Sultan Qaboos University Med J, November 2014, Vol. 14, Iss. 4, pp. e448−454, Epub. 14TH Oct 14 Submitted 14TH Mar 14 Revision Req. 14TH Apr; Revision Recd. 27TH Apr 14 Accepted 8TH May 14

REVIEW

Mechanical Prosthetic Valves and Pregnancy A therapeutic dilemma of anticoagulation *Prashanth Panduranga,1 Mohammed El-Deeb,1 Chitra Jha2

‫صمامات القلب الصناعية واحلمل‬ ‫املعضلة العالجية ملنع ختثر الدم‬

‫ �شيرتا جها‬،‫ حممد الديب‬،‫برا�شانت باندوراجنا‬ abstract: Choosing the best anticoagulant therapy for a pregnant patient with a mechanical prosthetic valve is controversial and the published international guidelines contain no clear-cut consensus on the best approach. This is due to the fact that there is presently no anticoagulant which can reliably decrease thromboembolic events while avoiding damage to the fetus. Current treatments include either continuing oral warfarin or substituting warfarin for subcutaneous unfractionated heparin or low-molecular-weight heparin (LMWH) in the first trimester (6–12 weeks) or at any point throughout the pregnancy. However, LMWH, while widely-prescribed, requires close monitoring of the blood anti-factor Xa levels. Unfortunately, facilities for such monitoring are not universally available, such as within hospitals in developing countries. This review evaluates the leading international guidelines concerning anticoagulant therapy in pregnant patients with mechanical prosthetic valves as well as proposing a simplified guideline which may be more relevant to hospitals in this region. Keywords: Heart Valve Prosthesis; Pregnancy; Warfarin; Low-Molecular-Weight Heparin; Thrombosis.

‫ ال يزال هختيار العالج الأمثل ملنع تخرث الدم على ال�صمامات ال�صناعية �أثناء احلمل حمل نقا�ش كما �أن الإر�شادات العالجية‬:‫امللخ�ص‬ ‫ واحلقيقة �أن ال�سبب الرئي�س لذلك هو عدم توفر العالج الذي مينع تخرث الدم ويف‬.‫ال حتوي توجيهات وا�ضحة بالن�سبة للعالج الأمثل‬ ‫ الأول يتمثل يف ا�ستمرار تعاطي دواء الوارفارين والآخر ا�ستبدال‬:‫ يف الوقت احلايل هناك طريقان للعالج‬.‫ذات الوقت ال ي�رض باجلنني‬ ‫ �أ�سبوع‬6-12 ‫الوارفارين بحيث يتعاطى املري�ضا لهيبارين غري املجزأ املعطى حتت اجللد �أو الهيبارين ذا الوزن اجلزيئي املنخف�ض من‬ ‫ورغم �أن �أنواع الهيبارين ذات الوزن اجلزيئي املنخف�ض ت�ستعمل وبكرثة يف هذه احلاالت �إال �أن‬.‫من احلمل �أو خالل �أي فرتة �أثناء احلمل‬ ‫ وللأ�سف فإن هذا الفح�ص غري متوفر يف معظم م�ست�شفيات‬،‫) يف الدم‬Xa( ‫متابعة العالج حتتاج �إىل فح�ص م�ستويات م�ضاد العامل‬ ‫ �إن الغر�ض من هذا البحث يتمثل يف مراجعة الإر�شادات والتوجيهات الطبية العاملية التي ن�رشت بخ�صو�ص عالج تخرث‬.‫البالد النامية‬ .‫الدم يف الن�ساء احلوامل وكذلك حماولة تقدمي طريقة مب�سطة للعالج الأمثل ملثل هذه احلاالت يف هذه املنطقة‬ .‫ �صمامات القلب ال�صناعية؛ احلمل؛ الوارفارين؛ الهيبارين ذا الوزن اجلزيئي املنخف�ض؛ تخرث الدم‬:‫مفتاح الكلمات‬

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urrently, the optimal anticoagulant therapy to use during pregnancy in patients with mechanical prosthetic valves (MPVs) remains controversial, with the published international guidelines lacking a clear-cut consensus on the issue.1‒4 This is due to the fact that presently there is no anticoagulant available which results in both an excellent maternal outcome, defined by fewer thromboembolic events (TEs), and minimal fetal damage, which is defined by the prevention of fetal loss or embryopathy. The case study that follows focuses on a pregnant patient with prosthetic valve thrombosis who was administered a fixed dose of lowmolecular-weight heparin (LMWH) throughout her first pregnancy. The leading international guidelines are then evaluated and a simplified approach to managing this type of patient is proposed.

Case Study A 28-year-old Omani pregnant woman was admitted to a regional hospital in Oman in August 2009 for monitoring. She had received a St. Jude Medical™ standard bileaflet MPV (St. Jude Medical, Inc., Saint Paul, Minnesota, USA) for mitral regurgitation in the UK 15 years previously. The patient had been on regular warfarin (6 mg per day) since receiving the implant with good international normalised ratio (INR) control. When her pregnancy had become apparent in January 2009, the warfarin was stopped and she was begun on LMWH instead. She was prescribed dalteparin which was administered subcutaneously once daily at a dosage of 10,000 IU. She continued taking LMWH throughout her pregnancy without being monitored for her anti-factor Xa levels as such monitoring was not available at the regional hospital.

Departments of 1Cardiology and 2Obstetrics & Gynaecology, Royal Hospital, Muscat, Oman *Corresponding Author e-mail: [email protected]

Prashanth Panduranga, Mohammed El-Deeb and Chitra Jha

Figure 1 A & B: Transoesophageal echocardiograms showing (A) a large, soft clot over the mechanical prosthetic bileaflet mitral valve on the atrial side (arrowheads) and (B) a thrombus with the immobile leaflet of a mechanical prosthetic bileaflet mitral valve in a closed position (arrowheads). The other leaflet can be seen to be opening well. LA = left atrium.

At 36 weeks, the patient underwent an emergency Caesarean section due to fetal distress, with a resultant live birth. Post-operatively, she developed acute pulmonary oedema which was managed with diuretics. The patient was then moved to the Royal Hospital, a tertiary hospital in Muscat, Oman, for further management. Her INR was 1.0 and her activated partial thromboplastin time (aPTT) was 30.1 seconds (range: 27.2–39.1 seconds). A transthoracic echocardiogram of the MPV showed a peak pressure gradient of 43 mmHg, a mean gradient of 25 mmHg (which had risen from a previously reported gradient of 16 mmHg at her regional hospital) and a calculated mitral valve area of 0.9 cm2. There was a loss of movement in one of the leaflets of the MPV. There was mild tricuspid regurgitation with a pulmonary artery systolic pressure of 85 mmHg and a left ventricular ejection fraction of 60%. Transoesophageal echocardiography confirmed

the presence of one immobile leaflet and detected a large soft immobile thrombus (1 cm2) towards the atrial side [Figures 1A & B]. In view of the patient’s recent surgery, thrombolysis was contraindicated. After a week-long continuous infusion of unfractionated heparin (UFH) with aPTT monitoring, the mean gradient on a repeat transthoracic echocardiogram was 16 mmHg. There were no embolic complications or bleeding. However, fluoroscopy showed that one of the leaflets was stuck in the closed position [Figures 2A & B]. The patient underwent a successful redo mitral valve replacement surgery using a size 27 St. Jude Medical™ MPV (St. Jude Medical, Inc.). At a oneyear follow-up, the patient was doing well and had a normally functioning MPV.

International Guidelines Current management strategies for pregnant women

Figure 2 A & B: Fluoroscopy showing (A) the immobile leaflet of the mechanical prosthetic bileaflet mitral valve stuck in the closed position, while (B) the opposite leaflet opens well.

Review

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Mechanical Prosthetic Valves and Pregnancy A therapeutic dilemma of anticoagulation

(up until 36–38 gestational weeks) with MPVs are varied. They include continuous oral warfarin; changing from warfarin to subcutaneous UFH or LMWH in the first trimester and then back to warfarin; continuous subcutaneous UFH, or continuous LMWH throughout the duration of the pregnancy.1‒4 In the absence of controlled clinical trials, most, if not all, of these recommendations are based on limited observational data. american college of cardiology/american heart a s s o c i at i o n

In their 2008 and 2014 guidelines for the selection of an anticoagulation regimen in pregnant patients with MPVs, the American College of Cardiology (ACC) and American Heart Association (AHA) suggest a detailed discussion with the patient regarding all of their anticoagulation therapeutic options during pregnancy.1,2 Specifically, warfarin is strongly recommended in pregnant patients with a MPV to achieve a therapeutic INR in the second and third trimesters. However, recommendations regarding the subcutaneous use of LMWH and UFH throughout pregnancy, as well as the subcutaneous use of UFH in the first trimester, have been removed completely from these guidelines. According to the 2014 ACC/AHA guidelines, the main risk period for complications is within the first trimester.1,2 The continuation of warfarin during the first trimester is permissible if the dose of warfarin does not exceed 5 mg per day. For those who require stronger doses of warfarin in the first trimester or among those whose preferred treatment option is LMWH, the LMWH should be administered twice daily and the dose should be adjusted to attain peak anti-factor Xa levels of 0.8–1.2 U/mL approximately 4–6 hours after the injection. Alternatively, to achieve a therapeutic anticoagulation, dose-adjusted continuous intravenous (IV) UFH (with an aPTT at least twice that of the control) during the first trimester is permissible if the dose of warfarin is greater than 5 mg per day. In addition, the guidelines recommend adding low-dose aspirin (75–100 mg per day) in the second and third trimesters. If warfarin is the preferred method of treatment throughout the pregnancy, the dose should be adjusted to attain a target INR of 3.0 (range: 2.5–3.5).1 However, the use of IV UFH in the first trimester is difficult from a practical standpoint, as a three-month hospital admission is required. european society of cardiology

Despite being released three years earlier than the

ACC/AHA guidelines, the 2011 European Society of Cardiology (ESC) guidelines for managing patients with valvular heart disease is very similar.3 These guidelines recommend that patients requiring less than 5 mg of warfarin per day should continue warfarin until 36 weeks of gestation (with an embryopathy risk of

Mechanical Prosthetic Valves and Pregnancy: A therapeutic dilemma of anticoagulation.

Choosing the best anticoagulant therapy for a pregnant patient with a mechanical prosthetic valve is controversial and the published international gui...
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