warfarin and Abortion--Habitual

The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Anti-thrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients. which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk poorly characterized. However, the presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. Clinical trials have demonstrated that patients with antiphospholipid antibodies and venous thromboembolism should be treated with vitamin K antagonists (warfarin); that ischemic stroke may be treated with aspirin or warfarin; and that women with recurrent pregnancy loss should receive prophylactic-dose heparin and aspirin. However, application of these trial results to patients with APS-associated thrombocytopenia can be challenging since there are limited data on the optimal use of antithrombotic agents in this setting. Issues such as determining the platelet threshold at which antithrombotic agents can be safely used and managing patients with both bleeding and thromboembolic complications remain unresolved. Ultimately the risks and benefits of antithrombotic therapy, balanced against the severity of the thrombocytopenia and its potential bleeding risks, need to be assessed using an individualized patient approach.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Aspirin; Blood Transfusion; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Lupus Erythematosus, Systemic; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Thrombocytopenia; Thrombophilia; Venous Thromboembolism; Warfarin

Thromboembolic disease is a rare, but important, complication of pregnancy that remains a leading non-obstetric cause of maternal death. The prevention and management of venous thromboembolism (VTE) in pregnant women is a complex area of medicine: a balance must be found between protecting the health of the mother and minimizing the risk to the unborn fetus. Until now, unfractionated heparin has been regarded as the drug of choice for the prevention and treatment of VTE during pregnancy. However, because of its significant side effects (osteoporosis and heparin-induced thrombocytopenia), the inconvenient mode of administration and need for monitoring, unfractionated heparin is now being replaced by low-molecular-weight heparin (LMWH). There is a convincing body of clinical evidence from well-designed studies and prospective case series that supports the efficacy and safety of LMWH in pregnant women. There are also encouraging observations on the efficacy of LMWH in the prevention of severe obstetric complications, which are frequently associated with inherited or acquired thrombophilias. The recently-published guidelines of The American College of Chest Physicians (ACCP), summarized in this review, allows the development of higher clinical standards. However, there is concern over the greater cost of LMWH compared with unfractionated heparin and oral anticoagulants, and cost-effectiveness studies are needed.

Topics: Abortion, Habitual; Analgesia, Epidural; Anticoagulants; Bone Density; Dalteparin; Female; Guidelines as Topic; Heparin, Low-Molecular-Weight; Humans; Incidence; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thromboembolism; Thrombophilia; Warfarin

More than a decade has gone by since the detailed clinical description of the Antiphospholipid (Hughes) Syndrome. Because of the wide spectrum of manifestations, virtually any physician may encounter patients with this potentially treatable condition. Because of limited controlled, prospective data, current therapy remains empirical and directed at coagulation mechanisms, immune mechanisms, or both. There is now good evidence that patients with antiphospholipid-associated thrombosis will be subject to recurrences and require prophylactic therapy. Although most authorities agree about the efficacy of warfarin alone or warfarin plus low-dose aspirin in preventing recurrences of venous and arterial thrombosis, there is still doubt regarding the intensity and duration of warfarin therapy. Steroids and immunosuppressive drugs have not provided long-term benefit. Controlled clinical trials of the treatment of pregnant women with antiphospholipid antibody demonstrated that prednisolone is ineffective, and possibly detrimental, in treatment of recurrent pregnancy loss and that heparin plus low-dose aspirin is beneficial.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Contraindications; Drug Therapy, Combination; Female; Heparin; Humans; Iloprost; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Recurrence; Thrombophilia; Thrombosis; Warfarin

Antiphospholipid antibody syndrome (APS) is one of the most important causes of thrombophilia, presenting most often as venous or arterial thrombosis, recurrent pregnancy loss, or thrombocytopenia. Both the lupus anticoagulant and anticardiolipin antibody are associated with APS. The mechanism of the prothrombotic state is not understood, but may involve beta-2 glycoprotein 1 (a naturally occurring anticoagulant), platelet aggregation, the protein C pathway, or endothelial cell function. The current treatment recommendation, after a venous or arterial thrombosis, is high-intensity, long-term warfarin therapy.

Topics: Abortion, Habitual; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Apolipoproteins; beta 2-Glycoprotein I; Endothelium, Vascular; Female; Glycoproteins; Humans; Lupus Coagulation Inhibitor; Platelet Aggregation; Pregnancy; Pregnancy Complications; Protein C; Thrombocytopenia; Thrombophlebitis; Thrombosis; Warfarin

Topics: Abortion, Habitual; Adult; Antigens; Aspirin; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Fetal Death; Heparin; Humans; Male; Middle Aged; Phospholipids; Pregnancy; Risk Assessment; Sensitivity and Specificity; Venous Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal loss; involvement of cardiac valves is also seen. A seronegative variant has been described previously. We report a case of a woman with recurrent pregnancy loss, prior strokes, and a negative workup for known antiphospholipid antibodies. During her current pregnancy, she presented with acute stroke and mitral valve vegetation. Her workup for antiphospholipid syndrome and other thrombophilias remained negative even after the stroke. Her mitral valve vegetation resolved completely with aspirin, heparin, and warfarin. We believe this to be the first report of complete resolution of valvular vegetation with antiplatelet and anticoagulant therapy alone in a patient with seronegative antiphospholipid syndrome. Moreover, this appears to be the first report of stroke associated with this condition.

Topics: Abortion, Habitual; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Cesarean Section; Female; Heparin; Humans; Infant, Newborn; Male; Mitral Valve Insufficiency; Pregnancy; Pregnancy Complications, Hematologic; Stroke; Warfarin

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Drug Monitoring; Female; Humans; International Normalized Ratio; Intracranial Embolism; Intracranial Thrombosis; Male; Middle Aged; Pregnancy; Recombinant Proteins; Recurrence; Risk; Seizures; Thromboembolism; Thrombophilia; Thrombophlebitis; Thromboplastin; Warfarin

We describe a test for LA based on the specific APTT behaviour of LA plasmas when the incubation time with the APTT reagent is increased from 1 to 20 min. "1-10 APTT" test was defined as the difference (s) between results of the APTT performed with 1 and the one performed with 10 min incubation. A test value > 11 s (upper normal limit determined on 134 normal plasmas) was considered positive for a LA. The test distinguished all the LA patients studied (n = 40) from patients with factor VIIIc inhibitors, patients receiving heparin or warfarin therapy and also patients with congenital factor deficiencies, except those with prekallikrein and factor XII deficiencies. The test detected LA in warfarin (n = 3) and in heparin (n = 2) LA anticoagulated patients. Among 195 patients referred for LA screening, the test detected LA in 5 patients with normal standard APTT. This simple test, using a single reagent for screening and confirmatory procedures is sensitive and fairly specific for LA when combined with mixing studies. However, since the test was defined using one APTT reagent, the performances of other reagents have to be assessed.

Topics: Abortion, Habitual; Female; Heparin; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Migraine Disorders; Partial Thromboplastin Time; Pregnancy; Sensitivity and Specificity; Time Factors; Warfarin

We studied fetal and neonatal outcome of women maintained on anticoagulants (warfarin and/or heparin) during pregnancy. Among 22 Chinese families, 13 mothers (59%) had a history of recurrent abortion or stillbirth while being maintained on warfarin treatment. Twenty-nine liveborn children (17 boys, 12 girls), ages 0.6-11.3 years at follow-up, were analysed for evidence of embryopathy. These were subdivided into 2 groups. Group 1 consisted of 18 children (12 boys, 6 girls) whose mothers were only given warfarin during pregnancy. Five were small for gestational age, and 12 had features of warfarin embryopathy such as nasal hypoplasia. One had subependymal intraventricular hemorrhage shown on neonatal ultrasonography. Group 2 consisted of 11 children (5 boys, 6 girls) whose mothers were maintained on warfarin and heparin during pregnancy. Three were premature deliveries, and 4 had nasal hypoplasia. One had cleft lip, cleft palate, cataract, microphthalmia, intraventricular hemorrhage, and hydrocephalus. We found that despite the high risk of fetal wastage, there was a relative lower risk of major complications, except for some minor cosmetic defects such as nasal hypoplasia. This might lead to readjustment of advice concerning contraception given to pregnant women who were maintained on anticoagulant therapy.

Topics: Abortion, Habitual; Child; Child, Preschool; Female; Fetal Diseases; Follow-Up Studies; Heparin; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Warfarin

Topics: Abortion, Habitual; Adrenergic beta-Agonists; Adult; Anticoagulants; Drug Therapy, Combination; Female; Heparin; Humans; Infarction; Placenta; Pregnancy; Warfarin