I. What is antiphospholipid syndrome? Antiphospholipid syndrome APS, is a systemic autoimmune disease. It is characterized by the presence of venous or arterial thrombosis and/or a pathological pregnancy in the setting of persistent laboratory evidence of aPL. Second, what does a history of a pathological pregnancy as defined by APS include? 1. greater than or equal to 1 unexplained fetal death at a gestational age greater than or equal to 10 weeks, but prenatal ultrasonography or direct postpartum physical examination demonstrates normal fetal anatomy. 2. Greater than or equal to 1 instance of preterm delivery of a morphologically normal infant at a gestational age of less than 34 weeks due to severe preeclampsia, eclampsia, or features consistent with placental insufficiency. 3, Greater than or equal to 3 unexplained, continuous, spontaneous fetal losses at a gestational age of less than 10 weeks requiring exclusion of abnormalities in the mother’s anatomy or hormone levels, as well as exclusion of chromosomal abnormalities in the mother and father. 3. How are women with morbid pregnancies treated? 1. For women with a diagnosis of APS based on the aPL laboratory criteria and the presence of 1 or more fetal losses greater than or equal to 10 gestational weeks or 3 or more consecutive unexplained spontaneous miscarriages less than 10 gestational weeks, it is recommended that low-dose aspirin therapy (50-100 mg/d) be initiated at the time of attempts to conceive and that prophylactic-dose LMWH therapy be initiated after confirmation of intrauterine pregnancy; Low-dose aspirin and prophylactic or moderate doses of regular heparin are also a reasonable alternative. Combination therapy appears to improve outcomes only slightly at best compared with aspirin alone. 2, In female patients with a past history of 2 or more fetal losses, live birth rates of 70% to 80% have been reported with drug therapy. However, the risk of pregnancy-related complications (preterm labor, preeclampsia, growth restriction) remains increased even in the group of patients who achieve live birth. 3. Preterm labor associated with uteroplacental insufficiency: For women with a diagnosis of APS based on a positive aPL and the presence of greater than or equal to 1 preterm delivery of a morphologically normal infant before 34 weeks of gestation due to severe preeclampsia, eclampsia, or other manifestations of placental insufficiency, we recommend that low-dose aspirin therapy (50-100 mg/d) be initiated at the end of the early gestation period (13 weeks of gestation) and continued until labor and delivery. Some clinicians will also give LMWH, but there are no trials to support or refute this recommendation. LMWH in combination with low-dose aspirin is given when aspirin therapy fails or when placental examination suggests extensive meconium inflammation and vasculopathy and/or thrombosis, although this regimen has not been validated in randomized trials. 5. aPL-positive patients who do not meet clinical criteria for APS: There are few data available to guide the treatment of pregnant women who are incidentally found to be persistently aCL or LA-positive but do not meet any of the clinical diagnostic criteria for APS. In the absence of pharmacologic therapy, more than 50% of such women will achieve a successful pregnancy. Treatment options for these patients include no treatment, low-dose aspirin alone (50-100 mg/d), or low-dose aspirin combined with prophylactic doses of heparin. Given the uncertainty of a morbid pregnancy in these patients, treatment decisions need to be made on an individual basis. Low-dose aspirin therapy alone is supported for these patients. 6. in vitro fertilization in aPL-positive female patients-We do not give prophylactic antithrombotic therapy to women who are positive for aCL or LA but do not meet the clinical criteria associated with APS during in vitro fertilization (IVF). The presence of aPL alone does not appear to adversely affect pregnancy rates or pregnancy outcomes in patients undergoing IVF. Couples undergoing IVF are not required to be evaluated for aPL, and the available data do not confirm that treatment of this population is justified. However, the issue remains controversial due to the heterogeneity of these studies and the different aCL assays used. IV.What needs to be monitored in APS pregnancies? 1, Increase the frequency of labor and delivery tests. 2, Regular testing of: platelet count, serum creatinine concentration, urine protein/creatinine ratio, serum alanine aminotransferase (ALT) and mentholatum transaminase (AST), and before-and-after comparisons can be made when APS disease is active or when other complications occur late in pregnancy. 3. Screen for anti-Ro/SSA and anti-La/SSB antibodies. If one of these lupus-associated autoantibodies is present, the other may also be present, and these antibodies can have an effect on the fetus/neonate. 4. Ultrasound screening by 20 weeks of pregnancy to estimate the date of delivery. A series of ultrasound examinations are performed 1 every 3-4 weeks starting in late mid or early late second trimester to assess fetal growth and amniotic fluid volume. V. Routine treatment of APS 1. Perinatal treatment: Heparin needs to be discontinued 24 hours before labor and delivery in order to give intrathecal anesthesia and minimize delivery-related bleeding. We scheduled labor (induction or cesarean section) at 39 weeks of gestation in order to control the timing of discontinuation of antithrombotic drugs. Patients with previous thrombotic events should not discontinue anticoagulants for more than 48 hours. 2. Low-dose aspirin can be discontinued at any time after 36 weeks’ gestation, ideally 7-10 days before delivery, and some studies have reported a slight increase in the risk of mild bleeding, mainly perioperative, if the drug is continued. In patients with a past history of serious atherothrombotic complications (e.g., stroke or myocardial infarction), the potential benefit of reduced risk from continued aspirin use throughout labor and delivery outweighs the lower risk of surgical incision bleeding. 3. Postpartum Treatment: Women who meet the aPL laboratory criteria and have a past history of arterial or venous thrombotic events are at higher risk of recurrence and usually require lifelong warfarin anticoagulation, and therefore should restart warfarin anticoagulation after delivery. There are no high-quality data available to guide postpartum therapy in patients with APS without a prior thrombotic event or in patients who are purely aPL-positive. Whether to initiate or continue anticoagulation in all such patients or in specific groups of them remains controversial. If a woman receives low-dose ASA and prophylactic-dose heparin prenatally, we continue its application for 6 weeks after her delivery. aPL-positive patients without a personal and family history of prior thrombotic events may not be at increased risk for pregnancy-related venous thrombotic events, but it is recommended that patients with a family history of thrombotic events receive anticoagulation postpartum. The Nimm Obstetricians, Gynecologists, and Hematologists Antiphospholipid Syndrome Study followed patients with APS who were diagnosed on the basis of a reproductive history without a history of thrombotic events for a median follow-up time of 9.3 years. These patients had an increased lifetime risk of deep vein thrombosis (aHR 1.85, 95% CI 1.50-2.28; annual incidence 1.46%) and an increased lifetime risk of stroke (aHR 2.10, 95% CI 1.08-4.08; annual incidence 0.17%) compared with women without thrombophilia. Although no specific studies have been performed, the postpartum risk in these patients may be particularly high because postpartum status is a risk factor for thromboembolic events. VI.SECOND-LINE OPTIONS AFTER FAILURE OF CONVENTIONAL TREATMENT 1. IV IMMUNOGLOBULIN: Intravenous gammaglobulin (iIVIG) has been attempted in patients who have failed conventional treatment [applied during the next attempted pregnancy, 0.4 g/(kg-d), 5 days per month], but the efficacy of this regimen has not yet been demonstrated. iIVIG should preferably be limited to clinical studies, but the authors on this topic have also performed multiple IVIG has been used in a small number of high-risk patients with multiple failed pregnancies combined with HELLP syndrome or catastrophic APS. A multicenter randomized preliminary study that included 16 women with well-defined APS found that treatment with IVIG did not significantly improve the incidence of preeclampsia, fetal growth restriction, poor fetal cardiac monitoring, and neonatal admission to the intensive care unit, and did not significantly improve neonatal gestational age at delivery or birth weight. gestational age at delivery and birth weight. However, it is not clear whether this is also a benefit for patients who fail initial treatment with low-dose ASA combined with heparin. There was no difference in the live birth rate between 53 female patients with APS treated with IVIG at one obstetric center and 29 female patients treated with both prednisone and low-dose ASA at another center (all of whom had had previous spontaneous abortions) (78% and 76%, respectively). However, the percentage of patients who developed hypertension or maternal diabetes was lower in the IVIG-treated group (5% vs 14%). A study that included 40 women compared the efficacy of low-dose ASA and LMWH combination therapy with the application of IVIG for the prevention of recurrent fetal loss. Each group received either LMWH (5700 U/d, subcutaneously) and ASA (75 mg/d) or IVIG (400 mg/kg intravenously for 2 days and 400 mg/kg monthly thereafter).The live birth rate was higher in the combined LMWH and low-dose ASA group than in the IVIG-treated group (84% and 57%, respectively), and in both groups there were There were no treatment-related serious adverse effects and no thromboembolic events. 2. Therapeutic plasma exchange: Therapeutic plasma exchange has been used to treat pregnant women with a confirmed diagnosis of APS who have failed to prevent pregnancy loss with first-line therapy (ASA and/or heparin). Data are currently limited to several case reports and one small case series study. Randomized trials and larger case series are needed to determine whether therapeutic plasma exchange with or without IVIG has a role in clinical practice that is not limited to the treatment of severe APS. Because of the potential for dramatic fluctuations in fluid exchange and serious complications during treatment, the use of therapeutic plasma exchange to improve pregnancy outcomes should be limited to clinical trials. 3, Hydroxychloroquine: In a mouse model, the antimalarial agent hydroxychloroquine appears to reverse platelet activation induced by human IgGaPL, thereby reversing the thrombotic properties of aPL, and appears to inhibit human aPL levels [. Women with APS-related recurrent pregnancy loss may benefit from this. Although high-quality data are not yet available, retrospective data on humans and experimental animal data suggest a possible benefit of hydroxychloroquine application in patients with APS. Case series studies have found no teratogenic effects of hydroxychloroquine in pregnant women with comorbid SLE and have received similar rates of spontaneous abortion as untreated female patients. 4. Glucocorticoids: Glucocorticoids (and other cytotoxic drugs such as cyclophosphamide and rituximab) have no proven utility in nonpregnant individuals with APS, and the drugs can cause adverse effects. aPL levels appear to be relatively resistant to immunosuppressive therapy, and there is little evidence that these drugs alter the course of hypercoagulable states. Studies assessing the efficacy of glucocorticoids in reducing the risk of adverse pregnancy outcomes have produced inconsistent results. However, studies have consistently confirmed that steroid therapy increases the risk of obstetric and maternal adverse events, including premature rupture of membranes, preterm delivery, fetal growth restriction, infections, preeclampsia, gestational diabetes mellitus, maternal bone loss (especially when used concomitantly with heparin), and ischemic necrosis, and therefore the regimen has been abandoned.