Obstetric Antiphospholipid Syndrome Research Articles

Transcriptomics analysis of differential gene expression and immune and inflammatory response mechanisms in patients with typical and non-criteria obstetric antiphospholipid syndrome (OAPS and NC-OAPS)

In this study, we investigated the molecular differences between patients with typical obstetric antiphospholipid syndrome (OAPS) and patients with non-criteria obstetric antiphospholipid syndrome (NC-OAPS) patients through transcriptome sequencing of peripheral blood samples from ten OAPS patients and ten NC-OAPS patients. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) analysis, and competitive endogenous RNA (ceRNA) network construction to identify hub genes. Verification was performed via Quantitative Real-time PCR (qPCR) in OAPS (n=9) and NC-OAPS (n=12) samples. We identified 240 DEGs in two groups. GO and KEGG analyses reviewed upregulated in pathways related to the inflammatory response; immune response; antigen processing and presentation; Th1, Th2, and Th17 cell differentiation; and NK cell-mediated cytotoxicity in OAPS patients. PPI and ceRNA network analyses identified key genes, with significant upregulation of CXCR2, JAK2, and MPO found in the OAPS group, which correlated with severe inflammation, JAK-STAT pathway activation, and increased NET activity in neutrophils. Other genes such as CD4, IL2RB, and NKG7, are involved in T-cell and NK cell regulation. Our results indicate enhanced inflammatory and immune responses in OAPS patients, suggesting more severe immune activity than in NC-OAPS patients, providing a basis for precise diagnostic and therapeutic strategies.

Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome

AimsSome patients with Obstetric Antiphospholipid Syndrome (OAPS) still experience miscarriage and placental dysfunction after routine treatment, which is related to an abnormal increase in neutrophil extracellular traps (NETs). The labeling of statins has been revised to remove the contraindication for use during pregnancy. Our aim is to investigate the effect of Simvastatin on pregnancy outcomes in OAPS and its correlation mechanisms with NETs. Main methodsThe effect of Simvastatin on pregnancy outcomes was observed. The effect of simvastatin on the function and apoptosis of neutrophils has evaluated. The effect of Simvastatin to NETs and the changes in oxidative stress levels were observed. Different groups of NETs were extracted to intervene the HTR8-Svneo.RNA-seq analysis of the mechanism of which Simvastatin reduces NETs. Seahorse experiment detected the effect of Simvastatin on neutrophil glycolysis levels. Fluorescence co-localization and flow cytometry and Co-IP were used to verify relevant mechanisms. Key findingsIn the OAPS mice, Simvastatin can reduce embryo absorption rate, reshape placental blood flow perfusion. Simultaneously reducing the production of NETs both in vivo and vitro, remolding oxidative stress. Simvastatin can improve neutrophil dysfunction caused by aPL-IgG. The reduction of NETs improved HTR8-Svneo's dysfunction. The intervention of Simvastatin on neutrophils under the stimulation of aPL-IgG showed a signature in glycolytic. The key rate limiting enzyme PKM2 in glycolysis interacts with Cit-H2b and PI3K/AKT signaling pathway. SignificanceOur study providing basic theoretical support for the treatment of OAPS with Simvastatin.

Thrombotic complications in pregnancy: a case-based review of the evidence

Pregnancy is a prothrombotic state due to an estrogen-driven shift in the coagulation system, increased venous stasis, and external restriction of blood flow caused by the gravid uterus. Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in pregnancy. Preventing, recognizing, and treating thrombosis in pregnancy, as well as the postpartum period, often challenges decision making in the clinical setting. In early pregnancy, guidance with respects to thrombophilia testing and anticoagulation in increasing the likelihood of live birth among patients with recurrent miscarriages is evolving. This review explores emerging data that support clinical decision making in thrombosis care in women with common thrombotic complications in pregnancy. The first case outlines VTE diagnosis in pregnancy, initial anticoagulation management, management around delivery and postpartum, and subsequent long-term anticoagulation treatment. The second case examines testing for inherited and acquired thrombophilia in the setting of recurrent miscarriage and the management of obstetric antiphospholipid syndrome. Lastly, the third case reviews VTE risk assessment and prevention in pregnancy and the postpartum period, as well as duration and dose of postpartum thromboprophylaxis. Review of these common clinical scenarios surrounding thrombotic complications in pregnancy demonstrates recent advances in high-quality data, current gaps in knowledge, and variation in expert opinion. Ultimately, multidisciplinary discussion and teamwork remain key to optimal, safe care. Clinicians must prioritize collaborative, high-quality trials and prospective clinical management studies to better understand and define best practice in this population.

Impact of the 2023 ACR/EULAR Classification Criteria in Women with Primary Antiphospholipid Syndrome during Pregnancy.

Background/Objectives: ACR/EULAR has recently developed new classification criteria for antiphospholipid syndrome (APS). The present study aims to analyze the impact of these new 2023 ACR/EULAR classification criteria in a cohort of pregnant women with primary APS. Methods: Retrospective cohort study of 93 consecutive pregnant women attending the Autoimmune Diseases Pregnancy Clinic, a multidisciplinary unit of a tertiary care teaching hospital, between 2005 and 2023. All of them fulfilled the Sydney classification criteria for APS. Women diagnosed with rheumatic autoimmune diseases other than APS were excluded. Results: Twenty-four out of ninety-three patients (25.8%) met the 2023 ACR/EULAR criteria for APS. Patients who met the new classification criteria were very similar to those who did not, except for being younger (p < 0.001), and had a lower number of clinical pregnancies (p = 0.004). The obstetric domain was clearly underrepresented in women who fulfilled the 2023 ACR/EULAR criteria (p < 0.001). Patients meeting the new classification criteria were primarily characterized by preterm births before 34 weeks due to severe placentation disorders (p = 0.004). Women with early and late fetal loss were significantly underrepresented (p < 0.0001 and 0.03, respectively). Nearly half of these patients had thrombocytopenia (p < 0.001). Serologically, these patients showed a higher frequency of persistent lupus anticoagulant (p = 0.02) and a lower frequency of IgM isotype antiphospholipid antibodies (p = 0.05). Conclusions: Almost three-quarters of the patients included in the study did not meet the 2023 ACR/EULAR criteria. Most patients who could not be classified according to these new classification criteria were those with early and/or late fetal deaths, as well as patients carrying only IgM aCL/AB2GPI antibodies. The high specificity of the 2023 ACR/EULAR criteria, restricted to severe placentation disorders, may leave the majority of patients with obstetric APS out of the new classification criteria.

Using Doppler ultrasound to assess fetal cardiac function and pregnancy outcomes in obstetric antiphospholipid syndrome pregnancies: a case-control study.

This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes. In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis. The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy. MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making.

Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases.

The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4/31 (13%) patients had decreased C3/C4, while 7/29 (24%) had elevated BC4d, 11/33 (33%) EC4d, and 12/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS/TP/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3/C4, and the poor inverse correlation between CB-CAPs and C3/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.

Clinical Features Between Primary Obstetric Antiphospholipid Syndrome and Non-Criteria Obstetric Antiphospholipid Syndrome and Risk Factors of Adverse Pregnancy Outcomes: A Retrospective Study of 1006 Cases.

To compare the clinical characteristics and pregnancy outcomes between patients with primary obstetric antiphospholipid syndrome (OAPS) and those with primary non-criteria obstetric antiphospholipid syndrome (NC-OAPS), and to identify the risk factors of adverse pregnancy outcomes in both groups. A retrospective single-center study was performed in a university hospital of western China, including 141 patients with OAPS and 865 patients with NC-OAPS. The clinical characteristics, pregnancy complications, and obstetric outcomes of the cohorts were collected from the hospital system and were compared by univariable analysis, and the independent risk factors for adverse pregnancy outcomes (APO) were investigated by logistic regression analysis in these two populations. The OAPS patients had a significantly higher risk for stillbirths compared to the NC-OAPS patients, while the NC-OAPS group had a significantly higher risk for preterm birth and overall APO. Double aPL positivity, triple aPL positivity, and gestational hypertension were the independent risk factors for APO in OAPS patients, whereas two of the double aPL positivity subtypes, triple aPL positivity and placenta previa were independent risk factors for APO in NC-OAPS patients. This study identified different rates in different APOs among OAPS and NC-OAPS patients. Additionally, this study revealed different risk factors for the development of APO between the two populations. These findings indicated that OAPS and NC-OAPS are two distinct entities of the same disease, providing new insights into the individualized management for patients with OAPS and NC-OAPS.

Examining postpartum anticoagulation practices: An international survey of healthcare providers

BackgroundThe risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period. ObjectiveWe sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE. MethodsWe conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses. ResultsOf the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis. ConclusionOur study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.

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.

Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-β2 glycoprotein Ⅰ domain Ⅰ antibody (aβ2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

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.