Elsevier

Thrombosis Research

Volume 124, Issue 3, July 2009, Pages 262-267
Thrombosis Research

Regular Article
Management of pregnant women with mechanical heart valve prosthesis: Thromboprophylaxis with Low molecular weight heparin

https://doi.org/10.1016/j.thromres.2008.12.005Get rights and content

Abstract

Introduction

Pregnancy increases the risk of mechanical heart valve (MHV) thrombosis. Warfarin is protective, but implies risks to the fetus. Unfractionated heparin (UFH) is less effective but does not harm the fetus. In general, anticoagulation is more stable and predictable with low molecular weight heparin (LMWH) than with UFH.

Method

Retrospective study of 12 pregnancies with MHV; 6 in aortic, 4 in mitral, and 2 in both positions, treated with therapeutic doses of subcutaneous LMWH twice daily throughout pregnancy. Doses were adjusted using anti-Xa monitoring. The frequency of thrombo-embolism with various anticoagulation regimes was calculated based on a literature review.

Results

Median LMWH dose was 15500 IU/24 h, range 10000–20000 IU/24 h; median dose 257 IU/kg/24 h. Median peak LMWH in blood plasma ranged 0.54–0.92 anti-Xa U/mL. Thromboembolism developed in two women with aortic MHV despite LMWH levels in target range. One had systemic embolic episodes; in the other woman valve thrombosis was successfully thrombolysed. Both had initially received subtherapeutic doses. Thrombo-embolism was not observed in ten pregnancies treated as recommended. The pregnancies resulted in thirteen healthy babies; eight delivered by Cesarean section. Bleeding occurred in two women after Cesarean section due to preeclampsia.

Conclusion

Treatment with adjusted therapeutic doses of LMWH was successful in 10 of 12 pregnancies, and was not associated with fetal complications. Thromboembolism occurred in two pregnancies, possibly attributed to subtherapeutic doses of LMWH during the initial 3 weeks. Compared to UFH prophylaxis, therapeutic doses of LMWH appears to be more efficacious.

Introduction

Pregnancy increases the risk of mechanical heart valve thrombosis [1], [2] and effective anticoagulation is mandatory [3]. Oral anticoagulants (OA) offer the best protection against thrombosis, but their use is associated with an appreciable risk of fetal malformations and pregnancy loss [4]. Substituting OA with unfractionated heparin (UFH) reduces the risk of fetal damage, but increases the risk of valve thrombosis, even when administered in adjusted doses [4], [5].

A woman with mechanical heart valve prosthesis (MHV) contacted us in 1996 because she wished to become pregnant. She had suffered from abortions while on warfarin during her earlier pregnancies and she demanded an alternative thromboprophylaxis. Low molecular weight heparin (LMWH) has a longer duration and results in more predictable plasma concentrations compared to UFH [6]. We concluded that prophylaxis with therapeutic doses of LMWH under frequent blood monitoring and echocardiographic examination would be a logical alternative for our patient. Pregnancy and delivery were uneventful and the regimen was outlined in the Journal of the Norwegian Medical Association [7]. The regimen was used in 11 additional pregnancies monitored at five Norwegian centers.

The present retrospective case series includes all the 12 pregnancies in women with MHV treated with adjusted, therapeutic doses of LMWH in Norway during 1997-2008. In addition, we have performed a systematic literature search and calculated the pooled frequencies of thromboembolism associated with the different anticoagulation regimes in pregnant women with MHV.

Section snippets

Patients

In order to include all relevant pregnancies, the plan of the present report was described in an article in the May 2006 issue of the Newsletter of the Norwegian Society of Cardiology. The importance of including all women with MHV that had been treated with therapeutic doses of LMWH was emphasized, and physicians were requested to contact the first author. Because local registries did not identify all relevant pregnancies, cardiologists, cardiac surgeons, hematologists, and internists engaged

Outcomes

Symptoms suggesting thrombosis or bleeding were not observed during any of the ten pregnancies in which therapeutic doses of LMWH had been used already within the first week after cessation of warfarin (Table 2). Two women with aortic valve prosthesis (Table 2, no 5 and 6) were prescribed subtherapeutic LMWH (110 IU/kg/24 h once daily in combination with aspirin 75 mg once daily, and 55 IU/kg/24 h twice daily, respectively) by their caring physicians during the initial 20 and 27 days,

Discussion

Effective anticoagulation in pregnant women with MHV is imperative. In the lack of properly sized randomized clinical studies, systematic reviews are important tools for comparisons. Covering the literature prior to 1998, Chan et al reported pooled estimates on the risk of thromboembolic complications. In order to reduce selection bias, these authors included only reports that concerned 6 or more pregnancies [4]. They reported, that with no anticoagulation, thromboembolism occurred in 25.4% of

Limitations of the study

All reports on the effect of LMWH prophylaxis in women with MHV, including the present case series, contain few patients. Although considerable effort was taken to include all relevant pregnancies, we may have missed some. Even when pooling the results, the results with various anticoagulation regimes mostly consist of few patients, and the risk estimates calculated have large confidence intervals.

Conflicts of interest

None

Acknowledgements

The following physicians participated in the monitoring of the patients: Stefan Elvström, Alf Ihlen, Idunn Myklebust, Tone Nerdrum, Anne Mette Njaastad, Gunnar Rongved, and Sigurd Vatn.

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