Antiphospholipid Syndrome Research Articles

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 outcomes of patients receiving long-term fondaparinux for thrombotic antiphospholipid syndrome.

Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting. We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records. 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding (p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding (p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009). We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies.

THE ANTICOAGULATION STRATEGIES FOR MANAGEMENT AND PREVENTION OF STROKE IN NEUROLOGICAL PRACTICE

Strokes are categorized as either ischemic or hemorrhagic and the specific interventions will be based on the type of stroke. About 13% of stroke is hemorrhagic and 87% is ischemic. Transient Ischemic Attacks require emergency intervention to decrease the threat of stroke, which is thought to be maximum within the first few days after TIA. Anticoagulants play a major role in the primary and secondary prevention of ischemic strokes. The optimal timing of anticoagulants initiation or resumption inpreventing and managing ischemic strokes is very important. This article will explore certain controversies surrounding this issue, while also highlighting the benefits of antithrombotic therapy used in prevention of ischemic strokes in antiphospholipid antibody syndrome (APS), atrial fibrillation, prosthetic heart valve, cancer, and vascular disorders. Aggressive local and regional efforts to organize stroke care and greater use of evidence-based recommendations may help improve outcomes. Peer Review History: Received 16 May 2024; Reviewed 11 July 2024; Accepted 24 August; Available online 15 September 2024 Academic Editor: Essam Mohamed Eissa, Beni-Suef University, Egypt, dressamceutics@yahoo.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Taha A.I. El Bassossy, Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt, tahachemist2008@gmail.com Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com

Severe Antiphospholipid Syndrome in a Child with Chicken Pox: Clinical Case

Background. Antiphospholipid syndrome develops at autoimmune diseases, pregnancy, or genetic predisposition, and it is characterized by high risk of thrombosis in arterial, venous, and capillary vessels. This syndrome in children is rare, and necrotic skin lesions occur in the most extreme cases. Clinical case description. A child, 1 year old, with chicken pox has developed hemorrhagic rash on his back, swelling of the left shoulder and forearm on the 4th day of the disease. Medical treatment included acyclovir, ceftriaxone, sodium heparin. Aggravation of hemorrhagic rash over the body, spread of edema from the left shoulder to upper arm and neck, formation of flaccid bubble and necrosis locus (75 cm) on the outer upper third of the left shoulder were noted on the 5th-6th day. Increase in the levels of antibodies to 2-glycoprotein I (IgG — 48.9 U/ml, IgM — > 100 U/ml) and cardiolipin (IgM — 73.0 U/ml) was revealed. The diagnosis “antiphospholipid syndrome” was established. All necrotized tissues were removed on the 11th day, and the wound defect (86 cm) was subsequently covered by mesh skin grafts. The levels of antibodies (IgG + IgM) to 2-glycoprotein I remained high, 45.2 U/mL, 12 weeks after the onset of the disease. Thus, it has confirmed the development of antiphospholipid syndrome. The child continued treatment with warfarin (3.75 mg/day) with INR control. Conclusion. Hemorrhagic skin lesions in children with infectious diseases requires laboratory diagnostics of antiphospholipid syndrome, early prescription of anticoagulant and antiplatelet therapy, and surgical support.

Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region.

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.

Assessing the effectiveness of preventing placenta-associated complications in patients with burdened obstetric history and circulating antiphospholipid antibodies

Assessing the effectiveness of preventing placenta-associated complications in patients with burdened obstetric history and circulating antiphospholipid antibodies

Outcomes of IVF treatments in women with antiphospholipid antibodies or antiphospholipid syndrome

BackgroundOvulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear. Materials and methodsA retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared. Results121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive β-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle. ConclusionOvarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation.

Establishment of cutoff values for anti-β2 glycoprotein I antibodies in women of reproductive age in Southwest China

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-β2 glycoprotein I (aβ2GPI) antibodies and aimed to establish the first population-based cutoff values for aβ2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-β2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aβ2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aβ2GPI IgA, 27.54 RU/mL for aβ2GPI IgM and 1.81 RU/mL for aβ2GPI IgG, which indicated that the levels of aβ2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aβ2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aβ2GPI IgA, 22.89% for aβ2GPI IgG, and 9.64% for aβ2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aβ2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

Thrombotic antiphospholipid syndrome: Recurrent thromboses

Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).The aim of this study was the evaluation of the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.Material and methods. The retrospective study included 98 patients with aPL who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with aPL, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2-glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2-glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/ IgM aPS/PT) and other thrombotic risk factors. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemoluminescence assay (CHLA).Results. Thrombosis recurrence was reported in 62 (63%) of 98 patients, and 36 (35%) did not. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). 24 (38.7%) of 62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) of the patients. In 17 (27.4%) of the patients, the recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity did not matter, but all had triple IgG aPL positivity. 5 had lupus anticoagulant (LA) at the onset of the disease before anticoagulant use. IgG aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG aPS/PT, compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPL was more frequent in CHMA than in ELISA. However, the definition of aPL in ELISA is recommended according to the latest classification criteria. Triple IgG positivity for aCL of IgG aß2GP1, IgG aß2GP1-D1 and CHMA remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than threefold. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese compared to non-obese patients (p=0.01).Conclusions. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk.The presence of any type of aPL IgG in both ELISA and CHLA influenced the recurrence rate of thrombosis in APS.Obesity was a significant risk factor for recurrent thrombosis.

The Effect of Lupus on Pregnancy and the Foetus: Should we really be Worried? A Single-Centre Retrospective Study.

Systemic Lupus Erythematosus (SLE), is common in women of childbearing age and is associated with obstetric complications. The aim of this study was to evaluate the course of pregnancy and its results in SLE patients with a history of pregnancy. Pregnant patients with SLE who applied to the Rheumatology outpatient clinic of between 2010 and 2020 were retrospectively screened. Fifty-five pregnancies of 31 SLE patients were included in the study. Spontaneous abortion was observed in 27.3% (n:15) and foetal loss in 18.2% (n:10). Neonatal loss or maternal death was not observed in any of the patients. The rate of patients with renal involvement was 34.5% (n:19), and the rate of exacerbation was higher in pregnant women with kidney involvement (26% vs 0% (p:0.006)). Antiphospholipid antibody syndrome (APS) was present in 32.7% (n:18) of the cases, and there was a history of foetal loss before diagnosis in 50% (n:9) of the cases with APS. The foetal loss was seen only in pregnant women with APS (55.6% (n:10) vs. 0% (n:0) (p<0.001)). Six (10.9%) of 55 pregnancies in our study were unplanned pregnancies. Of these, five resulted in abortion. Exacerbation was observed in 3 of the unplanned pregnancies. Pregnancy complications were significantly lower in patients who were in remission since contraception. Exacerbations were more common in unplanned pregnancies and in patients with renal involvement. The presence of APS was associated with increased pregnancy morbidity.

Right Ventricular Outflow Tract Mass as the Initial Presentation of Primary Antiphospholipid Syndrome

Abstract Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies and clinical manifestations, including thrombosis and pregnancy-related complications. While cardiac manifestations such as intracardiac thrombi, valvular disease, and intracardiac masses have been reported, the presentation of an intracardiac mass as the initial manifestation of primary APS (PAPS) is relatively uncommon. This case report describes a 40-year-old female patient who presented with an echogenic mass in the right ventricular outflow tract, subsequently diagnosed as a calcified amorphous tumor. Further investigation revealed elevated levels of anticardiolipin antibodies and beta-2 glycoprotein leading to the diagnosis of PAPS. The patient later developed digital ischemia, strengthening the suspicion of PAPS. This case highlights the importance of considering APS as a potential underlying cause for intracardiac masses, even in the absence of other typical manifestations. Early recognition and appropriate management, including anticoagulation and immunosuppressive therapy, are crucial to prevent further thrombotic complications and improve patient outcomes.

Optimal long-term anticoagulation after acute pulmonary embolism: current state of the art and a look into the near future.

This review aims to summarize the current state of the art and future directions in optimal long-term anticoagulation following acute pulmonary embolism (PE). Actual studies and guidelines underscore the preference for direct oral anticoagulants (DOAC) in standard therapeutic doses for maintenance therapy post-PE, while considering patient-specific factors and dose-reduction criteria. Risk stratification should always include the assessment of concomitant trigger- or risk factors regarding their strength and persistence. The use of tools like specific scores can facilitate the identification of optimal candidates for long-term therapy, emphasizing once more personalized approaches and strategies. Special patient groups, such as cancer associated thrombosis, chronic thromboembolic pulmonary hypertension or antiphospholipid syndrome require even more tailored therapy approaches. Optimal long-term anticoagulation post-PE should be guided by straightforward and individual risk assessment strategies. The array of indications for DOACs has gotten wider in last years, also within special patient groups. Still, chronic thromboembolic pulmonary hypertension and antiphospholipid syndrome remains domain of vitamin K agonists.

Platelet proteomics in the pathogenesis of systemic lupus erythematosus and antiphospholipid syndrome

Platelet proteomics in the pathogenesis of systemic lupus erythematosus and antiphospholipid syndrome

Red blood cell distribution width as a surrogate biomarker of damage and disease activity in patients with systemic lupus erythematosus.

Red blood cell distribution width (RDW) is a measure of variability in mean corpuscular volume. Alterations in RDW can be observed in a variety of human disorders, including inflammatory, cardiovascular, and hepatic or renal diseases. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ in the body. In this work, our objective was to analyse how a complete characterisation of disease characteristics in a large series of patients with SLE is related to RDW values. 284 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood count including RDW was assessed. Multivariable analysis was performed to analyse the relationship between RDW and SLE disease characteristics, including composite scores of disease activity and damage. After multivariable adjustment, RDW was higher in patients with SLE compared to controls (beta coefficient 0.8 [95% confidence interval: 0.3-1] %, p=0.003). Several disease characteristics, such as the presence of extractable nuclear antibodies and antiphospholipid syndrome, and the use of prednisone and azathioprine, were significantly associated with higher levels of RDW after adjustment for confounders. Of note, cumulative disease damage and disease activity scores were associated with higher RDW values after controlling for covariates. RDW may serve as a surrogate biomarker of accrual disease damage and activity in patients with SLE.

Hematological features and alternate diagnoses in critically ill thrombotic antiphospholipid syndrome patients.

Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome. This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied. One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients. Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated.

Quel bilan proposer après une grossesse compliquée de pathologie vasculo-placentaire ?

Vasculo-placental disorders include pregnancy complications resulting from placental dysfunction of vascular origin, i.e. pre-eclampsia, HELLP syndrome, intrauterine growth retardation (IUGR), placental abruption and stillbirth of vascular origin. Pre-eclampsia should be investigated for antiphospholipid syndrome (APS) in case of severe pre-eclampsia and premature delivery before 34 weeks of gestation. In addition to testing for APS, pathological report of the placenta can identify some anatomical predispositions to placental vascular malperfusion, as well as chronic placental inflammatory lesions and excess fibrin deposits. The latter two are associated with IUGR and recurrent stillbirth, reflecting a dysimmune process of maternal origin. The internal medicine and obstetrics consultation, organized two months after delivery, combines the postnatal visit with an assessment of the causes of vasculo-placental disorders, and enables to inform patients about the management of future pregnancies and their cardiovascular health.

The utility of the normal thin section skin biopsy in the assessment of systemic/extracutaneous disease and small fiber neuropathy

Diseases reflective of multiorgan vascular injury of diverse etiology, peripheral nerve disease, dysautonomia syndromes, and intravascular lymphoma may exhibit abnormalities on a normal skin biopsy that may be instrumental in establishing a diagnosis. A retrospective review of our database was conducted to uncover cases where a normal skin biopsy was performed to rule in or out such systemic diseases as complement-driven thrombotic microvascular disease (including atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, and severe or critical COVID-19), systemic capillary leak syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) intravascular B cell lymphoma, small fiber neuropathy, dysautonomia syndromes, and mast cell activation syndrome. Among the special studies were immunohistochemical staining to detect C5b-9, CD56, and myxovirus resistance protein A, as well as mast cell, B and T cell markers. Characteristic patterns were critical in establishing diagnoses such as : increased C5b-9 microvascular deposition in the deltoid area (atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, catastrophic antiphospholipid antibody syndrome, and severe or critical COVID-19); enhanced type I interferon signaling (systemic capillary leak syndrome); ultrastructural arteriopathic changes (CADASIL); reduced cutaneous autonomic innervation in the lower extremities (small fiber neuropathy and postural orthostatic tachycardia syndrome); presence of intravascular lymphocytes on biopsy of abdominal, thigh, and buttock skin (intravascular B cell lymphoma); and a higher than normal density of mast cells in the absence of other inflammatory cell types (mast cell activation syndrome). The skin is clearly a critical window for understanding extracutaneous disease, a concept well exemplified by the myriad of diseases suggested by the microscopic and/or ultrastructural examination of clinically normal skin and therefore establishing the normal skin biopsy as an important tool for understanding certain extracutaneous reactive, neoplastic and paraneoplastic syndromes as well as small fiber neuropathy.

Interaction between endothelial cell-derived extracellular vesicles and mononuclear phagocytes in the context of antiphospholipid syndrome

Interaction between endothelial cell-derived extracellular vesicles and mononuclear phagocytes in the context of antiphospholipid syndrome

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.