Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary centre experience

doi:10.1016/j.ejogrb.2011.09.011

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 159, Issue 2, December 2011, Pages 320-323

https://doi.org/10.1016/j.ejogrb.2011.09.011 Get rights and content

Abstract

Objective

This study was undertaken to analyze the maternal and perinatal outcome in women with prosthetic heart valves on different anticoagulant regimens.

Study design

A retrospective chart review of pregnancies in 40 women with mechanical valve prostheses at a tertiary referral centre from 1997 to 2010. The main outcome measures were major maternal complications and perinatal outcome.

Results

The valves replaced were mitral (67.5%), aortic (15.0%), or both (17.5%). Forty-nine pregnancies (72.1%) resulted in live births, 3(4.4%) had stillbirths, and 13(19.1%) had spontaneous abortions and 1(1.4%) underwent therapeutic abortions. The live birth rate was higher in women on heparin (78.3%) compared with those on warfarin (66.9%). There were 2 maternal deaths due to acute mitral valvular thrombosis while on acenocoumarol in the second trimester. Hemorrhagic complications occurred in 3 patients on heparin in the postpartum period, 2 of whom required transfusion. In addition one patient who was on acenocoumarol developed secondary hemorrhage.

Conclusion

No anticoagulant regimen can be said to be entirely safe for use during pregnancy as there is a degree of risk with each regimen. Further larger studies are needed to come up with sufficient evidence-based recommendations for the best possible management of such patients to reduce the maternal risks after mechanical heart valve replacement without compromising fetal outcome.

Introduction

The prevalence of women with mechanical valves becoming pregnant has been on the rise, especially in developing countries where the incidence of valvular diseases in children is still high. Many of them undergo valve replacement surgeries at a young age; subsequently they get pregnant. Patients with mechanical prosthetic valves require lifelong anticoagulation to minimize the high risk of associated thrombo-embolic complications. Being a physiologic hypercoagulable state, pregnancy further increases the risk of such events [1]. Even though there is an agreement regarding the use of mandatory therapeutic anticoagulation in pregnancy for these women, there is no agreement on the safest and the most effective method of anticoagulation.

Treatment options include oral anticoagulants (coumarin derivatives), unfractionated heparin (UFH) and low molecular-weight heparin (LMWH). The risk of thromboembolic complications in women on coumarin derivatives is reduced to 3.7%, if they are maintained on it throughout pregnancy, with a 0.5–1.8% risk of maternal death [2], [3]. However, its use must be tempered by its probable adverse effects on the fetus with a reported 12% rate of late fetal loss and 6.4% rate of congenital malformations [3], [4]. This has led many authorities to advocate the use of heparin as a replacement for coumarin derivatives, at least during the first trimester. One drawback of UFH is the high rate of treatment failure with reports of maternal mortality from thrombosed valves [3], [5].

The aim of our study is to analyze the maternal and perinatal outcome in these high risk pregnancies and also, to evaluate different regimes used in pregnant women with prosthetic heart valves.

Section snippets

Material and methods

All pregnant women with prosthetic heart valves registered in the Cardio-Obstetric (CO) Clinic at the Nehru Hospital, Postgraduate Institute of Medical Education & Research, Chandigarh during the time period from January 1997 to December 2010 are included in the study. By reviewing the clinic proforma we retrieved the maternal and neonatal data. Information on maternal age, parity, valve replacement procedure, anticoagulation regime, gestational age at delivery, mode of delivery,

Results

Over a 13-year period, we identified 70 pregnancies in 40 women with prosthetic heart valves. After excluding 2 pregnancies with unavailable delivery information, 68 pregnancies were only analyzed for the perinatal outcome. Maternal and disease characteristics are summarized in Table 1. A majority of the women had more than one pregnancy, with 40% having 2 pregnancies and 17.5% having 3 pregnancies. Most of the women underwent replacement of the mitral valve (67.5%). The type of the prosthesis

Comments

The present study presents the experience with different anticoagulant regimes used in a tertiary centre from a developing country. Overall, 72.1% resulted in live births and 69.2% had vaginal delivery. There were 2 maternal deaths due to acute valvular thrombosis The incidence of hemorrhagic complications was significantly higher in the group which received heparin in the first and the late third trimester with acenocoumarol in the second trimester. However there was an increased incidence of

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Cited by (25)

High-Versus Low-Dose Warfarin–Related Teratogenicity: A Case Report and Systematic Review
2018, Journal of Obstetrics and Gynaecology Canada
Citation Excerpt :
We were also limited by excluding non-warfarin VKA reports; however, we sought to reflect on North American practices. Despite this, we did identify four studies (n = 194) in which patients received acenocoumarol where two cases of teratogenicity were identified.43–45,51 Although these are important limitations, we do report the most comprehensive review of warfarin dose–related teratogenicity.
The optimal anticoagulant therapy during pregnancy in women with mechanical heart valves remains controversial. This study highlights a case of high-dose warfarin ingestion throughout pregnancy and performed a systematic review to assess rates of teratogenicity with high versus low warfarin dosing (≤5 mg daily).
A literature search for all case reports and available literature was conducted in PubMed, Medline, and EMBASE up to December 2016 using medical subject heading terms “mechanical prosthetic valves,” “pregnancy,” “oral anticoagulants,” “warfarin,” “coumarins,” “heparin, low-molecular-weight,” and “thromboembolism.” To be included, warfarin had to be administered anytime between 6 and 12 weeks of gestation with the dose being specified. The Newcastle-Ottawa Scale was used to assess quality of the cohort data.
The woman in the studied case received the highest reported warfarin doses throughout pregnancy (14.5–16.5 mg daily) and delivered a baby with no evidence of teratogenicity to the current age of 5 years. The study identified 23 case reports, with all demonstrating warfarin teratogenicity regardless of high-dose (n = 12) or low-dose (n = 11) warfarin. Twelve cohort studies identified a warfarin teratogenicity rate of 5.0%, with rates of 2.4% and 10.5% with low- and high-dose warfarin, respectively. Risk of bias was moderate (median Newcastle-Ottawa Scale score of 6) for all of the cohort studies.
Although a lower prevalence of warfarin-induced teratogenicity is reported with low-dose warfarin, a safe “cut-off” dose is misleading. Teratogenic risk with warfarin is unpredictable, mandating individual decisions regardless of the dose.
Il n'y a toujours pas de consensus quant à l'anticoagulothérapie optimale chez les femmes enceintes portant une valvule cardiaque mécanique. Cette étude examine un cas où la patiente a pris de la warfarine à forte dose tout au long de la grossesse et fait une revue systématique visant à déterminer les taux de tératogénicité de la warfarine à forte et à faible (≤5 mg par jour) doses.
Nous avons cherché dans PubMed, MEDLINE et Embase toutes les déclarations de cas pertinentes ainsi que des articles, jusqu'à décembre 2016, à partir des sujets médicaux (MeSH) suivants : « mechanical prosthetic valves », « pregnancy », « oral anticoagulants », « warfarine » « coumarins » « heparin, low-molecular-weight » et « thromboembolism ». Nous avons inclus les cas et études où la warfarine avait été administrée entre 6 et 12 semaines de grossesse, et où la dose était mentionnée. La qualité des données de cohorte a été évaluée selon la Newcastle-Ottawa Scale.
Dans le cas examiné, la patiente avait reçu les doses de warfarine les plus élevées jamais rapportées pour une grossesse complète (14,5–16,5 mg par jour), et, au moment de l'étude, il n'y avait toujours aucun signe de tératogénicité chez son enfant, qui avait alors cinq ans. Notre revue a recensé 23 déclarations de cas; chacune faisait état d'une tératogénicité de la warfarine, que la dose soit forte (n = 12) ou faible (n = 11). Douze études de cohorte ont été incluses; le taux de tératogénicité global était de 5,0 %, et plus précisément de 2,4 % et de 10,5 % à faible et à forte dose, respectivement. Chacune de ces études présentait un risque de biais modéré (score moyen sur la Newcastle-Ottawa Scale = 6).
Bien que les cas de tératogénicité de la warfarine soient moins fréquents à faible dose, dire qu'il existe un seuil sécuritaire serait trompeur. En effet, le risque est imprévisible, de sorte que les décisions doivent être prises en fonction de chaque patiente, quelle que soit sa dose.
Anticoagulation Regimens During Pregnancy in Patients With Mechanical Heart Valves: A Systematic Review and Meta-analysis
2016, Canadian Journal of Cardiology
Citation Excerpt :
All of the tests were 2-tailed. After an extensive literature search and review, we were able to include 51 studies (54 records), of which 37 studies (39 records) used a VKA regimen.14-52 Eleven included studies reported results in the low-dose subgroup of a VKA regimen,32,33,35,37,39,40,42-44,47,49 and 7 included studies reported high-dose subgroup results.32,35,37,40,44,47,49
Managing anticoagulation in pregnant women with mechanical heart valves remains challenging. Our aim was to evaluate the effectiveness and safety of 4 regimens in these women.
Relevant studies published before June 2015 were collected in several databases and analyzed with RevMan version 5.3 and SPSS version 19.0. Four regimens were defined as follows: a regimen of a vitamin K antagonist (VKA) throughout pregnancy; a heparin (H)/VKA regimen using VKAs except for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 6-12 weeks of pregnancy; a LMWH regimen of adjusted LMWH doses throughout pregnancy; and a UFH regimen of adjusted UFH doses throughout pregnancy. The low warfarin dose in the VKA regimen was defined as 5 mg/d or less.
Fifty-one studies comprising 2113 pregnancies in 1538 women were included. The rate of fetal wastage was significantly higher in the high warfarin dose subgroup than in the low dose one. Compared with the H/VKA regimen, the rate of maternal major thromboembolic event in the low-dose VKA regimen group was significantly lower, although the fetal outcomes were similar. Compared with the H/VKA regimen, the rate of fetal wastage in the LMWH regimen group was significantly lower, and the maternal outcomes were similar. The UFH regimen presented the worst maternal and fetal outcomes.
In the absence of large prospective trials, this meta-analysis showed that the VKA regimen should be best for pregnant women with a low warfarin dose, and the H/VKA regimen might be reasonable for those with a high warfarin dose. The LMWH regimen could be used for those who refuse VKA.
Le traitement anticoagulant chez les femmes enceintes munies de valvules cardiaques mécaniques demeure problématique. Notre objectif était d’évaluer l'efficacité de quatre traitements différents chez ces femmes.
Une série d’études pertinentes publiées avant juin 2015 ont été recueillies dans diverses bases de données et analysées à l'aide de la version 5.3 du logiciel RevMan et de la version 19.0 du logiciel SPSS. Les quatre traitements consistaient respectivement en: 1) l'administration d'un antagoniste de la vitamine K (AVK) pendant toute la grossesse; 2) l'administration d'héparine (H) et d'un AVK, c'est-à-dire un traitement à base d'un AVK auquel se substituait un traitement par une héparine non fractionnée (HNF) ou une héparine de faible poids moléculaire (HFPM) pendant 6 à 12 semaines de la grossesse; 3) l'administration d'héparine de faible poids moléculaire dont la dose était ajustée au besoin pendant toute la grossesse; et 4) l'administration d'héparine non fractionnée dont la dose était ajustée au besoin pendant toute la grossesse. Administrée en concomitance avec le traitement par l’AVK, une faible dose de warfarine était définie comme une dose de 5 mg ou moins de warfarine par jour.
Cinquante et une études portant sur 2113 grossesses chez 1538 femmes ont été retenues. Le taux de perte du fœtus était significativement plus élevé chez le sous-groupe de femmes recevant une dose importante de warfarine par rapport à celui qui recevait une faible dose de warfarine. Comparativement aux femmes traitées par l'héparine et l’AVK, l'incidence des événements thromboemboliques graves a été significativement inférieure chez celles traitées par un AVK à faible dose, mais les effets pour les fœtus ont été comparables. Par rapport au groupe traité par l'héparine et l’AVK, l'incidence de perte du fœtus a été significativement moindre dans le groupe traité par l’HFPM, tandis que les effets pour les mères ont été semblables. C'est le traitement par l’HNF qui entraîné les pires résultats tant pour les mères que pour les fœtus.
En l'absence d'importantes études prospectives, cette méta-analyse a permis de déterminer que le traitement par un AVK est vraisemblablement le plus approprié pour les femmes enceintes recevant une faible dose de warfarine, tandis que celui par l’H/AVK pourrait être jugé acceptable pour les femmes enceintes traitées par une forte dose de warfarine. Le traitement par l’HFPM pourrait pour sa part être offert aux femmes enceintes qui refusent de prendre un AVK.
Cardiac, obstetric, and fetal outcomes during pregnancy after biological or mechanical aortic valve replacement
2014, Canadian Journal of Cardiology
The aim of this study was to assess pregnancy-related cardiac, maternal, and fetal outcomes in women who underwent aortic valve replacement (AVR).
From 1978-2011, 67 women < 40 years of age underwent 74 isolated AVRs (52 mechanical prostheses and 22 bioprostheses). All patients were prospectively followed at our dedicated valve clinic. Patients with Turner syndrome, previous hysterectomy, or tubal ligation were excluded. Cardiovascular, obstetric, and fetal outcomes were gathered from medical records and telephone interviews.
A total of 27 pregnancies were reported in 14 patients (bioprosthetic AVR, n = 20; mechanical AVR, n = 7). In the bioprosthetic AVR group, the following adverse events occurred: hospitalizations for syncope (n = 2), prosthetic valve deterioration after pregnancy necessitating reintervention 6 months postpartum (n = 1), miscarriages (n = 9), and preterm birth (n = 1). In the mechanical AVR group, the following adverse events occurred: embolic myocardial infarctions with a decrease in systolic function (n = 2; 1 pregnancy was terminated and 1 was completed), miscarriage (n = 1), postpartum bleeding (n = 1), urgent cesarean section for placental abruption (n = 1), and preterm birth (n = 1).
Findings from this study suggest that pregnancies in women with mechanical AVRs are associated with a higher risk of cardiac and obstetric adverse events. Thus, from this limited cohort, it appears that pregnancies in women with bioprostheses are safer than those in patients with mechanical AVRs.
Le but de cette étude était d'évaluer les résultats cardiaques, maternels et fœtaux, liés à la grossesse chez les femmes qui avaient subi un remplacement valvulaire aortique (RVA).
De 1978 à 2011, 67 femmes < 40 ans ont subi 74 RVA isolés (52 prothèses mécaniques et 22 bioprothèses). Toutes les patientes ont été suivies de manière prospective à notre clinique de valves cardiaques. Les patientes qui avaient un syndrome de Turner, avaient subi une hystérectomie ou une ligature des trompes ont été exclues. Les résultats cardiovasculaires, obstétriques et fœtaux ont été recueillis dans les dossiers médicaux et lors des entrevues téléphoniques.
Un total de 27 grossesses ont été rapportées chez 14 patientes (RVA par bioprothèse, n = 20; RVA par bioprothèse mécanique, n = 7). Dans le groupe ayant subi un RVA par bioprothèse, les événements indésirables suivants sont survenus : hospitalisations en raison d'une syncope (n = 2), dégradation de la prothèse valvulaire exigeant une nouvelle intervention 6 mois après la grossesse (n = 1), avortements spontanés (n = 9) et naissance prématurée (n = 1). Dans le groupe ayant subi un RVA par prothèse mécanique, les événements indésirables suivants sont survenus : infarctus du myocarde par embolie associés à une diminution de la fonction systolique (n = 2; 1 grossesse a été interrompue et 1 a été menée à terme), avortement spontané (n = 1), hémorragie de la délivrance (n = 1), césarienne urgente en raison d'un abruptio placentae (n = 1) et naissance prématurée (n = 1).
Les résultats de cette étude montrent que les grossesses chez les femmes ayant subi un RVA par prothèse mécanique sont associées à un risque plus élevé d'événements cardiaques et obstétriques indésirables. Par conséquent, cette cohorte limitée semble montrer que les grossesses chez les femmes ayant subi un RVA par bioprothèse sont plus sûres que celles des patientes ayant subi un RVA par prothèse mécanique.
Thromboembolism in pregnancy: Challenges and controversies in the prevention of pregnancy-associated venous thromboembolism and management of anticoagulation in women with mechanical prosthetic heart valves
2014, Best Practice and Research: Clinical Obstetrics and Gynaecology
Thromboembolism in pregnancy is an important clinical issue. Despite identification of maternal and pregnancy-specific risk factors for development of pregnancy-associated venous thromboembolism, limited data are available to inform on optimal approaches for prevention. The relatively low overall prevalence of pregnancy-associated venous thromboembolism has prompted debate about the validity of recommendations, which are mainly based on expert opinion, and have resulted in an increased use of pharmacological thromboprophylaxis in pregnancy and postpartum. A pragmatic approach is required in the absence of more robust data. Anticoagulation management of pregnant women with mechanical prosthetic heart valves is particularly challenging. Continuation of therapeutic anticoagulation during pregnancy is essential to prevent valve thrombosis. Warfarin, the most effective anticoagulant, is associated with adverse fetal outcomes, including embryopathy and stillbirth. Fetal outcome is improved with therapeutic-dose low-molecular-weight heparin, but there may be more thromboembolic complications. More intensive anticoagulation, targeting higher trough anti-Xa levels, may reduce the risk of valve thrombosis.
Anticoagulant choices in pregnant women with mechanical heart valves: Balancing maternal and fetal risks - The difference the dose makes
2013, Thrombosis Research
Long-term anticoagulation is required in all patients with mechanical prosthetic heart valves to prevent complications with valve thrombosis and valve failure or systemic thromboembolism. The prothrombotic environment of pregnancy further increases the risks of these complications. Anticoagulant choices for pregnant women include oral vitamin K antagonists such as warfarin, or heparin – either unfractionated heparin (UFH) or low molecular weight heparin (LMWH). None of the options is without risk for the mother or her baby. Warfarin crosses the placenta and is associated with warfarin embryopathy and fetopathy but is very effective at preventing thromboembolic complications. The dose of warfarin may play a role in the risk of some, but not all fetal complications. Heparin does not cross the placenta but is less effective at preventing thrombosis and LMWH may be more effective than UFH. The optimal dose and target anti-Xa levels for LMWH have not been established. Measurement of trough anti-Xa levels in addition to peak anti-Xa levels may be important.
Treasure to the mother and threat to the fetus: case report of warfarin-associated fetal intracranial hemorrhage and review of literature
2023, Journal of International Medical Research

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Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary centre experience

Abstract

Objective

Study design

Results

Conclusion

Introduction

Section snippets

Material and methods

Results

Comments

J Am Coll Cardiol

Am J Obstet Gynecol

Am J Med

Chest

AJOG

Thromb Res

The hypercoagulable states

Ann Intern Med