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Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.

Obstet Gynecol 2002; 100:408-13.

Antiphospholipid syndrome and pregnancy

Akush Ginekol (Sofiia). 2004;43(1):36-42. The antiphospholipid antibody syndrome (APLS) is multisystem, autoimmune disease, which is characterized by: thrombosis, obstetrics complications and thrombocytopenia. The two most clinically significant antiphospholipid antibodies (APLa) that are associated with recurrent pregnancy loss and thrombosis are anticardiolipin antibodies (ACL) and lupus anticoagulant (LA). The laboratory diagnosis is based on the presence of moderate to high positive ACL and/or LA. The inhibitory effect of antiphospholipid antibodies /APLa/ on trophoblast intercellular fusion, hormone production and invasion may cause pregnancy loss. Once placentation is established their thrombogenic action leads to decreased placental perfusion and subsequent infarction. The APLa--mediated inhibition of trophoblastic invasion and APLa--mediated vasculopathy in the placental bed arteries result in abnormal uterine artery /UA/ Doppler waveforms. The association between APLa and high resistance index /RI/ and/or diastolic notch /DN/ in the Doppler waveforms is high predictive for adverse pregnancy outcome, including pre-eclampsia/eclampsia, intrauterine growth retardation, placental abruption, intrauterine fetal death. Maternal treatment and careful monitoring of fetal well-being are mandatory in the management of these high-risk pregnancies.

Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients

Authors: A. Denis, M. Guido, R. Adler, P. Bergh, C. Brenner, R. Scott, Jr. Source: Fertility and Sterility: June, 1997 (Vol. 67) Pages 1084-1090.

A study of sixty pregnancies in patients with the antiphospholipid syndrome.

Clin Exp Rheumatol. 1996 Mar-Apr;14(2):131-6.

Antiphospholipid Syndrome in Pregnancy: A Randomized, Controlled Trial of Treatment

Obstetrics & Gynecology 2002;100:408-413 © 2002 by The American College of Obstetricians and Gynecologists

Obstetric Implications of Antiphospholipid Antibodies: Pregnancy Loss and Other Complications

Clinical Obstetrics and Gynecology: Volume 44(1) March 2001 pp 2-10

Pregnancy Loss in the Antiphospholipid-Antibody Syndrome — A Possible Thrombogenic Mechanism

N Engl J Med 1997;337 (154-160)

TNF- Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss

The Journal of Immunology, 2005, 174: 485-490. The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, intrauterine growth restriction, and vascular thrombosis in the presence of antiphospholipid (aPL) Abs. Our studies in a murine model of APS induced by passive transfer of human aPL Abs have shown that activation of complement and recruitment of neutrophils into decidua are required for fetal loss, and emphasize the importance of inflammation in aPL Ab-induced pregnancy loss. In this study, we examine the role of TNF- in pregnancy complications associated with aPL Abs in a murine model of APS. We show that aPL Abs are specifically targeted to decidual tissue and cause a rapid increase in decidual and systemic TNF- levels. We identify the release of TNF- as a critical intermediate that acts downstream of C5 activation, based on the fetal protective effects of TNF- deficiency and TNF blockade and on the absence of increased TNF- levels in C5-deficient mice treated with aPL Abs. Our results suggest that TNF- links pathogenic aPL Abs to fetal damage and identify TNF blockade as a potential therapy for the pregnancy complications of APS.

Antiphospholipid Antibody Syndrome (APS) or Hughes and Pregnancy


Antiphospholipid antibodies and pregnancy loss

Antiphospholipid Antibody Syndrome and Pregnancy Article by Stella Nowicki, DDS

Background: Antiphospholipid syndrome (APS) is a recently recognized autoimmune condition that may manifest with fetal loss, thrombosis, or autoimmune thrombocytopenia. Women with these clinical features should be tested for lupus anticoagulant (LAC) and anticardiolipin (aCL) antibodies; most patients with APS have both LAC and aCL immunoglobulin G (IgG) antibodies. The diagnosis of APS requires the presence of both clinical and biological features. Systemic lupus erythematosus (SLE) is a chronic systemic disease with diverse clinical and laboratory manifestations. LAC (and aCL) predisposes to clotting in vivo, predominantly by interfering with the antithrombotic role of phospholipids (PLs); therefore, it is associated with clinical thrombosis, not bleeding. The antiphospholipid (aPL) autoantibodies bind moieties on negatively charged PLs or moieties formed by the interaction of negatively charged PLs with other lipids, PLs, or proteins. aPL antibodies belong to the large family of antibodies that react with negatively charged PLs, including cardiolipin, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and phosphatidic acid. Last Updated: September 4, 2005

Management of thrombosis in antiphospholipid syndrome and systemic lupus erythematosus in pregnancy.

Ann N Y Acad Sci. 2005 Jun;1051:606-12. Pregnancy is a high risk period for thrombosis in women with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with antiphospholipid antibodies (aPL). Thrombosis may affect the mother, both in the venous and arterial beds, and also have a role in pregnancy loss. Thromboprophylaxis thus is warranted in most of these women. However, specific regimens containing low-dose aspirin, unfractionated heparin (UH), low molecular weight heparin (LMWH), and even dicumarinics in some circumstances after the first trimester are still a matter of controversy. Women with previous thrombosis should receive full antithrombotic doses of UH or LMWH during the whole pregnancy. Treatment of pregnancy losses is more debated, consisting of low-dose aspirin with or without associated heparin. The choice of treatment for a given patient must always take into account the woman's opinion after a careful discussion with the treating physician. Peripartum thromboprophylaxis with LMWH in women receiving aspirin-only regimens and prevention of osteoporosis in those treated with heparin are considered essential in the medical management of these patients.

Antiphospholipid Antibody Syndrome

by Sara Marder, M.D. Instructor and Fellow in Maternal and Fetal Medicine Department of Obstetrics and Gynecology Yale University School of Medicine

Clearance of Antiphospholipid Antibodies in Pregnancies Treated With Heparin

Obstetrics & Gynecology 2001;97:394-398 © 2001 by The American College of Obstetricians and Gynecologists

Antiphospholipid Syndrome (aPL)

Antiphospholipid syndrome is an autoimmune disease in which the body produces large amounts of antiphospholipid antibodies. Phospholipids are a special type of fat containing phosphate that makes up the outer walls of the body's cells. Antiphospholipid antibodies attack the phospholipids. This causes many different problems including increased blood clotting. Cardiolipin is one type of phospholipid and specific anticardiolipin antibodies may develop.

Use of the Low-Molecular-Weight Heparin Nadroparin During Pregnancy: A Review

from Current Medical Research and Opinion Posted 04/02/2003. Summary: Antithrombotic therapy is often used during pregnancy for the treatment and prevention of venous thromboembolism, the prevention of systemic embolism in patients with heart valve prostheses and the prevention of foetal loss in patients with antiphospholipid syndrome. Low-molecular-weight heparins (LMWHs), including nadroparin, have largely replaced unfractionated heparin as the anticoagulant of choice. The use of the LMWH nadroparin in pregnant women at an increased risk of thromboembolism or foetal loss is discussed in this review. Deep vein thrombosis can be effectively treated or prevented with nadroparin without any serious adverse events. Nadroparin 0.1 ml/10 kg sc once daily prevents thromboembolic complications in pregnant women with heart valve prostheses. Nadroparin is also effective in preventing foetal loss, through contributing to normal placental development and in decreasing the risk of premature delivery in pregnant women with antiphospholipid syndrome or women with herpes and antiphospholipid syndrome. These results demonstrate nadroparin is effective, easy to administer and associated with a low incidence of foetal and maternal complications. The use of nadroparin at a prophylactic dose of 0.3 ml (2850 IU AXa, 95 IU/kg) (for high-risk patients, 0.3-0.6 ml) sc once daily, and a therapeutic dose of 0.1 ml/10 kg (95 IU/kg) sc twice daily, is in line with the latest international guidelines of the American College of Chest Physicians.

Antiphospholipid Syndrome (aPL)

Because of the higher risks for stroke, pregnancy loss, and other complications with aPL, mothers need close monitoring of the disease. More frequent prenatal visits are often needed.

Antiphospholipid Antibodies in Predicting Adverse Pregnancy Outcome

Annals of Internal Medicine. 15 March 1994 | Volume 120 Issue 6 | Pages 470-475

Two patients with antiphospholipid antibody developed disseminated intravascular coagulation

One hundred and eleven patients with antiphospholipid antibodies (aPL) were diagnosed at Mie University Hospital during the past 17 years. Two of these patients developed disseminated intravascular coagulation (DIC). The first patient twice developed DIC complicated by pancreatitis and pregnancy, while in the second case, no specific causative complications for DIC were identified. The details of these cases imply that aPL is associated with DIC and/or is a potent triggering factor for DIC.

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