Bad pregnancy and repeated miscarriage may be caused by this rheumatism!

*It is only for medical professionals to read for reference.
It is not easy to give birth to a baby! Sometimes recurrent miscarriage is not necessarily just a disease of obstetrics and gynecology, and it is also very related to rheumatism~ Case patient, female, 32 years old, due to "menopause for 17+1 weeks, abdominal distension, left lower extremity pain for 3 days" in 2021 He was admitted to the hospital in August
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History of present illness: The patient had no obvious nausea and vomiting in the early menopause, no abdominal pain and bloating, and no redness
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Three days ago, the patient had abdominal distension and discomfort without obvious incentives, left lower limb pain, no abdominal pain, no redness, no other joint swelling and pain, rash, oral ulcers, Raynaud’s phenomenon and other discomforts
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Since the onset of the illness, the patient has had poor mental sleep, poor diet, normal bowel movements, and no significant changes in weight
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Past history: No fetal heartbeat was seen under ultrasound at 10 weeks of gestation in 2018 without cause, and fetal heart beats disappeared at 7 weeks of gestation in 2019 without cause
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In 2020, I went to the Department of Reproductive Immunology, checked the anticardiolipin antibody-IgM 65 SGU↑, and started taking hydroxychloroquine 0.
1g bid and aspirin tablets 25mg qd for maintenance treatment
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Embryo transfer in April 2021, low-molecular-weight heparin will be added before the transfer
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Denying the history of irregular fever and redness, heat, pain, personal history, and family history
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Physical examination: T: 36.
9°C, R: 19 beats/min, P: 78 beats/min, BP: 134/76mmHg, appearance of anemia, not large superficial lymph nodes
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There was no congestion and ecchymosis under the skin and mucous membranes of the whole body, and the heart and lung auscultation was normal.
There was no redness, swelling and deformity of the limbs and joints, and the nervous system was not special
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Diagnosis: 17+1 weeks of pregnancy, threatened abortion, obstetric antiphospholipid antibody syndrome Treatment: hydroxychloroquine 0.
1g po bid, aspirin tablets 25mg po qd, enoxaparin 4000U ih qd obstetric antiphospholipid syndrome (OAPS) In the case of persistently positive phospholipid antibodies (aPLs), pathological pregnancy is the main clinical feature, with or without thrombosis
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Mainly manifested as early recurrent miscarriage, late embryo abortion, premature delivery due to placental insufficiency and eclampsia
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Which pregnant women’s adverse pregnancy outcomes may be related to OAPS? In recent years, abnormal aPLs has become one of the "causes" affecting women's poor pregnancy and reproductive health
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Domestic studies have reported that the probability of pathological pregnancy with antiphospholipid syndrome is 51.
0%-68.
4%, and the main manifestations are intrauterine and recurrent miscarriage
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Timely identification of OAPS and proper treatment can greatly improve pregnancy outcomes and reduce the incidence of mother and infant complications
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However, there are many controversies in the diagnosis and treatment of OAPS, such as insufficient understanding and overdiagnosis and treatment
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OAPS is not only a disease in obstetrics and gynecology, but also needs to be managed by rheumatologists
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In these three cases, the adverse pregnancy outcome of pregnant women may be related to OAPS: (1) One or more unexplained fetal death occurred in the uterus at 10 weeks and later, and ultrasound or visual examination did not find abnormal morphological structure.
(2) Epilepsy or severe preeclampsia or severe placental insufficiency before 34 weeks of gestation (including fetal heart monitoring prompting fetal hypoxemia, umbilical artery Doppler detection found lack of end-diastolic blood flow, oligohydramnios , Birth weight is below the 10th percentile of the average weight of the same gestational age) 1 or more preterm births with no abnormal morphological structure of the fetus; (3) 3 consecutive times or preterm births before 10 weeks of gestation Spontaneous abortion that cannot be explained more than 3 times
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It is necessary to exclude genetic abnormalities (no evidence of chromosomal abnormalities in couples and embryos), anatomical structures, and endocrine factors
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Which women with OAPS are more likely to have adverse pregnancy outcomes? (1) High-risk aPLs spectrum (see Table 1 for risk classification); Table: Antiphospholipid antibody risk classification (2) Combined systemic lupus erythematosus (SLE) or other autoimmune diseases; (3) Past thrombosis history and pathology History of pregnancy
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What are the clinical symptoms of OAPS? The clinical manifestations of OAPS are very diverse and vary greatly from patient to patient
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The most common manifestations are recurrent miscarriage, stillbirth, fetal growth restriction, fetal distress (hypoxia), early-onset severe preeclampsia, oligohydramnios, and thrombocytopenia
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What tests are needed to diagnose OAPS? (1) Lupus anticoagulant: Lupus anticoagulant (LA) in the plasma was positive for 2 times, with an interval of at least 12 weeks; (2) Anticardiolipin antibodies: Serum was detected by enzyme-linked immunosorbent assay (ELISA) Medium to high titers of IgG/IgM type anticardiolipin antibodies (aCL)
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IgG type aCL>40 GPL (1GPL is the activity of 1μg/ml purified IgG aCL binding antigen), IgM type aCL>40 MPL (1MPL is the activity of 1μg/ml purified IgM aCL binding antigen), or titer> 99th percentile; found twice at least 12 weeks apart; (3) Anti-β2 ferritin I antibody: medium and high titers of IgG/IgM type anti-β2 ferritin I antibody (anti-β2GPI) were detected in the serum by ELISA.
Ab)
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Titer> 99th percentile, found twice at least 12 weeks apart
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What indicators need to be tested during pregnancy for OAPS? The detection of OAPS patients during pregnancy emphasizes individualization
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(1) Laboratory testing ① Detect platelet count and blood creatinine, alanine aminotransferase, aspartate aminotransferase, thyrotropin, etc.

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It should be noted that reduced platelet counts in obstetric antiphospholipid antibody syndrome patients should be considered as a risk factor for poor prognosis
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②Anti-Ro/SSA and anti-LA/SSB antibody screening: For patients with secondary antiphospholipid syndrome (APS), if anti-Ro/SSA and anti-LA/SSB antibodies are positive, clinical attention should be paid to the effects of both on the fetal cardiac conduction system.
Impact
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③ Detection of aPLs: aPLs will be moderately reduced during pregnancy, but the correlation to pregnancy outcome is not yet clear
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Therefore, for patients with APS who have been diagnosed before or during the first trimester, changes in the aPLs antibody titers during pregnancy should not be used as a basis for drug dosage adjustment or drug withdrawal
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For asymptomatic healthy women who are positive for aPLs but do not meet the diagnostic criteria for APS, it is not clear whether it will increase the risk of pathological pregnancy
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But most of the evidence shows that there is no significant change in the risk of this group of people
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There is a lack of evidence for the correlation between antibodies and pregnancy outcomes, especially for spontaneous abortions with a gestational age of less than 10 weeks.
The predictive value of aCL or anti-β2GPI is unclear
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(2) Fetal detection The approved gestational week of the ultrasound examination during the first trimester, and the ultrasound evaluation of fetal growth, amniotic fluid volume, umbilical artery blood flow and fetal heart rate monitoring every 3-4 weeks from the third trimester
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Treatment of OAPS (1) Before pregnancy, it is recommended to use low-dose aspirin (LDA) 50-100mg per day for OAPS patients who plan to become pregnant during the entire pregnancy
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For patients with OAPS who have failed conventional treatment, OAPS with SLE or other systemic autoimmune diseases, high-risk spectrum and OAPS patients with a history of thrombosis, it is recommended that hydroxychloroquine 200-400mg/ d
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(2) Pregnancy ① For patients with OAPS, low molecular weight heparin (LMWH) should be used on the basis of daily application of LDA during the whole pregnancy.
The dosage and use time should be individualized according to the specific conditions of the patient
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a) Low-risk aPLs, preventive dose LMWH, maintained throughout pregnancy; b) Medium-high-risk aPLs spectrum, preventive or medium dose LMWH, maintained throughout pregnancy; c) Past history of thrombosis and pregnancy with thromboembolism For patients with sexual diseases, the therapeutic dose of LMWH is maintained throughout the pregnancy; d) For APS patients with SLE or other autoimmune diseases, on the basis of rheumatic immunotherapy, the preventive or therapeutic dose of LMWH is used throughout the entire pregnancy.
Maintenance application during pregnancy
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②For OAPS patients who have failed conventional treatment (also called refractory OAPS), the most common treatment option is to increase LMWH to the therapeutic dose; on the basis of starting LDA and hydroxychloroquine before pregnancy, consider adding small doses of prednisone during pregnancy Pine (early pregnancy ≤10mg/d) or other glucocorticoids at the same dose
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Intravenous immunoglobulin can only be tried as a non-first-line drug
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③For pregnant women who have no history of thrombosis, asymptomatic, and positive aPLs, the risk of adverse pregnancy outcomes is uncertain
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For this part of the population, it is still controversial whether it is necessary to intervene
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However, it is recommended that LDA treatment should be given throughout pregnancy
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④For atypical OAPS, it is recommended to use LDA alone or in combination with LMWH according to individualized risks (such as aPLs profile, SLE, previous live births, pregnancy loss, or thrombosis)
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(3) Puerperium ①For women with OAPS, use the preventive dose of LMWH for at least 6 weeks after delivery to prevent thrombosis
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②Patients with a history of thrombosis and thrombosis during pregnancy should use medium-dose or therapeutic dose of LMWH for at least 6-12 weeks after delivery
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Anticoagulant before pregnancy should be restored to the original long-term anticoagulant regimen
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③For simple aPLs positive and atypical OAPS (NOAPS), according to other high-risk factors of thrombosis, individualized preventive dose of LMWH or other measures to prevent thrombosis are adopted
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Summary: In recent years, with the gradual understanding of OAPS, it has been found that OAPS is one of the causes of pregnancy in cases.
Proper management of OAPS can significantly improve pregnancy outcomes
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However, there are many controversies in the diagnosis and treatment of OAPS, and the phenomenon of insufficient understanding and over-diagnosis and treatment coexist
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China's latest guidelines point out that hydroxychloroquine combined with LDA should be used before pregnancy.
On the basis of hydroxychloroquine and LDA during pregnancy, LMWH is added according to the individual's condition of the patient.
It is recommended to use low-dose technology for NOAPS patients
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During the puerperium, different doses of LMWH are used prophylactically after delivery according to the specific conditions of the patient
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The pregnancy of OAPS patients should be closely followed up under the close supervision of rheumatology and immunology department and obstetricians, and standardized and scientific treatment should be given to improve the pregnancy outcome of patients
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References: [1] Expert consensus on the diagnosis and management of obstetric antiphospholipid syndrome[J].
Chinese Journal of Perinatal Medicine, 2020,23(08):517-522.
[2]Zheng Xiaojuan, Deng Xiaoli, Liu Xiangyuan.
54 cases of antiphospholipid Pregnancy outcome of patients with syndrome[J].
Journal of Peking University (Medicine Edition),2014,46(02):323-328.
[3]Garcia D,Erkan D.
Diagnosis and Management of the Antiphospholipid Syndrome[J].
N Engl J Med,2018,378(21):2010-2021.
DOI:10.
1056/NEJMra1705454.
[4]Alijotas-Reig J,Esteve-Valverde E,Ferrer-Oliveras R,et al.
Comparative study of obstetric antiphospholipid syndrome(OAPS )and non-criteria obstetric APS(NC-OAPS): report of 1640 cases from the EUROAPS registry[J].
Rheumatology(Oxford),2020,59(6):1306-1314.
DOI:10.
1093/rheumatology/kez419.
[ 5] Liu Chang, Yu Ruohan, Liu Xiangyuan.
Challenges in the diagnosis and treatment of obstetric antiphospholipid syndrome[J].
Journal of Emergency and Critical Care Medicine,2017,23(02):105-108.