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Ann Thorac Surg 2000;69:264-265
© 2000 The Society of Thoracic Surgeons

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Case Reports

Low-molecular-weight heparin for prosthetic heart valves: treatment failure

^a Department of Thoracic and Cardiovascular Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

Address reprint requests to Dr Mohr, Department of Thoracic and Cardiovascular Surgery, Tel-Aviv Sourasky Medical Center, 6 Weizman St, Tel-Aviv 64239, Israel

	Abstract

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There is no adequate substitute therapy for patients with prosthetic heart valves, in whom anticoagulation with warfarin or unfractionated heparin must be withheld. In the literature there are several reports describing successful treatment with low-molecular-weight heparin in patients with prosthetic heart valves. We report two cases of low-molecular-weight heparin treatment failure resulting in thrombosed prosthetic heart valves with stormy clinical presentations, who underwent successful valve replacements.

	Introduction

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The role of low-molecular-weight heparin (LMWH) as an anticoagulant is well established [1]. Its properties make it an attractive substitute for unfractionated heparin or warfarin when these are contraindicated. There are no controlled trials investigating the suitability and safety of LMWH for patients with prosthetic heart valves. This report describes two cases of LMWH treatment failure resulting in thrombosed mechanical heart valves, with near fatal outcome.

	Case reports

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Patient 1
A 29-year-old woman with rheumatic mitral stenosis and regurgitation was operated on 3 years earlier for mitral valve replacement (MVR) with a mechanical bileaflet prosthetic valve (Sorin Bicarbon 33 mm; Sorin Biomedica Cardio SpA, Saluggia, Italy). Because of pregnancy, anticoagulation with warfarin was replaced by enoxaparin (Clexane, Rhone-Poulenc, France), subcutaneous, 40 mg once daily. Transesophageal echocardiography performed before discontinuation of warfarin was normal.

She was admitted in the 35th week of pregnancy, after 32 weeks of treatment with enoxaparin, with acute pulmonary edema and severe hemodynamic decompensation. Echocardiography confirmed the diagnosis of prosthetic valve thrombosis. Emergency cesarean section was carried out and midsternotomy was performed during the gynecologic procedure because of hemodynamic instability. The patient underwent MVR through a right atriotomy and a transseptal approach. A large organized thrombus was observed on the mitral prosthesis blocking the disks. A new mechanical bileaflet valve (Sorin Bicarbon 33 mm) was implanted. Postoperative course was uneventful for both mother and child. Anticoagulation with warfarin was resumed, because no contraindications existed after termination of pregnancy.

Patient 2
In the second case, a 72-year-old man underwent aortic valve replacement (AVR) and coronary artery bypass grafting 18 months earlier. A mechanical bileaflet valve (Sorin Bicarbon 21 mm) was implanted at the aortic position. Echocardiography at discharge demonstrated a normally functioning valve. Following a cerebral hemorrhagic, stroke treatment with warfarin was changed to enoxaparin, 40 mg twice daily. After 37 weeks of treatment with enoxaparin, the patient presented with severe pulmonary congestion. On fluoroscopy, the movement of only one leaflet was demonstrated and in echocardiography peak aortic gradient was 82 mm Hg and aortic valve area was 0.45 cm². Urgent AVR was performed using the standard approach. The artificial valve, severely obstructed with organized thrombus on both aortic and ventricular aspects, was explanted and replaced by a Carbomedics 21-mm reduced mechanical aortic valve (Sulzer Carbomedics, Austin, TX). Postoperative course was uncomplicated. Anticoagulation with warfarin was reluctantly renewed.

	Comment

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In this study we examined cases of LMWH treatment failure in patients with artificial heart valves. Currently, there is no adequate substitute therapy for the large group of patients with prosthetic heart valves, in whom conventional anticoagulation must be withheld. The efficacy of LMWH in the prevention and treatment of thromboembolism and unstable angina pectoris has been proved [1]. In comparative studies, LMWH proved to be as effective as, and in some reports superior to, unfractionated heparin. It is associated with a reduced risk of bleeding and, with a few exceptions, laboratory monitoring is unnecessary because of its better bioavailability, longer half-life, dose-dependent clearance, and decreased affinity to heparin binding proteins. Side effects such as heparin-induced thrombocytopenia and osteoporosis are far less common. Because it does not cross the placenta, LMWH is not teratogenic (as is warfarin). It is the anticoagulant of choice in pregnancy [1].

A literature search reveals several reports regarding the use of LMWH in patients with artificial heart valves. Therapy with LMWH (nadroparin calcium) was reported in 2 patients with mechanical Starr-Edwards (cage-ball) mitral valves during pregnancy [2]. Long-term anticoagulation (4–58 weeks) with LMWH (KABI 2165) was described in 6 patients with prosthetic heart valves. Indications for the changes made in therapy were cerebral and gastrointestinal bleeding during treatment with warfarin or unfractionated heparin [3]. In another report, oral anticoagulation was substituted by KABI 2165 in 12 patients with artificial heart valves, because of adverse events [4]. A recent report describes a patient with a mechanical aortic valve who was treated with enoxaparin (1 mg/kg, twice a day) because of poor compliance to oral anticoagulants [5]. In all of the above-mentioned cases, no major thrombotic events occurred and the authors concluded that LMWH is efficient and safe.

The issue of correct dosage remains unclear and it seems that therapeutic margins are very narrow. It is accepted that doses exceeding 100 antifactor Xa units per kilogram per body weight are associated with excessive bleeding. However, based on the cases presented here, it is apparent that the dose of 40 mg twice a day is insufficient, even for valves in the aortic position, which is considered to be less thrombogenic.

In our practice, both thrombogenic events occurred on Sorin Bicarbon valves. Unfortunately, we could not determine the incidence of LMWH treatment failure, because information regarding the prevalence of our patients with prosthetic valves placed on LMWH could not be obtained. Sorin Bicarbon valves represent the new-generation, low-profile prosthetic valves with acceptable antithrombogenic properties and well-determined, reproducible results. However, comparative accelerated wear studies, confirmed by clinical observations, demonstrated that the carbon coating on the hinge regions of the Sorin Bicarbon valve design has a higher tendency to erode, exposing the underlying titanium surface [6]. The St. Jude (St. Jude Medical, St. Paul, MN) and Carbomedics (Sulzer Carbomedics) mechanical valves proved to be more resistant. Whether the consequence of the loss of the pyrolytic carbon and the exposure of the titanium surface may predispose to thrombus formation, particularly in the presence of low-intensity anticoagulation, is not determined. Despite the above-mentioned, the same anticoagulation therapeutic ratios are recommended for all bileaflet-tilting-disk valves and in patients receiving adequate anticoagulation, the incidence of valve thrombosis is similar [7]. Whether a certain type of valve is more amenable to LMWH, and whether it is respective of valve position, is currently unclear.

According to the recommendations for antithrombotic therapy for patients with prosthetic heart valves, both presented cases were considered to be at low risk for thrombosis [7]. Anticoagulation with warfarin was substituted to enoxaparin only, with no addition of antiplatelet regimens. The addition of antiplatelet drugs to LMWH might have provided additional protection, but at the cost of increased risk of bleeding.

Finally, the type of LMWH is also of interest. The LMWHs are distinct compounds with different pharmacological profiles and it is uncertain whether results obtained with one drug can be extrapolated to another.

In conclusion, the use of LMWH as a substitute anticoagulant in patients with prosthetic heart valves is attractive, but until proper recommendations are established, its use carries a considerable risk.

	References

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1. Weitz J.I. Low-molecular-weight heparins. N Engl J Med 1997;337:688-698.[Medline]
2. Lee L.H., Liar P.C., Ng A.S. Low molecular weight heparin for thromboprophylaxis during pregnancy in 2 patients with mechanical mitral valve replacement. Thromb Haemost 1996;76:628-630.[Medline]
3. Harenberg J., Schwartz F., Dietz R., Leber G., Zimmerman R., Kubler W. Anticoagulation with low molecular weight heparin in patients with prosthetic heart valve replacement. Z Kardiol 1987;76:284-288.[Medline]
4. Harenberg J., Leber G., Dempfle C.E., Heene D.L., Zimmerman R., Kubler W. Long term anticoagulation with low molecular weight heparin in outpatients with side effects on oral anticoagulation. Nouv Rev Fr Hematol 1989;31:363-369.
5. Manley H.J., Smith J.A., Garris R.E. Subcutaneous enoxaparin for outpatient anticoagulation therapy in a patient with aortic valve replacement. Pharmacotherapy 1998;18:408-412.[Medline]
6. Taylor K.M. Overview. J Heart Valve Dis 1996;5(Suppl I):S7-S8.
7. Vongpatanasin W., Hillis L.D., Lange R.A. Prosthetic heart valves. N Engl J Med 1996;335:407-416.[Medline]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Amir Kramer Jacob Gurevitch Rephael Mohr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lev-Ran, O. Articles by Mohr, R. Search for Related Content PubMed PubMed Citation Articles by Lev-Ran, O. Articles by Mohr, R.