnancy: JACC Focus Seminar - PubMed (nih.gov) . Accessed on date October 21 2021.
6.Carlos J, David R, et al. Pregnancy-Associated Venous Thromboembolism : Insights From GARFIELD-VTE. Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE (nih.gov) . Accesed on date October 21 2021.
7.Karl E, Fionnuala. VTE Risk Assessment in Pregnancy. 2019. VTE risk assessment in pregnancy (nih.gov) . Accessed on date October 21 2021.
8.Nichols KM, Henkin S, and Creager MA. Venous thromboembolism associated with pregnancy: JACC Focus Seminar. Journal of the American College of Cardiology. 2020; 76(18): 2128-2141.
9.Lim, Annabel, Anusika Samarage, and Boon H Lim. Venous Thromboembolism in Pregnancy. 2016; 1-7.
10.ACOG. Thromboembolism in Pregnancy. 2018; 132(1): 1-17.
11.Ro A, Norimasa K, and Toshiji M. Pathophysiology of Venous Thromboembolism with Respect to the anatomical Features of the Deep Veins of Lower Limbs : A Review. Ann Vasc Dis. 2017; 10(2): 99–106.
12.Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, and Rodger M, Pulmonary embolism in pregnancy. The Lancet. 2013; 375(9713): 500-512.
13.Nutescu EA, Burnett A, Fanikos J, Spinler S, and Wittkowsky A. Pharmacology of anticoagulants used in the treatment of venous thromboembolism. Journal of thrombosis and thrombolysis. 2016; 41(1): 15-31.
14.De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, and Lip GY. General mechanisms of coagulation and targets of anticoagulants (Section I). Thrombosis and haemostasis. 2013; 109(04): 569-579.
15.Harter, Katherine et al. Anticoagulation Drug Therapy: A Review. Western Journal of Emergency Medicine. 2015; 16 (1): 11-17.
16.Ferreira JL, Wipf JE. Pharmacologic Therapies in Anticoagulants. Med Clin N Am. 2016; 695-718.
17.Yarrington CD, Valente AM, Economy KE. Cardiovascular Management in Pregnancy : Antithrombotic Agents and Antiplatelet Agents. Circulation. 2015; 132: 1354-1364.
18.Mandernach MW, Beyth RJ, Rajasekhar A. Apixaban for the Prophylaxis and Treatment of Deep Vein Thrombosis and Pulmonary Embolism: an Evidence-based Review. Therapeutics and Clinical Risk Management. 2015; 11: 1273-1282.
19.Komori M, Hayata E, Nakata M, Yuzawa H, Oji A, Morita M. Apixaban Therapy in a Pregnant Woman with Heparin-induced Thrombocytopenia and Venous Thromboembolic Events caused by Congenital Antithrombin Deficiency: a Case Report. Case Report in Women’s Health. 2020; 27.
20.Zachary A. Stacy, William B. Call, Aaron P. Hartmann, Golden L., Peters, Sara K. Richter. Edoxaban : A Comprehensive Review of The Pharmacology and Clinical Data for The Management of Atrial Fibrillation and Venous Thromboembolism.
2016; 5: 1-18.
21.James, AH. Pregnancy, Contraception and Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism). 2017; 22(2): 166-169.
22.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 and ISTH: reply. J Thromb Haemost 2016; 14: 195-197.
23.Beyer-Westendorf J, Michalski F, Tittl L, Middeldorf S, Cohen H, Abdul-Kadir R. Pregnancy Outcome in Patients Exposed to Direct Oral Anticoagulants and the Challenge of Event Reporting. Coagulation and Fibrinolysis. J Thromb Haemost 2016; 116: 651-658.
24.Sessa M, Mascolo A, Callerus T, Capuano A, Rossi F & Andersen M. Direct-Acting Oral Anticoagulants (DOACs) in Pregnancy: New Insight from Vigibase. Scientific reports. 2019; 9(7236).
25.Quinlan DJ, McQuillan A, and Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Annals of internal medicine. 2014; 140(3): 175-183.
26.Mclintock C, Brighton T, Chunilal S, Dekker G, Mcdonnell N, Mcrae S, Muller P, Tran H, Walters BN and Young L, Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Australian and New Zealand Journal of Obstetrics and Gynecology. 2012; 52(1): 14-22.
27.Sanches, Suzanna MV, et al. Thromboprophylaxis during the Pregnancy-Puerperal Cycle - Literature Review. Rev Bras Ginecol Obstet. 2020; 42(4): 218–227.
28.Galambosi P, Hiilesmaa V, Ulander VM, Laitinen L, Tiitinen A, and Kaaja R. Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density. Thrombosis research, 2016; 143: 122-126.
29.Fogerty, Annemarie MD. Challenges of Anticoagulation Therapy in Pregnancy. Curr Treat Options Cardio Med. 2017; 19(76): 1-13.
30.Sucker, Christoph, Rainer B. Zotz. Prophylaxis and treatment of venous thrombosis and pulmonary embolism in pregnancy. Reviews in Vascular Medicine 3. 2015; 24–30.
31.Jiang F, Hu X, Jiang K, Pi H, He Q, and Chen X. The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta- analysis. Taiwanese Journal of Obstetrics and Gynecology. 2021; 60(1): 1-8.
32.Goto M, Yoshizato T, Tatsumura M, Takashima T, Ogawa M, Nakahara H, Satoh S, Sanui A, Eguchi F, and Miyamoto S. Safety and efficacy of thromboprophylaxis using enoxaparin sodium after cesarean section: A multi-center study in Japan. Taiwanese Journal of Obstetrics and Gynecology, 2015; 54(3): 248-252.
33.Tang, Ai Wei, and Ian Greer. A systematic review on the use of new anticoagulants in pregnancy. Obstetric Medicine. 2013; 6: 64-71.
34.Dempfle C, et al. Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism. Thrombosis/Hemostasis. 2021; 27: 1-8.
35.Bapat P, et al. Transfer of dabigatran and dabigatran etexilate mesylate across the dually perfused human placenta. Obstet Gynecol. 2014; 123(6).
36.Carolis SD, et al. Fondaparinux in pregnancy: Could it be a safe option ? A review of the literature. Thrombosis Research. 2015; 135: 1049–1051.
37.Witt, Daniel M, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016; 41: 187–205.
38.Gibson P, Powrie R. Anticoagulants and pregnancy: when are they safe ?. Clev Clin J Med. 2009; 76(2): 113-127.
39.DeWald TA, Washam JB, Becker RC. Anticoagulants: Pharmacokinetics, Mechanisms of Action, and Indications. Neurosurg Clin N Am. 2018; 29(4): 503-515.
40.Alshawabkeh L, Economy KE, Valente AM. Anticoagulation During Pregnancy. American College of Cardiology Foundation : A Review. JACC. 2016; 68(16): 1804-1811.
