Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by clinical manifestations such as thrombocytopenia, thrombosis, and miscarriage caused by persistent positive antiphospholipid antibodies. The cardiovascular system is one of the main target systems involved, including valvular heart disease, coronary artery disease, myocardial disease, pulmonary hypertension, and intracardiac thrombus. The 2023 American College of Rheumatology(ACR)/European League Against Rheumatology(EULAR) Antiphospholipid Syndrome Classification Criteria were released, incorporating various clinical features including valvular heart lesions for quantitative assessment. Patients with APS with cardiovascular system involvement often have a poor prognosis, and there are currently no relevant guidelines or consensuses for the diagnosis and treatment of APS-related cardiovascular diseases. Therefore, it is crucial to identify the risk factors for APS-related cardiovascular diseases at an early stage and effectively predict their occurrence. This article elaborates on the risk of developing cardiovascular diseases in patients with APS.

Thrombotic antiphospholipid syndrome (APS) in Childhood-onset systemic lupus erythematosus (cSLE) remains a therapeutic frontier. Here, we report the first case of telitacicept (a TACI-Fc fusion protein)- induced remission in cSLE related antiphospholipid syndrome (cSLE-APS), where targeted dual BAFF(B cell-activating factor)/APRIL(a proliferation-inducing ligand) inhibition resolved life-threatening infarctions and achieved sustained disease control. During treatment, corticosteroids were successfully discontinued within six months, and a lupus low disease activity state (LLDAS) was maintained. Our findings indicate that telitacicept’s unique ability to regulate B-cell activity could target the dual pathology of cSLE-APS, offering a new therapeutic approach for this serious condition.

Homocysteine (Hcy) contributes to endothelial dysfunction and impaired thrombolysis, and genetic polymorphisms that elevate plasma Hcy concentrations have been linked to an increased risk of thrombosis. Notably, mutations in the cystathionine β-synthase (CBS) gene, which reduce enzymatic activity, are a well-established cause of hyperhomocysteinemia (HHcy). This case report presents a 15-year-old male with recurrent, severe deep vein thrombosis (DVT) of the lower extremities, accompanied by persistent positivity for antiphospholipid antibodies. Laboratory evaluation revealed elevated homocysteine levels and mutations in the CBS gene, highlighting an underlying genetic predisposition. The persistent presence of antiphospholipid antibodies further underscores the multifactorial nature of his thrombophilic condition, involving genetic, metabolic, and autoimmune mechanisms.

Chorea is a movement disorder observed in 1-2% of systemic lupus erythematosus (SLE) cases. Treatment options include anticonvulsants, dopamine antagonists, antiplatelets, anticoagulants, and immunosuppressants such as cyclophosphamide; however, no specific treatment has been established. Here, we report a 76-year-old woman with chorea associated with antiphospholipid antibodies (aPLs) as well as SLE, who exhibited marked improvement both clinically and serologically following initial treatment with glucocorticoids and subsequent combination therapy with hydroxychloroquine and belimumab. In parallel with the decline in the chorea severity score, all tested aPLs decreased after treatment, with normalization of activated partial thromboplastin time (from 70 to 25 sec), anti-β2-glycoprotein I IgM (from 22 to 12 U/mL), and phosphatidylserine-dependent anti-prothrombin IgG (from 58 to 15 U/mL). A systematic literature review revealed no previously reported cases of chorea associated with SLE treated with a combination of hydroxychloroquine and belimumab. Our case suggests this combination therapy may have a role in maintaining remission and modulating antiphospholipid autoimmunity of SLE-associated chorea.

New ACR/EULAR 2023 classification criteria for antiphospholipid syndrome, what should a gynaecologist know in 2025.

This article reviews the epidemiology, clinical presentation, diagnosis, and management of neurologic complications associated with hematologic disorders. Hematologic disorders may manifest with cerebrovascular and neuromuscular complications due to thrombotic, hemorrhagic, or immune-mediated mechanisms. Advances in screening, targeted therapies, and interdisciplinary care have improved outcomes for conditions such as sickle cell disease, myeloproliferative neoplasms, thrombotic microangiopathies, antiphospholipid antibody syndrome, and plasma cell dyscrasias. Neurologic complications of hematologic disorders range from cerebrovascular disease to peripheral neuropathy. Early recognition and appropriate management in collaboration with a hematologist are essential to reduce morbidity and mortality.

Antiphospholipid Syndrome: Evolving Evidence and the Nurse Practitioner Perspective

Factors associated with venous and arterial thrombosis in patients with Systemic Lupus Erythematosus: A systematic review and meta-analysis.

Daratumumab monotherapy reverses the immune and pro-fibrotic profiles in refractory lupus nephritis patients: a pilot case study.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency. Diagnosis is often challenging because most patients do not present with the classic pentad of findings. We report a 56-year-old woman with multiple comorbidities, including systemic lupus erythematosus and antiphospholipid syndrome, who presented with neurologic symptoms, hemolytic anemia, and severe thrombocytopenia without initial schistocytosis. Her condition was initially misattributed to isoniazid-induced thrombocytopenia, resulting in delayed recognition of TTP. Immune-mediated TTP was suspected based on her autoimmune disease history and was definitively confirmed when ADAMTS13 activity returned at <1%. Initiation of plasma exchange, corticosteroids, and caplacizumab led to rapid hematologic recovery. This case underscores the importance of maintaining a high index of suspicion for immune-mediated TTP, particularly in patients with underlying autoimmune disease, as early diagnosis and prompt treatment are critical to preventing fatal thrombotic complications.

Comment on: Loss of antiphospholipid antibody positivity decreases the risk of recurrent thrombosis in thrombotic antiphospholipid syndrome.

ATP is released from platelets through both degranulation and pannexin-1 (PANX1) channels. ATP then activates P2X receptors to amplify platelet activation via calcium-dependent signaling. The objective of this study was to evaluate the role of platelet PANX1 channels in the pathophysiology of antiphospholipid syndrome (APS), an acquired thromboinflammatory disorder characterized by platelet-activating antiphospholipid antibodies. Extracellular ATP release was measured in platelets isolated from patients with persistently positive antiphospholipid antibodies (n=36), patients with systemic lupus erythematosus (n=10), and healthy controls (n=16). In some assays, purified platelets were pretreated with the PANX inhibitor carbenoxolone. Platelet signaling, P-selectin exposure, and aggregation were assessed. Basal ATP release was significantly higher in APS platelets than in controls (P < 0.0001) and normalized in the presence of carbenoxolone (P=0.03). Carbenoxolone also reduced platelet ATP release and surface P-selectin expression induced by thrombin (P=0.002 and P=0.02, respectively) and convulxin (P=0.0001 and P=0.0012). Control platelets stimulated with IgG from patients with APS demonstrated enhanced phosphorylation of PANX1 at tyrosine-308 (P=0.03), which was accompanied by enhanced ATP release (P=0.0004). APS IgG boosted ADP-induced aggregation (P=0.0011), which was reduced by carbenoxolone (P=0.0007). The calcium chelator BAPTA-AM decreased APS IgG-mediated ATP release (P=0.03), P-selectin expression (P=0.0005), and aggregation (P=0.0007). Desensitizing P2X1 receptors with α,β-MeATP decreased APS IgG-induced P-selectin expression (P=0.0002) and aggregation (P=0.01). PANX1 channels appear to be important mediators of platelet activation in APS. Agents that block PANX1 may restore platelet homeostasis and limit thrombosis without impairing hemostasis.

BackgroundCatastrophic Antiphospholipid Syndrome (CAPS) is a rare but highly severe manifestation of antiphospholipid syndrome (APS), occurring in fewer than 1% of APS patients, but is associated with mortality of around 25-37%, despite treatment. It is characterized by rapid onset of widespread thrombotic events leading to microangiopathy, intravascular thrombosis with multiorgan failure, involving three or more organs within one week. Most published data originate from European or multinational registries like the CAPS Registry. However, data on CAPS in Latin American populations, who may differ in genetic background, socioeconomic status, and healthcare access, remain scarce.MethodsThe objective was to describe the clinical characteristics, treatment strategies, and outcomes of patients diagnosed with CAPS at a tertiary referral center in Mexico City over 5years. We conducted a retrospective cohort study of patients who fulfilled the CAPS classification criteria between January 2019 and December 2023.ResultsNineteen patients were included (74% female; median age 38.4 years). Six had primary APS, while 11 had concomitant systemic lupus erythematosus (SLE). Based on the 2019 EULAR aPL titers classification, seven patients were classified as low-risk and 12 as high-risk. In 47%, CAPS was the first manifestation of APS. Precipitating factors were identified in 94.7% of cases, most commonly infections and anticoagulant withdrawal. The most frequently affected were the arterial and venous circulation (74% and 68%, respectively), hematologic manifestations (47%), kidneys (42%), lungs (42%), and the heart (32%). Treatment strategies included anticoagulation (84%), corticosteroids (79%), plasma exchange (79%), triple therapy (74%), and, in selected cases, immunosuppressants. Overall mortality was 42%; among survivors, 75% achieved full recovery with no relapses.ConclusionThis study represents one of the largest single-center series of CAPS in a non-Caucasian population. Our findings reveal a predominance of high-risk, secondary APS-mainly SLE-associated-with thrombocytopenia. Nearly half presented with CAPS as the initial APS manifestation. Limited access to full triple therapy significantly impacted mortality, which decreased from 100% with partial therapy to 21% with complete regimens. Early recognition, prompt management, and multidisciplinary care were associated with favourable outcomes, underscoring the need for adaptable therapeutic strategies in resource-limited settings.

This study investigates risk factors, prenatal ultrasonographic characteristics, and pregnancy outcomes in patients with umbilical artery thrombosis (UAT) and umbilical vein thrombosis (UVT). A retrospective study was conducted at West China Second Hospital, Sichuan University, between April 2019 and April 2024. The umbilical cord thrombosis (UCT) group included women with pathologically confirmed UAT or UVT, whereas the control group consisted of women without UCT who registered and delivered during the same period in our hospital. Maternal clinical data, prenatal ultrasound findings, and pregnancy outcomes were collected and compared between the groups. A total of 110 patients, including 30 patients with UAT, 20 patients with UVT, and 60 controls, were included in the study. Compared with the control group, the UCT group showed significantly greater proportions of umbilical cord torsion, fetal hemodynamic abnormalities, prenatal ultrasound findings, preterm birth, emergency cesarean delivery, intrauterine fetal death (IUFD), low birth weight, and neonatal intensive care unit admission (all P < 0.05). The main hemodynamic abnormalities detected in the UCT group included a decreased systolic/diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) of the umbilical artery, as well as a decreased PI of the fetal middle cerebral artery (MCA). Among patients with UCT, the prevalence of antiphospholipid antibody syndrome (APS) was significantly greater among those who experienced IUFD than in those with live births (P < 0.05). Compared with the UVT group, more patients in the UAT group had detectable sonographic evidence of thrombosis, an earlier gestational age, and a lower neonatal Apgar score (all P < 0.05). Compared with the control group, the UVT group demonstrated a significantly lower pre-pregnancy body mass index, less gestational weight gain, and a greater proportion of conceptions via assisted reproductive technology (all P < 0.05). In most patients with UCT, the thrombi were predominantly located near the umbilical cord insertion site at the fetal abdominal wall. Our study demonstrated that UCT was extremely unfavorable to the perinatal outcomes. Umbilical cord torsion may be a risk factor for the development of UCT. The risk of IUFD was further increased in cases with UCT that coexisted with APS. UAT was more likely to be detected prenatally via ultrasound than UVT; however, UVT was more frequently observed in pregnant women who exhibited insufficient gestation weight gain or conceived through assisted reproductive technology. During routine ultrasound examination, color Doppler assessment of key anatomical sites, together with close monitoring of umbilical artery and MCA indices, might facilitate the early detection of UCT. Although prenatal diagnosis of UCT was significantly challenging, it remained feasible and can provide valuable assistance for clinical management.

Antiphospholipid syndrome (APS) is an autoimmune condition with thrombotic and/or obstetric manifestations (tAPS and oAPS respectively). Impaired sensitivity to activated protein C (APC), often referred to as "acquired APC resistance," is known to be an independent risk factor for thrombosis across a variety of conditions. In particular it has been implicated in the prothrombotic phenotype of APS and may serve as a prognostic marker in tAPS. However, data on APC sensitivity in oAPS remain inconclusive.We included 60 women less than 50 years of age from two prospective French cohorts with neither overlapping manifestations nor associated autoimmune diseases. APC sensitivity was assessed using calibrated automated thrombography with platelet-rich plasma. APC sensitivity ratio (APCsr) was defined as the ratio of endogenous thrombin potential (ETP) in the presence of 25 nM APC (ETP-APC25) to ETP in its absence (ETP0).A total of 60 women was analyzed (43 tAPS and 17 oAPS); 15 tAPS women received anticoagulant treatment. No difference in APCsr was observed between tAPS and oAPS patients. In anticoagulated tAPS women, ETP0 and ETP-APC25 levels were, as expected, significantly lower than non-anticoagulated women, but APCsr remained consistent in identifying patients with high-risk serological profile.Our findings suggest that decreased APC sensitivity is shared by the two main APS clinical phenotypes, which hence must have distinct pathogenic alterations as well. APC sensitivity can be investigated with CT even if clotting times are prolonged (lupus anticoagulant effect) and if thrombin generation is decreased as a result of anticoagulant treatment.

ObjectiveTo evaluate ethnic disparities among patients with systemic lupus erythematosus (SLE) managed within a universal, publicly funded healthcare system.MethodsCross-sectional study based on a retrospective review of medical records of patients with SLE who attended the rheumatology outpatient clinics of the Hospital Fundación Jiménez Díaz (Madrid, Spain) between 2023 and 2024. Eligible patients were those who had been followed in the unit at any time between 2010 and 2024 and who met well-established criteria for SLE. Patients of ethnically Spanish origin were classified as Spaniards, while those identified as Latin American (including individuals from South and Central America, and Brazil), Asian, or of African descent were grouped as non-Spaniards. Disease activity was assessed using the SLEDAI and SLEDAS scores, as well as the DORIS remission criteria. Comparative analyses included clinical features, disease activity, and treatment. Group comparisons were performed using the Mann-Whitney U test, Student's t-test, chi-squared test, or Fisher's exact test, as appropriate.ResultsOf the cohort of 324 SLE patients, 42.3% (n = 137) were non-Spaniards, primarily Latin American (88.3%), followed by Asian (10.2%) and individuals of African descent (1.5%). No significant differences were observed in clinical manifestations or lupus nephritis histology. However, antiphospholipid syndrome was more frequent among Spaniard patients (13.9%) compared to non-Spaniard patients (6.6%) (p = 0.04). In contrast, anti-Sm antibodies were more commonly detected in non-Spaniards (26.3% vs 16.6%; p = 0.03). Non-Spaniard patients exhibited greater disease activity, with higher mean SLEDAI-2K scores (mean ± standard deviation: 1.80 ± 2.65 vs 1.26 ± 1.84; p = 0.03) and SLE-DAS scores (2.06 ± 3.26 vs 1.34 ± 1.89; p = 0.01), as well as significantly lower DORIS remission rates (p = 0.03) compared to Spaniard patients. Current prednisone use was 41.3% among non-Spaniard patients versus 24.7% in Spaniards. The use of immunosuppressants was similar between the two groups.ConclusionIn a universal public healthcare system, we did not observe major ethnic disparities in clinical manifestations of SLE. Nonetheless, non-Spaniard patients showed higher disease activity, lower remission rates, and greater glucocorticoid use, suggesting differences in disease expression rather than inequities in care.

Abstract: OBJECTIVE: To investigate the clinical characteristics, management and outcomes of cerebral venous thrombosis (CVT) patients with antiphospholipid syndrome (APS) in a Chinese cohort. METHODS: A retrospective cohort study was conducted on 121 consecutive CVT patients admitted to Peking Union Medical College Hospital from 2015 to 2023. Data on demographics, clinical manifestations, imaging findings, laboratory tests, treatment, and outcomes at discharge were analyzed. RESULTS: APS was identified in 16.5% (20/121) of CVT patients. The median age at onset was 34.5 years, with 60% (12/20) being female. 75% of patients had not experienced other thrombotic and obstetric events before CVT. In APS-CVT cases, chronic onset was observed in 50% (10/20), with a median diagnostic delay of 20 days. Headache was the most common symptom. Additional risk factors were present in 85% of APS-CVT patients. All patients received anticoagulation therapy, and 80% achieved favorable outcomes (modified Rankin Scale: &lt; 2) at discharge. While most clinical and imaging features showed no significant differences, APS-CVT patients exhibited less frequent transverse/sigmoid sinus involvement (55% [APS-CVT] vs. 72.3% [non-APS-CVT], P = 0.045) and multisinus thrombosis (15% [APS-CVT] vs. 40.6% [non-APS-CVT], P = 0.020). Laboratory findings revealed lower hemoglobin levels (118 g/L [APS-CVT] vs. 130 g/L [non-APS-CVT], P &lt; 0.05) and a higher prevalence of concomitant extracranial venous thrombosis (45% [APS-CVT] vs. 11.9% [non-APS-CVT], P &lt; 0.001) in the APS-CVT group. CONCLUSION: APS represents a significant risk factor for CVT. CVT associated with APS primarily affects young individuals and women, often presents insidiously, and is frequently accompanied extracranial venous thrombosis. Given the challenges in diagnosing APS-CVT, screening for APS should be strongly considered in CVT patients with these clinical contexts. The characteristic pattern of venous sinus involvement in APS-CVT may provide insights into its unique pathogenesis. Most patients were treated with warfarin, which may be associated with a favorable outcome.

The diagnostic and prognostic values of non-criteria antiphospholipid antibodies in obstetric antiphospholipid syndrome.

Neutrophil extracellular traps (NETs) are increasingly recognised for their role in primary antiphospholipid syndrome (PAPS) pathogenesis. Herein, we examined underlying mechanisms driving NET formation and the thrombogenic effects of NETs in patients with PAPS, along with potential inhibitors. We examined NET release in PAPS, asymptomatic antiphospholipid autoantibodies (aPLs) carriers, and healthy controls (HCs) as well as NET-bound proteins by immunofluorescence, immunoblotting, quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). We assessed platelet-neutrophil aggregates by flow cytometry (CD61/CD66b staining) and autophagy using LC3B immunofluorescence and immunoblotting. Immunofluorescence was performed in paraffin-embedded kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS. Suppression of NET release via CD40-CD40L inhibition was tested in in vitro and venous thrombosis mouse models. Neutrophils from patients with PAPS exhibited increased NET release compared with asymptomatic aPL carriers and HCs. NETs from patients with PAPS expressed tissue factor (TF) that induced thrombin generation in platelet-poor plasma from HCs. aPL induced in vitro intracellular TF expression in HC neutrophils. TF-expressing NETs were abundant in the kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS, and colocalised with fibrinogen. NET release in PAPS neutrophils was driven by aPL-mediated platelet activation, subsequent platelet-neutrophil interaction, and autophagy induction. CD40-CD40L blockade reduced platelet activation, autophagy, and NET formation in patients with PAPS. In a mouse model, inhibition of CD40-CD40L reduced neutrophil-platelet aggregates and myeloperoxidase (MPO)-DNA complexes in mouse peripheral blood, and the presence of NETs in the formed thrombi. Targeting the platelet-neutrophil/autophagy/TF-expressing NETs axis by CD40-CD40L inhibition attenuates thromboinflammation in PAPS and should be explored as a potential therapeutic target.

Patterns of Antiphospholipid Antibody Testing and Positivity in a Real-World Laboratory over Two Decades: The Role of IgM.