Skip to main content



Mechanical heart valves pose a particular challenge in pregnancy, as the primary agent used to prevent valve thrombosis, coumadin (warfarin), is a known teratogen. Alternatives to coumadin, such as unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) are safer for the fetus, particularly during the first trimester of pregnancy, but expose the mother to potential valve failure. This review will examine these controversies and the complex literature regarding management in pregnancy.

Corresponding author
Cynthia Maxwell, Mount Sinai Hospital, Department of Obstetrics and Gynaecology, 600 University Avenue, Toronto ON, M5G 1X5Canada.
Hide All
1Kardon E. Prosthetic heart valves. 2007. eMedicine internet site.
2Goldsmith I, Turpie AGG, Lip GYH. ABC of antithrombotic therapy. Valvuar heart disease and prosthetic heart valves. Br Med J 2002; 325: 1228–231.
3Salem DN, Stein PD, Al-Ahmad A, Bussey HI, Horskotte D, Miller N et al. Antithrombotic therapy in valvular heart disease – native and prosthetic: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 457–82.
4Baudet EM, Puel V, McBride JT, Grimaud JP, Roques F, Clerc F et al. Long-term results of valve replacement with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1995; 109: 858–70.
5Bjork VO, Henze A. Management of thrombo-embolism after aortic valve replacement with the Bjork-Shiley tilting disc valve: medicamental prevention with dicumarol in comparison with dipyrimidamole-acetylsalicylic acid; surgical treatment of prosthetic thrombosis. Scand J Thorac Cardiovasc Surg 1975; 9: 183–91.
6Cappelleri JC, Fiore LD, Brophy MT, Deykin D, Lau J. Efficacy and safety of combined anticoagulant and antiplatelet therapy versus anticoagulant monotherapy after mechanical heart valve replacement: a meta analysis. Am Heart J 1995; 130: 547–52.
7Born D, Martinez EE, Almeida PAM, Santos DV, Carvalho ACC, Moron AF. Pregnancy in patients with prosthetic heart valves: the effect of anticoagulation on mother, fetus and neonate. Am Heart J 1992; 124: 413–17.
8Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71: 196201.
9Hanania G, Thomas D, Michel PL, Garbarz E, Age C, Millair A et al. Grossesses chez les porteuses de prostheses valvulaires: etude cooperative retrospective francaise (155 cas). [Pregnancy in patients with heart valve prosthesis. A French retrospective cooperative study (155 cases)] Arch Mal Coeur Vaiss 1994; 87: 429–37.
10Lee CN, Wu CC, Lin PY, Hsieh FJ, Chen HY. Pregnancy following cardiac prosthetic valve replacement. Obstet Gynecol 1994; 83: 353–56.
11Denbow CE, Matadial L, Sivapragasam S, Spencer H. Pregnancy in patients after homograft cardiac valve replacement. Chest 1983; 83: 540–42.
12Dore A, Somerville J. Pregnancy in patients with pulmonary autograft valve replacement. Eur Heart J 1997; 18: 1659–62.
13Elkayam U. Editorial comment. Pregnancy through a prosthetic heart valve. J Am Coll Card 1999; 33: 1642–45.
14McLeod AG, Ellis C. Prevention and treatment of venous thromboembolism in high risk situations in pregnancy. Fet Mat Med Rev 2005; 16: 151–70.
15Ginsberg JS, Brill-Edwards P, Burrows RF, Bona R, Prandoni P, Buller HR et al. Venous thrombosis during pregnancy: leg and trimester of presentation. Thromb Haemost 1992; 67: 519–20.
16Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999; 94: 730–34.
17Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999; 54: 265–71.
18Ginsberg JS, Hirsh J, Turner DC, Levine MN, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989; 61: 197203.
19Hall JAG, Paul RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122140.
20Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Int Med 2000; 160: 191–96.
21Robin F, Lecuru F, Desfeux P, Boucaya B, Taurelle R. Anticoagualation therapy in pregnancy. Eur J Obstet Gynecol Reprod Biol 1999; 83: 171–77.
22Shaul WL, Hall JG. Multiple congenital anomalies associated with oral anticoagulants. Am J Obstet Gynecol 1997; 127: 191–95.
23Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R. Heparin therapy during pregnancy: risk to the fetus and mother. Arch Int Med 1989; 149: 2233–36.
24Shapira Y, Sagie A, Battler A. Low-molecular-weight heparin for the treatment of patients with mechanical heart valves. Clin Cardiol 2002; 25: 323–27.
25Groce JB. “Bridging” therapy with low molecular weight heparin in pregnant patients and patients with mechanical prosthetic heart valves. J Thromb Thrombolysis 2003; 16: 7982.
26Stein PD, Alpert JS, Bussey HI, Dalen JE, Turpie AGG. Antithrombotic therapy in patients with mechanical and bioprosthetic heart valves. Chest 2001; 119: 220–27.
27Montalescot G, Polle V, Collet JP, Leprince P, Bellanger A, Gandjbakhch I. Low molecular weight heparin after mechanical heart valve replacement. Circulation 2000; 1010: 10831086.
28Maxwell CV, Poppas A, Dunn E, Sermer M. Pregnancy, mechanical heart valves and anticoagulation: Navigating the complexities of management during gestation. In: Rosene-Montella K, Keely EJ, Lee RV, Barbour LA (eds) From Medical Care of the Pregnant Patient, 2nd Edition. Philadelphia, American College of Physicians, 2007; 344355.
29Bates SM, Greer IA, Hirsh J, Ginsberg JS. Conference on antithrombotic and thrombolytic therapy use of antithrombotic agents during pregnancy – The seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 627–44.
30Lepercq J, Conard J, Borel-Derlon A, Darmon JY, Boudignat O, Francoual C et al. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. BJOG 2001; 108: 1134–140.
31Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound. Thromb Res 1984; 34: 557–60.
32Sanson BJ, Lensing AW, Prins MH, Ginsberg JS, Barkagan ZS, Lavenne-Pardonge E et al. Safety of low molecular weight heparin in pregnancy; a systematic review. Thromb Haemost 1999; 81: 669–72.
33Hunt BJ, Doughty HA, Majumdar G, Copplestone A, Kerslake S, Buchanan N et al. Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies. Thromb Haemost 1997; 77: 3943.
34Nelson-Piercy C, Letsky EA, de Swiet M. Low molecular weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at high risk. Am J Obstet Gynecol 1997; 176: 10621068.
35Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. NEJM 1995; 332:1330–336.
36de Valk HW, Banga JD, Wester JW, Brouwer CB, van Hessen MW, Meuwissen OJ et al. Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism: a randomized controlled trial. Ann Intern Med 1995; 123: 19.
37Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172). Thromb Haemost 1993; 70: 554–61.
38Douketis JD, Ginsberg JS, Burrows RF, Duku EK, Webber CE, Brill-Edwards P. The effects of long-term heparin therapy during pregnancy on bone density. Thromb Haemost 1996; 75: 254–57.
39Dahlman 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: 1265–270.
40Monreal M, Lafoz E, Olive A, del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications for coumarin. Thromb Haemost 1994; 71: 711.
41Pettila 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: 182–86.
42Bara L, Samama MM. Pharmacokinetics of low molecular weight heparins. Acta Chir Scand 1988; 543: 6572.
43Bradbrook ID, Magnani HN, Moelker HC, Morrison PJ, Robinson J, Rogers HJ et al. ORG 10172: a low molecular weight heparinoid anticoagulant with a long half life in man. Br J Clin Pharmacol 1987; 23: 667–75.
44Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688–98.
45Jordan RE, Oosta GM, Gardner WT, Rosenberg RD. The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin. J Biol Chem 1980; 255: 1008110090.
46Holmer E, Kurachi K, Soderstrom G. The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa and kallikrein by antithrombin. Biochem J 1981; 193: 395400.
47Holmer E, Soderberg K, Bergqvist D, Lindahl U. Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties. Haemostasis 1986; 16: 17.
48Bara L, Billaud E, Gramond G, Kher A, Samama M. Comparative pharmacokinetics of low molecular weight heparin and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res 1985; 39: 631–36.
49Alhenc-Gelas M, Jestin-Le Guernic C, Vitoux JF, Kher A, Aiach M, Fiessinger JN. Adjusted versus fixed doses of the low-molecular-weight heparin Fragmin in the treatment of deep vein thrombosis. Fragmin-Study Group. Thromb Haemost 1994; 71: 698702.
50Levine MN, Planes A, Hirsh J, Goodyear M, Vochelle N, Gent M. The relationship between antifactor Xa level and clinical outcome in patients receiving enoxaparine low molecular weight heparin to prevent deep vein thrombosis after hip replacement. Thromb Haemost 1989; 62: 940–44.
51Samama MM. Contemporary laboratory monitoring of low molecular weight heparins. Clin Lab Med 1995; 15: 119–23.
52Laposata M, Green D, Van Cott EM, Barrowcliffe TW, Goodnight SH, Sosolik RC. College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy: the clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban. Arch Pathol Lab Med 1998; 122: 799807.
53Boneu B. Low molecular weight heparin therapy: is monitoring needed? Thromb Haemost 1994; 72: 330–34.
54MedWatch, Aventis Pharmaceuticals Safetly Alert, 2002.
55Ginsberg JS, Chan WS, Bates SM, Kaatz S. Anticoagulation of pregnant women with mechanical heart valves. Arch Intern Med 2003; 163: 694–98.
56Imperiale TF, Petrulis AS. A meta-analysis of low-dose aspirin for prevention of pregnancy-induced hypertensive disease. JAMA 1991; 266: 260–64.
57Elkayam U, Singh H, Irani A, Akhter MW. Anticoagulation in Pregnant Women With Prosthetic Heart Valves. J Cardiovasc Pharmacol Ther 2004; 9: 107–15.
58Rowan JA, McCowan LM, Raudkivi PJ, North RA. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gynecol 2001; 185: 633–37.
59Abildgaard U, Gjestvang FT, Lossius P, Hodne E. Low molecular heparin in a pregnant women with heart valve prosthesis. Tidsskr Nor Laegeforen 1999; 119: 4319–20.
60Arnaout MS, Kazma H, Khalil A, Shasha N, Nasrallah A, Karam K, Alam SE. Is there a safe anticoagulation protocol for pregnant women with prosthetic valves? Clin Exp Obstet Gynecol 1998; 25: 101104.
61Bauersachs R, Lindhoff-Last E. Anticoagulation of pregnant women with mechanical heart valves using low-molecular-weight heparin. Arch Intern Med 2003; 163: 2788–789.
62Behrendt P, Schwartzkopff B, Perings S, Gerhardt A, Zotz RB, Stauer AB. Successful thrombolysis of St. Jude Medical Aortic Prosthesis with tissue-type plasminogen activator in a pregnant woman: A case report. Cardiol Rev 2002; 10: 349–53.
63Ellison J, Thomson AJ, Walker ID, Greer IA. Use of enoxaparin in a pregnant woman with a mechanical heart valve prosthesis. BJOG 2001; 108: 757–59.
64Lavoie JP, Leduc L, Mercier LA. Embolic myocardial infarction in a pregnant woman with a mechanical heart valve on low molecular weight heparin. Can J Cardiol 2004; 20: 917–19.
65Lee LH, Liauw PCY, Ng AS. Low molecular weight heparin for thromboprophylaxis during pregnancy in 2 patients with mechanical mitral valve replacement. Thromb Haemost 1996; 76: 628–30.
66Lev-Ran O, Kramer A, Gurevitch J, Shapira I, Mohr R. Low-molecular weight heparin for prosthetic heart valves: treatment failure. Ann Thoracic Surg 2000; 69: 264–66.
67Leyh RG, Fischer S, Ruhparwar A, Haverich A. Anticoagulation for prosthetic heart valves during pregnancy: Is low-molecular-weight heparin an alternative? Eur J Cardiothorac Surg 2002; 21; 577–79.
68Lisowska A, Prokop J, Hirnle T, Juszczyk G, Skibińska E, Musial WJ, Klonowska-Dziatkiewicz E, Wrabec K. Recurrent thrombosis of a mitral mechanical heart valve prosthesis during puerperium - A case report. Kardiologia Polska 2004; 61, 4952.
69Mahesh B, Evans S, Bryan AJ. Failure of low molecular-weight heparin in the prevention of prosthetic mitral valve thrombosis during pregnancy: Case report and a review of options for anticoagulation. J Heart Valve Dis 2002; 11: 745–50.
70Obergfell A, Langenfeld H, Hopp H, Steigerwald U, Grossmann R. Thrombosis of a prosthetic aortic valve during pregnancy despite therapeutic dosage of Nadroparin. Thromb Haemost 2004; 91: 839–40.
71Oles D, Berryessa R, Campbell K, Bhatti MA. Emergency redo mitral valve replacement in a 27-year-old pregnant female with a clotted prosthetic mitral valve, preoperative fetal demise and postoperative ventricular assist device: a case report. Perfusion 2001; 16: 159–64.
72Roberts N, Ross D, Flint S, Arya R, Blott M. Thromboembolism in pregnant women with mechanical prosthetic heart valves anticoagulated with low molecular-weight heparin. BJOG 2001; 108: 327–29.
73Geelani MA, Singh S, Verma A, Nagesh A, Betigeri V, Nigam M. Anticoagulation in patients with mechanical valves during pregnancy. Asian Cardiovasc Thorac Ann 2005; 13: 3033.
74Gohlke-Barwolf C, Acar J, Oakley C, Butchart E, Burckhart D, Bodnar E et al. Guidelines for prevention of thromboembolic events in valvular heart disease: study group of the working group on valvular heart disease of the European Society of Cardiology. Eur Heart J 1995; 16: 1320–30.
75Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. (Writing Committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 2006; 114: e84231.
76Evans WA, Laifer SA, McNanley TJ, Ruzycky A. Management of Thromboembolic Disease Associated With Pregnancy. J Matern Fetal Med 1997; 6: 2127.
77Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M et al. Prevention of infective endocarditis: guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; April: ePublication. 1736–54.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Fetal and Maternal Medicine Review
  • ISSN: 0965-5395
  • EISSN: 1469-5065
  • URL: /core/journals/fetal-and-maternal-medicine-review
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Full text views

Total number of HTML views: 2
Total number of PDF views: 1 *
Loading metrics...

Abstract views

Total abstract views: 73 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th November 2017. This data will be updated every 24 hours.