warfarin and Abortion--Spontaneous

Management of a pregnant patient with mechanical heart valve is a complex issue for all health care providers involved in the care of such patients. Complications may arise at any stage due to the increased haemodynamic load imposed by pregnancy or because of impaired cardiac performance often seen in these patients. In addition, the use of various cardiovascular drugs in pregnancy (especially anticoagulants) may lead tofoetal loss or teratogenic complications. Additionally, the risk of thrombo-embolic complications in the mother is increased by the hypercoagulable state of pregnancy. In this review, we have attempted to draw inferences to guide management of such patients based on the available literature. It seems that in pregnant women with mechanical heart valves, recent data support warfarin use throughout pregnancy, followed by a switch to heparin and planned induction of labour. However, the complexity of this situation demands a cafeteria approach where the patient herself can choose from the available options that are supported by evidence-based information. Unfortunately there is no consensus on such data. An overview of the available literature forms the basis of this review. In conclusion, a guideline comprising pragmatic considerations is preffered.

Topics: Abortion, Spontaneous; Anticoagulants; Aspirin; Drug Administration Schedule; Female; Fetal Diseases; Heart Valve Prosthesis; Heparin; Humans; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Assessment; Thromboembolism; Warfarin

The antiphospholipid syndrome is an antibody mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. Several studies have determined that the frequency of antiphospholipid syndrome in patients presenting with a venous thromboembolic event is between 4% and 14%. Classical criteria include the presence of anticardiolipin antibody or lupus anticoagulant with typical complications of thrombosis or pregnancy loss. Other common associated manifestations include livedo reticularis, thrombocytopenia, valvular heart disease, and nephropathy with renal insufficiency, hypertension and proteinuria. Because of the high risk for recurrent thromboembolism in these patients, current recommendations suggest a longer, potentially lifelong, course of antithrombotic therapy following an initial event. For an initial venous thromboembolic event, a target INR of 2.0 to 3.0 is supported by two prospective, randomized clinical trials. In contrast, relatively limited data exist for an initial arterial thromboembolic event in patients who have the antiphospholipid syndrome, and therapeutic recommendations range from aspirin to warfarin with a high target INR. Recurrent thromboembolic events can be extremely difficult to treat, and some patients may benefit from the addition of immunosuppressive therapies. It is very important to evaluate in this setting additional, coincident prothrombotic risk factors.

Topics: Abortion, Spontaneous; Acenocoumarol; Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolytic Agents; Heparin; Humans; Lupus Coagulation Inhibitor; Male; Platelet Aggregation Inhibitors; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thrombophilia; Thrombosis; Warfarin

For haemostatic and circulatory reasons pregnancy is associated with an about 6-fold relative increase of thrombotic risk which is further raised by additional risk factors, such as history of thrombosis or acquired and hereditary thrombophilia, respectively. Recently, the thrombophilias have been revealed as risk factors for severe preeclampsia, abruptio placentae, fetal growth retardation, abortion and still birth as well. Thus, there are several situations in which the question for the need of antithrombotic medication is raised in a pregnant woman, either for therapy of acute thromboembolism or for prophylaxis of thrombosis and obstetrical complications, respectively. While acute thromboembolism has to be treated in every case, indication for prophylaxis has to be weighed in the light of the individual risk profile of the pregnant woman and the potential side effects and inconvenience of the medication. The first part of this article deals with the pregnancy related problems of coumarins, heparins and aspirin and demonstrates that the low molecular weight heparins are the anticoagulants of choice for most indications in pregnancy. The second part of this overview shows in which specific situations and how the antithrombotic medications mentioned above are used in pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abruptio Placentae; Administration, Oral; Adult; Anticoagulants; Aspirin; Blood Coagulation Tests; Coumarins; Female; Fetal Death; Fetal Growth Retardation; Fibrinolytic Agents; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Pulmonary Embolism; Risk Factors; Thrombocytopenia; Thrombophilia; Thrombosis; Warfarin

In patients with mechanical prosthetic heart valves, long-term anticoagulant therapy is mandatory to prevent thromboembolic phenomena. Anticoagulation is also necessary in patients with mitral valvular disease and atrial fibrillation. The risk of maternal thromboembolic events is heightened during pregnancy because of the patient's hypercoagulable state. Controversy exists concerning the appropriate treatment of these patients. No method of anticoagulation is risk free. Coumarin derivatives provide adequate protection against thromboembolism and should be used during pregnancy in patients with mechanical prostheses. The administration of coumarin derivatives in the first trimester is associated with an incidence of 26.7% of spontaneous abortion and a risk of 4.1% of coumarin embryopathy. Heparin does not cross the placental barrier and it is the obvious therapeutic alternative. The teratogenic effects of the coumarinics are prevented if these agents are discontinued and replaced by heparin from before the 6th until the end of the 12th week of gestation. However, subcutaneous unfractionated heparin, in the doses that have been employed, does not provide adequate prophylaxis against thromboembolism in these women. In patients treated with heparin, the incidence of spontaneous abortion is similar to that observed when the mothers are treated with coumarin agents. In order to avoid the delivery of an anticoagulated infant, intravenous heparin in full doses, should be substituted for the coumarin agent in the last two weeks of gestation.When anticoagulant therapy is not necessary, the course of pregnancy in women with bioprostheses is similar to that of the general population. However, the short duration of tissue valves is a clear disadvantage for these women

Topics: Abortion, Spontaneous; Adult; Anticoagulants; Coumarins; Female; Fetus; Gestational Age; Heart Valve Prosthesis; Heparin; Humans; Injections, Intravenous; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thromboembolism; Time Factors; Warfarin

The gold standard for treatment of the antiphospholipid antibody syndrome (APS) after thrombosis remains high-intensity warfarin, and, in pregnancy, heparin and aspirin. Exciting developments include the potential role of hydroxychloroquine as a prophylactic drug, stem cell transplantation, and B-cell tolerance. Animal models appear to be a fruitful "proving ground" of new therapies. The introduction of revised classification criteria for APS should aid in appropriate characterization of, and selection of, patients for clinical trials.

Topics: Abortion, Spontaneous; Antiphospholipid Syndrome; Aspirin; B-Lymphocytes; Hematopoietic Stem Cell Transplantation; Heparin; Humans; Immunization, Passive; Injections, Intravenous; Plasmapheresis; Platelet Aggregation Inhibitors; Thrombosis; Warfarin

Ischemic stroke is a complex multifactorial disorder. Anticoagulation is a growing research area, with the main goal of preventing systemic embolization and stroke. We report the case of a 41-year-old woman with antiphospholipid syndrome who was unsuccessfully treated with Dabigatran, a new oral anticoagulant, as she developed a major stroke involving the right carotid artery, due to deep venous thrombosis with pulmonary embolism. We therefore suggest a closer monitoring of the safety and efficacy of dabigatran. Moreover, in the presence of multifactorial causes of pro-coagulation, we believe that warfarin should remain the mainstay of oral anticoagulation.

Topics: Abortion, Spontaneous; Acenocoumarol; Adult; Antiphospholipid Syndrome; Antithrombins; Carotid Arteries; Computed Tomography Angiography; Dabigatran; Female; Follow-Up Studies; Humans; Product Surveillance, Postmarketing; Pulmonary Embolism; Stroke; Treatment Outcome; Venous Thrombosis; Warfarin

To explore the influence of the single use of perinatal warfarin anticoagulation therapy on pregnancy outcome after the mechanical heart-valve replacement surgery in pregnant women.. Fifty-eight cases of pregnant women after heart-valve replacement surgery (2005.1-2009.12) received low-dose warfarin anticoagulation therapy. The perinatal outcomes included: (1) maternal complications: thrombosis, hemorrhage, heart failure, etc., and (2) adverse perinatal outcomes: miscarriage, stillbirth, neonatal death, fetal malformation, preterm delivery, such as warfarin syndrome.. In 58 patients, valve thrombosis was found in one case of pregnancy, general hemorrhage was found in 16 cases, spontaneous abortion was found in two cases, malformation was found in two cases. There were no stillbirth and neonatal death. Three cases were premature delivery. Thirty-two of 56 cases were late pregnancy vaginal delivery. Twenty-four cases were cesarean section produced, in which heart failure happened in 1 case and late postpartum hemorrhage happened in one case.. The low-dose and low-intensity warfarin anticoagulation therapy during pregnancy is good for patients with good compliance and low rate of fetal malformations and can effectively prevent maternal complications.

Topics: Abortion, Spontaneous; Adult; Anticoagulants; Aortic Valve; Cardiac Valve Annuloplasty; Cesarean Section; Congenital Abnormalities; Delivery, Obstetric; Ecchymosis; Epistaxis; Female; Gingival Hemorrhage; Heart Valve Prosthesis; Humans; Mitral Valve; Pregnancy; Premature Birth; Thrombosis; Warfarin; Young Adult

A pro-thrombotic condition was described in 1983 which was characterised by the presence of circulating antiphospholipid antibodies, as well as peripheral thrombosis (e.g. DVT), a tendency to internal organ involvement, repeated miscarriage, and, occasionally, thrombocytopenia (aPL) (Hughes, Br Med J 287:1088-1089, 1983). Previously, there had been a number of observations, mainly in patients with lupus having "false positive" tests for syphilis, miscarriage and circulating lupus anticoagulants. The description in 1983 had three notable features (a) a detailed comprehensive clinical picture of the syndrome; (b) this description differed from other coagulopathies in showing a propensity for arterial thrombosis (e.g. stroke and heart attack); and (c) this was a syndrome quite independent from lupus. There are indications that the primary antiphospholipid syndrome will turn out to be more common than lupus, though this could still be a reflection of referral practice.

Topics: Abortion, Spontaneous; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Arterial Occlusive Diseases; Aspirin; Brain Diseases; Cardiovascular Diseases; Constriction, Pathologic; Female; Heparin, Low-Molecular-Weight; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infarction; Pregnancy; Thrombosis; Warfarin

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

Topics: Abortion, Spontaneous; Academic Medical Centers; Acenocoumarol; Adult; Anticoagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Incidence; India; Medical Records; Mitral Valve; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Retrospective Studies; Thrombosis; Warfarin; Young Adult

Patients with mechanical heart valves require anticoagulation which is associated with significant maternal mortality (1-4%) and fetal complications (31%) in pregnancy. The study aim was to identify anticoagulant protocols and outcomes for pregnant women undergoing heart valve replacement (HVR) in the United Kingdom.. Women aged between 18 and 45 years and registered with the United Kingdom Heart Valve Registry (UKHVR) each completed a questionnaire, and their obstetric notes were reviewed. The data analyzed included valve type (mechanical, bioprosthetic, homograft), valve site (mitral, aortic, tricuspid, pulmonary), anticoagulation at confirmation of pregnancy, between 6-12 weeks and from 12 weeks to term, delivery, maternal and fetal outcomes, and cause of death. The summary statistics and a descriptive review of the findings are reported.. Of 2,532 women eligible for the study, 922 responded. Among these women, 72 became pregnant, with 60 pregnancies in the mechanical valve (MV) group and 45 in the tissue valve (TV) group. Three anticoagulation regimes were used during early pregnancy: unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or warfarin. All women received warfarin in the second trimester and heparin for delivery. Live births were recorded in 30% of MV pregnancies and in 60% of TV pregnancies. Miscarriage rates differed markedly (37% MV versus 2% TV). Fetal outcome was poorest in the warfarin-only group, with embryopathy occurring at a dose level of 6 mg. The maternal outcomes did not differ significantly among groups. High-dose heparin during the first trimester and for delivery was effective for the majority of mechanical valves.. The study results illustrate the diverse and uncertain manner in which UKHVR patients are managed during pregnancy. A national notification system would record much-needed prospective information on anticoagulation and pregnancy outcomes, thus aiding evidence-based management.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anticoagulants; Bioprosthesis; Cause of Death; Dose-Response Relationship, Drug; Female; Fetal Diseases; Heart Failure; Heart Valve Prosthesis Implantation; Heparin; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors; United Kingdom; Warfarin

The aim of this retrospective study was to compare the different anticoagulation regimens used in pregnant women with prosthetic heart valves. We reviewed 196 pregnancies in 110 women from 1974 to 2000. The patients were divided into two groups: group 1 (142 pregnancies) had warfarin throughout pregnancy; and in group 2 (54 pregnancies), warfarin was replaced by subcutaneous heparin during the first trimester and last two weeks of pregnancy. There were no maternal complications in 129 pregnancies in group 1 and 44 in group 2. There were significantly fewer normal births in group 1 (56; 39.4%) compared to group 2 (39; 72.2%). Group 1 had a significantly higher rate of spontaneous abortion (46.5% vs 14.8%), but group 2 had a higher rate of valve thrombosis. In group 1, women with a warfarin requirement < 5 mg had a lower rate of spontaneous abortion. Warfarin is an effective anticoagulant in pregnant women with mechanical valves but it results in significant fetal loss when the dose is > 5 mg. Heparin is a less effective anticoagulant resulting in more maternal complications, but it is more protective of the fetus.

Topics: Abortion, Spontaneous; Administration, Oral; Adult; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fetus; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Heparin; Humans; Injections, Subcutaneous; Patient Selection; Pregnancy; Pregnancy Complications, Cardiovascular; Prosthesis Design; Retrospective Studies; Risk Assessment; Thrombosis; Treatment Outcome; Warfarin

Anticoagulation in pregnancy was evaluated in 33 women with a mechanical heart valve prosthesis who had 53 pregnancies between 1994 and 2006. Their mean age at valve operation was 24.4 +/- 5.4 years, and 22 (67%) had isolated mitral valve disease. Of these patients, 22 had a single pregnancy, 5 had 2 pregnancies, 3 had 3, and 3 had 4. In 43 pregnancies, the patients took warfarin throughout; in the other 10, heparin was used in the first trimester followed by warfarin until the last 15 days. Mean international normalized ratio and warfarin levels before, during, and after pregnancy were similar. Complications occurred in 3 (6%) women who had thrombosed valves: 2 (20%) in the heparin group and 1 (2%) who had warfarin only. Live births resulted from 37 (70%) pregnancies. There were significantly more abortions in the heparin group (6; 60%) than the warfarin group (8; 19%). Hemorrhage requiring transfusion occurred in 2 (5%) patients in the warfarin group. All live births resulted in healthy babies. It was concluded that anticoagulation with warfarin is safe during pregnancy in women with mechanical heart valves.

Topics: Abortion, Spontaneous; Administration, Oral; Adult; Anticoagulants; Drug Administration Schedule; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin; Humans; Pakistan; Patient Selection; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Prosthesis Design; Risk Assessment; Thrombosis; Time Factors; Treatment Outcome; Warfarin

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin

To evaluate maternal complications and perinatal outcomes in women with mechanical heart valves treated with warfarin and heparin during pregnancy.. A retrospective chart review was performed on 45 pregnancies in 28 women who were previously fitted with mechanical valve prostheses and treated between 1991 and 2005 at Seoul National University Hospital. Outcome parameters were maternal complications and perinatal outcomes.. Overall, there were 27 live births (60%), 7 stillbirths (15.6%), 2 therapeutic terminations in the second trimester (4.4%), 9 first-trimester spontaneous abortions (20%) and 2 neonatal deaths after preterm delivery. After excluding 9 first-trimester spontaneous abortions and 3 pregnancies administered warfarin throughout pregnancy, there were significantly more live births among patients administered heparin only after a diagnosis of pregnancy than among those administered warfarin from the second trimester (11 of 11 vs. 13 of 22, p = 0.015). One patient with mitral valve thrombosis during heparinization in the first trimester received valve replacement surgery and then aborted. Late postpartum hemorrhage occurred in 1 patient. All stillbirths and therapeutic terminations occurred in women being administered warfarin.. Warfarin use from the second trimester in combination anticoagulation regimens increases the risk of an adverse perinatal outcome.

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Adult; Anticoagulants; Aortic Valve; Female; Fetal Death; Gestational Age; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Retrospective Studies; Thrombosis; Warfarin

This study was undertaken to evaluate the risks and pregnancy outcome in women with prosthetic heart valves on different anticoagulent regimens.. A retrospective chart review of 82 pregnancies in 33 women with mechanical valve prostheses at a tertiary referral center from 1987 to 2002. The main outcome measures were major maternal complications and perinatal outcome.. The valve replaced was mitral (60.6%), aortic (18.2%), and both (21.2%). Fifty-four pregnancies (65.9%) resulted in live births, 9 (11.0%) had stillbirths (all on warfarin), and 12 (14.6%) had spontaneous and 7 (8.5%) therapeutic abortions (all on warfarin). The rate of spontaneous abortion was highest in women on warfarin throughout pregnancy (P < .01). The live birth rate was higher in women on heparin compared with those on warfarin (P < .01), and in those on heparin/warfarin compared with warfarin alone (P < .01). There were no maternal deaths; however, 3 patients had mitral valve thrombosis (2 on heparin and 1 on warfarin) necessitating surgery in 1 patient and medical thrombolysis in 2 patients. Hemorrhagic complications occurred in 5 patients, 4 of whom required transfusion.. No single anticoagulant regimen confers complete protection from thromboembolic phenomena in pregnancy. Despite a high maternal morbidity rate, the perinatal outcome is acceptable when pregnancy progresses beyond the first trimester.

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Birth Weight; Delivery, Obstetric; Female; Fetal Death; Fetal Growth Retardation; Gestational Age; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies; Thrombosis; Vitamin K; Warfarin

To examine if fetal risks associated with Warfarin anticoagulation during pregnancy may have been over-estimated at the time the drug was contraindicated during pregnancy.. Seven case series with the same therapeutic objective for Warfarin anticoagulation published after 1980 were identified. The frequencies of fetal complications were calculated and compared with those of the 1980 compilation.. The frequencies of embryopathy, stillbirths, and neonatal deaths were similar to the 1980 database, but higher with respect to spontaneous abortions (24.1 vs. 8.6%) and premature deliveries (13.9 vs. 4.6%), and lower regarding live births (73.3 vs. 83.7%).. Fetal risks associated with Warfarin anticoagulation during pregnancy have not been overestimated. Warfarin should not be given in cases where other anticoagulants do not increase the risk for the expecting mother.

Topics: Abortion, Spontaneous; Anticoagulants; Contraindications; Female; Fetal Death; Fetal Diseases; Heart Valve Diseases; Humans; Infant, Newborn; Maternal Exposure; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Cardiovascular; Retrospective Studies; Risk Assessment; Warfarin

To assess the determinants of pregnancy outcome in patients with mechanical valve prostheses anticoagulated with warfarin.. Between January 1987 and January 2000, 52 patients with mechanical valve prostheses who had 71 pregnancies were anticoagulated with warfarin for the entire duration of pregnancy. Warfarin was withdrawn 48 hours before and 24 hours after a scheduled cesarean delivery carried out by the end of the 37th gestational week. The targeted international normalized ratio ranged between 2.25 and 4.0, depending on the prosthetic model. Exact univariate and multivariable analyses were performed to assess which among the following variables predicted poor pregnancy outcome: patient age, prosthetic model, site of implantation, average international normalized ratio, and average daily dose of warfarin.. Pregnancy loss occurred in 23 of 71 of pregnancies, stillbirth in five of 71, embryopathy in four of 71 (two aborted fetuses and two full-term infants). There were no maternal deaths or thromboembolic or hemorrhagic complications. Warfarin daily dosage over 5 mg per day was a significant predictor of poor pregnancy outcome (P <.001).. The risk for pregnancy complications in patients treated with sodium warfarin is higher when the mean daily dose exceeds 5 mg.

Topics: Abortion, Spontaneous; Adult; Age Distribution; Dose-Response Relationship, Drug; Female; Fetal Death; Heart Valve Prosthesis; Humans; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, High-Risk; Prenatal Care; Probability; Retrospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Warfarin

To study the outcome of pregnancy in women with artificial heart valves treated in major European centres, and to compare the safety and efficacy of different anticoagulant regimens and of mechanical and bioprosthetic valves.. Retrospective study.. The information was obtained by questionnaire sent to all major cardiac centres in Europe sending one cardiologist from each centre a covering letter suggesting that the questionnaire be handed on where appropriate to the most relevant colleague.. 214 pregnancies were reported in 182 women; 151 pregnancies in 133 women with mechanical valves, and 63 pregnancies in 45 women with bioprostheses. Most women were in New York Heart Association class I or II and in sinus rhythm. 150 women with mechanical valves and 11 (17%) with bioprostheses received anticoagulants during pregnancy. One patient with an aortic valve prosthesis refused to take anticoagulants. Including the spontaneous abortions reported as well as the therapeutic abortions 83% of the pregnancies in women with bioprostheses and 73% in those with mechanical valves resulted in a healthy baby, full term or premature, who did well (NS). The incidence of stillbirths (3% and 6%) and of reported spontaneous abortions are excluded (because they are unlikely to have been fully reported), the success rate was 91% for women with bioprosthetic valves and 84% for women with mechanical valves (NS). 114 (53%) of the women had taken warfarin for some part of the pregnancy (46 (40%) of these during the first trimester) but there were no embryopathies. There were 13 valve thromboses (four fatal), eight embolic events (two fatal), and seven bleeds in women with mechanical valves. Most of these complications occurred with heparin but fatal aortic valve thrombosis occurred in the one woman who refused anticoagulant treatment out of the 151 women with mechanical valves. There were no maternal deaths in the bioprosthesis group but in 17/49 (35%) of these valves functional deterioration led to urgent replacement during pregnancy (two) or soon after.. The outcome of pregnancy was similar for women with mechanical valves or bioprostheses. Warfarin treatment was safe and effective and was not associated with embryopathy. Heparin treatment was associated with more thromboembolic complications and more bleeding complications. Bioprostheses deteriorate rapidly during pregnancy.

Topics: Abortion, Spontaneous; Adolescent; Adult; Aortic Valve; Bioprosthesis; Cardiology Service, Hospital; Europe; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Medical Audit; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Retrospective Studies; Warfarin

The members of this family with ATIII deficiency have been followed for at least 12 years (1976-1989). All those with previous venous thrombo-embolism have been free from recurrence when on warfarin. During the half century 1931-1981, all 11 full term pregnancies in four affected patients were associated with venous thromboembolism; one patient was enigmatic having one full term pregnancy, without thrombotic event; between 1982 and 1989 three pregnancies have been actively managed with no clinical thrombosis. Management involved use of monitored, self administered, subcutaneous heparin before or very soon after conception and throughout pregnancy (warfarin having been stopped), planned delivery under cover of intravenous antithrombin III, reduction of heparin dosage at delivery and reintroduction of warfarin in the puerperium. The recognised hazards of heparin therapy in pregnancy did not occur. The involvement of the arterial system is reviewed. Clinical evidence provides tentative suggestions on (a) possible additional risk of cigarette smoking (b) avoidance of venography (c) avoidance of varicose vein surgery. A probe is now available for the defective antithrombin III gene in this family, but there has been no occasion yet to apply this in antenatal diagnosis.

Topics: Abortion, Spontaneous; Adult; Antithrombin III; Antithrombin III Deficiency; Cause of Death; Contraindications; Drug Administration Schedule; Female; Follow-Up Studies; Genetic Counseling; Heparin; Humans; Incidence; Infant, Newborn; Male; Metabolism, Inborn Errors; Pedigree; Phlebography; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Warfarin

Lupus anticoagulants are associated with venous and arterial thrombosis and with recurrent spontaneous abortion resulting from placental infarction. Treatment with high-dose prednisone and aspirin has been reported to reduce the otherwise very high frequency of spontaneous abortion in affected women. We report the case of a young woman with an idiopathic lupus anticoagulant who had a history of arterial and venous thrombosis and of previous spontaneous abortion; anticoagulation throughout pregnancy was associated with normal fetal growth and with an absence of placental infarction. We conclude that anticoagulation without concurrent prednisone or aspirin may provide an alternative approach to prevention of habitual abortion in some women with lupus anticoagulants.

Topics: Abortion, Spontaneous; Adolescent; Anticoagulants; Blood Coagulation Factors; Contraceptives, Oral; Female; Humans; Lupus Coagulation Inhibitor; Pregnancy; Thrombophlebitis; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Anticoagulants; Bone Diseases; Female; Heart Valve Diseases; Hemorrhage; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

Adjusted subcutaneous heparin was used for thromboembolism prophylaxis during 18 pregnancies in 16 women with an artificial heart valve. Oral warfarin was replaced by subcutaneous heparin as soon as pregnancy was confirmed. The dosage of heparin was adjusted to maintain a partial thromboplastin time at 1.5 times the control value and treatment was administered during the first trimester and the last 3 weeks of gestation. Warfarin was used between the 13th and 37th week. There were no maternal thromboembolic complications and none of the live-born infants showed congenital malformations, indicating that this regimen is effective. However, there were nine spontaneous abortions, including five that occurred in the first 12 weeks. The early abortions were probably related to warfarin exposure at the beginning of pregnancy. The preconception replacement of warfarin by heparin in these patients may be indicated.

Topics: Abortion, Spontaneous; Administration, Oral; Adult; Drug Therapy, Combination; Female; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Injections, Subcutaneous; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Thromboembolism; Warfarin

During the 13 year period 1971 to 1984 there were 38 pregnancies in 21 renal transplant patients at the Johannesburg Hospital. Twenty-two ended with live births and included two sets of twins; there were nine spontaneous abortions, six therapeutic abortions, and one stillbirth. Maternal complications were mild in the majority but five patients suffered deterioration in renal function, two undergoing transplant nephrectomy as a result of this. There were seven neonatal deaths, including both sets of twins; death was due to prematurity in six and congenital malformation (diaphragmatic hernia) in one. A further infant had congenital pyloric stenosis which was corrected surgically. Pregnancies were analysed according to whether or not their outcome was successful. Those with a successful outcome had less exposure to warfarin during pregnancy (p = 0.0025) and showed a tendency towards lower immunosuppressive doses of prednisone and azathioprine although these did not reach significance. Although these results indicate an unhappy prognosis for both the mother and fetus, two redeeming features are to be noted. Pregnancy outcome improved markedly in the latter years, possibly owing to non-exposure to warfarin, less immunosuppression, and improvement in neonatal care, and four of the five mothers who suffered deterioration in renal function were notoriously unco-operative in their medical care. Pregnancy can only be recommended in the transplanted patient who has stable renal function, is compliant in taking of medications, and whose graft is of such age that the immunosuppressive drug dose is minimal. Warfarin should be avoided.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Acute Kidney Injury; Adolescent; Adult; Dose-Response Relationship, Drug; Female; Fetal Death; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Transplantation; Patient Compliance; Pregnancy; Pregnancy Complications; Warfarin

A syndrome occurring recently in young women and consisting of recurrent abortions, thromboses, and a circulating anticoagulant is described. It is suggested that an antiphospholipid antibody may be responsible for this clinical complex.

Topics: Abortion, Spontaneous; Adult; Female; Glucocorticoids; Heparin; Humans; Partial Thromboplastin Time; Pregnancy; Recurrence; Thrombosis; Warfarin

Between 1979 and 1982, the efficacy of fixed low-dose heparin, administered subcutaneously as thromboembolic prophylaxis, was studied during 14 pregnancies in 10 patients with mechanical heart valves. Calcium heparin (5000 units every 12 hours) was substituted for warfarin during the first trimester and the last month of pregnancy. Although the regimen was well tolerated and was associated with only 14% of first-trimester abortions, five episodes of thromboembolism occurred in four patients. Thus, this fixed, low-dose heparin regimen did not provide adequate thromboembolic prophylaxis in patients with prosthetic heart valves during pregnancy.

Topics: Abortion, Spontaneous; Female; Heart Valve Prosthesis; Heparin; Humans; Injections, Subcutaneous; Mitral Valve; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

During the past 15 years, 12 patients with prosthetic valves were treated during 18 pregnancies in the four Dublin maternity hospitals. These patients were on long-term anticoagulants and their pregnancies were reviewed to assess the problems associated with anticoagulation. One baby had warfarin embryopathy, six pregnancies ended in spontaneous abortions and there were two intrauterine deaths. On the basis of the findings a policy on the most appropriate anticoagulant regimen in such cases was formulated.

Topics: Abortion, Spontaneous; Adult; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Embryo, Mammalian; Female; Fetal Death; Humans; Infant, Newborn; Pregnancy; Warfarin

This report is based on information obtained from a questionnaire sent to major cardiac centres in the United Kingdom. This produced details of 39 pregnancies in 34 patients after valve replacement. The 39 pregnancies gave rise to 30 healthy babies. The small size of the series probably reflects both the increasing rarity of young women with rheumatic heart disease in this country and the cautious attitude of their cardiologists. This makes it likely that these women represented the best end of the spectrum of cardiac function after valve replacement. Twenty-four pregnancies in 20 women who were not given anticoagulants producted 23 healthy babies and 1 spontaneous abortion. This group comprised 6 patients with free aortic homografts, 1 patient with a fascia lata mitral valve, 1 with a Beall tricuspid prosthesis, 1 with a combined mitral homograft and Starr Edwards aortic prosthesis, and 1 with mitral and aortic frame-mounted fascia lata valves. There were no maternal deaths or thromboembolic complications in this group which included 5 patients who were in atrial fibrillation. Fifteen pregnancies in 14 women who received anticoagulants gave rise to 7 healthy babies. The fetal losses were one stillbirth, one intrauterine death at 34 weeks, and 3 spontaneous abortions; one surviving child has hydrocephalus as a result of blood clot and there were 2 maternal deaths. This group included 13 patients with Starr Edwards valves, 11 mitral and 2 aortic. A patient with a Hammersmith mitral valve was the only one to have been treated with heparin and her valve thrombosed. One patient with a mounted mitral homograft had a cerebral embolus. Nine of these patients were in atrial fibrillation. In 3 additional patients the valve replacement was carried out during pregnancy. Two of the patients survived operation. In one of these who was treated with warfarin the pregnancy well, but there is an increased fetal wastage in patients pregnancy gave rise to a congenitally malformed baby who died in the neonatal period. The baby born to the mother who did not receive anticoagulants has a hare-lip and talipes. Women with artificial valves can tolerate the haemodynamic load of pregnancy well, but there is an increased fetal wastage in patients taking oral anticoagulants. This is probably largely attributable to fetal haemorrhage but there is also a risk of malformation caused by a teratogenic effect of warfarin. Experience gained in non-pregnant patients suggests that withholdin

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adolescent; Adult; Anticoagulants; Female; Fetal Death; Heart Valve Prosthesis; Heparin; Humans; Intracranial Embolism and Thrombosis; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Topics: Abortion, Missed; Abortion, Spontaneous; Adult; Anticoagulants; Female; Fetal Death; Fetus; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve Insufficiency; Mitral Valve Stenosis; Phenindione; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin