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CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/a-2325-5658
Position Paper

Anticoagulant Therapy in Pregnant Women with Mechanical Heart Valves: Italian Federation of Centers for Diagnosis and Surveillance of the Antithrombotic Therapies (FCSA) Position Paper

Elena Campello 
1   Department of Medicine, General Medicine and Thrombotic and Hemorrhagic Unit, University of Padova, Padova, Italy
,
Paolo Bucciarelli
2   Fondazione IRCCS Ca' Granda – Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
,
Filippo Catalani
1   Department of Medicine, General Medicine and Thrombotic and Hemorrhagic Unit, University of Padova, Padova, Italy
,
Nicoletta Erba
3   Medical Division, Emergency, ONG Onlus, Milan, Italy
,
Alessandro Squizzato 
4   Research Center on Thromboembolic Disorders and Antithrombotic Therapies, ASST Lariana, University of Insubria, Como, Italy
,
Daniela Poli
5   Thrombosis Center, “Careggi” Hospital, Florence, Italy
,
Scientific Reviewer Committee › Author Affiliations
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Abstract

The management of anticoagulant therapy in pregnant women with mechanical heart valves (MHVs) is difficult and often challenging even for clinicians experienced in the field. These pregnancies, indeed, are burdened with higher rates of complications for both the mother and the fetus, compared to those in women without MHVs. The maternal need for an optimal anticoagulation as provided by vitamin K antagonists is counterbalanced by their teratogen effect on the embryo and fetus. On the other hand, several concerns have been raised about the efficacy of heparins in pregnant women with MHVs, considering the high risk of thrombotic complications in these patients. Therefore, numerous clinical issues about the management of pregnant women with MHVs remain unanswered, such as the selection of the best anticoagulant agent, the optimal anticoagulation levels to be achieved and maintained, and the evaluation of long-term effects for both the mother and the fetus. Based on a comprehensive review of the current literature, the Italian Federation of the Centers for the Diagnosis and the Surveillance of the Antithrombotic Therapies (FCSA) proposes experience-based suggestions and expert opinions. Particularly, this consensus document aims at providing practical guidance for clinicians dealing with pregnant women with MHVs, to optimize maternal and fetal outcomes while guaranteeing adequate anticoagulation. Finally, FCSA highlights the need for the creation of multidisciplinary teams experienced in the management of pregnant women with MHVs during pregnancy, delivery, and postpartum, in order to better deal with such complex clinical issues and provide a comprehensive counseling to these patients.

Keywords

pregnancy - prosthetic heart valves - thromboembolism - heparin - vitamin K antagonists

* Scientific Reviewer Committee Members: Gregory Y. H. Lip, Vanessa Roldan, Stefania Basili, Florian Langer, Jennifer Lewey.




Publication History

Received: 12 October 2023

Accepted: 18 February 2024

Accepted Manuscript online:
14 May 2024

Article published online:
01 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J. et al; ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018; 39 (34) 3165-3241
    CrossrefPubMedGoogle Scholar
  • 2 van Hagen IM, Roos-Hesselink JW, Ruys TPE. et al; ROPAC Investigators and the EURObservational Research Programme (EORP) Team*. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease ROBAC. Circulation 2015; 132 (02) 132-142
    CrossrefPubMedGoogle Scholar
  • 3 Sillesen M, Hjortdal V, Vejlstrup N, Sørensen K. Pregnancy with prosthetic heart valves - 30 years' nationwide experience in Denmark. Eur J Cardiothorac Surg 2011; 40 (02) 448-454
    PubMedGoogle Scholar
  • 4 Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med 2000; 160 (02) 191-196
    CrossrefPubMedGoogle Scholar
  • 5 Xu Z, Fan J, Luo X. et al. Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a systematic review and meta-analysis. Can J Cardiol 2016; 32 (10) 1248.e1-1248.e9
    CrossrefPubMedGoogle Scholar
  • 6 Hassouna A, Allam H. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis. Interact Cardiovasc Thorac Surg 2014; 18 (06) 797-806
    CrossrefPubMedGoogle Scholar
  • 7 Abildgaard U, Sandset PM, Hammerstrøm J, Gjestvang FT, Tveit A. Management of pregnant women with mechanical heart valve prosthesis: thromboprophylaxis with low molecular weight heparin. Thromb Res 2009; 124 (03) 262-267
    CrossrefPubMedGoogle Scholar
  • 8 Alshawabkeh L, Economy KE, Valente AM. Anticoagulation during pregnancy: evolving strategies with a focus on mechanical valves. J Am Coll Cardiol 2016; 68 (16) 1804-1813
    CrossrefPubMedGoogle Scholar
  • 9 Lewey J, Andrade L, Levine LD. Valvular heart disease in pregnancy. Cardiol Clin 2021; 39 (01) 151-161
    CrossrefPubMedGoogle Scholar
  • 10 Vitale N, De Feo M, De Santo LS, Pollice A, Tedesco N, Cotrufo M. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol 1999; 33 (06) 1637-1641
    CrossrefPubMedGoogle Scholar
  • 11 D'Souza R, Ostro J, Shah PS. et al. Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis. Eur Heart J 2017; 38 (19) 1509-1516
    CrossrefPubMedGoogle Scholar
  • 12 Quinn J, Von Klemperer K, Brooks R, Peebles D, Walker F, Cohen H. Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience. Haematologica 2009; 94 (11) 1608-1612
    CrossrefPubMedGoogle Scholar
  • 13 Bhagra CJ, D'Souza R, Silversides CK. Valvular heart disease and pregnancy part II: management of prosthetic valves. Heart 2017; 103 (03) 244-252
    CrossrefPubMedGoogle Scholar
  • 14 Steinberg ZL, Dominguez-Islas CP, Otto CM, Stout KK, Krieger EV. Maternal and fetal outcomes of anticoagulation in pregnant women with mechanical heart valves. J Am Coll Cardiol 2017; 69 (22) 2681-2691
    CrossrefPubMedGoogle Scholar
  • 15 Steffel J, Collins R, Antz M. et al; External reviewers. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23 (10) 1612-1676
    CrossrefPubMedGoogle Scholar
  • 16 Kleindorfer DO, Towfighi A, Chaturvedi S. et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a Guideline from the American Heart Association/American Stroke Association. Stroke 2021; 52 (07) e364-e467
    CrossrefPubMedGoogle Scholar
  • 17 Otto CM, Nishimura RA, Bonow RO. et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143 (05) e72-e227
    CrossrefPubMedGoogle Scholar
  • 18 Eikelboom JW, Connolly SJ, Brueckmann M. et al; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013; 369 (13) 1206-1214
    CrossrefPubMedGoogle Scholar
  • 19 Duraes AR, de Souza Lima Bitar Y, Schonhofen IS. et al. Rivaroxaban versus warfarin in patients with mechanical heart valves: open-label, proof-of-concept trial - The RIWA study. Am J Cardiovasc Drugs 2021; 21 (03) 363-371
    CrossrefPubMedGoogle Scholar
  • 20 Lameijer H, Aalberts JJJ, van Veldhuisen DJ, Meijer K, Pieper PG. Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review. Thromb Res 2018; 169: 123-127
    CrossrefPubMedGoogle Scholar
  • 21 Lester W, Walker N, Bhatia K. et al. British Society for Haematology guideline for anticoagulant management of pregnant individuals with mechanical heart valves. Br J Haematol 2023; 202 (03) 465-478
    CrossrefPubMedGoogle Scholar
  • 22 De Santo LS, Romano G, Della Corte A. et al. Mechanical aortic valve replacement in young women planning on pregnancy: maternal and fetal outcomes under low oral anticoagulation, a pilot observational study on a comprehensive pre-operative counseling protocol. J Am Coll Cardiol 2012; 59 (12) 1110-1115
    CrossrefPubMedGoogle Scholar
  • 23 Roos-Hesselink JW, Budts W, Walker F. et al. Organisation of care for pregnancy in patients with congenital heart disease. Heart 2017; 103 (23) 1854-1859
    CrossrefPubMedGoogle Scholar
  • 24 Vahanian A, Baumgartner H, Bax J. et al; Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology, ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: the task force on the management of valvular heart disease of the European Society of Cardiology. Eur Heart J 2007; 28 (02) 230-268
    PubMedGoogle Scholar
  • 25 Oran B, Lee-Parritz A, Ansell J. Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy. Thromb Haemost 2004; 92 (04) 747-751
    PubMedGoogle Scholar
  • 26 Berresheim M, Wilkie J, Nerenberg KA, Ibrahim Q, Bungard TJ. A case series of LMWH use in pregnancy: should trough anti-Xa levels guide dosing?. Thromb Res 2014; 134 (06) 1234-1240
    CrossrefPubMedGoogle Scholar
  • 27 Barbour LA, Oja JL, Schultz LK. A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol 2004; 191 (03) 1024-1029
    CrossrefPubMedGoogle Scholar
  • 28 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
    CrossrefPubMedGoogle Scholar
  • 29 Elkayam U, Bitar F. Valvular heart disease and pregnancy: part II: prosthetic valves. J Am Coll Cardiol 2005; 46 (03) 403-410
    CrossrefPubMedGoogle Scholar
  • 30 Salazar E, Izaguirre R, Verdejo J, Mutchinick O. Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses. J Am Coll Cardiol 1996; 27 (07) 1698-1703
    CrossrefPubMedGoogle Scholar
  • 31 Vause S, Clarke B, Tower CL, Hay C, Knight M. (on behalf of UKOSS). Pregnancy outcomes in women with mechanical prosthetic heart valves: a prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system. BJOG 2017; 124 (09) 1411-1419
    CrossrefPubMedGoogle Scholar
  • 32 Khader KAAM, Saad AS, Abdelshafy M. Pregnancy outcome in women with mechanical prosthetic heart valves treated with unfractionated heparin (UFH) or enoxaparin. J Obstet Gynecol India 2016; 66 (05) 321-326
    CrossrefPubMedGoogle Scholar
  • 33 Snape E, Thachil J, Clarke B, Vause S. Anti-Xa based dose changes during low molecular weight heparin anticoagulation for mechanical prosthetic heart valves during pregnancy. J Obstet Gynaecol 2018; 38 (05) 721-722
    CrossrefPubMedGoogle Scholar
  • 34 Elkayam U. Anticoagulation therapy for pregnant women with mechanical prosthetic heart valves: how to improve safety?. J Am Coll Cardiol 2017; 69 (22) 2692-2695
    CrossrefPubMedGoogle Scholar
  • 35 Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71 (02) 196-201
    CrossrefPubMedGoogle Scholar
  • 36 Khamoushi AJ, Kashfi F, Hosseini S, Alizadeh Ghavidel AR, Samiei N, Haddadzadeh M. Anti-coagulation during pregnancy in women with mechanical heart valves: a prospective study. Int J Fertil Steril 2011; 5 (01) 47-51
    PubMedGoogle Scholar
  • 37 Cousin B, Guglielminotti J, Iung B, Montravers P. Retrospective study of anaesthetic management of pregnancy patients with mechanical heart valve prosthesis and anticoagulants. Anaesth Crit Care Pain Med 2018; 37 (03) 225-231
    CrossrefPubMedGoogle Scholar
  • 38 Samiei N, Kashfi F, Khamoushi A. et al. Pregnancy outcome after mechanical mitral valve replacement: a prospective study. J Tehran Heart Cent 2012; 7 (03) 117-120
    PubMedGoogle Scholar
  • 39 Meschengieser SS, Fondevila CG, Santarelli MT, Lazzari MA. Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart 1999; 82 (01) 23-26
    CrossrefPubMedGoogle Scholar
  • 40 Bian C, Qi X, Li L, Zhao J, Liu X. Anticoagulant management of pregnant women with mechanical heart valve replacement during perioperative period. Arch Gynecol Obstet 2016; 293 (01) 69-74
    CrossrefPubMedGoogle Scholar
  • 41 Akhtar RP, Abid AR, Zafar H, Cheema MA, Khan JS. Anticoagulation in pregnancy with mechanical heart valves: 10-year experience. Asian Cardiovasc Thorac Ann 2007; 15 (06) 497-501
    CrossrefPubMedGoogle Scholar
  • 42 Kariv S, Azibani F, Baard J. et al. Haemorrhage and other complications in pregnant women on anticoagulation for mechanical heart valves: a prospective observational cohort study. Cardiovasc J S Afr 2018; 29 (05) 289-295
    CrossrefPubMedGoogle Scholar
  • 43 Lee JH, Park NH, Keum DY, Choi SY, Kwon KY, Cho CH. Low molecular weight heparin treatment in pregnant women with a mechanical heart valve prosthesis. J Korean Med Sci 2007; 22 (02) 258-261
    CrossrefPubMedGoogle Scholar
  • 44 Basude S, Hein C, Curtis SL, Clark A, Trinder J. Low-molecular-weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study. BJOG 2012; 119 (08) 1008-1013 , discussion 1012–1013
    CrossrefPubMedGoogle Scholar
  • 45 Bhutta SZ, Aziz S, Korejo R. Pregnancy following cardiac surgery. J Pak Med Assoc 2003; 53 (09) 407-413
    PubMedGoogle Scholar
  • 46 Suri V, Keepanasseril A, Aggarwal N. et al. Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary centre experience. Eur J Obstet Gynecol Reprod Biol 2011; 159 (02) 320-323
    CrossrefPubMedGoogle Scholar
  • 47 Heuvelman HJ, Arabkhani B, Cornette JMJ. et al. Pregnancy outcomes in women with aortic valve substitutes. Am J Cardiol 2013; 111 (03) 382-387
    CrossrefPubMedGoogle Scholar
  • 48 Erba N, Gatti S, Hassan SAA. et al. Pregnancy outcomes in women with mechanical valve prostheses using vitamin K antagonist therapy: the experience of the Salam Centre for Cardiac Surgery in Sudan. Front Pediatr 2022; 10 (10) 918547
    CrossrefPubMedGoogle Scholar
  • 49 Keepanasseril A, Pillai AA, Baghel J. et al. Alternatives to low molecular weight heparin for anticoagulation in pregnant women with mechanical heart valves in middle-income countries: a cohort study. Glob Heart 2021; 16 (01) 68
    CrossrefPubMedGoogle Scholar