Abstracts
Guidelines provide great contribution to the reduction of potential obstetric and fetal risks and to the improvement of health care during pregnancy and puerperium. However, there are still controversies regarding the management of anticoagulation in women with heart diseases. The importance of this issue is based on the fact that thromboembolism is considered one of the main causes of maternal death in women with heart diseases; therefore, the acquisition of knowledge about how to prevent this disorder is mandatory. The strategy of the antithrombotic treatment is based on the risk of thrombosis imposed by the maternal clinical picture and on the adverse effects of the anticoagulants for the conceptus. In the present study, we discussed the stratification of maternal risk of thromboembolism, the properties of the anticoagulants indicated for its prevention, and the therapeutic strategy at different moments of pregnancy, delivery and puerperium of women with heart diseases.
Thromboembolism; anticoagulation; heart disease; pregnancy
Diretrizes em muito contribuem para minimizar os potenciais riscos obstétricos e fetais e melhorar a assistência durante o ciclo gravídico-puerperal. Contudo, há controvérsias a respeito do manuseio da anticoagulação em mulheres portadoras de cardiopatias. A importância deste assunto assenta-se no fato de que o tromboembolismo é considerado uma das principais causas de morte materna em portadoras de cardiopatia, o que torna obrigatório o conhecimento sobre sua prevenção. A estratégia do tratamento antitrombótico é ponderada pelo risco de trombose imposto pela situação clínica materna e pelos efeitos adversos que os anticoagulantes podem causar ao concepto. Neste artigo, serão discutidas a estratificação do risco materno ao tromboembolismo, as propriedades dos anticoagulantes indicados para a sua prevenção e a estratégia terapêutica nos diversos momentos da gestação, parto e puerpério da mulher portadora de cardiopatia.
Tromboembolismo; anticoagulação; cardiopatia; gravidez
REVIEW ARTICLE
Anticoagulation during pregnancy of woman with heart disease
Walkiria Samuel Ávila
Professora livre-docente em Cardiologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil, Médica-chefe, Setor de Cardiopatia e Gravidez do Instituto do Coração (InCor), Hospital das Clínicas da FMUSP, São Paulo, SP, Brazil
Correspondence
ABSTRACT
Guidelines provide great contribution in reducing potential obstetric and fetal risks and improving health care during pregnancy and puerperium. However, there are controversies regarding the management of anticoagulation in women with heart diseases. The importance of this issue is based on the fact that thromboembolism is considered one of the main causes of maternal death in women with heart diseases; therefore, the acquisition of knowledge about how to prevent this disorder is mandatory. The strategy of the antithrombotic treatment is based on the risk of thrombosis imposed by the maternal clinical picture and on the adverse effects of the anticoagulants for the conceptus. In the present study, the stratification of maternal risk of thromboembolism, the properties of anticoagulants indicated for its prevention, and the therapeutic strategy at different moments of pregnancy, delivery and puerperium of women with heart diseases are discussed.
Keywords: Thromboembolism, anticoagulation, heart disease, pregnancy.
Introduction
Anticoagulation during pregnancy is a situation which habitually provokes a dilemma in medical practice, since it means searching prevention for maternal thromboembolism and safety, avoiding hemorrhage and fetal teratogenicity.
Thromboembolism risk during pregnancy
Thromboembolism is considered one of the main causes of death during pregnancy for women suffering from heart diseases.1Rheumatic valvular disease, that remains the most common heart disease in young women, increases the risk conditions to the occurrence of thromboembolism during pregnancy, whether of natural valve or of valve prosthesis.
In a study conducted with 19 cases of thromboembolism during pregnancy, it was observed that valvular rheumatic disease corresponded to 12 (63.1%) and six (31.6%) cases distributed in congenital heart disease and lung hypertension, respectively.1
Thromboembolic potential is centered usually in the patient's clinical situation, but it is aggravated by the particularities inherent to pregnancy, such as those of rheological, mechanical and hormonal nature,(Table 1) specially from the second trimester of pregnancy on and culminating in puerperium. Other factors, such as age, parity, smoking, obesity, prolonged rest, cesarean section add to this situation, increasing the incidence of thromboembolic phenomenon during pregnancy and puerperium.
Guidelines of anticoagulation during pregnancy take into account the thrombosis risk of heart diseases,(Table 2) in which the advantage of anticoagulation must be balanced with obstetric and fetal damage. High risk situations demand permanent anticoagulation, while in those of lower risk it may be transitory or controversial.2
Thromboembolism and hemorrhagic complications constitute the greater disadvantages in mechanical prostheses, corresponding to 20 to 2.5% of the cases, respectively. In the period ranging from 2000 to 2006 at the Instituto do Coração (Heart Institute - InCor) 650 heart disease-carrying pregnant women were studied, among which 64 (9.8%%) used anticoagulants. Rheumatic valve disease corresponded to 50% of this casuistic, including patients with atrial fibrillation and mechanical prostheses; congenital heart disease to 14% and dilated cardiomyopathy to the other 12% of heart disease-carrying women.1
Properties of anticoagulants in pregnancy
Unfractionated heparin (UH) and low-molecular weight heparin (LMWH) did not cross placental barrier, therefore, they are conceptually preferential anticoagulants during pregnancy. However, their prolonged use is associated to maternal side effects, including thrombocytopenia, hemorrhage and osteoporosis. Added to these are the discomfort of its application, the difficulty of controlling anticoagulation and the cost.
Advantages of LMWH in comparison to UH are its superiority in relation to bioavailability (100 versus 30%), average life after application (2 hours versus 1 hour), to subcutaneous absorption (100 versus variable) and to lower incidence of thrombocytopenia (0 versus 2.7%). Yet, there are limitations to its use which include inadequate neutrality by the protamine sulphate and its monthly cost.3
Permanent use of warfarin is indicated in patients who have mechanical prostheses and atrial fibrillation, but it crosses the placental barrier and it may be associated with fetal embryopathy, which includes from chondrodysplasia punctata, in mildest form, to nasal hypoplasia, atrophy optic and metal retardation in the severe forms. The reported fetal risks vary widely, but its average is 6%. This warfarin syndrome happens when the fetus is exposed to warfarin between the sixth and the ninth weeks of gestation. In addition, the use of warfarin is associated with spontaneous abortion in around 10 to 30% of the cases. During the second and third trimesters of gestation, warfarin is associated with a high incidence of restriction to intrauterine fetal growth, premature baby, central nervous system anomaly and neonatal death due to cerebral hemorrhage.4
Recommendations for the use of anticoagulants during pregnancy
There is no universal consensus on which would be the best anticoagulation method for pregnant women suffering from heart diseases in face of the various risks resulting from thrombosis, because no pharmacological option, whether isolated or combined, provided evidence related to the efficacy in not bringing about side effects for mother or fetus.
The clinical studies continue to support the use of warfarin in permanent anticoagulation for those carrying mechanical prostheses and discouraging the use of subcutaneous UH. Data from InCor reinforce those in literature when they show that 85% of thromboembolism cases during pregnancy in patients who carry mechanical prostheses are associated to the use of subcutaneous UH.5,6
However, LMWH use increases as a safe and effective anticoagulant alternative to warfaring during the first trimester of gestation and before labor and delivery. There is a tendency to indicate LMWH in situations with a lower risk of thrombosis, including permanent atrial fibrillation, pulmonary hypertension, stroke previous to or during electric cardioversion. In these situations, the time of use of the anticoagulant may be limited to the third semester and puerperium, moments of hypercoagulability.
Chan et al.7reviewed 1,234 pregnancies of women carrying mechanical prostheses and showed that replacing warfarin with heparin in the first trimester can eliminate fetal embriopathy, but increases the risk of thromboembolism.
The current recommendations of Pregnancy and Heart Disease Division of Heart Institute of Clinical Hospital of Medical School of University of São Paulo to anticoagulation in pregnant women must be according to the heart disease risk of thrombosis as exposed below.
Higher risk situations
Option 1: it is recommended, in the first week of menstrual delay and with positive human chorionic beta-gonadotropin (βHCG), replacing warfarin with LMWH subcutaneous enoxoparine 1 mg/kg/dose every 12 hours up to the 13th week; reintroducing oral VO warfarin and maintaining it up to the 36th week, when the patient should be hospitalized. In this moment the warfarin should replace unfractionated heparin in a 10-12 UI/kg/h IV up to 4 hours before delivery. Six hours after delivery, reintroducing heparin IV in the same administration models as in pre-delivery and 48 hours after that, warfarin again.
Option 2: in women whose first prenatal medical visit was after the sixth week of pregnancy, warfarin should not be interrupted until the 36th week, following option 1.
Option 3: the patient who initiates pre-natal without anticoagulant repeats option 1.
Adjustments of dosage should be performed according to laboratorial tests, in order for warfarin dose to be controlled by the International Normalized Ratio (INR) between 2.5 and 3.5 per week, and afterwards every 15 days; enoxoparin should be administered maintaining anti-Xa factor between 0.6 and 0.8 UI/mL, and be collected 4 hours after application, with weekly control, the unfractionated heparin dose must be regulated by activated partial thromboplastin time (APTT) which should be maintained between 1.5 and 2.5 times normal value, controlled two times a day until it reaches therapeutic level and, afterwards, once every day. Platelets count should be periodically followed up due to the risk of thrombocytopenia.
Indication of delivery type is obstetrical, but for patients using warfarin Sodium during labor, the option is cesarean section to reduce the risk of neonatal cerebral hemorrhage. In cases of urgency cesarean section with high INR value under use of warfarin sodium, the INR should be adjusted with the IV administration of fresh plasma 10 mL/kg (two and three bags) + Vitamin K (Kanakion MM 2.5 mg IM) or, substituting for the latter, prothrombin complex 10 UI/kg diluted in 50 mL of physiological solution for infusion IV. INR for performance of safe cesarean section must be ? 1.5; if it is between 2.0 and 5.0, it must be corrected with fresh plasma or prothrombinic complex; if it is > 5.0, fresh plasma or prothrombinic complex should be administered associated with vitamin K. The use of warfarin in puerperium does not contraindicate breastfeeding.
Lower risk situations
Option 1: enoxoparin 40mg/day until 13th week; afterwards, warfarin (maintaining INR between 2 and 2.5) until 36th week; return to enoxoparin in a prophylactic level until 24 hours before delivery; maintain without anticoagulant medication and, six hours after puncture or catheter withdrawal, reintroduce enoxoparin (which should be maintained until the proper adjustment of INR); 48 hours after restarting warfarin.
Option 2: enoxoparin 40 mg/day during the whole pregnancy period.
Option 3: unfractionated heparin 10,000 U SC 12/12 h until 13th week and, after 36th week, 10,000 SC 8/8h.
Familial planning
The orientation for planning on future pregnancy and contraception demands the respect for the autonomy of the patient who permanently uses oral anticoagulants. It is important, thus, to highlight that there is no contraindication to pregnancy, but to warn about the possible morbidity of using warfarin sodium. Generally, there is a tendency to discourage an offspring of more than two children due to maternal and fetal morbidity and lethality, which include hemorrhage, thromboembolism, abortion, teratogenesis, adding to these the costs and prolonged hospitalization. Open dialog with the couple is crucial.
In this aspect, the choice for tubal ligation for couples who do not intend to have children should be pondered, as well as reversible contraceptive methods to other situations.8Among the contraceptives that do not provoke interaction with anticoagulants, composites with progesterone are highlighted, including trimestrial injectable forms, oral and those implanted in subcutaneous tissue.
Concluding, the role of the cardiologist is that of increasing the patient's awareness that being properly anticoagulated represents an essential condition for the development of pregnancy, but it does not prevent risks for herself and her child.
References
- 1. Ávila WS, Rossi EG, Ramires JAF, et al. Pregnancy in patients with heart disease: experience with 1,000 cases. Clin Cardiol. 2003;26:135-42.
- 2. Ávila WS, Grinberg M. Anticoagulação, gravidez e cardiopatia. Uma tríade, três domínios e cinco momentos. Arq Bras Cardiol. 2005;84:44-8.
- 3. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S-203S.
- 4. Cotrufo M, De Feo M, De Santo LS, et al. Risk of warfarin during pregnancy with mechanical valve prostheses. Obstet Gynecol. 2002;99:35-40.
- 5. Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):627S-44S.
- 6. Ginsberg JS, Chan WS, Bates SM, Kaatz S. Anticoagulation of pregnant women with mechanical heart valves. Arch Intern Med 2003;163:694-8.
- 7. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160:191-6.
- 8. Gouveia AMM, Ávila WS, Martins CR, et al. Sucesso da contracepção reversível em mulheres portadoras de cardiopatias. Arq Bras Cardiol. 2005;83(Suppl 1):45.
Correspondência:
Publication Dates
-
Publication in this collection
23 Apr 2010 -
Date of issue
2010
History
-
Received
09 Feb 2009 -
Accepted
17 Dec 2009
