Antiphospholipid Syndrome Group Research Articles

7-year follow-up atherosclerotic plaque progression in patients with antiphospholipid syndrome versus diabetes mellitus and healthy controls.

Patients with antiphospholipid syndrome (APS) carry a substantial burden of cardiovascular disease and subclinical atherosclerosis. We aimed to assess a 7-year follow-up atherosclerotic plaque progression in APS patients vs diabetes mellitus (DM) and healthy controls (HC). Eighty-six patients with thrombotic APS, 86 with DM and 86 HC (all age- and sex-matched) who underwent a baseline ultrasound of carotid and femoral arteries were invited for a 7-year follow-up ultrasonography examination. We compared atherosclerosis progression among the three groups and examined determinants of plaque progression in APS patients. Sixty-four APS patients (75% females, 43.8% with primary APS), 58 patients with DM and 66 HC were included in the 7-year ultrasound re-evaluation. New plaque was detected in 51.6%, 36.2% and 25.8% of APS, DM and HC subjects, respectively. After adjusting for traditional cardiovascular risk factors (CVRFs) and baseline plaque presence, APS patients showed a 3-fold (OR = 3.07, p= 0.007) higher risk for atherosclerosis progression vs HC and 2-fold (OR = 2.25, p= 0.047) higher risk than DM patients. In multivariate analysis in the APS group, plaque progression was independently associated with systemic lupus erythematosus (SLE) co-existence (OR = 7.78, p= 0.005) and number of CVRFs (OR = 3.02, p= 0.002), after adjusting for disease-related parameters and CVRF-related medications. Sustained low-density lipoprotein target attainment reduced plaque progression risk (OR = 0.34, p= 0.021). Half of APS patients develop new atherosclerotic plaques over a 7-year follow-up, having a three-times higher risk vs HC. Concomitant SLE and number of traditional CVRFs are associated with plaque progression, supporting the need for thorough CVRF assessment and control.

Risk and Outcomes of Hospitalizations in Patients with Anti-Phospholipid Syndrome Admitted with Autoimmune Hemolytic Anemia: A Nation-Wide Analysis

Introduction: Autoimmune hemolytic anemia (AIHA) can occur as a primary disorder or as a secondary manifestation of an underlying autoimmune condition. The coexistence of anti-phospholipid syndrome (APS) and AIHA can be very complex and challenging to manage given the intertwining of the prothrombotic and hemolytic states. In this study, we explored the outcomes of underlying antiphospholipid syndrome in autoimmune hemolytic anemia hospitalizations. Method: The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for AIHA and then the data was subclassified into hospitalizations with and without APS. Demographics, comorbidities, and outcomes were identified using appropriate ICD 9/10 codes. Propensity score matched cohorts were generated for APS status and adjusted for age, race, sex, smoking, obesity, DM, CHF, CKD/ESRD, and liver disease. Results: A total of 7,609 AIHA hospitalizations were included, with 76 patients having underlying APS and 7,533 did not have APS. Mean age was younger in the APS cohort and there were also more females, blacks and Hispanics compared to the non-APS cohort. Propensity score matching was used to generate two cohorts, adjusting for age, race, sex, and for co-morbidities including obesity, smoking, DM, CHF, CKD/ESRD and liver disease. The adjusted analysis showed an 8.59 times higher risk of developing venous thromboembolic events (VTE) in AIHA with APS as compared to those hospitalizations without APS (Odds ratio (OR): 8.59, CI: 1.05-70.5; p=0.03). There was also a statistically significant increase in mean hospitalization cost in the APS group (p=0.001). A trend towards more arterial athero-embolic events (AAE), major bleeding events, and AKI as well as longer length of stay was seen in hospitalizations with APS, but it did not reach statistical significance. No significant difference in in-hospital mortality was seen between the two groups. The results are summarized in the Figure 1. Conclusion: APS confers additional risk to AIHA hospitalizations with significantly higher VTE events and added costs. Further studies should address the complex management of anticoagulation and prothrombotic risk in APS in the setting of active hemolytic anemia.

Arterial stiffness tested by pulse wave velocity and augmentation index for cardiovascular risk stratification in antiphospholipid syndrome.

Cardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS. ArS was evaluated by carotid-femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group. We included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [β = -0.142 (95% CI -0.514, 0.230), p = 0.454] but increased AIx@75 [β = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [β = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [β = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [β = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-β2-glycoprotein I IgM positivity [β = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [β = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [β = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [β = 0.425 (95% CI 0.187, 0.663), p = 0.001]. APS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.

Immune Thrombocytopenia Could be an Independent Clinical Phenotype of Antiphospholipid Syndrome: A Prospective Cohort Study.

Patients with persistent positive antiphospholipid antibodies (aPLs) and immune thrombocytopenia (ITP) hardly develop thrombosis but share many similar characteristics with antiphospholipid syndrome (APS). This is a prospective cohort study consecutively enrolling thrombocytopenic patients with continuous positive aPLs. Patients developing thrombotic events are classified as the APS group. Then we compare the clinical characteristics and prognosis between aPLs carriers and patients with APS. This cohort included 47 thrombocytopenic patients with continuous positive aPLs and 55 with diagnosed primary APS. The proportion of smoking and hypertension are higher in the APS group (p = 0.03, 0.04, 0.03, respectively). The platelet count of aPLs carriers at admission was lower than APS patients [26 × 109/l (9 × 109/l, 46 × 109/l) vs. 64 × 109/l (24 × 109/l, 89 × 109/l), p = 0.0002]. Triple aPLs positivity is more common in primary APS patients with thrombocytopenia [24 (51.1%) vs. 40 (72.7%), p = 0.04]. Regarding the treatment response, the complete response (CR) rate is similar between aPLs carriers and primary APS patients with thrombocytopenia (p = 0.2). Nonetheless, the proportion of response, no response, and relapse differed significantly between the two groups [13 (27.7%) vs. 4 (7.3%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001; 5 (10.6%) vs. 8 (14.5%), p < 0.0001, respectively]. In Kaplan-Meier analysis, primary APS patients had significantly more thrombotic events than aPLs carriers (p = 0.0006). In the absence of other high-risk factors for thrombosis, thrombocytopenia could be an independent and long-lasting clinical phenotype of APS.

Effect of maternal autoimmune diseases on fetal pulmonary artery Doppler indices: A case-control study.

To compare the fetal pulmonary artery Doppler indices of pregnant women with autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and antiphospholipid syndrome (APS) with healthy pregnant women. Thirty-nine pregnancies were included in the case group, 19 of them SLE, 12 with SS, and eight with APS. The gestational age-matched 54 healthy pregnant women were included in the control group. Peak systolic velocity, time-averaged velocity, systolic/diastolic ratio, pulsatility index, resistance index, acceleration time (AT), ejection time (ET), and AT/ET ratio were obtained from pulmonary artery waveform by using spectral Doppler ultrasound. Significantly shorter AT and lower AT/ET ratio were detected in the case group (p=<.001, p=<.001, respectively). The shortening of AT and decreasing of the AT/ET ratio were more predominant in the APS group. However, there was no significant difference between the SLE, SS, and APS groups in fetal pulmonary artery Doppler indices. Also, a moderate correlation was found between maternal disease duration (years) and fetal pulmonary artery AT (r=-.516, p=.001) and AT/ET ratio (r=-.558, p=<.001). Fetal pulmonary artery Doppler indices may be affected in maternal autoimmune diseases. Further studies are needed to evaluate fetal pulmonary Doppler indices such as AT and AT/ET ratio to predict neonatal respiratory morbidity and lung maturation in pregnant women with SLE, SS, and APS.

Non-Criteria Obstetric Antiphospholipid Syndrome: How Different Is from Sidney Criteria? A Single-Center Study.

This study aims to compare the demographic characteristics, clinical features, serology, and fetal-maternal outcomes between women with obstetric antiphospholipid syndrome (APS) and those with non-criteria (NC)-APS and seronegative (SN)-APS. Two-hundred and sixty-three women with APS obstetric morbidity ever pregnant were included. Of those, 66 met the APS classification criteria, 140 were NC-APS, and 57 were SN-APS. Patients with other autoimmune diseases were excluded. Adverse pregnancy outcomes (APO) included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. The mean age of the study group was 33.6 ± 5.3 years, and patients were followed up for 129.5 ± 81.9 months. In the NC-APS group, 31 (22.1%) did not fulfill clinical and serological criteria (Subgroup A), 49 (35%) did meet clinical but not serologic criteria (Subgroup B), and 60 (42.9%) fulfilled the serologic criteria but not the clinical ones (Subgroup C). The cardiovascular risk burden was higher in the APS group, due to a higher proportion of smoking. Patients with criteria APS received more intensive treatment than patients in the other study groups. The addition of standard of care (SoC) treatment significantly improved live birth and decreased APO in all groups. Significant clinical differences were observed between the study groups. However, when treated with SoC, fetal-maternal outcomes were similar, with a significant improvement in live births and a decrease in APO. Risk stratification in patients with obstetric morbidity associated with APS can help individualize their treatment.

Preliminary Study on the Imbalance Between Th17 and Regulatory T Cells in Antiphospholipid Syndrome.

ObjectivePatients with antiphospholipid syndrome (APS) have immune cell abnormalities that remain poorly understood. This study compared primary APS (PAPS) and secondary APS (SAPS) patients with healthy controls with respect to peripheral blood lymphocytes, CD4+T cell subsets, and cytokine levels. The correlation between antiphospholipid antibody titres and T helper 17 (Th17) and T regulatory (Treg) cell subsets was also analyzed, together with the correlations between cytokine profiles and the clinical characteristics of APS patients.MethodsThe retrospective study population consisted of 67 APS patients (12 with PAPS, 55 with SAPS) and 40 healthy controls. Absolute numbers of peripheral blood lymphocyte subsets and CD4+ T cell subsets were detected by flow cytometry, and serum cytokine levels by flow cytometry bead array.ResultsPatients with SAPS had lower absolute values of T, B and CD4+T cells than the healthy control group, while only natural killer (NK) cell levels were decreased in patients with PAPS. Absolute numbers of T, B, NK, and CD4+T cells were significantly higher in the PAPS than SAPS group. The trends in CD4+T cell subsets were the same in PAPS and SAPS patients as in healthy controls, with increased Th1, decreased Th2, and decreased Treg levels, and thus an increased Th17/Treg ratio. Th2, Th17, and Treg cell counts were higher in the PAPS than SAPS group. Cytokine analysis showed that only IL-10 levels differed between the two APS groups. However, the levels of all of the studied cytokines were higher in APS patients than healthy controls, and correlated with the clinical characteristics of the patients. In the PAPS group, the titres of two autoantibodies correlated positively with the Th17/Treg ratio and negatively with the levels of D-dimer and Treg subsets.ConclusionsOur study clearly showed that APS patients have immune disturbances, the most prominent of which is an increase in the Th17/Treg ratio, due to a decrease in the number of Treg cells. These abnormalities may be involved in the occurrence and progression of APS. An additional finding was a higher level of peripheral blood lymphocytes in PAPS than SAPS patients, which may be related to the immunosuppressive treatment of SAPS patients.

Clinical and prognostic significance of antinuclear antibodies in primary antiphospholipid syndrome: A multicenter retrospective study.

The antiphospholipid syndrome (APS) (1) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (aPL). Antinuclear antibodies (ANA) can be detected in primary APS patients without any clinical systemic autoimmune disease. The presence of ANA antibodies could confer a specific phenotype in primary APS. To evaluate the characteristics of APS patients with antinuclear antibodies without other autoimmune disease (ANA positive APS patients) in comparison with primary APS without ANA or secondary APS patients with associated systemic lupus erythematosus (SLE). Clinical and biologic data from 195 APS were retrospectively collected and patients were classified as primary APS with positive ANA (ANA-positive APS), primary APS without any ANA (ANA-negative APS), and SLE-associated APS (SLE-APS). Fourty patients (21%) were classified into ANA-positive APS group, 77 (39%) in ANA-negative APS and 78 (40%) in SLE-APS. In ANA-positive APS patients, 20 patients (51%) had arterial thrombosis, 14 (41%) had veinous thrombosis and 19% had obstetrical complications. There was no difference between the three groups for the frequency of thrombotic manifestations and obstetrical complications. ANA-positive APS patients had more non-criteria manifestations than ANA-negative APS (48% versus 25%; P≤0.01). ANA-positive APS had more triple aPL positivity (59% versus 18%; P<0.001) and more thrombosis and obstetrical recurrences (63% versus 36%; P<0.01) in comparison with ANA-negative APS patients. ANA-positive APS had more triple aPL positivity than SLE-APS patients (54% versus 33%; P<0.05). ANA-positive APS and SLE-APS patients had similar clinical manifestations, and recurrences. Despite a limited follow-up (28 months (11-50)) none of the ANA-positive APS develop SLE. Antiplatelet and anticoagulant therapies were similar for the three groups. SLE-APS patients received more immunomodulatory therapies. ANA positivity in patients with APS enables to individualize a subset of patients with a more severe phenotype. Whereas the ANA positivity does not seem to be associated with the risk to develop SLE, prospective studies with a longer follow-up are necessary, in particular to evaluate the effect of additional therapies in this subset of APS.

CIRCULATING LEVEL OF INTERLEUKIN 6 IN PATIENTS WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME

Background: The antiphospholipid syndrome (APS) is an autoimmune systemic disorder that carries many mortality and morbidity. Many cytokines come up in APS; IL6 is one of this cytokines. Objective: Assessing Circulating Level of Interleukin 6 (IL 6) and its relations to thrombotic risk in patients with primary APS. Patients and Methods: This study was carried out on sixty patients suffering antiphospholipid syndrome, and thirty healthy volunteers as a control. They were selected from inpatient and outpatient clinic of Internal Medicine and Unit of Immunology Departments from Al-Azhar University Hospitals (Al-Hussein, New Damietta and Al-Azhar University Hospitals), during the period from November 2017 to December 2019. They were divided into three equal groups: Group A; suffering from primary APS, Group B; suffering from secondary APS, Group C; healthy normal volunteers as a control group. All patients and controls were subjected to complete history, clinical assessment and laboratory investigations. Serum level of interleukin-6 was assessed. Results: There was a statistical significant increase in IL6 among patients with 1ry APS as well as patients with 2ry APS. The commonest presentation among our studied patients with 1ry APS was venous thrombosis (17%) arterial thrombosis (9%) and unexplained abortion (10%). The significant signs that were detected on general examination of those patients were livedo reticularis (10%), Raynoud phenomen (15%) and purpuric eruption (13%). As regard 2ry APS, the commonest presentation among studied patients was venous thrombosis (23%) arterial thrombosis (24%) and unexplained abortion (12%). The significant signs detected on general examination of those patients were livedo reticularis (6%), Raynoud phenomen (10%), and purpuric eruption (13%). As regard the mean IL-6, there was a high significant difference between 1ry APS, 2ry APS and control groups (P<0.001). This study showed a positive correlation of IL-6 with arterial thrombosis among patients with 1ry APS. No correlation was detected between IL-6 and arterial thrombosis among patients with 2y APS. Regarding the correlation between venous thrombosis and IL-6 in patients with 1ry APS and 2ry APS, there were no statistically significant positive correlations as regard IL6. Conclusion: IL-6 was found in patients to be elevated with primary APS. Serum IL-6 was showed to be positively correlated with arterial thrombosis.

Antiphospholipid syndrome (APS): Clinical and immunoserological differences between primary and secondary APS in a Colombian cohort

IntroductionAntiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent thrombosis that can affect the arterial and venous circulation. ObjectivesTo analyze the immunological and pharmacological differences, as well as the clinical outcomes of a cohort of patients with primary antiphospholipid syndrome and secondary antiphospholipid syndrome. Materials and methodsA retrospective cohort study was conducted that included 352 records of patients diagnosed with APS and treated between 2014 and 2018. A description is presented of the sociodemographic, clinical, and immunological profile of the population. A bivariate analysis performed using the chi-squared test to determine differences between groups with primary APS and secondary APS, and finally a multivariate analysis to search for associations with thrombotic clinical outcomes in patients with APS. ResultsThe mean age was 42.4 ± 14 years, and 84.6% were females. Two-thirds (67.6%) of the patients had a diagnosis of primary APS, and 32.4% of secondary APS, of which 84% were associated with systemic lupus erythematosus (SLE). Among the thrombotic events, the most frequent were deep vein thrombosis (17.3%) and stroke (9.9%). Obstetric events were frequent, with a prevalence of 39.4% for miscarriages. No differences were found in the sociodemographic or immunoserological profile when comparing the group of primary vs. secondary APS. Thrombotic events were more frequent in the primary APS group, although only pulmonary embolism reached statistical significance. There were no differences between the two groups as regards obstetric events, such as miscarriages. Women were found to be 5 times more likely to have a stroke and 3 times more to have deep vein thrombosis. The anti-B2GPI type IgM increased the probability of presenting miscarriages about 3 times in women with APS. ConclusionThe study contains one of the largest Colombian cohorts with APS reported so far, and although it is both clinically and sociodemographically similar to other cohorts, there is a higher prevalence of primary APS. There was a lower frequency of thrombotic complications compared to other cohorts. Patients with primary APS had a tendency to develop thrombosis, as has already been reported in the literature.

AB0330 ANTIPHOSPHOLIPID ANTIBODIES AND ANTICOAGULANT TREATMENT: CAPILLAROSCOPIC FINDINGS

Background:Antiphospholipid syndrome (APS) is an autoimmune condition characterized by arterial and/or venous thrombosis and/or obstetric morbidity, associated with the presence in the serum of antiphospholipid antibodies (aPL) [1]. Subjects with confirmed positivity of aPL in absence of thrombotic/obstetric manifestations are identified as aPL carriers [2] The microangiopathy detected by nailfold videocapillaroscopy (NVC) in APS and in aPL-carrier patients is poorly investigated, as well as the possible interference of anticoagulant drugs [3].Objectives:To compare microvascular damage in APS, aPL carriers and a group of patients (CTR) without aPL positivity and on regular warfarin therapy for cardiovascular indicationsMethods:NVC investigations were performed as part of standard procedures in APS patients (18, mean age 50.0±12.8 years), aPL carriers (24, mean age 46.4±16.4 years) and CTR without aPL (18, mean age 74±12.5 years) in therapy with oral anticoagulant (warfarin) for non-immunological vascular complications (atrial fibrillation, mechanical heart valve, deep venous thrombosis). Only patients affected by primary APS form were selected from data files (2006 Sapporo classification criteria). The following NVC parameters were availble: dilated capillaries, giant capillaries, microhemorrhages (with particular attention to linear and thin hemosiderin deposits, arranged perpendicularly and parallel to the nailfold bed, “comb-like”), abnormal shape (i.e. brunched “bushy” capillaries) and capillary number reduction. Those parameters were scored according to a semi-quantitative scale [4,5]. Statistical analysis was performed by non-parametric tests. Any p values equal or lower than 0.05 was considered statistically significant.Results:APS patients showed a higher score for dilated capillaries (p=0.001), more frequent microhemorrhages (p=0.03), in particular “comb-like” microhemorrhages (p=0.007) than simply aPL carriers. Of note, there wasn’t a statistically significant difference in the number of microhemorrhages between APS and CTR group (p=0.23), but again the number of “comb-like” hemorrhages, was almost absent in the CTR group (p=0.03). No significant correlation was found between the different aPL subtypes and the NVC parameters.Conclusion:APS patients showed significantly higher number of non-specific NVC abnormalities than aPL carriers. Anticoagulant treatment could represent a further risk factor for the appearance of microhemorrhages in all the patients, being the NVC “comb-like“ pattern mainly associated with the APS. Further investigations with larger cohorts of patients are needed for the definition of a possible APS specific NVC-pattern.

Risk of Systemic Lupus Erythematosus in Patients With Anti-phospholipid Syndrome: A Population-Based Study.

Objective: To investigate the association between anti-phospholipid syndrome (APS) and the risk of newly diagnosed systemic lupus erythematosus (SLE).Methods: We used 2003–2013 data derived from Taiwan's National Health Insurance Research Database to conduct this nationwide, population-based. We identified AS patients newly diagnosed between 2005 to 2013 as the study group and applied age-sex matched (1:20) and propensity score-matched (PSM) (1:2) non-SLE individuals as controls. The association between APS and risk of incident SLE was determined by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox proportional hazard regression analysis.Results: We identified 1,245 patients with APS as well as 24,900 age- and sex-matched non-APS controls and 727 APS patients as well as 1,454 PSM non-APS controls. We found that the risk for incident SLE in the APS group was 80.70 times higher than the non-APS group, and the association remained robust after PSM (HR, 28.55; 95% CI, 11.49–70.91). The increased risk for SLE in patients with APS mainly existed within 5 years after the diagnosis of APS. The sensitivity analyses found that the risk for SLE in patients with APS was consistent excluding patients with ITP/AIHA and using distinct definitions of SLE.Conclusion: The present population-based study revealed a robust association between SLE risk and recent APS and highlights the need for vigilance of SLE-associated symptoms in patients who had been diagnosed with APS.

Is the presence of antiphospholipid antibodies a poor prognostic factor for patients with hemolysis, elevated liver enzymes, and low platelet count syndrome?

The characteristics of antiphospholipid syndrome-associated hemolysis, elevated liver enzymes, and low platelet count syndrome are poorly described, likely because of the low frequency of this combination of syndromes. This study aimed to compare the characteristics and prognosis of hemolysis, elevated liver enzymes, and low platelet count syndrome in patients with and without antiphospholipid syndrome. In this multicenter, case-control study, adult women diagnosed with hemolysis, elevated liver enzymes, and low platelet count syndrome before 34 weeks' gestation and who were also tested for antiphospholipid antibodies according to international diagnostic recommendations were included. Cases labeled "HELLP-APS+" were defined as patients who fulfilled the international classification criteria for antiphospholipid syndrome; they were retrospectively recruited by screening the 672 patients with antiphospholipid syndrome in our antiphospholipid syndrome database. Control cases labeled "HELLP-APS-" were defined as patients who did not fulfill the criteria for antiphospholipid syndrome; they were retrospectively recruited from our hospital admission database. Overall, 71 patients were included (mean age, 30±5 years), with 23 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome group and 48 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome group. The live birth rate was significantly lower for patients with hemolysis, elevated liver enzymes, and low platelet count with antiphospholipid syndrome than for those with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (43.5% vs 89.4%; P<.001). The patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome gave birth prematurely more often than the patients without antiphospholipid syndrome (24 weeks' gestation; 22.0-28.0 weeks vs 30 weeks' gestation; 27.0-33.0 weeks; P<.001). Among the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, 39% required an induced abortion owing to hemolysis, elevated liver enzymes, and low platelet count syndrome severity vs 8.5% of the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.006). The intensive care unit admission rate was 61.9% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, which was significantly higher than the rate of 27.7% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.007). None of the mothers died. Our results suggest that the presence of antiphospholipid syndrome is a poor prognostic factor for both the mother and fetus in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.

Risk factors for pregnancy morbidity in women with antiphospholipid syndrome

Antiphospholipid syndrome (APS) increases the risk of obstetric complications, but risk factors for pregnancy morbidity in women with APS remain incompletely characterized. This retrospective study included pregnant women with APS and a control group without APS admitted to Peking University People’s Hospital between January 2013 and September 2019. Clinical data were extracted from medical records. Univariate and multivariate logistic regression analyses were used to identify factors associated with adverse pregnancy outcomes (fetal loss, premature birth, fetal growth restriction [FGR], preeclampsia and neonatal death). We included 64 pregnancies in 59 patients with APS (age, 32.3 ± 4.3 years) and 256 pregnancies in 256 women without APS (age, 30.4 ± 3.3 years). Compared with the control group, the APS group had higher incidence rates of preeclampsia (10.9 % vs. 2.3 %, P = 0.002), premature rupture of membranes (17.2 % vs. 3.9 %, P < 0.001), postpartum hemorrhage (23.4 % vs. 4.3 %, P < 0.001), fetal loss (4.7 % vs. 0.8 %, P = 0.024) and premature delivery at ≤34 weeks (7.8 % vs. 2.3 %, P = 0.047). The incidence rates of hypertension during pregnancy, HELLP syndrome, gestational diabetes, oligohydramnios and FGR were similar in both groups. Multivariate logistic regression revealed that three or more prior spontaneous miscarriages (odds ratio [OR], 6.162; 95 % confidence interval [CI], 1.271–29.882; P = 0.024) and double-positivity for antiphospholipid antibodies (OR, 4.024; 95 %CI, 1.025−15.794; P = 0.046) were independently associated with adverse pregnancy outcomes. APS increases the risks of adverse maternal and fetal outcomes during pregnancy. Three or more spontaneous miscarriages and double-positivity for antiphospholipid antibodies are risk factors for adverse pregnancy outcomes in women with APS.

Anticardiolipin Positivity Is Highly Associated With Intrauterine Growth Restriction in Women With Antiphospholipid Syndrome.

The purpose of our study was to evaluate pregnancy outcomes of women with antiphospholipid antibodies (aPL) positivity and assess risk factors associated with adverse pregnancy outcomes. Pregnant women with aPL positivity were enrolled prospectively in China from January 2017 to March 2020. Treatment of low-dose aspirin and low molecular weight heparin were given. Pregnancy outcomes and coagulation function were recorded and compared with normal pregnancies. Multivariable logistic regression was performed to identify risk factors associated to intrauterine growth restriction (IUGR). 270 pregnant women, including 44 diagnosed as Antiphospholipid syndrome (APS), 91 as non-criteria APS (NCAPS) and 135 normal cases as control, were enrolled in the study. The live birth rate in aPL carriers and APS group was 97% and 95.5%, respectively. Adverse pregnancy outcomes did not show significant difference between aPL carriers and normal pregnancies, and between APS and NCAPS, except for IUGR. The incidence of IUGR was significantly higher in aPL carriers than normal pregnancies, and in APS patients than NCAPS (P < 0.05). After controlling for age, in vitro fertilization (IVF), pregnancy losses related to APS and treatment, anticardiolipin (aCL) positivity was the only variable significantly associated with IUGR, with an adjusted odds ratio of 4.601 (95% CI, 1.205-17.573). Better pregnant outcomes of aPL positive women, include APS and NCAPS, were achieved in our study with treatment based on low-dose aspirin (LDA) plus low molecular weight heparin (LMWH). The incidence of IUGR was still higher in them, and aCL positivity was the only one risk factor associated with IUGR.

Comparison of the Serum Metabolic Signatures Based on 1 H NMR between Thrombotic Antiphospholipid Syndrome (APS) Patients and Healthy Individuals

Antiphospholipid syndrome (APS) is an acquired immuno-mediated disorder, in which antiphospholipid antibodies (aPL) against a variety of phospholipids and phospholipid transport proteins are persistently produced. aPL include a heterogeneous group of circulating immunoglobulins: lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-β2glycoprotein-I (anti-β2GPI). Their presence is related to diverse clinical phenomena including arterial and venous thrombosis, which can be related to different pathogenic properties, such as its effect on the clotting pathways, endothelium and platelets. Metabolomic can be useful improving diagnosis, prognostic and therapeutic interventions, in vascular disease (Kirlikaya B. et al, 2019) The aim of this study was to identify metabolic alterations in patients with thrombotic APS characterized by deep venous thrombosis (DVT) compared to healthy individuals using liquid-state 1H-NMR data acquisition combined with chemometrics analysis. We evaluated ten serum samples of patients with APS (mean age 39 years; 6 female/4 male), who attended at the outpatient clinic of Hemocentro of Campinas, Unicamp-Brazil, from 2013 to 2017 (Table 1). The exclusion criteria were the presence of cancer and renal disease, smoking and alcoholism. The samples were collected up to 2 years the last thrombotic episode. All patients except one (suprahepatic vein) suffered DVT of the lower limbs and only two of them presented 2 thrombotic episodes. Six patients were classified as primary APS and four with secondary (three presented systemic lupus erythematosus (SLE) and one were diagnosed with psoriasis). All patients with secondary APS were using immunosuppressive drugs: prednisone and azathioprine, or methotrexate. None of the patients were triple positive. The control group were healthy individuals (mean age 41 years; 5 female/5male), from staff of the Hemocentro and the exclusion criteria were the same as for patients. Multivariate analysis pointed to slight differential metabolic profiles among APS and controls, and between primary and secondary APS. Different metabolites associated to energy metabolism, such as increased glucose consumption and lactate production, as well as differences at spectral regions corresponding to some aromatic amino acids were identified in APS group when compared to controls. Our results are promising, such as different profiles could be observed, both regarding patients vs. controls, such as primary vs. secondary APS. The use of immunosuppressive drugs in secondary APS may contribute to these changes. Although questions regarding the translatability of metabolomics findings into clinical practice, our results showed the high sensitivity and specificity of NMR spectroscopy to distinguish healthy and APS. To have a better understanding of the metabolic alterations potentially involved in the APS, additional analyses including mean spectra are being made. Disclosures No relevant conflicts of interest to declare.

Transcranial Doppler findings in antiphospholipid syndrome.

Transcranial Doppler is a method that enables the assessment of different cerebral hemodynamic parameters. It also allows for the evaluation of the presence of right-to-left circulation shunts (RLS) and for the detection of microembolic signals (MESs), which might be associated with an increased risk of cerebrovascular events. For instance, the presence of MESs on transcranial Doppler in patients with systemic lupus erythematous (SLE) and antiphospholipid syndrome (APS) is associated with an increased risk of stroke. Therefore, transcranial Doppler could be a useful tool for stroke risk stratification in these patients. Our objective was to evaluate transcranial Doppler cerebral mean blood flow velocities as well as the presence of MESs and RLS in patients with antiphospholipid syndrome and SLE. Twenty-two patients with primary APS (PAPS), 24 patients with secondary APS (SAPS), 27 patients with SLE without APS and 21 healthy controls were evaluated. Clinical and epidemiological data were compiled from medical charts, and all subjects underwent transcranial Doppler examination with breath-holding index calculation. Both middle cerebral arteries were monitored for 60 min for the detection of MESs. RLS was investigated with agitated saline injected as a bolus. There were no significant differences in mean blood flow velocities among the groups. MESs were more frequently found in patients with SLE when compared with controls and patients with APS (SLE: 17.4%, SAPS: 4.3%, PAPS: 0%, controls: 0%, p = 0.03). Anticoagulant therapy was more frequently used in the APS group (PAPS: 81.8%, SAPS: 75.2%, SLE: 1.7%, p < 0.001). Patients with APS had a higher frequency of RLS when compared with volunteers (63.6% versus 38.1%, p = 0.05). Breath-holding index values tended to be lower in patients with SAPS than in control subjects and patients with PAPS and SLE ( p = 0.06). Patients with APS had a higher frequency of RLS than healthy controls. This finding alerts to the importance of cardiac investigation in patients with stroke and APS, because further therapies such as RLS occlusion might eventually add protection. The higher frequency of MES in patients with SLE could suggest an effect of anticoagulant therapy on MES prevention, more frequently used in patients with APS.

Study on the correlation between CD4+ CD25+ Tr cells and IL-17 levels in peripheral blood of patients with antiphospholipid syndrome

Objective To explore the changes of Tr cells and IL-17 levels in peripheral blood of patients with antiphospholipid syndrome(APS) and the clinical significance. Methods The quantity of the CD4+ CD25+ Tr cells and proportion of CD4+ CD25+ Tr cells/CD4+ T cells were detected by flow cytomety, and the levels of IL-17 were detected by ELISA in 60 cases with APS(APS group) and 60 healthy people(control group). Results The levels of Tr, Tr/CD4+ , Foxp+ 3Tr/Tr in the APS group were (3.03±0.40)%, (0.11±0.02), (0.40±0.10), respectively, which in the control group were (5.76±0.84)%, (0.15±0.03), (0.73±0.15), respectively, the differences were statistically significant(t=22.73, 8.59, 14.18, all P<0.01). The levels of serum IL-17 and IL-17/Tr cells in APS group were (15.31±2.00)pg/mL, (5.05±0.29)pg/mL, respectively, which in the control group were (6.63±1.52)pg/mL, (1.15±0.14)pg/mL, respectively, there were statistically significant differences(t=29.17, 93.81, all P<0.05). The levels of serum IL-17 was negatively correlated with Tr cells level in peripheral blood of patients with APS(r=-0.801, P<0.01). Conclusion There is peripheral blood cellular immune function disorder in APS patients, the number and active changes of CD4+ CD25+ Tr cells and IL-17/Tr ratio imbalance may play a role in the pathogenesis of APS. Key words: Antiphospholipid syndrome; T-Lymphocytes, helper-inducer; Interleukin-17

Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid syndrome: analysis of 58 patients.

The study aims to analyse the clinical and immunological manifestations of paediatric antiphospholipid syndrome (APS) in patients, based on the 2006 revised classification criteria of definite APS. Fifty-eight paediatric patients with APS were enrolled and analysed retrospectively. A total of 37 female and 21 male patients with a mean age of 14±3years at disease onset were included. Fourteen (24%) cases were primary APS, and 40 (69%) cases were secondary to systemic lupus erythaematosus (SLE). Anti-nuclear antibody (ANA) positivity and hypocomplementemia were more common in secondary APS than in primary APS. The most common manifestations of thrombosis were deep vein thrombosis of the lower extremities (25 cases, 37%). Non-thrombotic manifestations were mainly immunologic thrombocytopenia, autoimmune haemolytic anaemia, skin lesions, arthritis, pulmonary hypertension, heart valve vegetations and spontaneous abortion. LA, ACL and anti-β2GPI were positive in 42 (95%), 28 (64%) and 34 (77%) cases, respectively. Over half (23 cases, 52%) of the patients were triple-positive for antiphospholipid (aPL) antibodies. Among patients with single-positive LA and anti-β2GPI, the proportion with venous thrombosis was 100% (5 cases) and 0% (0 cases), respectively. The arterial thrombosis proportions were 22% (5 cases), 21% (3 cases) and 14% (1 case) in the triple-, double- and single-aPL-positive groups, respectively (P>0.05). Fifty-three (91%) cases were followed up for 3 to 140months, with a median time of 32months. Seven (13%) cases had recurrences or appearances of thrombosis during follow-up, all of which were double- or triple-aPL positive. APS in the paediatric patients is mostly secondary to SLE. ANA positivity and hypocomplementemia are more common in secondary APS, but there are no differences in the other clinical manifestations between the primary and secondary APS groups. Deep vein thrombosis is the most common thrombotic event. Positive LA may increase the risk of venous thrombosis. Multiple-aPL positivity does not increase the proportion of thrombosis. Long-term anticoagulant or antiplatelet therapy is needed to prevent thrombosis recurrence in double- or triple-positive aPL cases.