Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases.

The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4/31 (13%) patients had decreased C3/C4, while 7/29 (24%) had elevated BC4d, 11/33 (33%) EC4d, and 12/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS/TP/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3/C4, and the poor inverse correlation between CB-CAPs and C3/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.

Vitamin K antagonist anticoagulation in the antiphospholipid syndrome: time in therapeutic range and clinical outcomes.

BACKGROUND: Thrombosis in the antiphospholipid syndrome is still frequently treated with vitamin K antagonists with a target international normalized ratio of 2-3. Time in therapeutic range of international normalized ratio of ≥ 70% is considered optimal. Time in therapeutic range among antiphospholipid syndrome patients is not well documented and the clinical consequences of poor international normalized ratio control are uncertain. AIMS: To determine the proportion of vitamin K antagonist -treated antiphospholipid syndrome patients achieving time in therapeutic range ≥ 70%, to define the features associated with poor control and to determine its association with thrombotic and bleeding events. METHODS: This medical records review included antiphospholipid syndrome patients treated with vitamin K antagonists, between 2012-2023. The proportion of patients achieving a time in therapeutic range≥ 70% was determined and thrombotic and bleeding events were compared between patients with time in therapeutic range ​​≥ 70% versus < 70%. RESULTS: 67 antiphospholipid syndrome patients were studied. 29.9% achieved time in therapeutic range ≥ 70%. 9.1% of patients with 3 or more comorbidities achieved time in therapeutic range values ≥ 70% compared to 40% of patients with less than 3 comorbidities. Fewer recurrent arterial and overall thrombotic events occurred with time in therapeutic range ​​≥ 70%. CONCLUSIONS: A minority of antiphospholipid syndrome patients treated with vitamin K antagonist s achieve optimal anticoagulation and are at risk for recurrent thrombotic events, particularly arterial. Presence of multiple comorbidities is associated with poor international normalized ratio control. Careful monitoring of this patient population is warranted.

Dancing with disorder: chorea - an unusual and neglected manifestation of antiphospholipid syndrome.

OBJECTIVES: Chorea, characterised by involuntary, irregular movements, is a rare neurological manifestation of antiphospholipid syndrome (APS). The specific clinical features remain unclear. This study aimed to summarise the available evidence on antiphospholipid antibody (aPL)-associated chorea. METHODS: We used a mixed-methods approach, combining data from patients with chorea with aPL positivity admitted to Peking Union Medical College Hospital (PUMCH) from 2014 to 2024, with cases identified in public databases since 1983. We collected and analysed clinical, laboratory, and imaging results, along with their treatments and outcomes. RESULTS: A total of 180 patients with incident aPL-associated chorea were included (13 from PUMCH and 167 from the literature). The majority (81.7%) were female, with a mean age of chorea onset 22.8 years (SD=16.0). Chorea was the initial symptom in 87.9% of cases and often occurred as a single episode (67%), involving bilateral limbs (58.8%) and both upper and lower limbs (87.2%). 43.3% met the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria. Thrombocytopenia (30.0%) and arterial thrombosis (29.1%) were the most common manifestations. Lupus anticoagulant was positive in 84.2% of patients, anticardiolipin IgG in 70.8%, and anti-ß2 glycoprotein I IgG in 52.9%. Among those who had results available for the three tests, 57.6% were triple-positive. ANAs were positive in 63.6%. MRI revealed basal ganglia lesions in only 14.8% of patients, whereas all positron emission tomography (PET) scans showed contralateral striatal hypermetabolism. Treatment varied, with most receiving combination therapies of neuroleptics, anticoagulants, antiplatelets, steroids and immunosuppressants. Chorea completely or partially improved in 95.5% of patients. CONCLUSION: Chorea is a significant but under-recognised manifestation of APS, predominantly affecting young women and often presenting as the initial symptom. Characteristic PET findings of contralateral striatal hypermetabolism can assist in diagnosis. Treatments with glucocorticoids and immunosuppressive therapies appear beneficial. Further research is needed to understand the pathophysiology and optimise management strategies for aPL-associated chorea.

Antiphospholipid Antibodies Modify the Prognostic Value of Baseline Platelet Count for Clinical Outcomes After Ischemic Stroke.

BACKGROUND: Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. METHODS AND RESULTS: A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2-year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03-7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12-5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. CONCLUSIONS: The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Identification of common MicroRNAs expression signatures in antiphospholipid syndrome and thromboembolic disease: A scoping review.

BACKGROUND: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by distinct pathophysiological mechanisms leading to heterogeneous manifestations, including venous and arterial thrombosis. Despite the lack of specific markers of thrombosis risk in APS, some of the mechanisms responsible for thrombosis in APS may overlap with those of other thromboembolic diseases. Understanding these similarities is important for improving the assessment of thrombosis risk in APS. MicroRNAs (MiRNAs) are RNA molecules that regulate gene expression and may influence the autoimmune response and coagulation. PURPOSE: In this scoping review we aimed to investigate shared miRNAs profiles associated with APS and other thromboembolic diseases as a means of identifying markers indicative of a pro-thrombotic profile among patients with APS. DATA COLLECTION AND RESULTS: Through a comprehensive search of scientific databases, 45 relevant studies were identified out of 1020 references. miRs-124-3p, 125b-5p, 125a-5p, and 17-5p, were associated with APS and arterial thrombosis, while miRs-106a-5p, 146b-5p, 15a-5p, 222-3p, and 451a were associated with APS and venous thrombosis. Additionally, miR-126a-3p was associated with APS and both arterial and venous thrombosis. CONCLUSION: We observed that APS shares a common miRNAs signature with non-APS related thrombosis, suggesting that miRNA expression profiles may serve as markers of thrombotic risk in APS. Further validation of a pro-thrombotic miRNA signature in APS is warranted to improve risk assessment, diagnosis, and management of APS.

Direct Oral Anticoagulants in Antiphospholipid Syndrome-Associated Venous Thromboembolism: Real World Evidence.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. RESULTS: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840). CONCLUSION: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.

Case report: Timing of eculizumab treatment in catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition of small-vessel thrombosis with acute multiple-organ involvement and visceral damage. In this report, we present a case of a patient with CAPS who is refractory to conventional therapy. For the first time in a patient with CAPS, marked C5b-9 formation was demonstrated on microvascular endothelial cells, suggesting the usefulness of therapeutic complement inhibition in this setting. Eculizumab, a C5-blocking monoclonal antibody, is remarkably effective in the treatment of different forms of thrombotic microangiopathy by controlling complement system hyperactivation. It halted the "thrombotic storm" and promptly achieved full recovery of thrombocytopenia. However, kidney function did not recover, possibly because eculizumab was administered too late. Conceivably, the timing of treatment is crucial to achieving disease remission before irreversible structural damage occurs in target organs, thereby preventing their complete functional recovery.

Clinical Features Between Primary Obstetric Antiphospholipid Syndrome and Non-Criteria Obstetric Antiphospholipid Syndrome and Risk Factors of Adverse Pregnancy Outcomes: A Retrospective Study of 1006 Cases.

PROBLEM: To compare the clinical characteristics and pregnancy outcomes between patients with primary obstetric antiphospholipid syndrome (OAPS) and those with primary non-criteria obstetric antiphospholipid syndrome (NC-OAPS), and to identify the risk factors of adverse pregnancy outcomes in both groups. METHODS: A retrospective single-center study was performed in a university hospital of western China, including 141 patients with OAPS and 865 patients with NC-OAPS. The clinical characteristics, pregnancy complications, and obstetric outcomes of the cohorts were collected from the hospital system and were compared by univariable analysis, and the independent risk factors for adverse pregnancy outcomes (APO) were investigated by logistic regression analysis in these two populations. RESULTS: The OAPS patients had a significantly higher risk for stillbirths compared to the NC-OAPS patients, while the NC-OAPS group had a significantly higher risk for preterm birth and overall APO. Double aPL positivity, triple aPL positivity, and gestational hypertension were the independent risk factors for APO in OAPS patients, whereas two of the double aPL positivity subtypes, triple aPL positivity and placenta previa were independent risk factors for APO in NC-OAPS patients. CONCLUSION: This study identified different rates in different APOs among OAPS and NC-OAPS patients. Additionally, this study revealed different risk factors for the development of APO between the two populations. These findings indicated that OAPS and NC-OAPS are two distinct entities of the same disease, providing new insights into the individualized management for patients with OAPS and NC-OAPS.

Spontaneous coronary artery dissection and valvular disease revealing an antiphospholipid syndrome in a young woman: Case report.

Antiphospholipid syndrome (APS) is characterized by hypercoagulability, manifesting as venous or arterial thrombosis, and pregnancy-related complications, such as fetal loss, pre-eclampsia, and eclampsia. These conditions occur in the presence of antiphospholipid antibodies (aPL), including anticardiolipin antibodies (aCL) and/or a positive lupus anticoagulant (LA) test. Antiphospholipid syndrome (APS) can manifest as a primary, isolated condition or be associated with connective tissue diseases, such as systemic lupus erythematosus (SLE). The cardiac system is one of the main target organs affected by APS. This report describes a rare clinical case involving a young woman with a history of recurrent miscarriages, who presented with cardiac complications, including severe mitral regurgitation and Spontaneous coronary artery dissection. Etiological assessment identified antiphospholipid antibody syndrome as the underlying cause. The multidisciplinary management plan included initiating therapeutic-dose anticoagulation, followed by referring the patient for potential mitral valve replacement surgery.

Catastrophic Antiphospholipid Syndrome in a Lupus Patient With Severe Recurrent Life-Threatening Clinical Manifestations.

Catastrophic antiphospholipid syndrome (CAPS) is a rare, severe, and life-threatening form of antiphospholipid syndrome (APS). Early recognition and rapid treatment are of great importance to improve patient outcomes and decrease mortality. Herein, we present a case of lupus and APS with obstetric complications, recurrent thrombosis, and renal and hematological manifestations of APS which showed great response to the treatment.