Asian Cardiovasc Thorac Ann 2002;10:306-309
© 2002 Asia Publishing EXchange Pte Ltd
Effect of Oral Anticoagulant During Pregnancy With Prosthetic Heart Valve
Ashok K Srivastava, MCh,
Ashok K Gupta, MS,
Arvind V Singh, MS,
Tanveer Husain, MSc
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Department of Cardiovascular and Thoracic Surgery Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, Uttar Pradesh, India
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For reprint information contact: Ashok K Srivastava, MCh Tel: 91 522 44 0004 Fax: 91 522 44 0017 email: ashok{at}sgpgi.ac.in Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
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ABSTRACT
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This retrospective study aimed to evaluate the risks and outcome of oral anticoagulant use during pregnancy in women with prosthetic heart valves. Between December 1989 and November 1998, 192 females of childbearing age underwent heart valve replacement with a mechanical prosthesis. There were 37 pregnancies in 30 patients during follow-up. Pregnancy was terminated on medical grounds in 5 cases, there were 2 (6%) spontaneous abortions, and 1 (3%) premature birth of a normal baby who died 24 hours later due to asphyxia. The other 29 pregnancies (91%) went to full term and the mothers continued taking oral anticoagulants until a week before the expected date of delivery, then switched to heparin. There was no thromboembolism, valve thrombosis, or maternal mortality. Three babies (10%) had a skeletal deformity: nasal hypoplasia in all 3, with cleft pinna in 1. Continuation of oral anticoagulants during pregnancy provided adequate protection against thromboembolism and valve thrombosis, but the risks of fetal abnormalities and premature delivery should be explained to women of childbearing age with a mechanical valve prosthesis.
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INTRODUCTION
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Pregnancy poses several problems for patients with prosthetic heart valves who require lifelong anticoagulant therapy to prevent thromboembolic phenomena and prosthetic valve thrombosis.1,2 Controversy remains concerning the choice of anticoagulant during pregnancy. Antiplatelet agents alone, such as dipyridamole or aspirin, do not provide sufficient protection against thromboembolism in this situation. Oral anticoagulants adequately protect the mother against thromboembolism but carry serious risks to the fetus, such as embryopathy and fetal loss, especially if the drugs are administered during the first trimester.3–5 On the other hand, heparin does not cross the placenta and is therefore not teratogenic, but it does not guarantee protection from prosthetic valve thrombosis, and it is not technically feasible to administer parenteral heparin throughout pregnancy.6 This retrospective study aimed to assess the risks and evaluate the outcome of continuing oral anticoagulants during pregnancy in women who had received mechanical heart valves in our institute.
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PATIENTS AND METHODS
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Between December 1989 and November 1998, 1007 patients (500 men, 507 women) underwent heart valve replacement with a mechanical prosthesis in our institute. Of these, 192 were females of childbearing age. They were informed of the choice of prostheses, and opted for a mechanical valve because of the proven long-term durability, despite awareness of the adverse effects of oral anticoagulants and the risk of thromboembolism during pregnancy. Over 9 years, 37 pregnancies were recorded in 30 patients. Twenty-five women had received a mitral prosthesis, 3 had undergone both mitral and aortic valve replacements, and 2 had an aortic valve prosthesis only. The mechanical valves inserted included Medtronic-Hall (Medtronic, Inc., Minneapolis, MN, USA) in 20 cases (16 in the mitral and 4 in the aortic position), Sorin (Sorin Biomedica, Saluggia, VC, Italy) in 10 (9 mitral and 1 aortic), 1 St. Jude Medical (St. Jude Medical, Inc., St. Paul, MN, USA) and 1 Starr-Edwards (Baxter Healthcare, Edwards CVS Division, Santa Ana, CA, USA) in the mitral position. Most patients reported their pregnancy between 2 and 4 months of gestation when the advantage of heparin therapy to prevent warfarin embryopathy had been lost. Thus, there was no choice other than to continue oral warfarin throughout the pregnancy. Warfarin was stopped one week prior to the expected date of delivery and replaced with parenteral heparin. In addition to routine clinical and hematological examinations during antenatal check-up, all patients underwent a complete fetal ultrasound examination at 20 weeks gestation. Clinical data obtained from medical records for analysis included age, New York Heart Association functional class, cardiac rhythm, anticoagulant dosage, number of pregnancies and their sequelae.
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RESULTS
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Only 30 of the 37 pregnancies proceeded beyond 28 weeks. The clinical data of these pregnancies are listed in Table 1
. Twenty-four women conceived once, 5 conceived twice, and one became pregnant 3 times. Five women opted for termination of pregnancy on medical grounds during the first trimester as they decided they had completed their families. The majority of patients (80%) received oral warfarin in a dosage of 2 to 3 mg daily, and this was continued throughout the pregnancy to maintain a prothrombin time of 1.5 to 2 times the control value. There was no incidence of thromboembolic phenomena or prosthetic valve thrombosis. There were 2 spontaneous abortions (6%) between 6 and 8 weeks of gestation. These occurred in mothers taking high doses of warfarin (3–4 mg) because their prothrombin times could not be maintained within the therapeutic range on a lower dose.
Of the 30 pregnancies that proceeded beyond 28 weeks, one (3%) ended in premature labor as a result of local sepsis. A normal female baby of low birth weight was born with no congenital deformity, but she died 24 hours after birth due to asphyxia. The other 29 pregnancies reached full term. A normal vaginal delivery was achieved in 22 cases, and 7 patients underwent a lower segment cesarean section. There was no incidence of antepartum or postpartum hemorrhage. The mean birth weight was 2.57 kg (range, 1.3 to 3.5 kg). Three children (10%) developed a skeletal deformity in the form of nasal hypoplasia in 2, and cleft pinna of the left ear in addition to nasal hypoplasia in one.
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DISCUSSION
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Rheumatic heart disease is still rampant in the developing world, in spite of improvements in socioeconomic factors and greater awareness. This necessitates heart valve replacement at a young age.6,7 The ideal choice of prosthesis for women of childbearing age is still unresolved despite advancements in the design of prosthetic heart valves. A mechanical prosthesis although durable and with an excellent hemodynamic performance, requires lifelong anticoagulation to prevent thromboembolic complications.4,8 A bioprosthesis avoids the need for anticoagulation but confers only a temporary advantage because pregnancy leads to accelerated structural deterioration that ultimately requires reoperation. Reoperation rates in mothers with a bioprosthesis range from 13% to 59% at 7 to 12 months after delivery.2,5,9 Pregnancy in women with a mechanical heart valve prosthesis carries increased risk for both mother and fetus.10 A hypercoagulable state exists in pregnancy because of increased levels of circulating fibrinogen and clotting factors, decreased fibrinolytic activity, increased platelet turnover, and increased viscosity.11,12 These factors greatly increase the risks of valve thrombosis and thromboembolic phenomena. Therefore, women with mechanical valves require more scrupulous anticoagulant treatment during pregnancy. The risks are greater for those with a mitral rather than aortic valve prosthesis.13 In this series, there was no incidence of thromboembolism or valve thrombosis. A similar study from South Africa reported no thromboembolic complications or death even though only 39% of mothers had an international normalized ratio within the target range.9 A report from India of a similar protocol for 47 pregnancies in 37 patients described valve thrombosis in 2 patients who were successfully treated surgically.8 Other studies have shown that oral anticoagulants provide adequate protection during pregnancy in mothers with prosthetic valves.14–16
The use of heparin instead of an oral anticoagulant before conception and during the first and third trimesters has been advocated, but this has resulted in hemorrhagic complications throughout pregnancy, leading to fetal intracranial microhemorrhage and fetal loss from abortion and stillbirth due to placental separation and hemorrhage.4,9 Ben Ismail and colleagues17 in a series of 71 pregnancies in 51 Tunisian women with cardiac valve prostheses, found that heparin was less effective than oral anticoagulant, and concluded that changing to heparin in the first trimester was not justified. They did not observe any teratogenic effects. Wang and colleagues18 encountered 5 thromboembolic events in 14 pregnancies after substituting subcutaneous heparin for warfarin in the first trimester. Larrea and colleagues19 noted a lower incidence of fetal complications in women who had changed to intravenous heparin in the first trimester than in those taking warfarin throughout, but at the expense of higher maternal mortality. Increased risk to the fetus is related primarily to oral anticoagulants during the first trimester.6,9 The incidence of spontaneous abortion in our study was 6%, much lower than in other studies with rates of 15% to 23.4%.19 The low rate of spontaneous abortion in our series was attributed to lower doses of warfarin required to maintain optimal anticoagulation. Only one patient in this study went into labor prematurely; this was unrelated to the use of oral anticoagulant. The 10% incidence of embryopathy is a little higher than other series (4%–7.9%), although much less than the highest reported rate of 29.6% in a study where geneticists identified the abnormalities.20 Vitale and colleagues21 observed a close correlation between warfarin dosage and fetal complications.
The findings of this study support the continuation of oral anticoagulants during pregnancy in women with prosthetic heart valves, because adequate protection against thromboembolism and valve thrombosis was provided. As pregnancy in women with mechanical valves carries a higher risk for both the mother and the fetus, women should be encouraged to complete their families before valve replacement. Those desiring children should be aware that the likelihood of a successful pregnancy is in the order of 90%.
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ABSTRACT
INTRODUCTION
