Antiphospholipid syndrome and thrombosis

The antiphospholipid syndrome is an autoimmune condition in which venous or arterial thrombosis is a primary clinical feature. The other primary clinical feature is adverse pregnancy outcome, specifically recurrent miscarriage, fetal death, or preterm delivery due to severe preeclampsia or placental insufficiency. The diagnostic autoantibodies for antiphospholipid syndrome are lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I.     

Antiphospholipid syndrome and pregnancy

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 syndrome and recurrent miscarriages

Sixty percent of recurrent spontaneous abortions are unexplained. Antiphospholipid syndrome is a multisystem disease with the predominant features of venous and arterial thrombosis, recurrent pregnancy loss, foetal death and the presence of antiphospholipid antibodies. Many epidemiological studies focus on antiphospholipid autoantibodies syndrome (APS) as a cause of recurrent spontaneous abortion (RSA). It is found that 7-25% of RSA would have APS as the main risk factor. 'Association not being synonymous with cause', the proportion of abortions due to the APS is difficult to estimate for several reasons: definition of recurrent abortion is variable, the assays for antiphospholipid antibodies are not well standardised, inclusion of patients in the study group according to the antibodies titre is author dependent. Recent studies suggest association of antiphospholipid antibodies syndrome not only with recurrent abortions but also with infertility. New mechanisms are described by which antiphospholipid antibodies could cause placental thrombosis and infarction, acting directly on the surface anticoagulant expressed on trophoblastic cells. Only lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) assays are sufficiently standardised to be usable in routine. Testing for other antiphospholipid antibodies (aPLs) should remain investigational. Several treatments have been proposed: low doses of aspirin, low or immunosuppressive doses of corticosteroids, and preventive or effective dose of heparin, intravenous immunoglobulin.     

Antiphospholipid syndrome and human reproduction

Recurrent pregnancy loss is secondary to multiple illnesses. An important cause sometimes undiagnosed is the antiphospholipid syndrome, an autoimmune disease with various clinical alterations (miscarriage, hypertensive disorders, preterm delivery, vascular thrombosis, intrauterine retard growth, death intrauterine, abruption placentae). There are major and minor clinical criteria and precise indications that guide the physician to its recognition. Antibodies related with the syndrome are anticardiolipin and lupic anticoagulant, but other phospholipids seems to be implicated on this pathology and its participation on trombotic events is even unknown. Opportune diagnosis is of vital importance for fetomaternal morbidity and mortality. The repercussions are important during gestational stage, but effects c an persist o r even appear during the puerperium, predisposing t o trombotic events. The antiphospholipid s yndrome th at accompanies gestation, requires of efficient valuation and a special treatment, with a narrow prenatal surveillance. The best therapy for reproductive future which has less undesirable effects, is with heparin and acetylsalicylic acid administration; prednisone (steroids) is used in cases of active illness. The current knowledge about this disease makes possible that a pregnancy at term can be achieved with the least as possible number of complications.     

Pregnancy complicated with autoimmune diseases

Autoimmune disorders such as SLE and ITP occur more commonly in young women and are the most common complications in pregnancy. There is considerable controversy concerning the risk to the mother and fetus, and the optimal prepartum management for minimizing that risk. 1. SLE is an autoimmune disorder in which IgG antibodies such as anti dsDNA-IgG, anticardiolipin IgG, and anti SS-A/Ro IgG are produced. Lupus nephropathy accompanied by diminished serum complement (CH50) and a rise in antibodies against dsDNA is a frequent clinical problem during pregnancy, which represents the adverse effect of hypertension or superimposed toxemia and causes fetal death or intrauterine fetal growth retardation. Habitual abortion or fetal death is common in a case with high anticardiolipin IgG titre. Anti SS-A antibodies are often found in the infants of antibody-positive mothers, and the deposition of antibodies in the perinodal region cause congenital heart block. IgG or immune complexes crossing the placenta directly injures the cardiac conduction system. In these cases which have high titre crossing the placenta directly injuries the cardiac conduction system. In these cases which have high titre of autoimmune antibodies, corticosteroid therapy should be started. 2. Management of ITP in pregnancy involves the consideration of three issues: 1) treatment of maternal thrombocytopenia, 2) prediction of fetal thrombocytopenia, 3) obstetrical management. ITP increases the risk for postpartum bleeding of sufficient severity to require blood transfusion. In most of these cases, maternal platelet counts are found to be less than 30,000/mm3. Women who have symptomatic severe steroid-unresponsive ITP may benefit from intravenous IgG(IvIgG) given as elective treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy and autoimmune diseases

Autoimmune diseases (AID) are more prevalent in women than in men, and pregnancy-related factors such as hormonal modulation and fetal microchimerism may influence the future risk of maternal AID. For women with AID, optimizing reproductive health requires a continuum of multidisciplinary care that initiates well before the desire for pregnancy is articulated. Family planning is essential so that pregnancy can be timed when disease is stable and to allow for appropriate medication adjustments. When contraception is used, the choice of method needs to take into consideration underlying disease and laboratory features. For females undergoing gonadotoxic therapy, options for preserving ovarian health and fertility warrant consideration, even among those who are not contemplating future pregnancy. Both maternal and fetal outcomes are optimized with multispecialty care as well as close monitoring during pregnancy and the postpartum period and when treatment regimens compatible with pregnancy are maintained to control underlying disease activity.     

妊娠合并自身免疫性疾病的抗凝治疗

妊娠合并自身免疫性疾病患者因病理生理性的血栓形成倾向大大增加,常导致严重的母胎并发症。低分子肝素和阿司匹林等抗凝药物作为妊娠期安全用药,在改善此类患者的母胎结局中发挥着重要作用。因此,规范抗凝治疗有助于改善母胎不良结局。     

妊娠合并抗磷脂综合征13例临床分析

目的探讨妊娠合并抗磷脂综合征患者的孕期治疗与母儿结局。方法回顾性分析北京大学人民医院1990年1月至2013年7月妊娠合并抗磷脂综合征患者的临床资料。结果妊娠期共13例患者符合抗磷脂综合征的诊断。其中,按诊断时间分孕前诊断10例,孕期诊断3例;按类型分原发性抗磷脂综合征12例,继发性抗磷脂综合征1例。13例患者中3次以上胎停育或胎死宫内病史者8例。孕期治疗以小剂量阿司匹林治疗2例,以低分子肝素治疗3例,以小剂量阿司匹林联合强的松治疗3例,以小剂量阿司匹林联合低分子肝素治疗3例,由于血小板减少以糖皮质激素及丙种球蛋白治疗1例,单独丙种球蛋白1例。母儿结局：13例患者均获活产新生儿,围产死亡率0%。足月分娩11例,早产2例,平均体重（2 921.43±1326.6）g。胎儿宫内生长受限2例。重度子痫前期1例,妊娠高血压1例。结论孕期适当的干预治疗可改善妊娠合并抗磷脂综合征患者的妊娠结局,应重视并提高对妊娠期出现的抗磷脂综合征的及时诊断及必要的治疗。     

Premature ovarian insufficiency and autoimmune diseases

Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years and has a potentially devastating effect upon women's health, both physically and psychologically. An underlying autoimmune disease has been identified in approximately 20% of patients with POI, the most common of which are disorders of the thyroid and adrenal glands. Nevertheless, in the majority of cases, the etiology is unknown. The damage mechanism to the ovary is usually caused by antibodies, and autoimmune POI is usually characterized by cellular infiltration of the theca cells of growing follicles by various inflammatory cells. Yet, other various factors and proteins of unknown clinical significance are present.The major diagnostic tool for otherwise idiopathic POI is the presence of autoantibodies against various ovarian components that strongly support the option of autoimmune etiology of POI.Treatment of the underlying cause of POI is the main strategy, although immunosuppressive therapy should be considered in a selected population of well-defined autoimmune POI and, as in idiopathic POI, in whom the resumption of ovarian activity is possible.     

Multiple autoantibodies associated with autoimmune reproductive failure

Purpose : Autoimmune factors are involved in some of the cases of reproductive failure. The aim of this paper is to discuss the association between autoantibodies and reproductive failure. Methods : Literature review of autoantibodies associated with reproductive failure. Results : Several autoantibodies were found in association with such clinical manifestations, mainly in patients having systemic lupus erythematosus or the antiphospholipid syndrome. These autoantibodies include classical antiphospholipid antibodies such as anticardiolipin, anti-2-glycoprotein-I, antiphosphatidylserine, and antiphosphatidylethanolamine. There are also some nonclassical antiphospholipid antibodies directed to prothrombin, thromboplastin, or mitochondrial antibodies of M5 type, which were also found in patients with reproductive failure. Moreover, animal models as well as some human studies support a role for other autoantibodies in these clinical manifestations including antithyroglobulin, antilaminin-1, anti-corpus luteum, antiprolactin, anti-poly(ADP-ribose), and lymphocytotoxic antibodies. Conclusions : Even though there is not enough data currently to support a firm association between some of these autoantibodies and reproductive failure, future studies are likely to help us determine and expand the number of autoantibodies screened in these patients.     

Antiphospholipid syndrome: Diagnosis and management in the obstetric patient

Antiphospholipid syndrome (APS) is a rare condition clinically characterized by thrombotic events or pregnancy complications and confirmed by one or more repeatedly positive antiphospholipid antibodies on two or more occasions at least 12 weeks apart. Several factors are thought to have roles in the pathogenesis of adverse obstetric events related to APS, including platelet and endothelial cell activation, complement activation, and ultimate activation of the thrombotic pathway. Despite standard treatment with a heparin agent and low-dose aspirin, 30% of women with definite APS cannot achieve a successful pregnancy outcome. Additional treatment options are still controversial, and prospective trials with appropriate controls are needed to investigate the efficiency of alternative treatments. In this chapter, we discuss diagnostic, clinical, and therapeutic approaches in the treatment of APS syndrome in pregnancy.     

Antiphospholipid syndrome: obstetric diagnosis,management, and controversies

Antiphospholipid syndrome, a condition characterized by one or more thrombotic or pregnancy-related clinical features in association with medium to high levels of antiphospholipid antibodies, has emerged as an important diagnostic consideration in several medical fields. Antiphospholipid syndrome is one of the few treatable causes of pregnancy loss, and successful pregnancy rates of 70% or more can be achieved with appropriate treatment. Heparin, usually combined with low-dose aspirin, is used in patients at risk for thrombosis. Pregnancy in these women is associated with increased rates of preeclampsia, placental insufficiency, and preterm delivery, so that attentive clinical care is required for best outcomes. Recent studies indicate that women at low risk for thrombosis may be treated with low-dose aspirin. However, remaining controversies and unanswered questions in the field of antiphospholipid syndrome are a source of clinical confusion. This review highlights the most important controversies, taking into account the results of recent obstetric treatment trials and our own clinical experience.