Manifestations Of Antiphospholipid Syndrome Research Articles

Autoantibodies against complement proteins in patients with antiphospholipid syndrome: Prevalence and clinical associations.

Seventy-seven patients with antiphospholipid syndrome were tested for autoantibodies against C1q, C3, FB, FH, and C4bp. Fifty-seven patients had at least one anti-complement antibody. IgM anti-FH positivity was associated with thrombosis when anti-C3 and anti-FB were, negatively or positively, associated with various noncriteria manifestations of antiphospholipid syndrome.

Chronic abdominal aortic occlusive disease related to antiphospholipid syndrome: a rare presentation

ObjectiveChronic abdominal aortic occlusive disease (CAAOD) is an uncommon manifestation of antiphospholipid syndrome (APS), impacting cardiovascular health and peripheral arterial circulation. We investigated CAAOD in antiphospholipid antibodies (aPL)-positive patients, aimed...

Stroke and Risk Factors in Antiphospholipid Syndrome.

Stroke is considered one of the most common and life-threatening manifestations of antiphospholipid syndrome (APS), which leads to high mortality and permanent disability. This study investigated the prevalence and the potential risk factors of stroke in APS. We enrolled 361 APS patients retrospectively from 2009 to 2022 at Peking University People's Hospital. Stroke was found in 25.8% (93/361) of the participants. The multivariate logistic regression showed that hypertension, diabetes, livedo reticularis, and other central nervous system involvements were significant related factors for stroke. The use of hydroxychloroquine appeared to relate to a lower incidence of stroke. During a median follow-up of 3.0 years, 11.8% (11/93) of the individuals with a previous stroke developed stroke recurrence, and thrombocytopenia seemed to be a predictor of stroke recurrence.

Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients.

The aim of this study was to determine the thrombogenicity of lupus anticoagulant (LA) antibodies using a modified thrombin generation assay (TGA) with the addition of activated protein C (APC) in a group of 85 patients with LA-positive samples. Of these, 58 patients had clinical manifestations of antiphospholipid syndrome (APS) according to the Sydney criteria classification, i.e., each patient had thrombosis or foetal loss, and 27 patients did not show any clinical manifestations of APS. A comparison of the two groups' TGA results revealed statistically significant differences (Fisher's test p = 0.0016). The group of patients exhibiting clinical manifestations of APS showed higher thrombogenicity in 56.9% of patients, while the group of patients not yet exhibiting clinical manifestations of APS showed higher thrombogenicity in 25.9% of patients. There were no significant differences in the specificity of the TGA test between the groups of patients exhibiting similar clinical manifestations. Receiver operating characteristic curve analysis showed a more significant relationship (p = 0.0060) for TGA than for LA titre (p = 0.3387). These data suggest that the determination of LA thrombogenicity with the TGA assay leads to an increased prediction of the manifestation of a thromboembolic event. Our findings appear to be particularly relevant for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.

An extrapyramidal manifestation of antiphospholipid syndrome (APS) and approach to its treatment; a case report

An extrapyramidal manifestation of antiphospholipid syndrome (APS) and approach to its treatment; a case report

Hematological Activity in Primary Antiphospholipid Syndrome: A Common Manifestation Outside the Classification Criteria

Introduction: Thrombocytopenia and autoimmune hemolytic anemia (AIHA) are extra-criteria manifestations of antiphospholipid syndrome (APS). They have a higher incidence in secondary cases, and there is little information on primary antiphospholipid syndrome (pAPS). Aim: To evaluate the clinical characteristics and profile of antibodies in pAPS with hematological activity. Material and methods: A retrospective study included patients with pAPS, diagnosed according to the Sapporo criteria with follow-up at third level of care in Mexico City from 1990 to 2021. Descriptive statistics were used, and chi-squared test, Mann-Whitney U test, and logistic regression were performed. Results: A total of 97 patients with pAPS were included; 73.2% (71) were women with a mean age of 33.9 + 11.5 years and a mean follow-up of 132 months (24-360). We found that 77% (75) presented thrombotic and 37% (36) obstetric manifestations. In 68% (66) of patients, hematological manifestations (non-exclusive groups) were found. Further, 63.9% had thrombocytopenia, the most common kind being severe, and a minority had AIHA in 13.4%. Table 1 describes the clinical manifestations. Patients with thrombocytopenia were younger, with 32 + 10.3 years vs 37 + 13 years ( p = 0.046). A total of 59.7% (37) had a triple marker. In comparison with patients without thrombocytopenia, 69.4% (43) presented positive lupus anticoagulant vs 48.6% ( p = 0.043) and OR 2.5 (CI 95% 1.06-6.1). An 83.9% (52) had positive IgG anticardiolipin vs 62.9% ( p = 0.019), OR 3.21 (CI 95% 1.19-8.63) with a higher titer of 19.4 vs 6.1 ( p = 0.017) and OR 1.01 (CI 95% 0.99-1.04). They had higher titers of antiβ2 glycoprotein-I IgM of 6.8 vs 5.2 ( p = 0.019) with OR 1.03 (CI 95% 0.99-1.06) and of antiphosphatidyl serine/prothrombin IgM of 52.8 vs 16.8 ( p = 0.004), OR 1.01 (CI 95% 1- 1.02). In patients with AHAI, anti-β2 glycoprotein-I IgM antibody titers of 7.1 vs 5.9 were identified, which were higher compared with those who did not present it ( p = 0.026). Those without hematological activity had more thrombosis ( p < 0.001). When comparing the groups with and without thrombosis, we observed that those with thrombosis had lower titers of antiβ2 glycoprotein-I IgM in 5.8 vs. 7.4, p = 0.036, OR 0.97 (CI 95% 0.94-1) and higher anti-phosphatidyl serine/prothrombin titers in 61.2 vs 12.1, p = 0.021 with OR 1.02 (CI 95% 1-1.04). A total of 76.3% (74) received anticoagulant and 24.7% (24) received antiplatelet. Immunosuppression was prescribed in 38.1% (37). Those with severe thrombocytopenia received: prednisone in 54.5% (18) of cases, methylprednisolone in 36.4% (12), rituximab in 3% (1), and splenectomy in 36.4% (12). In patients with AHAI, 84.6% (11) received immunosuppressants and 46.2% (6) underwent splenectomy. Conclusion: A higher incidence of hematological activity was identified in pAPS, mostly in young women. The most common kind was severe thrombocytopenia, as opposed to what was described in literature as mild to moderate. Differences were found regarding the titer and positivity of antibodies. With thrombocytopenia, there was a higher frequency of positive lupus anticoagulant, anticardiolipin IgG and antiβ2 glycoprotein-I IgM with higher titers. Patients had anti-phosphatidyl serine/prothrombin antibodies as an extended panel and a correlation with hematological activity was identified. Knowing the serology of pAPS is useful to identify in good time patients who may present severe hematological manifestations. No patient died of a hematologic complication; however splenectomy was required in some cases. To our knowledge this is one of the few studies that evaluate hematological manifestations in pAPS.

Risk factors in antiphospholipid antibody-associated valvular heart disease: A 383-patient cohort study

Valvular heart disease (VHD) is a prevalent cardiac manifestation in antiphospholipid syndrome (APS) patients. However, risk factors and predictors for antiphospholipid antibody-associated VHD (aPL-VHD) remain vague. We aimed to assess the risk of developing aPL-VHD in aPL-positive patients, by establishing a clinical prediction model upon a cross-sectional cohort from APS-Shanghai database, including 383 APS patients and durable aPL carriers with transthoracic echocardiography investigation. The prevalence of aPL-VHD was 11.5%. Multivariate logistic regression analysis identified three independent risk factors for aPL-VHD: anti-β2GPI IgG (OR 5.970, P < 0.001), arterial thrombosis (OR 2.758, P = 0.007), and stratified estimated glomerular filtration rate levels (OR 0.534, P = 0.001). A prediction model for aPL-VHD, incorporating the three factors, was further developed, which demonstrated good discrimination with a C-index of 0.855 and 0.841 (after bootstrapping), and excellent calibration (P = 0.790). We provide a practical tool for assessing the risk of developing VHD among aPL-positive patients.

Antiphospholipid syndrome nephropathy: Current knowledge and unanswered questions

The definition of acute and chronic antiphospholipid syndrome (APS) nephropathy was recently updated using a multiphase methodology in the context of the development of the new APS classification criteria. Currently, there is no consensus for the treatment of APS nephropathy, which mainly relies on the general recommendations for the management of APS. Based on evidence from experimental studies and a few clinical studies and case series, targeted treatments such as B-cell depletion, anti-B-cell activating factor antibody, complement inhibition, mammalian target of rapamycin inhibition, and neutrophil extracellular traps or interferon targeting may show promise for the treatment of microvascular manifestations in APS, including APS nephropathy. Validation of the new APS nephropathy definition and/or efforts for improvement in proposed terminology, along with the assessment of the safety and efficacy of potential targeted treatments in randomized controlled trials, are major future research directions. In this review, we summarize the current knowledge of APS nephropathy and discuss unanswered questions.

Antibodies to Domain I β2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of β2-glycoprotein 1 (β2-GP1), IgG anti-β2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-β2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-β2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-β2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-β2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-β2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-β2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-β2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-β2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-β2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-β2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-β2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

#2691 GLOMERULAR LESIONS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Abstract Background and Aims Antiphospholipid syndrome (APS) is a complex autoimmune systemic disease, characterized by the presence of circulating antibodies directed against anionic phospholipids and the protein bound to them (aPL), leading to recurrent thrombosis and/or obstetrical complications. Renal manifestation of antiphospholipid syndrome conform a wide spectrum of disease renal syndrome. APS nephropathy (APSN) is considered a renal small-vessels vasculopathy, that can present acutely or chronically. The aim of the study is to identify glomerular lesions in patients with APSN. Method We studied retrospectively 114 patients (51 male, 63 female; age between 19 and 58 years; duration of follow-up was between 2 and 16 years) fulfilling classification criteria for APS. Renal and extra-renal symptoms were analyzed. None of the patients developed SLE in follow up. 18 patients with evidence of renal involvement underwent renal biopsy. All cases had proteinuria and five of them presented nephrotic syndrome. Results Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p&amp;lt;0,05), had LA positive test (p&amp;lt;0,005) and low complement levels (p&amp;lt;0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine. Conclusion Of 18 patients with kidney biopsy, 8 (44,44%) were male and 10 (55,56%) - female. Four of patients with renal biopsy had membranous glomerulonephritis, two had diffuse proliferative glomerulonephritis, 2 - mesangial C3 nephropathy, 2 - minimal change disease, 1- focal segmental glomerulosclerosis, the other seven had classic pathologic findings consistent with APSN. Chronic lesions with fibrous intimal hyperplasia being the most common. Thrombotic microangiopathy (TMA) in glomeruli was characterized by fibrin thrombi without inflammatory cells or immune complexes. Double contour of the glomerular basement membrane was associated with mesangiolysis and endothelial cell swelling in 5 patients with APSN. Electron microscopy confirmed subendothelial edema. Segmental glomerulosclerosis was observed in 4 patients. Tubulointerstitium was injured with interstitial fibrosis and tubular atrophy. Patients with APS and renal involvement were older (p&amp;lt;0,05), had LA positive test (p&amp;lt;0,005) and low complement levels (p&amp;lt;0,05). Hypertension is present in all cases with APSN, reduced glomerular filtration rate – in 4. All cases had proteinuria and five of them presented with nephrotic syndrome. Microscopic hematuria is observed in 4 patients. The treatment of APSN includes standard anticoagulant treatment for APS, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, intravenous immunoglobulin, cyclophosphamide and azathioprine.

Prevalence, risk factors, and prognosis of central nervous system manifestations in antiphospholipid syndrome

The central nervous system (CNS) is considered as one of the most frequently affected organs in antiphospholipid syndrome (APS). This study investigated the prevalence of CNS manifestations in APS and associated risk factors and evaluated stroke recurrence. We carried out this retrospective study from 2009 to 2021 at Peking University People’s Hospital, which enrolled 342 APS patients, and 174 neurologic events were suffered by 119 patients (34.8%). Patients with and without CNS involvement were compared regarding demographics and laboratory parameters. The analysis showed that older age, livedo reticularis, and dyslipidaemia were significant related factors for CNS manifestations (P = 0.047, 0.038, and 0.030 respectively). The use of anticoagulants (P = 0.004), and/or hydroxychloroquine (P = 0.016) appeared to associated with a lower incidence of CNS manifestations. During a median follow-up of 4.1 years, 10 individuals developed new episodes of stroke in APS patients with previous ischemic strokes. Livedo reticularis, smoking and male gender may predict the risk of recurrent stroke (P = 0.020, 0.006, and 0.026 respectively). Collectively, our results indicated the protective and risk factors for CNS manifestations, as well as demonstrated that APS patients appeared at high risk of stroke recurrence despite current therapy.

Efficacy of telitacicept in patients with lupus‐ and antiphospholipid syndrome‐associated refractory thrombocytopenia

AbstractIntroductionThrombocytopenia, a common noncriteria manifestation of antiphospholipid syndrome (APS), is severe in approximately one‐third of patients with APS. However, there are no guidelines for treating such thrombocytopenia. B‐cell‐targeting therapy may be an option in refractory cases; however, its efficacy has not been firmly established. Here, we report on two patients with refractory antiphospholipid antibodies (aPLs)‐associated thrombocytopenia treated with telitacicept.Case DescriptionCase 1, a 39‐year‐old woman, presented with systemic lupus erythematosus (SLE) and APS with diffuse alveolar hemorrhage, persistent thrombocytopenia, and recurrent miscarriages. The thrombocytopenia had been refractory to multiple lines of treatments, the most recent being mycophenolate mofetil and prednisone (5 mg/day). After receiving telitacicept (160 mg/week) for 3 months, she had presented with decreased titers of aPLs and a slight increase in platelet counts (14 × 109 to 35 × 109/L). Case 2, a 51‐year‐old woman, presented with SLE and APS with refractory thrombocytopenia. She had been diagnosed with pulmonary tuberculosis 4.5 years ago and received antituberculosis therapy for 2 years. She had also undergone pulmonary lobectomy 4 years ago for lung adenocarcinoma. Her thrombocytopenia relapsed (lowest 14 × 109/L) when prednisone was tapered to &lt;10 mg/day. After adding telitacicept (160 mg/week) to cyclosporin A (150 mg/day) and hydroxychloroquine (400 mg/day) for 5 months, aPLs decreased and platelet counts increased (78 × 109 to 183 × 109/L), enabling halving of her dose of prednisone from 15 to 7.5 mg/day. Neither patient had any adverse effects.ConclusionTelitacicept can safely reduce aPLs titers and improve refractory thrombocytopenia in patients with secondary APS. Randomized‐controlled trials to assess its effectiveness are urgently required.

Chorea as the Initial Manifestation of Antiphospholipid Syndrome (P9-5.020)

<h3>Objective:</h3> To discuss a rare case of chorea presenting as the initial manifestation of autoimmune disease. <h3>Background:</h3> Autoimmune chorea, including paraneoplastic, post-infectious, and idiopathic etiologies, is one of the leading causes of adult-onset chorea behind Huntington’s and vascular diseases.¹ In particular, in primary antiphospholipid syndrome (APS) and systemic lupus erythematosus, chorea is the initial manifestation of disease in 0.9 to 2% of cases.^1,2 <h3>Design/Methods:</h3> Verbal and written consent were obtained from the patient. <h3>Results:</h3> 73-year-old female with PMH of ITP, left MCA ischemic stroke, SDH, and DVT on anticoagulation who presented initially to ED with choreoathetoid movements starting 3 days prior to admission. History was unremarkable for triggering factor. Head imaging was unremarkable for acute intracranial process. B12, folate, TSH, electrolytes, RPR, serum copper, ANA, anti-dsDNA, SS-A, SS-B, Smith, and RNP antibodies negative. Lupus anticoagulant, β2 glycoprotein, and anti-cardiolipin antibodies positive. EEG unremarkable. Pelvic ultrasound negative. Genetic testing for Huntington’s negative. LP normal with exception of positive Coxsackie B1–B6 and A24 antibodies. After five-day course of IVIg, movements improved and she was discharged on no immunosuppression. Five weeks later, patient returned to ED with worsening of choreoathetoid movements. Repeat head CT again negative for acute pathology. Repeated spinal was unremarkable. Patient received Solumedrol 1g for four days with significant improvement in symptoms, and discharged on Prednisone 60 mg daily with recommendation to follow-up with rheumatology and neurology. On follow-up several months later, patient maintained on Prednisone 5 mg daily with no recurrence of choreoathetoid movements. <h3>Conclusions:</h3> While chorea is not the most commonly reported movement disorder in the context of autoimmune disease, it is often a delayed diagnosis, resulting in recurrent admissions and healthcare costs. Laboratory testing for autoimmune disorders should be included in the initial work-up of new-onset chorea to establish the diagnosis and properly treat as to prevent development of fulminant disease. <b>Disclosure:</b> Ms. Alayon has nothing to disclose. Mrs. Goodis has nothing to disclose. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eisai. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Feinberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Feinberg has stock in Amarin. Stuart N. Kieran, MD has nothing to disclose. Dr. Wirkowski has nothing to disclose.

Heart Valve Involvement in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Study of a Single Centre.

Valve involvement is the most common cardiac manifestation in antiphospholipid syndrome (APS). The objective of the study was to describe the prevalence, clinical and laboratory features, and evolution of APS patients with heart valve involvement. A retrospective longitudinal and observational study of all APS patients followed by a single centre with at least one transthoracic echocardiographic study. 144 APS patients, 72 (50%) of them with valvular involvement. Forty-eight (67%) had primary APS, and 22 (30%) were associated with systemic lupus erythematosus (SLE). Mitral valve thickening was the most frequent valve involvement present in 52 (72%) patients, followed by mitral regurgitation in 49 (68%), and tricuspid regurgitation in 29 (40%) patients. Female sex (83% vs. 64%; p = 0.013), arterial hypertension (47% vs. 29%; p = 0.025), arterial thrombosis at APS diagnosis (53% vs. 33%; p = 0.028), stroke (38% vs. 21%; p = 0.043), livedo reticularis (15% vs. 3%; p = 0.017), and lupus anticoagulant (83% vs. 65%; p = 0.021) were more prevalent in those with valvular involvement. Venous thrombosis was less frequent (32% vs. 50%; p = 0.042). The valve involvement group suffered from higher mortality (12% vs. 1%; p = 0.017). Most of these differences were maintained when we compared patients with moderate-to-severe valve involvement (n = 36) and those with no or mild involvement (n = 108). Heart valve disease is a frequent manifestation in our cohort of APS patients and is associated with demographic, clinical and laboratory features, and increased mortality. More studies are needed, but our results suggest that there may be a subgroup of APS patients with moderate-to-severe valve involvement with its own characteristics that differs from the rest of the patients with mild valve involvement or without valve involvement.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study

Several antiphospholipid antibody (aPL) profiles (“triple” and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-β2 glycoprotein-I antibody (aβ2GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aβ2GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aβ2GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aβ2GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001). Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome.

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

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

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

Global Antiphospholipid Syndrome Score (GAPSS) in patients with primary antiphospholipid syndrome

Stratification of patients into groups of high and low risk of adverse outcome is necessary for timely and early prevention of the disease, as well as the selection of adequate therapy.Objective: to validate the global risk scale for the development of clinical manifestations of antiphospholipid syndrome (GAPSS) in a cohort of patients with primary antiphospholipid syndrome (PAPS).Material and methods. The study included 64 patients with PAPS. Data on clinical manifestations, traditional cardiovascular risk factors, and antiphospholipid antibody profile were collected. GAPSS values were calculated for each patient by summing the scores corresponding to risk factors as follows: 3 points – for hyperlipidemia; 1 point – for arterial hypertension; 5 points – for antibodies to cardiolipin (aCL) IgG/IgM; 4 points – for antibodies to â2-glycoprotein 1 (anti-â2GP1) IgG/IgM and 3 points – for antibodies to the phosphatidylserine-prothrombin complex (aPS/PT) IgG/IgM.Results and discussion. GAPSS indicators were comparable in women and men with PAPS – 12.0 [9.0; 13.0] points. GAPSS values did not differ in patients with thrombosis and obstetric pathology: in thrombosis they were 10.0±4.46 (range 0.0–14.0) points, in obstetric pathology – 9.26±5.08 (range 0.0–14.0) points.The localization of thrombosis did not affect the GAPSS values, which reached 9.23±5.21 points in arterial thrombosis, 10.44±4.01 points in venous thrombosis, and 10.33±4.18 points in combined ones. Patients with recurrent thrombosis had higher GAPSS scores compared to patients without relapse: 8.19±5.25 points versus 11.00±3.65 points (p=0.01). There were no significant differences in GAPSS scores in obstetric pathology at different gestational ages.GAPSS values ≥6 showed a higher risk of thrombosis recurrence: odds ratio 5.23 (95% CI 1.34–20.37). GAPSS scores ≥6 demonstrated the highest accuracy, with sensitivity and specificity of 72% and 66%, respectively. According to ROC analysis, the AUC value for GAPSS was 0.675 (95% CI 0.542–0.808; p=0.01).Conclusion. The use of GAPSS makes it possible to identify patients at increased risk of recurrent thrombosis. GAPSS scores ≥6 have high sensitivity (72%) and specificity (66%), which can be used to stratify patients with PAPS into high and low risk groups for recurrent thrombosis.

Combined central retinal artery and vein occlusion as the first manifestation of antiphospholipid syndrome: case report of an infrequent presentation

Combined central retinal artery and vein occlusion as the first manifestation of antiphospholipid syndrome: case report of an infrequent presentation

Značaj određivanja fosfolipaze A2 udružene sa lipoproteinom kod pacijenata sa antifosfolipidnim sindromom

Introduction: Lipoprotein-associated Phospholipase A2 (Lp-PLA2) is an essential mediator of inflammation, which has a vital role in inflammatory diseases of the vascular system. It has a significant role in the occurrence of thrombosis, the main manifestation of antiphospholipid syndrome. Aim: To investigate the values of Lp-PLA2 in patients with antiphospholipid syndrome (APS) regarding the distribution of all data, age, gender, disease duration, and type of disease. Material and methods: This experimental work analyzed samples of 74 patients diagnosed with APS. Concentrations of Lp-PLA2 were determined by ELISA (Enzyme-Linked Immunosorbent Assay) method. Results: The activity of Lp-PLA2 was higher than the recommended referent values. There is no significant difference in the values of Lp-PLA2 concerning patients' age, gender, disease duration, and type of disease (p &gt; 0,05). There was a statistically significant correlation between the patients' age and the disease duration (rho = 0.359; p = 0.002). Conclusion: Elevated values of Lp-PLA2, so as the correlation between the years of age and duration of APS can be important information to doctors in the appropriate treatment of these patients. It is up to future prospective studies to confirm the significance of Lp-PLA2 determination in patients with APS.