Eur J Cardiothorac Surg 2002;21:577-579
© 2002 Elsevier Science NL
Anticoagulation for prosthetic heart valves during pregnancy: is low-molecular-weight heparin an alternative?
Rainer G. Leyh*,
Stefan Fischer,
Arjang Ruhparwar,
Axel Haverich
Division of Thoracic and Cardiovascular Surgery, Hanover Medical School, Carl Neuberg Strasse 1, 30623 Hannover, Germany
Received 25 May 2001;
received in revised form 27 November 2001;
accepted 12 December 2001.
* Corresponding author. Tel.: +49-532-6581; fax: +49-532-5404
e-mail: leyh{at}thg.mh-hannover.de
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Abstract
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We report on the treatment failure of low molecular weight heparin (LMWH) for anticoagulation in a pregnant woman that underwent artificial mitral valve replacement 10 years prior to her pregnancy. Until she became pregnant warfarin was administered for anticoagulation, but due to the often mentioned increased risk for warfarin-induced maternal and fetal complications, at gestational week 5 the anticoagulation regimen was switched to subcutaneous application of low molecular weight heparin. At gestational week 24 our patient developed acute life-threatening pulmonary edema and hemodynamic instability due to acute mitral valve thrombosis and underwent emergency valve re-replacement with a biological porcine valve. She recovered uneventfully and gave birth to a healthy child at gestational week 35. In addition to our case presentation we review the sparse evidence in the literature regarding anticoagulation in pregnant women with mechanical heart valves and discuss the rational of different anticoagulation regimens with regards to maternal and fetal outcome. Special consideration is directed towards LMWH administration as an alternative to oral anticoagulation during pregnancy in women with mechanical heart valves.
Key Words: Pregnancy • Anticoagulation • Prosthetic heart valves • Low molecular weight heparin
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1. Introduction
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Patients with mechanical heart valves require lifelong anticoagulation to reduce the risk of thromboembolic events. Coumarin derivatives are the drugs of choice for continuous oral anticoagulation. However, controversy exists about the most efficient and safest anticoagulation regimen in women with mechanical heart valves during pregnancy [1–8]. Low molecular weight heparin (LMWH) was considered to be a potential alternative to coumarin for anticoagulation during pregnancy and it has been shown to be safe and effective in pregnant women with a history of deep vein thrombosis [9]. However, there is only little evidence in the literature regarding the effect of LMWH for long-term anticoagulation in pregnant women with mechanical heart valves [10–16]. Here we report on a case of a LMWH treatment failure resulting in life-threatening mechanical valve thrombosis in a pregnant woman who received a mechanical mitral valve 6 years prior to her pregnancy. Our patient was successfully treated by a biological mitral valve re-replacement. In addition, we discuss the rational of different anticoagulation regimens with regards to maternal and fetal outcome and with special consideration to LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.
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2. Case presentation
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A 24 year-old woman with complex mitral valve pathology received a mitral valve replacement with a 29 mm Carbomedics mechanical bileaflet prosthetic valve (Sulzer Carbomedics, Austin, TX) in 1994. In 2000 she became pregnant. Oral anticoagulation with warfarin was stopped at the 5th week of gestation in order to reduce the risk of warfarin-induced embryopathy and LMWH (Reviparin, 3500 anti Xa U/thrice a day) was administered. Routine echocardiography after discontinuation of warfarin revealed normal heart function with no abnormal findings. A routine standard ECG performed by her family doctor prior to pregnancy showed sinus rhythm. The woman was admitted to our hospital at her 24th week of gestation with acute pulmonary edema and hemodynamic instability. Echocardiography showed a severe thrombosis of the mitral valve prosthesis. Emergency mitral valve re-replacement was performed. During the operation the fetus was monitored by cardiotocography by an obstetrician and tocolytic agents were administered. Anesthesia was maintained with continuous propofol and fentanyl infusions. A standard non-pulsatil extracorporal circulation set up was used. The prime solution was composed of 1125 ml of Ringer's lactate, 250 ml of albumin 5% and 125 ml of manitol 20%. Normothermic cardiopulmonary bypass was initiated after cannulation of the aorta and the superior and inferior vena cava. Maternal blood pressure was set to be 80 mmHg and the pump blood flow was 
2.5 l/m2 per min. When fetal bradycardia developed the pump flow was increased. For myocardial protection cold blood cardioplegia was infused into the aortic root. The patient underwent mitral valve re-replacement through a standard transseptal approach. A large thrombus was found on the mitral valve prothesis avoiding adequate function of both leaflets. After detailed discussion with our patient regarding technical approaches to and outcome following various kinds of valve replacement strategies with special regards to the data published in the literature, the patient decided her thrombosed mechanical mitral valve to be replaced by a biological valve. The post operative cause was uneventful and the patient was disconnected form mechanical ventilation at the day of operation. Normal fetal heart rates were observed on cardiotocographic examinations postoperatively. The woman was discharged from hospital at the 23th postoperative day and the pregnancy was carried out uneventfully.
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3. Comment
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Sufficient anticoagulation after mechanical heart valve replacement is mandatory to prevent thromboembolic complications. Pregnant women represent a special problem due to the hypercoaguable state during pregnancy and the lack of reliable data on safety and efficacy of different anticoagulation regimes during pregnancy. Three different anticoagulation regimens have been recommended in the literature: (i) administration of coumadin derivatives throughout pregnancy and subcutaneous unfractioned heparins (UFH) near term; (ii) substitution of coumadin derivatives with subcutaneous UFH in the first trimester and near term; and (iii) subcutaneous UFH application throughout pregnancy [1–8].
Each of the three ‘standard’ anticoagulative approaches renders mother and fetus to different anticoagulation-related complications. Chan and coworkers comprehensively reviewed the literature from 1966 until 1997, which is the most detailed overview on the evidence from reported cases and patient cohorts regarding anticoagulation strategies in pregnant women with mechanical heart valves [17]. These data clearly demonstrate that the maternal risk of thromboembolic events and death is increased when coumadin was replaced by UFH [17]. The majority of maternal deaths was caused by thrombosis of the prosthetic valve [17]. Since most of the maternal complications occurred when UFH's were used for anticoagulation, LMWH's were considered to be an alternative. Whereas the effectiveness of LMWHs as a substitute of coumadin derivatives for the prevention of thrombosis and pulmonary thromboembolism during pregnancy has been established [9], the role of LMWHs in preventing valvular thrombosis or thromboembolic events in patients with artificial heart valves has yet to be clarified. The evidence in the literature regarding the long-term application of LMWH as the only anticoagulant after mechanical heart valve replacement is limited only to a few reports with a total number of 24 patients and with catastrophic treatment failure in 17% (four out of 24 patients) (Table 1) [10–16]. Underdosage of LMWH's might account for some of the treatment failures reported. However, there are no data available in the literature regarding dose finding studies for LMWH's in the prevention of thromboembolic events after mechanical heart valve replacement during pregnancy.
In summary, considering the limited evidence from the literature and our own clinical observations, we believe that a sufficient evidence-based anticoagulation therapy is mandatory in order to reduce the maternal risk of thromboembolic complications following mechanical heart valve replacement. Both coumadin derivatives and heparins (LMWH and UFH) for anticoagulation carry hazards during pregnancy, but whereas coumadin derivatives bring a small risk to the fetus, heparins jeopardize the mother whose long-term safety is paramount.
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Top
Abstract
1. Introduction
