Obstetric Antiphospholipid Syndrome Research Articles

Bulk T-cell receptor sequencing confirms clonality in obstetric antiphospholipid syndrome and may as a potential biomarker

The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRβ repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.

Impact of Inherited Thrombophilia in Women with Obstetric Antiphospholipid Syndrome: A Single-Center Study and Literature Review.

Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.

Antiphospholipid-exposed trophoblast-derived extracellular vesicles express elevated levels of TLR7/8-activating microRNAs and induce endometrial endothelial activation, in part, through TLR7

Women with antiphospholipid syndrome (APS) are at high risk for miscarriage and preeclampsia. Unlike pro-thrombotic systemic APS, obstetric APS is associated with insufficient placentation, as well as inflammation and vascular dysfunction at the maternal-fetal interface. Antiphospholipid antibodies (aPL) can target the placental trophoblast and induce inflammation. We reported that aPL trigger trophoblast cells to produce elevated levels of IL-8 through activation of Toll-like receptor 4 (TLR4). Downstream of TLR4, we found this IL-8 response is mediated by a TLR8-activating microRNA (miR), miR-146a-3p, which is also released by the trophoblast via extracellular vesicles (EVs). Since endothelial dysfunction is a feature of obstetric APS, we sought to determine if other miRs that can activate the RNA sensors, TLR7 and/or TLR8, are released by the trophoblast via EVs after exposure to aPL, and if these EVs can activate human endometrial endothelial cells (HEECs). Using a human first trimester extravillous trophoblast cell line we found that aPL elevated their release of small EVs (<150 nm). These extracellular vesicles released from trophoblast cells exposed to aPL expressed elevated levels of TLR7/8-activating miR-21a and miR-29a, in addition to the previously reported miR-146a-3p. Extracellular vesicles from aPL-exposed human trophoblast cells triggered human endometrial endothelial cells to generate an inflammatory IL-8 response, in part through TLR7. This study highlights EVs as a mode of communication between the placenta and the maternal vasculature, as well as a potential role for TLR7/8-activating miRs in contributing to inflammation at the maternal-fetal interface in obstetric APS.

Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications—a population-based study

BackgroundAntiphospholipid syndrome (APS) can present with either a thromboembolic event (thrombotic APS, TAPS) or an obstetric complication (obstetric APS, OAPS). Data on long-term complications in the different APS phenotypes are limited. ObjectivesWe aimed to compare obstetric history, antiphospholipid antibody profiles, obstetric and thromboembolic complications, and pregnancy outcomes between TAPS and OAPS. MethodsThis retrospective cohort study included women who delivered singleton pregnancies between 1998 and 2020. One hundred sixteen thousand four hundred nine women were included, resulting in 320,455 deliveries. Among the included patients, 71 were diagnosed with APS, 49 were classified as OAPS, and 22 as TAPS. The demographics, obstetric, neonatal, and thrombotic outcomes were compared among TAPS, OAPS, and the general obstetric population. ResultsOAPS patients had an increased risk of thrombotic events compared with the general obstetric population (odds ratio [OR] 18.0; 95% CI, 8.7-37.2). In pregnancies following the diagnosis of APS, despite standard antithrombotic treatment, OAPS patients exhibited an elevated risk of placenta-related and neonatal complications compared with the general obstetric population (late fetal loss [adjusted OR {aOR}, 15.3; 95% CI, 0.5-27.5], stillbirth [aOR, 5.9; 95% CI, 2.2-15.4], placental abruption [aOR, 4.8; 95% CI, 1.5-15.3], preeclampsia [aOR, 4.4; 95% CI, 2.5-7.7], fetal growth restriction [aOR, 4.3; 95% CI, 8.5-27.5], small for gestational age neonate [aOR, 4.0; 95% CI, 2.4-6.6], and low Apgar scores [Apgar'1: aOR, 2.6; 95% CI, 1.3-10.4; Apgar'5: aOR, 3.7; 95% CI, 1.3-10.4]). TAPS patients exhibited increased risk of preeclampsia (aOR, 3.1; 95% CI, 1.2-8). ConclusionOAPS patients exhibit a heightened risk of thrombotic events compared with the general obstetric population. Despite treatment, OAPS and TAPS still presented obstetric complications. These findings, after confirmation in prospective studies, need to be taken into consideration when planning the treatment approach for these patients.

WCN24-1287 Features of obstetric catastrophic antiphospholipid syndrome

WCN24-1287 Features of obstetric catastrophic antiphospholipid syndrome

Can complement activation be the missing link in antiphospholipid syndrome?

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognised, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet mediated complement activation in this setting and provides an overview on clinical implications and current therapeutics.

Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome

ObjectivesObstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to...

Deep proteomic analysis of obstetric antiphospholipid syndrome by DIA-MS of extracellular vesicle enriched fractions

Proteins in the plasma/serum mirror an individual’s physiology. Circulating extracellular vesicles (EVs) proteins constitute a large portion of the plasma/serum proteome. Thus, deep and unbiased proteomic analysis of circulating plasma/serum extracellular vesicles holds promise for discovering disease biomarkers as well as revealing disease mechanisms. We established a workflow for simple, deep, and reproducible proteome analysis of both serum large and small EVs enriched fractions by ultracentrifugation plus 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). In our cohort study of obstetric antiphospholipid syndrome (OAPS), 4270 and 3328 proteins were identified from large and small EVs enriched fractions respectively. Both of them revealed known or new pathways related to OAPS. Increased levels of von Willebrand factor (VWF) and insulin receptor (INSR) were identified as candidate biomarkers, which shed light on hypercoagulability and abnormal insulin signaling in disease progression. Our workflow will significantly promote our understanding of plasma/serum-based disease mechanisms and generate new biomarkers.

Risk factors of first thrombosis in obstetric antiphospholipid syndrome

ObjectiveThere is limited evidence on long-term thrombosis risk in patients with obstetric antiphospholipid syndrome (OAPS). This study aimed to investigate the clinical features and risk factors associated with the first...

Proteomics of Serum Samples for the Exploration of the Pathological Mechanism of Obstetric Antiphospholipid Syndrome.

Obstetric antiphospholipid syndrome (OAPS) is a multisystem disorder characterized by thrombosis or recurrent fetal loss. In this study, we aim to explore the pathological mechanism of OAPS. Herein, we carried out data-independent acquisition (DIA) mass spectrometry quantitative proteomic analysis of serum samples from OAPS patients and healthy controls. A set of 93 differentially expressed proteins was identified, including 75 upregulated and 18 downregulated proteins compared with the levels in controls. Those proteins are enriched in KEGG pathways related to autoimmune diseases, allergic diseases, and pathogen infection. Interestingly, metabolic pathways such as fatty acid degradation and type I diabetes were enriched, indicating that OAPS is metabolic disease related. The significantly increased triglyceride also supported this idea. The differentially expressed proteins insulin-like growth factor-binding protein-1 (IGFBP-1), C-reactive protein (CRP), and ferritin light chain (FTL) were validated by ELISA. Our study presented a deep serum proteomics of OAPS and advanced our understanding of OAPS pathogenesis.

Examining Postpartum Anticoagulation Practices: An International Survey of Healthcare Providers

Background Prophylactic anticoagulation is usually recommended for six weeks postpartum (PPM) for individuals at high risk of developing venous thromboembolism (VTE). However, there are no randomized controlled trials (RCTs) assessing optimal duration of prophylactic anticoagulation post-partum. Moreover, the risk is not equivalent throughout the six weeks as evidenced by a sharp decline in VTE risk following the third week PPM. These observations call into question the optimal duration of PPM thromboprophylaxis and whether a full six weeks is needed. Objective This study sought to determine postpartum anticoagulation practices and to explore practitioners' willingness to consider reduction of the duration of PPM prophylactic anticoagulation. Methods We conducted a cross-sectional study between December 2022 and April 2023 using a self-administered electronic questionnaire on the ‘SurveyMonkey’ platform to gauge international preferences for the use, dose and duration of postpartum anticoagulation . The survey was validated for face and content validity and explored expert preferences across complex PPM scenarios. Physician characteristics, years in practice, specialty and continent of practice were also collected. We employed various methods of dissemination including email, scientific conferences, expert groups, and social media. Results Of the 113 participants that responded to the initial invitation, 78 completed the survey with the following regional distribution: 53.9% from Europe, 23.1% from North America, and 19.0% from Australia and New Zealand. Among the respondents, 60% were haematologists, 20% were general obstetric physicians, and 13% were maternal-fetal medicine (MFM) experts. For prior unprovoked or hormone-associated deep venous thrombosis (DVT) or pulmonary embolism (PE), non-hormone associated provoked DVT/PE, cerebral venous sinus thrombosis (CVST) and splanchnic vein thrombosis, 97.4%, 93.5%, 91.0% and 88.5% of experts selected six weeks of prophylactic anticoagulation with LMWH postpartum compared to 3 weeks or prophylaxis with unfractionated heparin. This practice was also supported by 70.5%, 78.2% and 87.2% of experts in individuals with sickle cell disease (SCD), obstetric antiphospholipid syndrome (APS) and high-risk thrombophilia, respectively. For individuals with a history of unprovoked PE/DVT or history of thrombosis at atypical sites (splanchnic thrombosis or CVST) approximately half of the experts (48.7% and 47.4 %) were willing to offer thromboprophylaxis with 3 weeks of LMWH followed by 3 weeks of aspirin, while approximately one-third (34.6% and 32.1%) would consider 3 weeks of LMWH only (Table 1). Respondents managing more than 10 patients per year (p=0.0001), with over 5 years of practice experience (p=0.0004) and specialization in Haematology or MFM demonstrated a greater willingness to explore shorter durations. For scenarios of individuals with SCD, obstetric APS and myeloproliferative neoplasms (MPNs), with no history of VTE, a higher percentage of respondents (69.2%, 60.3%, 67.9%) would support 3 weeks of LMWH followed by 3 weeks of aspirin or no anticoagulation PPM (Table 1). For SCD, Haematologists were slightly less supportive (68.1%) than MFM (80%) and obstetric medicine physicians (75%) of shorter durations, although the difference was not statistically significant (p=0.45). For MPNs, Haematologists were more supportive of shorter durations (76.6%) than MFMs (60%) and obstetric medicine physicians (50%) (p=0.047). For obstetric APS, there was no significant difference amongst the specialties with respect to explore shorter anticoagulation durations. Conclusion The majority of experts (90%) prescribe a 6 week LMWH regimen for patients with a background of DVT/PE, thrombosis in atypical sites, or high-risk thrombophilias, while fewer adopt this approach for SCD, obstetric APS. Half of the specialists would consider shorter durations of prophylactic anticoagulation PPM for individuals with prior DVT/PE, thrombosis in atypical sites and even more (60-70%) for SCD, obstetric APS and MPNs. Experience and caseload influence acceptance of shorter durations. There is an urgent need for prospective studies addressing peripartum management of anticoagulation such as appropriate type, dosage, initiation timing and duration in different diseases, to provide evidence regarding optimal strategies.

Shall We Rethink the Timing of Epidural Anesthesia in Anticoagulated Obstetrical Patients?

(Am J Obstet Gynecol. 2023;257–260) Low–molecular-weight heparins (LMWH) are often used to induce prophylactic anticoagulation for patients who experience venous thromboembolism, thrombophilia, and obstetrical antiphospholipid syndrome. It is theorized that unfractionated heparin delivered intravenously may be a possible alternative for the use of LMWH in pregnant patients.

Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis

Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1β and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome.Graphical

Antiphospholipid Syndrome: State of the Art of Clinical Management.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Currently, treatment is mainly focused on anticoagulation, but therapies targeting mechanisms involved in APS autoimmune pathogenesis could play an important role in specific settings. An evidence-based therapeutic approach is limited by the broad clinical spectrum of the syndrome and the nature of a "rare disease" that makes it difficult to carry out well-designed prospective studies. Vitamin K antagonists (AVK), notably warfarin, are the standard treatment for preventing recurrent venous thrombosis and perhaps also arterial thrombosis. Direct oral anticoagulants (DOACs) are not recommended at least in patients with triple positivity APS. Treatment options for the prevention of pregnancy complications in obstetric APS, as combined use of aspirin and heparin, low-dose prednisolone, hydroxychloroquine, intravenous immunoglobulin (IVIG), may improve pregnancy outcome. The catastrophic antiphospholipid syndrome (CAPS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. Glucocorticoids, heparin, plasma exchange or IVIG, rituximab, or eculizumab must be added to concurrent treatment of precipitating factors (e.g. infections) as rescue therapies. Finally, it has been observed that SARS COV2 infection may produce vascular complications mimicking the clinical and pathophysiological features of APS and particularly of CAPS. From this point of view, attention has been focused on the "protective" role of anticoagulant therapy in preventing thrombotic complication when these clinical conditions coexist.

Correlation of placental lesions in patients with systemic lupus erythematosus, antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and adverse perinatal outcomes

IntroductionWe aimed to describe the pattern of placental injuries in women with systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) and non-criteria obstetric APS (NC-OAPS), and to correlate the placental findings with the occurrence of adverse perinatal outcomes. MethodsThe perinatal outcomes and placental findings of pregnancies of women with SLE, APS, and NC-OAPS and gestational-age matched healthy controls were analyzed and classified according to the 2015 Redline - Classification of placental lesions. Results91 women with SLE, APS, and NC-OAPS and 91 controls were included. Mean values of placental weight differed between groups, being significantly lower in NC-OAPS and APS groups compared to controls. Furthermore, 14.3% of placentas in the APS group were under the 3rd percentile, which was significantly higher in comparison with other groups.Regarding histopathological placental findings, maternal-side malperfusion was significantly increased in APS (46.4%) compared to NC-OAPS (14.3%) and SLE (9.5%). Fetal-side maldevelopment was significantly increased in NC-OAPS (19.1%) compared to controls (1.1%) and SLE (2.4%). A significantly increased prevalence of adverse perinatal outcomes (APOs) was observed in all studied groups compared to healthy controls (controls 3.3%, SLE 52.4%, NC-OAPS 57.1%, APS 64.3%). Overall, both maternal (OR 6.8, 95%CI 2.1–22) and fetal-side (OR 4.1, 95%CI 1.3–13.5) lesions were significantly associated with APO. Maternal malperfusion and fetal maldevelopment were the lesions most strongly associated with APOs. DiscussionPregnant women with SLE, APS, or NC-OAPS showed a different pattern of histopathological findings. Compared to controls, SLE, APS, and NC-OAPS conferred an increased risk of APOs that was strongly associated with placental maternal-side malperfusion and fetal-side maldevelopment.

Pregnancy complicated with adrenal adenoma causing ACTH-independent Cushing's syndrome, accompanied by obstetric antiphospholipid syndrome and severe pre-eclampsia: case report and literature review.

This case report shares the management experience of a patient with pregnancy combined with adrenal adenoma causing ACTH-independent Cushing's syndrome (CS), accompanied by obstetric antiphospholipid syndrome (OAPS) and severe pre-eclampsia. The case was a 26-year-old that presented with typical clinical symptoms and signs of CS. The patient had a history of 4 spontaneous abortions in the last 4 years. The 24-hour urinary free cortisol was significantly increased, an abnormal cortisol circadian rhythm was demonstrated by a high late-night salivary cortisol, blood ACTH was suppressed (< 1ng/dL), anticardiolipin antibody was positive, and imaging examination showed an adrenal tumor. The patient underwent laparoscopic adrenal tumor resection under general anesthesia at 23 weeks of gestation. The tumor was pathologically confirmed to be an adrenocortical adenoma. The patient underwent a cesarean section at 39 weeks of gestation to give birth to a healthy baby girl with an Apgar score of 10. Pregnancy complicated by CS is clinically rare, easily masked by normal physiological changes of pregnancy, and is difficult to diagnose. The determination of 24-hour urinary free cortisol, the circadian rhythm of serum cortisol, ultrasound, and MRI can be helpful in the diagnosis of CS during pregnancy. Surgery is the first choice for the treatment of CS during pregnancy. As a subtype of antiphospholipid syndrome, patients with OAPS are prone to thrombotic events and recurrent miscarriages if not treated accordingly. To our knowledge no cases of CS with OAPS and severe pre-eclampsia have been reported. We summarize the experience of the treatment of this patient and review the literature to improve clinicians' awareness of this disease.

Added value of antiphosphatidylserine/prothrombin antibodies in the workup of obstetric antiphospholipid syndrome: communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

BackgroundThe added value of antiphosphatidylserine/prothrombin antibodies (aPS/PT) in the diagnostic workup of antiphospholipid syndrome (APS) is unclear. Currently, diagnosis of thrombotic APS (TAPS) and obstetric APS (OAPS) requires persistent presence of lupus anticoagulant (LAC), anticardiolipin (aCL) immunoglobulin (Ig) G/IgM, or anti-β2-glycoprotein I (aβ2GPI) IgG/IgM antibodies. ObjectivesTo evaluate the role of aPS/PT IgG and IgM in OAPS. MethodsaPS/PT IgG/IgM, aCL IgG/IgM, aβ2GPI IgG/IgM, and LAC were determined in 653 patients (OAPS, TAPS, and controls). In-house aPS/PT cut-off values were calculated, titers and prevalence were compared between OAPS, TAPS, and controls and type of pregnancy morbidity. Sensitivity, specificity, likelihood ratios, and odds ratios (OR) with 95% CI were calculated. ResultsIn OAPS, aPS/PT IgG and IgM showed an OR of 4.32 (95% CI, 2.54-7.36) and 3.37 (95% CI, 1.93-5.89), respectively, but the association was not independent of LAC. Prevalence and titers of aPS/PT IgG and IgM were lower in OAPS than in patients with TAPS. aPS/PT were more prevalent and showed higher titers in patients with late pregnancy loss than in patients with early pregnancy loss with a positivity of 86.4% and 39.3%, respectively. Higher aPS/PT titers did not increase the likelihood of having OAPS. ConclusionThe added value of aPS/PT testing in the current diagnostic workup of OAPS seems limited compared with LAC, aCL, and aβ2GPI. aPS/PT might be useful in specific subsets of patients with OAPS. However, future multicentric studies are needed to elucidate the risk of less frequent and most severe obstetrical manifestations.

Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group

IntroductionObstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. MethodsWe haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. ResultsOverall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24–38] vs. 35 weeks [27–38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DiscussionData from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.

Hemorrhage complications in obstetric antiphospholipid syndrome: Risk factors and association with adverse pregnancy outcomes.

Bleeding complications are recognized as relatively infrequent manifestations of antiphospholipid syndrome (APS), and the safety of antithrombotic therapy during pregnancy is of concern. This study aims to assess the risk factors and possible associations between bleeding complications and adverse pregnancy outcomes (APOs) in patients with APS. A retrospective cohort study was conducted at the Peking University People's Hospital. The clinical and immunologic features, bleeding complications, treatment, and pregnancy outcomes of patients with APS were collected. Univariate and multivariate logistic regression analyses were applied to assess the associations between APOs and bleeding complications. A total of 176 participants with obstetric APS were included in the analysis. There were 66 (37.50%) patients with APS with hemorrhage complications and 86 (48.86%) patients with APS with APOs. Mucocutaneous hemorrhage was associated with APOs including fetal death after 12 weeks [odds ratio (OR) = 10.73, 95% confidence interval (CI): 1.61-71.74, p = 0.014], preterm delivery prior to 34 weeks (OR = 8.30, 95% CI: 2.31-29.84, p = 0.001), and small for gestational age (OR = 4.17, 95% CI: 1.22-14.21, p = 0.023) in univariate logistic regression analyses. It also independently associated with preterm delivery prior to 34 weeks (OR = 40.29, 95% CI: 1.45-1121.32, p = 0.030) in multivariate logistic regression analyses. Receiver operating characteristic (ROC) analysis evaluating the accuracy of these factors for preterm delivery prior to 34 weeks showed that the area under ROC curve was 0.871. The study shows that mucocutaneous hemorrhage may be an indication of the occurrence of APOs in obstetric patients with APS.

Clinical phenotype, treatment strategy and pregnancy outcome of non-criteria obstetric antiphospholipid syndrome.

To illustrate the clinical features, treatment strategy, and pregnancy outcome of patients with obstetric antiphospholipid syndrome (OAPS), non-criteria obstetric antiphospholipid syndrome (NC-OAPS) METHOD OF STUDY: A single-center nested case-control study was designed. Patients with a diagnosis of OAPS and NC-OAPS were enrolled. The medical history, coagulation status, and antibody profile data were collected. Patients were given standard anticoagulation therapy with or without glucocorticoids (GC) and/or hydroxychloroquine (HCQ) during pregnancy and were observed for their pregnancy outcome. A total of 47 patients with OAPS and 120 patients with NC-OAPS were finally included, of whom 55 patients met the clinical criteria (subgroup C) and 65 met the laboratory criteria (subgroup L). Pregnancy morbidity showed significant differences: gravida, pregnancy loss in OAPS versus NC-OAPS. The coagulation function was not significantly different between OAPS and NC-OAPS groups, while TT and FIB were significantly higher in the subgroup C. Thromboelastography (TEG) results showed a significantly lower ANGEL in the NC-OAPS group, a higher ANGEL and lower EPL, LY30 in the subgroup L. No differences between groups were observed in treatment strategy. The pregnancy outcomes were not significantly different between NC-OAPS and OAPS groups. Clinical and laboratory differences were found between OAPS and NC-OAPS groups in this study. Patients in different subgroups of NC-OAPS could be identified with different clinical phenotypes. A relatively hypercoagulable status existed in the OAPS group compared to NC-OAPS, and also in the subgroup L.