Background: Addison's disease (AD) is a rare disorder that often develops in the context of autoimmune polyglandular syndromes. However, the prevalence of rheumatological autoimmune diseases and corresponding autoimmune markers in AD is poorly investigated. Therefore, the present study aims to explore systemic and organ-specific immune markers in a cohort of AD patients from a single tertiary endocrine center. Material and methods: In total, 43 adult AD patients and 31 controls were included in the study. 21-hydroxylase autoantibodies (21OHAb), glutamic acid decarboxylase autoantibodies (GADAbs), zinc transporter-8 autoantibodies (ZnT8Abs), antibodies against nuclear antigens (ANAs), autoantibodies against cyclic citrullinated peptides (CCPAbs), rheumatoid factors (RFs), IgG autoantibodies against cardiolipin (ACLAbs), and autoantibodies against beta-2-Glycoprotein I (β2-GPIAbs) were measured in all participants. Results: An increased prevalence of antibodies against RFs (27.91% vs. 0%, p < 0.001) and ANAs (13.95% vs. 0%, p = 0.037) was found in AD patients compared to controls. Moreover, the titers of 21-hydroxylase and RF antibodies correlated positively (r = +0.269, p = 0.020). The AD patients tended to show an increased prevalence of subthreshold ACL antibody reactivity compared to controls. All patients diagnosed with type 1 diabetes mellitus were GADAb- but not ZnT8Ab-positive. Conclusions: The results show an increased prevalence of ANA and RF positivity in AD patients compared to controls and a significant association between 21-OHAb and RF positivity. ZnT8Ab positivity was not typical for adult AD patients from our ethnic group, while GADAbs were an essential marker for autoimmune diabetes mellitus. Extensive studies in different ethnic groups are needed to establish the clinical significance of various immunological markers for AD comorbidity and the appropriate follow-up protocols for patients with different antibody positivity.

Antiphospholipid syndrome (APS) can affect the kidneys, leading to renal artery and vein thrombosis, allograft loss following transplantation, and microvascular damage referred to as aPL-nephropathy (aPL-N). APL-N is a complex and frequently underdiagnosed condition characterized by an incomplete understanding of its etiopathogenesis and associated with unfavorable renal outcomes. The 2023 ACR/EULAR classification criteria for APS included aPL-N within the microvascular domain. The gold standard for aPL-N is the biopsy, revealing lesions associated with acute thrombotic microangiopathy and chronic vascular changes. Nevertheless, reluctance for biopsies due to anticoagulation and thrombocytopenia underscores the need for noninvasive diagnostics. Common clinical features include hypertension, microscopic hematuria, proteinuria, and renal insufficiency. Antiphospholipid antibodies seem crucial to kidney damage through thrombotic and inflammatory processes. Studies and experimental models of thrombotic microangiopathy lesions suggest the involvement of the complement cascade, tissue factor, and mammalian target of the rapamycin complex activation pathway. Currently, the management of aPL-N is based mainly on expert opinion, with limited evidence supporting the use of anticoagulants, leading to controversy in their application. Treatment may include heparin, intravenous immunoglobulin, plasma exchange, and targeted therapies tailored to aPL-N mechanisms. Future multicenter studies are essential to clarify their roles. The goal of this review is to inform clinicians and create a research agenda to address the unmet needs in diagnosing and managing APL-N.

Background/PurposeAPS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA).MethodsThe registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment. For the primary comparison of demographic, clinical, and serologic characteristics in this retrospective study, we divided patients into two groups: TP/AIHA ever and never. Thrombocytopenia was defined as a platelet count of <100,000 x 109/L tested twice at least 12 weeks apart, and AIHA was defined as anemia with hemolysis and a positive direct antiglobulin test (DAT). For the secondary analysis, we compared patients with TP versus AIHA, and the immunosuppressive use stratified by systemic lupus erythematosus (SLE) classification.ResultsAs of April 2022, of 1,039 patients (primary aPL/APS: 618 [59%]; SLE classification: 334 [31%]) included in the registry, 228 (22%) had baseline (historical or current) TP and/or AIHA (TP only: 176 [17%]; AIHA only: 35 [3%], and both: 17 [2%]). Thrombocytopenia and/or AIHA was significantly associated with Asian race, SLE classification, cardiac valve disease, catastrophic/microvascular APS, triple aPL (lupus anticoagulant, anticardiolipin antibody, and anti-β2-glycoprotein-I antibody) positivity, and SLE-related serologic and inflammatory markers. When 101/618 (16%) primary aPL/APS patients and 101/334 (34%) SLE patients with TP and/or AIHA were compared, azathioprine and mycophenolate mofetil were more commonly reported in lupus patients, however corticosteroid, intravenous immunoglobulin, and rituximab use were similar between groups.ConclusionIn our large multi-center international cohort of persistently aPL-positive patients, approximately one-fifth had active or historical TP and/or AIHA at registry entry; half of these patients had additional SLE. Cardiac valve disease, catastrophic/microvascular APS, and triple aPL-positivity were aPL-related clinical and laboratory manifestations associated with TP and/or AIHA, suggesting a more severe APS clinical phenotype in aPL-patients with TP and/or AIHA.

Antiphospholipid syndrome (APS) is an autoimmune, thromboinflammatory disease, which affects children and adults. There are particular features of the disease and nuances to diagnosis and management in a pediatric population, which must be appreciated to improve clinical care.

Pediatric-specific epidemiological studies highlight that pediatric APS is quite rare with incidence in some populations of 0.2 per 100 000. There are new classification criteria in APS, which include a wider range of clinical features increasingly identified in registry data and case series of pediatric APS, though validation in pediatric APS is still needed. There is a particularly high proportion of pediatric APS patients with noncriteria antiphospholipid antibodies (aPL). Recurrent thrombosis is especially common in pediatric APS, highlighting the difficulty of management of this disease with high morbidity in children.

Recent research has enhanced understanding of pediatric-specific APS epidemiology, laboratory findings, the wide variety of clinical features, and challenges in successful treatment. Future directions could include evaluation of potentially unique features in pediatric pathophysiology, an evaluation of the new APS classification criteria in children, broader prospective data on clinical and laboratory features, and a continued search for treatment beyond committing young patients to lifelong anticoagulation.

This study focused on the prevalence and impact of ANA in aPL-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs).

Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Patients with concomitant SARDs were excluded.

A total of 430 aPL-positive patients were included in the analysis, 56% ANA-positive (ANA+) and 44% ANA-negative (ANA-). ANA positivity was significantly associated with history of haematologic manifestations (persistent autoimmune haemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA+ vs 7% of ANA-, P = 0.006). Triple aPL-positivity was more frequent in the ANA+ subgroup (P = 0.02), along with low baseline C3 and C4 levels (P = 0.05 and P = 0.009, respectively), and higher frequency for ENA. Among aPL-positive patients with no APS classification, ANA+ patients showed a higher rate of arthritis (P = 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA+ and 96 were ANA-; ANA- patients had a higher number of pregnancies (P = 0.018), and number of live births (P = 0.014). A wider proportion of ANA+ patients were treated with HCQ (P < 0.001).

When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA+ patients showed higher rates of systemic autoimmune features, including haematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA- had a higher rate of pregnancies and live births.

We describe the case of a woman in her 40s on lifelong anticoagulation with warfarin due to antiphospholipid syndrome presenting with acute right upper quadrant pain. Liver tests were only slightly elevated, and non-invasive imaging such as Doppler ultrasound and contrast-enhanced CT were non-diagnostic. As suspicion for a thrombotic complication persisted, repeat CT imaging ultimately confirmed the diagnosis of Budd-Chiari syndrome (BCS), and angiography was performed allowing for effective treatment with balloon angioplasty. This case highlights both the need for a high degree of clinical suspicion for BCS in patients with prothrombotic features (even those on anticoagulation) and also the diagnostic and therapeutic potential of interventional radiology in selected cases.

Previous literature has reported cases of reversible visual loss associated with pre-eclampsia. Here, we present a patient with severe pre-eclampsia and a history of antiphospholipid syndrome (APS) who experienced irreversible visual loss.

An 18-year-old woman, gravida 2, abortion 1, with a history of antiphospholipid syndrome, was diagnosed with severe pre-eclampsia at 34 weeks of gestation. The patient had highly triple positive antiphospholipid antibodies and was on aspirin and enoxaparin 40 mg daily throughout her pregnancy. Despite timely cesarean section and control of blood pressure, the patient developed bilateral visual loss due to serous retinal detachment and acute angle-closure glaucoma. Although the patient received ophthalmologic interventions, anticoagulant, and immunosuppressive therapy, her vision failed to recover, and at five years of follow-up, the patient remained legally blind.

Our case highlights the importance of monitoring pregnant women with APS who, despite receiving aspirin and LMWH treatments throughout pregnancy, still present with pre-eclampsia. This underscores the need for proper prophylaxis and timely interventions to prevent catastrophic outcomes.

Antiphospholipid syndrome (APS), a disorder characterized by the presence of antiphospholipid antibodies, is commonly associated with thrombotic events and pregnancy complications. Although cardiac involvement of APS is very common, intracardiac thrombus is rare and easily misdiagnosed. In order to reduce missed diagnosis and misdiagnosis, we investigated the clinical features of APS with intracardiac mass by summarizing 50 cases (1 newly presented case and 49 additional cases collected from PubMed from 1985 to the present). There were 10 males and 40 females, with ages ranging from 8 to 75 years (median age 35.5). Intracardiac masses were distributed in four cardiac chambers. Mass size ranged from a diameter of 0.5 to 7.1 cm. Clinical manifestations were heterogeneous, including dyspnea, fever, hemiparesis, limb ischemia, and other nonspecific symptoms. In 41 cases with available pathology results, 33 cases were confirmed as thrombus, 2 cases as myxoma, 3 cases as non-bacterial endocarditis, 2 cases as fibrous tissue, and 1 case as inflammatory necrosis. Among 41 cases, 18 cases were suspected of primary cardiac tumors preoperatively, while pathological examination revealed none was tumor. APS patients with intracardiac masses are extremely rare, mostly seen in young or middle-aged people, and they present with a variety of clinical manifestations. Most masses disappear following medical treatment. APS can be accompanied by cardiac myxomas. APS should be promptly investigated in young patients presenting with thrombotic events without any underlying risk factors.

BackgroundAntiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy complications associated with the presence of antiphospholipid antibodies (aPLs). Although the exact mechanisms are unclear, aPLs can increase the expression of tissue factor on platelets, leukocytes, and endothelial cells, leading to hypercoagulability. Extracellular vesicles (EVs) can also be released during this process and play a key role in immune regulation and thrombosis related to APS.AimsTo evaluate the association between circulating levels of EVs and thrombosis related to APS, as well as inflammatory markers.MethodsCase-control study including patients with thrombotic APS (t-APS) and healthy controls (HC). EVs expressing the following antigens were quantified by flow cytometry: CD41 (platelet integrin alpha IIb), CD162 (P-selectin glycoprotein ligand 1), CD31 (platelet and endothelial cell adhesion molecule 1), CD142 (tissue factor), and CD62 (P-selectin). EV levels were compared between groups and correlated with APS clinical and inflammatory parameters.ResultsA total of 69 t-APS patients and 46 HC were included. CD162+EV, CD31+EV, and CD41+EV levels were higher in t-APS patients compared to controls. CD41+EV levels were associated with venous thrombosis (p = .04) and multiple thrombosis (p = .07). Levels of CD162+EV, CD31+EV, CD142+EV and CD62P + EV were positively correlated with levels of interleukin-1 beta (IL-1β).ConclusionEVs expressing antigens related to platelet and endothelial cell activation and adhesion, as well as platelet-leukocyte interaction, were associated with thrombosis related to APS. The correlation between EV levels and IL-1β levels further underscore the association between EV release and thromboinflammatory responses in APS. Our results demonstrate the involvement of EVs in the interaction between inflammation and thrombosis in APS.

Antiphospholipid syndrome (APS) is a heterogeneous autoimmune disease with persistent antiphospholipid antibodies. This study aimed to identify unrecognized APS subgroups from multicenter cohorts (n = 760, training: n = 415; validation: n = 345). Patients are stratified through unsupervised K-means clustering analysis. Prognostic outcomes are evaluated using Kaplan-Meier survival analyses. Proteomic analysis is conducted on primary APS patients (n = 36) and healthy controls (n = 12). Key molecule insulin-like growth factor 1 is validated using ELISA. Three clusters are identified. Cluster 1 (n = 320, 42.1%) is completely consisted of females (100%), with predominant occurrence of pregnancy morbidity (88.8%) but low incidences of thrombocytopenia (18.4%) and thrombosis (15.0%), and a favorable prognosis. Cluster 2 (n = 309, 40.7%) is predominantly female (99.4%) and characterized by high thrombosis (85.8%) and thrombocytopenia (46.6%), low pregnancy morbidity (13.6%), and poor prognosis. Cluster 3 (n = 131, 17.2%) is predominantly male (99.2%), exhibiting highest thrombosis (96.2%) and moderate thrombocytopenia (32.8%), with worst prognosis. Immunological and proteomic analyses clearly differentiated three clusters. This study reveals a distinct difference between obstetric and thrombotic APS, and a sex-based distinction within thrombotic APS. Three APS subgroups display unique clinical and molecular characteristics, and marked difference in prognostic outcomes.

Objectives: We describe a case of anti-phospholipid syndrome (APLS) vasculopathy presenting with Moyamoya syndrome (MMS) and show the associated intracranial vessel wall MRI (VWI) findings. Methods: A 37-year-old-woman presented with acute onset dizziness and left-sided weakness. Neurologic exam revealed a left facial droop and left hemiparesis. She underwent a comprehensive laboratory work-up for stroke. Neuroimaging included a CT head, CT angiogram, VWI, and digital subtraction angiography. Results: Work-up revealed a triple-positive APLS antibody profile. CT of the head showed an acute right basal ganglia infarction and right frontal subarachnoid hemorrhage. CT angiogram revealed severe stenosis of the right internal carotid artery terminus in a Moyamoya pattern. Intracranial VWI showed long-segment concentric vessel wall thickening and homogeneous vessel wall enhancement and T2-hyperintense wall edema of the stenotic right ICA terminus, M1 middle cerebral artery, and A1 anterior cerebral artery. She was treated with long-term anticoagulation with warfarin and a right superficial temporal artery to middle cerebral artery bypass. Discussion: We present intracranial VWI features of vessel wall pathology in a patient with primary APLS presenting with MMS.

Background and AimIn this retrospective, descriptive study, we aimed to identify clinical and laboratory characteristics, and prognoses of patients with Budd-Chiari syndrome (BCS) secondary to antiphospholipid syndrome (APS) and to compare with non-BCS vascular thrombotic APS patients.MethodsData of 194 patients with thrombotic APS (17 with BCS) ± systemic lupus erythematosus (SLE) in a single center between 1982 and 2023 were evaluated. Antiphospholipid serology consisting of lupus anticoagulant (LA), anticardiolipin (aCL) IgG/IgM, anti-beta2 glycoprotein I (aβ2GPI) IgG/IgM and adjusted global APS score (aGAPSS) were evaluated to determine thrombotic risk. Damage was identified for all patients by applying the damage index for APS (DIAPS). All patients with BCS were screened for hereditary or acquired prothrombotic disorders.ResultsPatients with BCS had higher aGAPSS and recurrent thrombosis (70.6% vs 40.7%) compared to those with non-BCS. BCS was the first thrombotic event in eight patients and three had recurrent thrombosis. The most common presenting manifestation of BCS was abdominal pain which was followed by abdominal distention and fever. The second prothrombotic factor was detected in six patients: three had heterozygous factor V Leiden mutation, three were in pregnancy period. Additionaly, two patients had SLE flare. The DIAPS of the patients in the BCS and non-BCS groups were similar, but those in the BCS group had higher mortality rates.ConclusionsAPS patients with BCS may have a higher risk of recurrent thrombosis and mortality. Acquired or hereditary prothrombotic disorders are not uncommon in this group and should be screened in APS patients with BCS.

Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.

Background/Objectives: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis or obstetric complications and the laboratory detection of antiphospholipid antibodies. Although vascular thrombosis is the main manifestation of the disease, other rarer complications have also been described. Avascular necrosis (AN) is considered a rare manifestation of APS. The aim of our case series is to study patients with APS and AN. Methods: A retrospective study was performed on 80 patients diagnosed with APS. Results: AN was observed in 3 patients out of 80 diagnosed with APS. AN of the femoral head was observed in all cases. Case (1): A 54-year-old woman presented due to multiple ischemic infarctions in the brain, as detected in magnetic resonance imaging of the brain, Raynaud's phenomenon, and AN of the femoral head. In laboratory testing, a prolongation of activated partial thromboplastin time was recorded. A heterozygous mutation was also found in the gene MTHFR C677T, and the patients was positive for lupus anticoagulant (LA). The patient was given clopidogrel and acenocoumarol. Case (2): A 52-year-old man was diagnosed with APS, based on the clinical presentation (stroke) and positivity for LA and anti-β2GPI (anti-β2 glycoprotein I antibody). In his medical history, episodes of vertigo and an episode of AN of the femoral head 2 years ago were described. Case (3): A woman aged 43 years presented due to AN of the femoral head. Due to suspected APS, immunological testing was performed, and positivity for LA and IgM anticardiolipin antibodies was detected. She was treated with acenocoumarol. Conclusions: AN is a rare clinical manifestation of APS, which may precede the diagnosis of APS for many years.

Portal vein thrombosis in non-cirrhotic individuals, although uncommon, is an increasingly explored condition that affects mainly young people, consequently representing a significant disease burden. Reports primarily including western European populations have recently shed light regarding the pathophysiology, risk factors, natural history, treatment, and prognosis of this entity. Underlying predisposing conditions are documented in ~70% of cases, encompassing local risk factors, inherited and acquired thrombophilia, cancer, and systemic inflammatory conditions. Non-cirrhotic portal vein thrombosis can cause significant portal hypertension in the acute setting, but, more frequently, significant portal hypertension-related complications arise when the condition becomes chronic and portosystemic collaterals develop, increasing the risk for variceal bleeding and ascites. The diagnostic approach to screen for underlying thrombophilia remains a challenge, and recommendations in this regard, although scarce and backed by scarce evidence, have changed notably in the last years, leaning toward a universal screen in patients who develop this condition without a clear provoking factor. Recently, studies have shown that long-term anticoagulation may be appropriate even in the absence of clear provoking factors or underlying thrombophilia. Future studies should address which patients may benefit from this approach, which patients may not need it, and what the most appropriate strategies are to approach patients who do not recover portal vein patency with anticoagulation to further prevent portal hypertension-related complications.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of thrombotic or obstetrical events in patients with persistent antiphospholipid antibodies (aPL). Thrombotic events, the primary pathological hallmarks and clinical manifestations, are among the leading causes of mortality in APS. Our understanding of the mechanism underlying APS-related thrombosis has significantly advanced in recent years. The presence of aPL, particularly anti-β2-glycoprotein I (anti-β2GPI) antibodies, is a major driver of thrombosis. The proposed pathophysiological mechanisms of aPL-mediated pro-thrombotic events can be broadly categorized into three types: disruption of anticoagulant reactions and fibrinolysis, interference with coagulation cascade cells, and complement activation. A triggering 'second hit' is typically necessary to initiate thrombosis. The development of animal models of APS has further refined our understanding of the role of aPL in thrombosis. In this review, we focused on the role of β2GPI-dependent aPL in thrombosis of thrombotic APS.

Antiphospholipid syndrome is a rare, autoimmune thrombophilia defined by vascular thrombosis and pregnancy morbidity, in the setting of documented persistent antiphospholipid antibodies including the lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I antibodies. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome, which involves widespread coagulopathy over a very short period of time. The degree of risk associated with antiphospholipid syndrome depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. The current standard treatment for unprovoked thrombosis is long-term warfarin. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin in pregnant patients. The use of direct oral anticoagulants in patients with antiphospholipid syndrome is still being debated. Their use is generally contraindicated, especially in high-risk patients, such as those with all 3 antiphospholipid antibodies present, but they may potentially be of some use in some low-risk patients.

Clinical guidelines recommend warfarin for patients with antiphospholipid syndrome (APS) and ischemic stroke; however, robust evidence is lacking. We investigated the clinical benefits of different categories of antithrombotic medications in ischemic stroke patients positive for antiphospholipid antibodies (aPLs) in real-world practice. We reviewed data from patients with ischemic stroke or transient ischemic attack who tested positive for aPLs. Based on their secondary preventive antithrombotic medications, patients were classified into antiplatelet and anticoagulant categories, and further into warfarin, single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), and direct oral anticoagulant groups. The outcome of interest was a composite of recurrent thrombosis and major bleeding events. Time-varying Cox proportional hazards model was used. Among 167 eligible patients, 28 experienced composite outcome events over 601.1 person-years. SAPT and DAPT demonstrated clinical benefits over warfarin (SAPT vs. warfarin, adjusted hazard ratio [95% confidence intervals], 0.24 [0.07-0.83]; DAPT vs. warfarin, 0.25 [0.08-0.81]). Notably, DAPT was advantageous regarding major bleeding (DAPT vs. warfarin, 0.10 [0.02-0.47]), while the risk of recurrent thrombotic events was comparable between the antiplatelet and warfarin groups. Antiplatelet therapy may be a safe and effective alternative to warfarin for secondary prevention of aPL- and APS-related stroke. Further prospective validation is required.

Hypoprothrombinemia is a rare coagulopathy that complicates surgical interventions and is an uncommon manifestation of lupus anticoagulant. Perioperative coagulopathy is a major challenge in cardiac surgery. To our knowledge, the management of cardiac surgery in patients with hypoprothrombinemia has not been described in prior literature. This case report outlines the challenging surgical intervention of mitral valve replacement in a 47-year-old female patient with rheumatic valve disease (RHD) and a rare prothrombin deficiency secondary to lupus anticoagulant. This report details the multidisciplinary perioperative hemostasis management and outcomes.

Antiphospholipid syndrome (APS), is an autoimmune systemic disorder known to manifest with thrombosis in almost all vessels throughout the body, can also be accompanied by pregnancy morbidity, and is persistent with the presence of antiphospholipid antibodies, including lupus anticoagulant antibodies, or relatively high titers of anticardiolipin, or anti-β2Glycoprotein I antibodies. APS can occur alone or in association with other diseases, more commonly systemic lupus erythematous. In patients with both underlying diseases episodes of arthritis, skin changes in the form of livedo reticularis, thrombocytopenia and leucopenia were more common. Cardiac manifestations have also been reported. Here we present a complicated case of a young female patient with antiphospholipid syndrome and an underlying systemic lupus erythematosus.

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder characterized by thrombosis and pregnancy morbidity. Although PAPS is distinct from systemic lupus erythematosus (SLE), the two conditions share clinical features and susceptibility genes. Progression from PAPS to SLE is well recognized. However, risk factors for this transition are poorly understood. We aimed to identify predictors of progression to SLE in patients with PAPS.

A longitudinal single-centre study was conducted at Hokkaido University Hospital from 1990 to 2021. Baseline characteristics, including clinical features, laboratory data, and antiphospholipid antibody profiles, were compared between patients who progressed to SLE (SLE group) and those who did not (non-SLE group).

Among 64 patients diagnosed with PAPS at baseline, nine (13.8%) progressed to SLE over a mean follow-up duration of 9 years (incidence rate, 1.61 per 100 person-years). At the time of the diagnosis of PAPS, the SLE group had a higher prevalence of phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) and anti-dsDNA antibodies compared to the non-SLE group. Other clinical findings, autoantibody profiles, and serum complement levels were similar between the two groups. Multivariate Cox analysis showed that aPS/PT IgG was significantly associated with SLE development (hazard ratio: 10.3, 95% confidence interval: 1.13-92.6, P = .04).

aPS/PT IgG may be a predictive factor for new-onset SLE in patients with PAPS, suggesting its utility in guiding risk stratification and monitoring strategies for these patients.

Women with adverse pregnancy outcomes suggestive of obstetric antiphospholipid syndrome (OAPS), but not fulfilling clinical and/or laboratory international classification criteria, are increasingly recognized both in clinical practice and in the literature. This entity is termed non-criteria OAPS (NC-OAPS). It includes clinical scenarios such as two unexplained pregnancy losses, three non-consecutive pregnancy losses, late pre-eclampsia/eclampsia/signs of placental insufficiency, or recurrent implantation failure, as well as positive low-titers of antiphospholipid antibodies (aPLs) and non-classical aPLs. To address the NC-OAPS heterogeneity, a nomenclature proposal was developed. In recent years, retrospective and prospective cohort studies have been designed to clarify the characteristics and outcomes of the different subsets of NC-OAPS. In general, the studies support that NC-OAPS may benefit from treatment with antithrombotic, anticoagulant and/or immunomodulator agents, but several considerations must be made on the robustness and nuances of the scientific evidence. The objective of this review is to critically analyze the available evidence supporting the diagnosis of NC-OAPS, categorize its subsets, and evaluate the impact of treatment strategies on its outcome. We also remark on questions that are still unanswered, such as the lack of consensus on diagnostic criteria or treatment protocols.

Thrombosis in 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. This study aimed 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.

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% vs < 70%.

Sixty seven antiphospholipid syndrome patients were studied. It was observed that 29.9% achieved time in therapeutic range ≥ 70% and 9.1% of patients with 3 or more comorbidities achieved time in therapeutic range values ≥ 70% compared with 40% of patients with less than 3 comorbidities. Fewer recurrent arterial and overall thrombotic events occurred with time in therapeutic range ​​≥ 70%.

A minority of antiphospholipid syndrome patients treated with vitamin K antagonists 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.

Several systemic autoimmune diseases predispose to the enhancement of Atherosclerotic Cardiovascular Disease (ASCVD). These findings underline the role of inflammation in atherogenesis. Dermatomyositis (DM) and polymyositis (PM) are polygenic autoimmune disorders involving mainly skeletal muscles. The association between PM/DM and ASCVD has not been well addressed and explored. We aimed to investigate the association between PM/DM and ASCVD events, we examined the incidence, mortality, and interaction of disease-modifying agents, autoantibodies, and traditional cardiovascular disease (CVD) risk factors in a large population-based sample.

We conducted a retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All DM and PM patients diagnosed between 2000 and 2016 were included and matched with healthy controls by age and sex in a 1:5 ratio. Follow-up continued until the first diagnosis of ASCVD or death. The incidence of ASCVD was compared between the groups using univariate and multivariate models adjusting for baseline cardiovascular risk factors.

The study population included 1899 PM/DM patients and 7676 controls. The mean age at the index date was 32.5 years (SD ± 19 years), and the female proportion was 60.3 %, similar for both groups. Traditional cardiovascular risk factors were similar in both groups. The Median follow-up time was 8.4 years (3.6-12.8) in the PM/DM group compared to 8.6 (3.7-12.9) in the control group. 47 (3.0 %) PM/DM patients were diagnosed with ischemic heart disease (IHD) compared to 1.8 % (140) in the controls, yielding a multivariate HR (95%CI) of 1.61 (1.15-2.25). Multivariate HR for cerebrovascular accident (CVA) in the PM/DM group was (95%CI) 2.45 (1.63-3.70). Multivariate HR for ASCVD. (95%CI) was 1.75 (1.35-2.27) in the PM/DM group. APLA-associated antibodies presence was more associated with ASCVD among PM/DM groups than non-ASCVD PM and DM patients (OR 2.33, 95 % CI 1.41-3.86, p < 0.001).

Our study demonstrates that PM and DM are associated with an increased risk of IHD and CVA. Furthermore, PM and DM patients positive for APLA-associated antibodies exhibited excessive rates of ASCVD. These findings support the increased need for awareness and surveillance of cardiological, neuronal, and vascular outcomes in patients suffering from PM/DM.

Antiphospholipid syndrome (APS) is a highly prothrombotic autoimmune disease characterized by the persistent presence of antiphospholipid autoantibodies (aPL) in association with thrombotic or nonthrombotic macro- and microvascular manifestations and/or pregnancy complications. This review is restricted to thrombotic APS. Since the publication of the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS, several authors have emphasized the difference between "classification" and "diagnosis" as a potential pitfall for clinicians. In addition to challenges associated with the diagnosis of APS, there are many unresolved areas in understanding pathogenesis and in the management of both thrombotic and obstetric APS. Although APS is an antibody-mediated autoimmune disease, secondary thrombosis prevention is achieved by anticoagulation, mainly with vitamin K antagonists, such as warfarin, rather than immunomodulation. Evidence is convincing for the use of vitamin K antagonists in triple-positive APS with venous thromboembolism. However, the best anticoagulant approach in the management of venous thromboembolism patients with single or dual positive aPL is not clear. Management of patients with stroke or arterial thrombosis with aPL remains a major unresolved issue, although some guidelines recommend the use of warfarin rather than antiplatelet therapy as the first-line treatment of stroke in APS. Recurrent thrombosis, despite therapeutic anticoagulation, remains a frequent problem and may be explained by the contribution of thrombo-inflammation in patients with thrombotic APS. In this narrative review, we discuss some of the unresolved issues in the diagnosis and management of thrombotic APS.

Activated partial thromboplastin time (APTT) is susceptible to reagent composition. This study aimed to investigate a large number of specimens and determine the cause of discrepancies.

This study included 18,994 subjects who underwent coagulation tests at our hospital from May 2020 to December 2020. Measuring reagents included HemosIL SynthASil APTT (APTT-SS, Instrumentation Laboratory) and Coagpia APTT-N (APTT-N, Sekisui Medical).

A total of 451 patients demonstrated APTT-N of >39 seconds and an APTT-N/SS ratio of >1.3. A C-reactive protein (CRP) level of ≥1.4 mg/L demonstrated a significant positive correlation, with a higher APTT-N/SS indicating higher CRP levels. All 28 subjects receiving no anticoagulants and who had remaining specimens underwent a cross-mixing test (CMT). Of them, 17 were suspected for lupus anticoagulant (LA) by both the waveform shape and the index of circulating anticoagulant (ICA) value, 6 by the ICA value, and 5 were difficult to determine.

This study revealed that the APTT-N prolongation correlated with CRP degree and the transient involvement of LA in CMT results due to CRP. This study indicated various reactivities depending on the assay reagents used. Further testing is warranted if LA is suspected, considering the patient's background.

Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a widely prevalent chronic autoimmune disease that can affect any organ system in the body. Although the pathogenesis of this disease is rather complex and poorly understood, ultimately there is an overproduction of multiple self-reactive antinuclear antibodies. These autoantibodies are one of the laboratory hallmarks of the diagnosis and disease activity of SLE. Lupus has a myriad of symptoms and imaging manifestations. Serositis, one of the most common manifestations of the disease, usually occurs with pleural or pericardial effusion with or without associated serosal inflammatory changes. The pulmonary manifestations are heterogeneous, with mostly acute (eg, diffuse alveolar hemorrhage, acute lupus pneumonitis) and some chronic (eg, fibrosing interstitial lung disease, shrinking lung syndrome) lung findings. Cardiac and vascular manifestations include myocarditis; coronary artery disease, including accelerated atherosclerosis; myocardial infarction; and spontaneous dissections, along with vasculitis, aneurysms, Libman-Sacks endocarditis, and arterial and venous thromboembolism. Although patient history and risk factor assessment have a vital role in diagnosing lupus, familiarity with the imaging manifestations aids radiologists in optimizing patient care, assessing for complications, and uncovering undiagnosed cases of lupus. This fact emphasizes the importance of recognizing the complex multisystem involvement of lupus seen at imaging. In this article, the authors review the thoracic and cardiovascular imaging manifestations of lupus. © RSNA, 2024.

Although autoimmune abnormalities are common in patients with endometriosis, it is unknown whether patients with endometriosis have a higher risk of developing antiphospholipid syndrome (APS).

We conducted a retrospective cohort study by using the multi-institutional research network TriNetX from 1 January 2012 to 31 December 2021. A total of 13 131 782 women aged 20-60 years from networks within the USA were included. The risks of APS were compared between an endometriosis cohort and a non-endometriosis cohort in subgroup analyses by age, obesity and systemic lupus erythematosus (SLE), and the sensitivity analysis was stratified by the presence or absence of a history of surgery of the uterus.

After 1:1 propensity score matching, the endometriosis and non-endometriosis cohorts each included 50 078 participants. Compared to individuals without endometriosis, patients with endometriosis had a higher risk of incident APS (log-rank test, P < 0.001). The hazard ratios (HRs) ranged from 1.82 [APS within 30 days to 1 year after the index date, 95% confidence intervals (CIs) 1.40-2.53] to 2.44 (APS within 30 days to any time after the index date, 95% CI 1.65-3.61). In the subgroup analyses, an increased risk of APS was observed in all ages, White race, and subgroups without smoking, obesity, asthma, inflammatory bowel disease and SLE (HR range 1.85-2.84). Sensitivity analyses revealed that the risk of APS increased in patients without surgery history of the uterus.

Patients with endometriosis had a higher risk (2.84-fold) of developing APS. Future large-scale prospective studies are warranted to confirm our results.

Machine learning and artificial intelligence tools were used to investigate the discriminatory potential of blood serum metabolites for thromboembolism and antiphospholipid syndrome (APS). 1H-NMR-based metabonomics data of the serum samples of patients with arterial or venous thromboembolism (VTE) without APS (n = 32), thrombotic primary APS patients (APS, n = 32), and healthy controls (HCs) (n = 32) were investigated. Unique metabolic profiles between VTE and HCs, APS and HCs, and between VTE and triple-positive APS groups were indicative of the significant alterations in the metabolic pathways of glycolysis, the TCA cycle, lipid metabolism, and branched-chain amino acid (BCAA) metabolism, and pointed to the complex pathogenesis mechanisms of APS and VTE. Histidine, 3-hydroxybutyrate, and threonine were shown to be the top three metabolites with the most substantial impact on model predictions, suggesting that these metabolites play a pivotal role in distinguishing among APS, VTE, and HCs. These metabolites might be potential biomarkers to differentiate APS and VTE patients.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent vascular thrombotic events. Catastrophic APS (CAPS), which can result in multiple organ failure and even death, is the most severe manifestation of APS. Herein, we report the case of a pediatric patient with CAPS, including the clinical course, diagnosis, and treatment, with the goal of expanding the literature on this condition, as reports of CAPS in pediatric patients are rare.

A 7-year-old girl presented with cranial hypertension. She was initially admitted to the hospital with a diagnosis of cerebral venous sinus thrombosis (CVST) and was discharged following symptom improvement. However, only 3 days later, the patient was re-presented with cranial hypertension and multiple thromboses and was ultimately diagnosed with CAPS based on multidisciplinary consensus. Despite treatment with a series of anticoagulation and thrombolytic therapies, the child's condition progressed rapidly, and she eventually died of pulmonary embolism.

CAPS in children is rare and associated with a high mortality rate, making early recognition and diagnosis critical but difficult. Based on the presented case, we recommend routine screening for antiphospholipid antibodies in children with CVST without obvious triggers, or a multidisciplinary collaboration, to facilitate the early diagnosis of CAPS.

Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening form of antiphospholipid syndrome (APS) defined by the rapid onset of large and small vessel thrombosis occurring simultaneously across multiple sites, resulting in multiorgan dysfunction. The presence of underlying immune dysfunction causing activation of coagulation and, in many cases, abnormal complement regulation predisposes these patients to thrombotic events. CAPS is often preceded by triggering factors such as infection, surgery, trauma, anticoagulation discontinuation, and malignancy. Given the high mortality rate, which may exceed 50%, prompt recognition and initiation of management is required. The detection of antiphospholipid antibodies and the histopathologic identification of microvascular ischemia via tissue biopsy are required to diagnose CAPS. However, these patients are often too unwell to obtain results and wait for them. As such, investigations should not delay CAPS therapy, especially if there is strong clinical suspicion. Management of CAPS requires "triple therapy" with glucocorticoids, intravenous heparin, therapeutic plasma exchange, and/or intravenous immunoglobulin. Treatment for refractory disease is based on poor-quality evidence but includes anti-CD20 (rituximab) or anticomplement (eculizumab) monoclonal antibodies and other immunosuppressant agents, either alone or in combination. The rarity of this syndrome and the subsequent lack of randomized clinical trials have led to a paucity of high-quality evidence to guide management. Continued international collaboration to expand ongoing CAPS registries will allow a better understanding of the response to newer targeted therapy.

Antiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes.

The aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles.

This observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care.

Forty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-β2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %).

Treatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

The primary antiphospholipid syndrome and protein S deficiency are known hypercoagulable states predisposing to strokes. We present a 34-year-old woman presented to rheumatology clinic complaining of right side weakness and aphasia for 2 months before the visit. There was joint pain in the right elbow and shoulder joints, hyperpigmentation on her face and dry painful red eyes mainly the right eye in addition to dry mouth. She had a history of recurrent abortions. Neurological examination showed hypertonia on right lower and upper limb and normal on left one, while the power was grade 3 on right side and normal in left one. Upper motor neuron signs and facial palsy was noted. Hyperpigmentation in the face was observed. MRI brain showed that left temporoparietal hemorrhagic infraction involving the basal ganglia and MRV brain showed left transverse sinus thrombosis and attenuation of sigmoid and internal jugular vein. B2-glycoprotein Ig AGM, lupus anticoagulant, anticardiolipin (IgG, IgM, and IgA), protein S were positive. ANA profile was borderline for PCNA. We report unusual venous sinus thrombosis with primary antiphospholipid syndrome and acquired protein S deficiency.

Antiphospholipid syndrome (APS) is a group of rare autoimmune diseases caused by antiphospholipid antibodies that is mainly associated with arterial or venous thrombosis and/or complications during pregnancy. Skin lesions occur in approximately 30% of APS patients as initial manifestations. However, previous studies have primarily focused on the treatment of APS rather than the management of skin lesions. Here, the authors report a case of an APS-related lower limb skin ulcer that had remained unhealed for more than 7 years. The difficulties in this case were the diagnosis of APS, the risk of bleeding during debridement, wound infection, biofilm formation, reduced venous return from the lower limbs, and compliance with compression therapy and follow-up. A three-step wound care regimen based on a multidisciplinary team approach resulted in effective control of APS and healing of the ulcer to the lower leg in 95 days. Over two follow-ups, there was no recurrence of the ulcer.