Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy

Betul Oran; Aviva Lee-Parritz; ack Ansell

doi:10.1160/TH04-06-0337

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 747-751
DOI: 10.1160/TH04-06-0337

Review Article

Schattauer GmbH

Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy

Betul Oran

¹Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA

,

Aviva Lee-Parritz

²Department of Obstetrics/Gynecology, Boston University Medical Center, Boston, Massachusetts, USA

,

ack Ansell

¹Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA

› Author Affiliations

Abstract

Summary

Increased thromboembolic events occur in women with mechanical prosthetic valves during pregnancy, and selecting an effective and safe anticoagulant is still a challenge. Low molecular weight heparin (LMWH) is a promising alternative, but a recent warning and label change about its use in patients with mechanical prosthetic valves has caused confusion among physicians. The aim of the present study was to review the risks of maternal and fetal complications with mechanical heart valves treated with LMWH during pregnancy. We performed a review of the current medical literature through MEDLINE and EMBASE (1989 to 2004). Additional data sources included abstract proceedings, and reference lists of selected articles. Among 81 pregnancies in 75 women, the proportion of valve thrombosis was 8.64% (7/81; 95% CI, 2.52%–14.76%). The frequency of overall thromboembolic complication (TEC) was 12.35% (10/81; 95% CI, 5.19%–19.51%). Nine of ten patients with TEC received a fixed dose of LMWH and two of these received a fixed low dose of LMWH. Among 51 pregnancies whose anti-factor Xa levels were monitored, only one patient was reported to have a thromboembolic complication. The frequency of live births with LMWH was 87.65% (95%CI, 80.49%94.81%). In pregnant women with mechanical heart valves, LMWH appears to be a suitable option to a vitamin K antagonist. The use of LMWH warrants monitoring and appropriate dose adjustments to maintain a 4–6 hr post-injection anti-factor Xa level at a minimum of 1.0 U/ml to decrease the incidence of TEC.

Keywords

Pregnancy - LMWH - mechanical heart valves

Full Text

References

References
1 Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prosthesis. Circulation 1994; 89: 635-41.
2 Born D, Martinez EE, Almeida PA. et al. Pregnancy inpatients with prosthetic heart valves: the effects of anticoagulation on mother, fetus and neonate. Am Heart J 1992; 124: 413-7.
3 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: 191-6.
4 Ginsberg JS, Hirsh J, Turner DC. et al. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989; 61: 197-203.
5 Pauli RM, Hall JG, Wilson KM. Risks of anticoagulation during pregnancy. Am Heart J 1980; 100: 761-2.
6 Flessa HC, Kapstrom AB, Glueck HI. et al. Placental transport of heparin. Am J Obstet Gynecol 1965; 93: 570-3.
7 Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71: 196-201.
8 Salazar E, Izaguirre R, Verdejo J. et al. 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: 1698-703.
9 Hirsh J, Warkentin TE, Raschke R. et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 5 Suppl 489S-510S.
10 Lovenox injection (Package Inser). Aventis Pharmaceuticals. 2002
11 Ginsberg JS, Chan WS, Bates SM. et al. Anticoagulation of pregnant women with mechanical heart valves. Arch Intern Med 2003; 163: 694-8.
12 Elkayam U. Pregnancy through a prosthetic heart valve. J Am Coll Cardiol 1999; 33: 1642-5.
13 Oles D, Berryessa R, Campbell K. et al. 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.
14 Leyh RG, Fischer S, Ruhparwar A. et al. Anticoagulation for prosthetic heart valves during pregnancy: is low-molecular-weight heparin an alternative?. Eur J Cardiothorac Surg 2002; 21: 577-9.
15 Lev-Ran O, Kramer A, Gurevitch J. et al. Low-molecular-weight heparin for prosthetic heart valves: treatment failure. Ann Thorac Surg 2000; 69: 264-5.
16 Rowan JA, McCowan LM, Raudkivi PJ. et al. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gynecol 2001; 185: 633-7.
17 Ellison J, Thomson AJ, Walker ID. et al. Use of enoxaparin in a pregnant woman with mechanical heart valve prosthesis. BJOG 2001; 108: 757-9.
18 Roberts N, Ross D, Flint SK. et al. Thromboembolism in pregnant women with mechanical prosthetic heart valves anticoagulated with low molecular weight heparin. BJOG 2001; 108: 327-9.
19 Lee LH, Liauw PC, Ng AS. Low molecular weight heparin for thromboprophylaxis during pregnancy in 2 patients with mechanical mitral valve replacement. Thromb Haemost 1996; 76: 628-30.
20 Mahesh 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.
21 Izaguirre R, De La Pena A, Ramirez A. et al. Anti-Xa activity with low-molecular-weight heparin, enoxaparin, during pregnancy in women with mechanical heart valves. Proc West Pharmacol Soc 2002; 45: 127-8.
22 Arnaout MS, Kazma H, Khalil A. et al. Is there a safe anticoagulation protocol for pregnant women with prosthetic valves?. Clin Exp Obstet Gynecol 1998; 25: 101-4.
23 Harenberg J, Huhle G, Piazolo L. et al. Longterm anticoagulation of outpatients with adverse events to oral anticoagulants using low-molecular-weight heparin. Semin Thromb Hemost 1997; 23: 167-72.
24 Vural KM, Ozatik MA, Uncu H. et al. Pregnancy after mechanical mitral valve replacement. J Heart Valve Dis 2003; 12: 370-6.
25 Lee LH. Low molecular weight heparin (LMWH) for thromboprophylaxis during pregnancy in patients with mechanical heart valves. Blood 2000; 96: 97b.
26 Meschengieser SS, Salviu MJ, Sanchez ALuceros. et al. Low molecular weight heparin (LMWH) in pregnant women with mechanical prosthetic heart valves (MPHV). J Thromb Haemost. 2003 suppl 1 Abt #P1479.
27 Lindhoff-Last E, Schinzel H, Erbe M. et al. Anticoagulation of pregnant women with mechanical heart valve prostheses. Z Kardiol 2001; 90 (Suppl. 06) 125-30.
28 Abildgaard U, Gjestvang FT, Lossius P. et al. Low molecular heparin in a pregnant woman with heart valve prosthesis. Tidsskr Nor Laegeforen 1999; 119: 4319-20.
29 Vitale N, De Feo M, De Santo LS. et al. Dosedependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol 1999; 33: 1637-41.
30 Evans W, Laifer SA, McNanley TJ. et al. Management of thromboembolic disease associated with pregnancy. J Matern Fetal Med 1997; 06: 21-7.
31 Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688-98.
32 Hirsh J, Warkentin TE, Raschke R. et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 5 Suppl 489S-510S.
33 Warkentin TE, Levine MN, Hirsh J. et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330-5.
34 Montalescot G, Polle V, Collet JP. et al. Low Molecular Weight Heparin After Mechanical Heart Valve Replacement. Circulation 2000; 101: 1083-6.
35 Sanson BJ, Lensing AW, Prins MH. et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668-72.
36 Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001; 119: 122S-131S.
37 Casele HL, Laifer SA, Woelkers DA. et al. Changes in the pharmacokinetics of the lowmolecular-weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol 1999; 181: 1113-7.
38 Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heart valves. N Engl J Med 1996; 335: 407-16.
39 Wilcox AJ, Weinberg CR, O’Connor JF. et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189-94.
40 Personal communication. Lesa Hobright-Turner: St. Jude Medical, Inc.;