Antiphospholipid Syndrome Patients Research Articles

LncRNAs dysregulation in monocytes from primary antiphospholipid syndrome patients: a bioinformatic and an experimental proof-of-concept approach.

Antiphospholipid syndrome (APS) is the main cause of acquired thrombophilia where peripheral circulating cells such as monocytes have a key role. Currently, several studies have linked long non-coding RNAs (lncRNAs) in different inflammatory and autoimmune processes, including lupus. However, the role of lncRNAs in antiphospholipid syndrome is unknown, therefore, we aimed to select and measure expression levels of three lncRNAs based on its abundancein monocytes from APS patients. Selection of lncRNAs candidates were carried out based on its abundancein monocytes and their relationship with Perez-Sanchez miRNA signature by using miRNet 2.0 bioinformatic tool, then lncRNAs expression levels was measured in monocytes by RT-qPCR. This is the first study to report that lncRNAs: FGD5-AS1, OIP5-AS1 and GAS5 are promising candidates for play a role on APS monocytes and they are expressed differently between patients and controls. OIP5-AS1, FGD5-AS1 and GAS5 are downregulated on monocytes from APS patients.

Primary Anti-Phospholipid Antibody Syndrome: Real-World Defining Features of Rethrombosis in the Course of Disease.

We aimed to identify features that allow differentiation of primary antiphospholipid syndrome (PAPS) patients that suffer recurrent thrombotic events (RTE) despite anticoagulation, from the other diagnosed PAPS patients. This was an exploratory study of anticoagulated PAPS patients attending an Autoimmune Diseases Unit (1998-2018). From 2016, anti-phospholipid antibodies and lupus anticoagulant were determined for each patient at consecutive visits, collected together with retrospective clinical characteristics, laboratory, and therapeutic markers and compared according to the occurrence of thrombotic events during follow-up. Overall, two thirds of the patients were female, 93% were Caucasian, with a median age of 40 years at diagnosis, for a median time of 11.5 years in follow-up. Out of 54 patients, 10 were identified with RTE. There were no significant differences among the RTE and non-RTE patients as far as classical risk factors for clotting disorders. The RTE group was characterized by a higher proportion of younger patients, male sex and positivity for all laboratory markers, and initially and over follow-up as well as a sustained high-risk profile based on APS laboratory markers. Anticardiolipin IgG at onset was the only statistically significant marker of the RTE group. At the end of follow-up, consistent reversion to negative status was a rare event, observed in 20% of RTE vs. 25% of non-RTE patients. Despite therapy, we were able to identify features associated to thrombotic events in patients with PAPS. Prospectively regular clinical and laboratory monitoring might be warranted in order to treat APS more assertively.

Application Value of Combined Detection of Anti-β2-GPI, ACL, and Lupus Anticoagulant in the Diagnosis of Patients with Antiphospholipid Syndrome.

To investigate the application value of combined detection of anti-beta 2-glycoprotein I antibody (anti-β2-GPI), anti-cardiolipin antibody (ACL), and lupus anticoagulant (LA) in the diagnosis of patients with antiphospholipid syndrome (APS). 30 APS patients in our hospital between Jan. 2020 and Jan. 2021 were chosen as the experimental group, and 30 healthy persons with normal physical examination during the same period were selected as the control group The anti-β2-GPI and ACL indexes of both groups were detected by enzyme-linked immunosorbent assay (ELISA), with the LA levels tested by modified dilute Russell's viper venom time (dRVVT) and LA ratio calculated. The diagnostic efficacy of single detection and combined detection was analyzed by plotting the receiver operating characteristic (ROC) curve. The serum indexes in the experimental group were remarkably higher than those in the control group (P < 0.001). ROC curve analysis suggested that in the diagnosis of APS, the area under the ROC curve by detecting anti-β2-GPI, ACL, LA ratio alone and simultaneously were 0.517, 0.583, 0.683, and 0.817 respectively, and the combined detection of the three had remarkably higher sensitivity and specificity than those of each single detection. The indexes of anti-β2-GPI, ACL, and LA ratio were highly expressed in APS patients, and the combined detection of the three has high diagnostic value and can effectively screen and assist the diagnosis of APS.

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center

To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-β2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added.

Non-criteria antiphospholipid antibodies (aPLs) increase the diagnostic value for antiphospholipid syndrome (APS) and contribute to better recognition of seronegative APS (SNAPS). However, the clinical utility and the diagnostic value of non-criteria aPLs are inconsistent. This study aimed to investigate the prevalence and clinical significance of 7 non-criteria aPLs in a large APS cohort. Seven non-criteria aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT) antibodies IgG/IgA/IgM, anti-phosphatidylethanolamine antibodies (aPE) IgG/IgA/IgM, anti-Annexin V antibodies (aAnnexinV) IgG/IgA/IgM, anti-phosphatidylserine antibodies (aPS) IgM, aPS IgG, antibodies directed againsta mixture of phospholipids(APhL) IgG, and APhL IgM were tested among 175 patients with APS, 122 patients with other autoimmune diseases (as disease controls), and 50 healthy controls. In the present study, the highest prevalence of non-criteria aPLs was seen in aAnnexinV (58.86%). APhL IgG and aPS IgM showed the highest specificity (95.35%) and aPS/PT showed the highest Youden index (0.3991) for the diagnostic value of APS. The aAnnexinV also showed the highest prevalence in SNAPS (43.3%), followed by APhL IgM (21.7%), aPE (16.7%) and aPS/PT (16.7%). APhL IgG, aPS/PT, and aPS IgG showed positive association with thrombotic events in APS patients [APhL IgG: odds ratio (OR) = 2.26, 95% confidence interval (CI) 1.18-4.34, p = 0.013; aPS/PT: OR = 2.48, 95% CI: 1.32-4.69, p = 0.004; aPS IgG: OR = 1.90, 95% CI 1.01-3.60, p = 0.046; respectively). The inclusion of the non-criteria aPLs increased the accuracy of APS diagnosis from 65.7% to 87.4%. Our data provide evidence that adding the non-criteria aPLs can improve the diagnostic accuracy in APS. APhL IgG, aPS/PT, and aPS IgG may be potential biomarkers to predict the risk of thrombosis in APS.

Differences in Antiphospholipid Antibody Profile between Patients with Obstetric and Thrombotic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by the presence of antiphospholipid antibodies (aPL) associated with vascular thrombosis and/or pregnancy complications. In a cohort of 74 yet diagnosed APS individuals fulfilling Sydney laboratory criteria (twice positive for lupus anticoagulant, anticardiolipin, aCL, and/or anti-β2glycoprotein I, aβ2GPI), 33 out of 74 were obstetric APS (OAPS) and 41 thrombotic APS (TAPS) patients. 39% of TAPS patients were women. Although aPL detection was persistent, we observed an oscillatory aPL positivity in 56.7% and a transient seroconversion in 32.4% of APS patients at enrolment. Thus, we tested their sera in a line immunoassay that simultaneously detected IgG or IgM for criteria (aCL and aβ2GPI) and non-criteria (anti-phosphatidylserine, aPS; anti-phosphatidic acid, aPA; anti-phosphatidylinositol, aPI; anti-annexin 5, aA5; anti-prothrombin, aPT; anti-phosphatidylethanolamine; anti-phosphatidylglycerol, and anti-phosphatidylcholine) aPL. OAPS and TAPS patients displayed different but overlapping clusters based on their aPL reactivities. Specifically, while OAPS patients showed higher aPA, aPS, aA5, aβ2GPI and aPT IgM levels than TAPS patients, the latter displayed higher reactivity in aCL, aPI and aA5 IgG. Eventually, with a cut-off of the 99th percentile established from a population of 79 healthy donors, TAPS patients significantly tested more positive for aCL and aA5 IgG than OAPS patients, who tested more positive for aPA, aPS and aβ2GPI IgM. Transiently seronegative APS patients showed non-criteria aPL positivity twice in sera obtained 3 months apart. Overall, our data show that APS patients presented clusters of aPL that define different profiles between OAPS and TAPS, and persistent non-criteria aPL positivity was observed in those who are transiently seronegative.

TIMELESS is a key gene mediating thrombogenesis in COVID-19 and antiphospholipid syndrome

Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein–protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.

Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients.

Objective: The potential contribution of asymmetric dimethylarginine (ADMA) and high-sensitivity C reactive protein (hsCRP) to endothelial dysfunction in APS patients has not been studied in detail, until now. The study involved 105 APS patients (59 diagnosed with primary APS (PAPS) and 46 APS associated with systemic lupus erythematosus (SAPS)) who were compared to 40 controls. Endothelial dysfunction was assessed by measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate dilatation (NMD) of the brachial artery. ADMA (micromol/L) was analyzed by ELISA. Results: FMD in patients with APS was significantly lower than that of the controls (p < 0.001), with no difference between the PAPS and the SAPS groups. ADMA and hsCRP concentrations were significantly higher in the patient cohort than in the control group (p < 0.001, p = 0.006, respectively), as was the case with the SAPS group as compared to the PAPS group (p < 0.001, p = 0.022, respectively). FMD impairment correlated to ADMA (ρ 0.472, p < 0.001) and to hsCRP (ρ 0.181, p = 0.033). In the regression model, the ADMA concentration confirmed the strength of its association (B 0.518, SE 0.183, Wald 8.041, p = 0.005, Exp(B) 1.679, 95% CI 1.174–2.402) to FMD impairment. The synergistic probability model of ADMA and hsCRP caused FMD impairment when the positivity of β2GPIIgG was added. ADMA may be used as a simple and low-cost tool for verifying the presence of endothelial dysfunction in APS patients. According to the results of the study, we could presume that hsCRP, together with aPL, has a preparatory effect on the endothelium in causing endothelial dysfunction.

Relevance of inflammatory and complement activation biomarkers profiling in antiphospholipid syndrome patients outside acute thrombosis.

To evaluate whether inflammatory and complement biomarkers are associated with specific characteristics of antiphospholipid syndrome (APS). Serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, interferon-α (IFN)-α, IFN-γ, vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule (VCAM)-1, and plasma levels of soluble C5b-9 (sC5b-9), C3a, C4a, Bb fragment were measured in unselected APS patients. Twenty-five healthy blood donors were included as controls. Between January 2020 and April 2021, 98 APS patients were included outside acute thrombosis (median time from the last APS manifestation: 60 (23;132) months). Levels of IL6, VCAM-1, sC5b-9, C3a, C4a, and Bb were significantly increased in APS patients compared to controls. A cluster analysis allowed to divide patients into two clusters: "inflammatory" (higher levels of IL-6 and VCAM-1) and "complement". In APS, elevated IL-6 was associated with hypertension, diabetes, BMI, and hypertriglyceridaemia. 85% of our APS patients had elevated levels of at least one complement biomarker. Elevated Bb (34%) was associated with aPL positivities, especially with triple aPL positivity (50% vs. 18%, p<0.001). 7/8 patients with history of catastrophic APS had elevated levels of complement biomarkers. Our findings suggested that APS patients outside acute thrombosis might be divided into two clusters: "inflammatory" and "complement". Elevated IL-6 was associated with cardiovascular risk factors and metabolic parameters, whereas Bb fragments, a marker of alternative pathway complement activation, was strongly associated with aPL profile at highest risk of severe disease.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Meta-Analysis.

Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), long-term anticoagulation is recommended. For decades, vitamin K antagonists (VKAs) have been the gold standard for thromboprophylaxis in these patients. Due to the widespread use of direct oral anticoagulants (DOACs) in various thromboembolic conditions and their potential advantages compared to VKAs, several studies have been conducted to evaluate their safety and efficacy in APS.We performed a literature search using PubMed, Embase, and Cochrane databases for studies comparing DOACs to VKAs in patients with APS. Relative risk (RR) and the corresponding 95% confidence intervals (95% CI) were estimated for recurrent thromboembolic events, bleeding, and mortality.A total of 1437 patients pooled from 12 studies were analyzed. The risk of recurrent thrombosis, especially arterial thrombosis, doubled with DOACs compared to VKAs (RR 2.61, 95% CI 1.44-4.71; p=0.001). The risk further increased in patients with a triple-positive antiphospholipid antibody profile (RR 4.50, 95% CI 1.91-10.63; p=0.0006) and with the use of rivaroxaban (RR 1.95, 95% CI 1.10-3.45; p=0.02). The risk of major bleeding and mortality were not significantly different between the two arms. A trend favoring DOACs compared to VKAs was observed for all bleeding events. This meta-analysis comes in agreement with previous studies and supports the use of VKAs in APS. Our study revealed that VKAs remain the gold standard for the management of APS, especially triple-positive APS. DOACs, particularly rivaroxaban, are not as effective in preventing recurrent thromboembolism in high-risk APS patients. Further studies are needed to evaluate the role of DOACs apart from rivaroxaban with a focus on their efficacy in the management of isolated or double-positive APS.

Antiphospholipid Antibody Syndrome-Associated Increased Surface Expression of VLA4 Integrin on Human Monocytes.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and/or obstetric complications in the presence of antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of the disease, in which microvascular thromboses develop rapidly, leading to multiorgan failure. Monocytes, along with endothelial cells, are critical players in the pathogenesis of APS. Recruitment of these cells to the site of injury/inflammation involves a series of events, including capture, rolling, adhesion enhancement, and transmigration, which are controlled by surface adhesion molecules. The aim of our study was to investigate the surface adhesion profile of monocytes from APS patients and monocytes stimulated in vitro with aPL from a CAPS patient. The surface expression of the adhesion molecules LFA1, L-selectin, MAC1, PSGL1, and VLA4 was analyzed by flow cytometry. To our knowledge, this preliminary study was the first to show that VLA4 was significantly increased on the surface of monocytes from APS patients. Moreover, in vitro stimulations mimicking CAPS showed an even greater increase in VLA4. Our data suggest that the surface adhesion profile on monocytes is altered in APS and CAPS and may be involved in the thrombotic pathophysiology of the disease by enhancing monocyte adhesion.

Prevalence, characteristics and outcome of cardiac manifestations in critically-ill antiphospholipid syndrome patients

AimsAntiphospholipid syndrome (APS) is a rare autoimmune disease defined by thrombotic events occurring in patients with persistent antiphospholipid antibodies. Cardiac manifestations in critically-ill APS patients are poorly investigated. We conducted a study to assess the prevalence, the characteristics and the prognosis of cardiac manifestations in thrombotic APS patients admitted to intensive care unit (ICU). Methods and resultsA French, national, multicentre, retrospective study, conducted, from January 2000 to September 2018, including all APS patients admitted to 24 participating centres’ ICUs with any new thrombotic (arterial, venous or microvascular) manifestation. Cardiac manifestations were defined as any new cardiac abnormalities relying on clinical examination, cardiac biomarkers, echocardiography, cardiac magnetic resonance (CMR) and coronarography. One hundred and thirty-six patients (female 72%) were included. Mean age at ICU admission was 46 ± 15years. Cardiac manifestations were present in 71 patients (53%). In patients with cardiac involvement, median left ventricular ejection fraction (LVEF) was 40% [28–55], troponin was elevated in 93% patients, coronary angiogram (n = 19, 27%) disclosing a coronary obstruction in 21%. CMR (n = 21) was abnormal in all cases, with late gadolinium enhancement in 62% of cases. Cardiac manifestations were associated with a non-significant increase of mortality (32% vs. 19%, p = 0.08). After 1-year follow-up, median LVEF was 57% [44–60] in patients with cardiac involvement. ConclusionCardiac involvement is frequent in critically-ill thrombotic APS patients and may be associated to more severe outcome. Increased awareness on this rare cause of myocardial infarction with or without obstructive coronary artery is urgently needed.

Thromboembolic Antiphospholipid Syndrome (APS): Efficacy and Safety of Different Anticoagulants-Results of the APSantiCO Registry.

Background: The particular challenge in dealing with patients with thromboembolic antiphospholipid syndrome (APS) is to establish an adequate therapy regime, as patients suffer from an increased risk of relapse despite antithrombotic treatment (ATT). Vitamin K antagonists (VKA) are the standard medication of choice. The current data on the use of direct oral anticoagulants (DOAC) in APS patients remain limited. Methods: The results of the retrospective APSantiCO registry are presented. In 80 patients with APS, the efficacy and safety of different ATT regimens were analyzed. Results: At the time of inclusion, 43.8% of patients were treated with VKA and 36.3% with DOAC. Medication regimes changed several times and 279 treatment phases were further analyzed with a total treatment length of 7529 months. The incidence of recurrent arterial thrombosis was significantly larger in the DOAC group compared with the VKA group (p < 0.001), while the incidence of recurrent venous thrombosis was comparable between both groups, as was the incidence of bleedings. Heavy menstrual bleeding was the most frequently observed bleeding complication. Conclusions: The data suggest that DOAC may be an alternative to VKA for APS patients with venous thromboembolism, while VKA should be used in APS-related arterial thrombosis.

Thrombocytopenia in the first trimester predicts adverse pregnancy outcomes in obstetric antiphospholipid syndrome.

BackgroundThrombocytopenia is a common manifestation of antiphospholipid syndrome (APS), and is a main concern for bleeding on the standard treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) in obstetric APS (OAPS).ObjectiveThis study assesses the possible relationship between thrombocytopenia during the first trimester and adverse pregnancy outcomes (APOs) in OAPS patients.MethodsA case-control study was conducted at Peking University People’s Hospital, Beijing, China. The clinical, immunologic, and pregnancy outcomes of the OAPS patients were collected. Univariate and multivariate logistic regression analyses were applied to assess the relationship between APOs and thrombocytopenia in the first trimester.ResultsA total of 115 participants were included in the analysis. There were no difference on antepartum and postpartum hemorrhage between the two groups. The gestational age in the thrombocytopenia group was less than that in the control group (34.12 ± 8.44 vs. 37.44 ± 3.81 weeks, p = 0.002). Hypocomplementemia, double aPL positive, and high titers of anti-β2 glycoprotein I were more frequent in APS patients with thrombocytopenia (p < 0.05). Compared to the control group, thrombocytopenia in the first trimester was correlated with SGA (12.12% vs. 31.25%, p = 0.043), premature birth <37 weeks (16.16% vs 43.75%, p = 0.010) and intrauterine fetal death (2.02% vs 12.50%, p = 0.033). Thrombocytopenia in first-trimester independently increased the risk of preterm birth <37 weeks (OR = 5.40, 95% CI: 1.35-21.53, p = 0.02) after adjusting for demographic and laboratory factors. After adding medication adjustments, these factors above become insignificant (p > 0.05). Of note, the number of platelets increased after delivery in 14 thrombocytopenia patients with live fetuses (p = 0.03).ConclusionThis study demonstrates that thrombocytopenia in the first trimester increases the risks of preterm birth in women with APS. The effective OAPS treatments may improve pregnancy outcomes and not increase the risk of antepartum and postpartum hemorrhage.

SAMD1 attenuates antiphospholipid syndrome-induced vascular injury and pregnancy complications.

ObjectiveThis study was intended to investigate the effect of SAMD1 on antiphospholipid syndrome (APS)‐induced vascular injury in human umbilical vein endothelial cells (HUVECs) and pregnancy complications in mice.MethodsThe expression of SAMD1 in APS patients and healthy controls was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Anti‐B2GPI and anticardiolipin antibody (ACA) levels were tested by enzyme‐linked immunosorbent assay, MMP‐9, iNOS, ICAM‐1, and MCP‐1 mRNA and protein levels determined by qRT‐PCR and Western blot, cellular senescence detected by β‐galactosidase staining, cell proliferation ability detected by CCK‐8 assay, cell viability detected by trypan blue staining, cell mobility detected by Transwell, and cell angiogenesis ability detected by matrigel tube formation assay. An APS pregnant mouse model was constructed, and the embryo absorption rate was calculated.ResultsSAMD1 expression was low in serum of APS patients, which was correlated with the history of thrombosis and the number of adverse pregnancies. Anti‐B2GPI and ACA levels were increased in APS. The expressions of MMP‐9, iNOS, ICAM‐1, and MCP‐1 were also significantly upregulated in HUVECs treated with APS serum. APS promoted HUVEC senescence and inhibited cell proliferation, migration, and angiogenesis. Overexpression of SAMD1 reversed the above results. Experiments on the APS pregnant mouse model confirmed that overexpression of SAMD1 reduced the rate of fetal loss.ConclusionSAMD1 may reduce APS‐induced vascular injury and embryo loss by regulating cellular senescence, proliferation, migration, and angiogenesis.

Direct oral anticoagulants versus warfarin in patients with antiphospholipid syndrome: A meta-analysis of randomized controlled trials.

This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome (APS). We performed a literature search using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. We also performed a meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness and safety of DOACs versus warfarin in patients with APS. Five RCTs involving 648 patients with APS (330 in DOAC-treated and 318 in control groups) were included in the meta-analysis. Among the patients included in the analysis, 29 (8.8%) patients experienced recurrent thrombosis in the DOAC treatment group, and 10 patients (3.1%) had thrombosis recurrence in the warfarin treatment group, resulting in a higher incidence in DOAC-treated than in the warfarin-treated groups [odds ratio (OR) = 2.163, 95% CI = 0.985-4.748, p = 0.055]. Incidence of arterial thrombosis was significantly higher in DOAC-treated patients than in warfarin-treated patients (OR = 5.168, 95% CI = 1.567-17.04, p = 0.007). Stroke and thrombosis occurrences were significantly higher in the triple positivity group than in the warfarin therapy group (OR = 12.03, 95% CI = 2.249-64.36, p = 0.004; OR = 2.940, 95% CI = 1.016-8.504, p = 0.047). However, venous thrombosis occurrences did not differ significantly between the DOAC-treated and warfarin-treated groups. There were no significant differences between the DOAC and warfarin groups in terms of any bleeding, major bleeding, minor bleeding, and all-cause mortality. DOACs were associated with higher rates of arterial thrombosis than warfarin in patients with APS, especially in the triple-positive group. However, a higher risk of recurrent venous thrombosis was not found in APS patients treated with DOACs compared to those treated with warfarin.

Primary and secondary antiphospholipid syndrome characteristics in an Egyptian cohort

Aim of the workTo describe the clinical and laboratory characteristics of patients with primary and secondary antiphospholipid syndrome (APS) in an Egyptian cohort. Patients and methodsSixty APS patients were enrolled. 12 had primary APS and 48 had secondary. Patients were further classified according to the presence of double or triple antiphospholipid antibodies (aPL). ResultsThe study included 55 (91.7 %) females and 5 (8.3 %) males, with a mean age of 33.9 ± 9.1 years, and mean disease duration of 6.2 ± 93.04 years. The obstetric complication in the form of fetal loss was the commonest manifestation of APS (70 %), followed by lower limb deep venous thrombosis (DVT) (50 %), recurrent abortion (45 %), thrombocytopenia (25 %), cutaneous manifestations (20 %), and Raynaud’s phenomenon (18.3 %). Urinary findings are mostly related to secondary APS. 15 (25 %) patients were thrombocytopenic and 1 (1.7 %) had autoimmune hemolytic anemia. Primary APS patients showed higher frequency of cutaneous manifestations compared to secondary (50 % vs 12.5 %; p = 0.04), and higher levels of β2 glycoprotein I IgG (71.8 ± 22.4 U/ml vs 59.3 ± 17.1 U/ml; p = 0.047). Secondary APS patients showed positive antinuclear antibodies (ANA) and anti-double stranded deoxyribonucleic acid antibodies (anti-dsDNA) in 97.9 % and 93.8 % respectively and were negative in all primary APS patients. On comparing patients with double (n = 34) and triple (n = 26) aPL, no differences were found between both groups except for platelet count being significantly lower in the triple aPL (p = 0.045). ConclusionEgyptian APS patients showed a high frequency of obstetric complications and lower limb DVT. Primary APS patients had higher frequency of cutaneous manifestations.

Ethnicity and Antiphospholipid Syndrome in Israel.

Antiphospholipid syndrome (APS) is an acquired coagulopathy associated with the presence of antiphospholipid antibodies. Whether ethnicity modulates APS clinical course is not known. The aim of our study was to assess the interplay of ethnicity and APS in Israel. We retrospectively evaluated the ethnic distribution of APS patients from 3 medical centers in Israel compared to the general population. Ethnic groups were defined according to the Israeli Bureau of Statistics as Ashkenazi (European), former Union of Soviet Socialist Republics (USSR), North African, Asian (West Asia, Greece, and Turkey), Israeli Arab individuals, and others. Our cohort included 382 patients. The prevalence of Ashkenazi and Asian ethnicities was more pronounced (33% versus 12.8% and 15.4% versus 7.7%, respectively; P < 0.001), while Israeli Arabs were less represented (5.2% versus 31.1%; P < 0.001) relative to their part in the general population. Arab patients were younger at presentation (mean ± SD 28 ± 10 years versus 34 ± 13 years; P < 0.001) and were more likely to present with venous thrombosis (50% versus 35%; P = 0.037) and to suffer from venous thrombotic recurrence (45% versus 16%; P < 0.001) compared to other ethnicities. Mortality was higher among patients of Asian ethnic origin (8.8% versus 1.1%; P = 0.005); intriguingly, this group experienced cardiovascular risk factors more often (i.e., dyslipidemia and hypertension). Ethnicity may affect the prevalence and/or natural course of APS, which is less prevalent and differs clinically in Israeli Arab patients, while mortality was linked with Asian ethnicity.

Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious.We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types.A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49–8.93; I2 = 29%, P = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56–4.42; I2 = 0, P = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99–10.29; I2 = 0, P = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences.In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Dyslipidemia is insufficiently treated in antiphospholipid syndrome patients.

Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for unachieved cholesterol levels in a real-life APS population. Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination. Cholesterol level targets for each patient were defined according to 2019 ESC/EAS guidelines for the management of dyslipidemia. Between January 2020 and April 2021, 114 APS patients were included (male 37 (32.5%); mean age 49 ± 14years). Among them, 40 (35.1%) had a history of dyslipidemia, 48 (42.1%) were under lipid-lowering therapies, and 59 (51.8%) had a history of cardiovascular disease (CVD). Mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride were, respectively, 110 ± 40mg/dL, 60±20mg/dL, and 120 (80-190)mg/dL. Unachieved LDL-C levels were found in 77 (67.5%) patients of whom 53 had history of CVD. Overall, 90 (78.9%) had protective HDL-C and 31 (27.2%) had hypertriglyceridemia. In the multivariate analysis, independent risk factors for unachieved LDL-C levels were older age and history of CVD; triple aPL negativity, defined as complete disappearance of aPL over time in APS patients who were previously positive in accordance to international criteria, was an independent protective factor for unachieved LDL-C. Our finding suggested that dyslipidemia is frequent in APS patients and mainly insufficiently treated, especially in patients with history of CVD, who are at highest risk of future CV events.