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Background: 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., 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% vs < 70%., Results: 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%., Conclusions: 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis, pathological pregnancies and persistent antiphospholipid antibodies. The occurrence and development of APS are complex and associated with immune disorders, with its prognosis remaining uncertain. Owing to its pathogenesis, anticoagulation therapy is the primary treatment for patients with APS. In recent years, with increased attention on APS, research on its treatment strategies has flourished, and preclinical and clinical relevance studies are being conducted to re‑evaluate the mechanism of action of existing drugs and to develop new drugs. Recent evidence suggests that vitamin D (VD) may help improve immune disorders in patients with APS by regulating the balance between immune cells. In this review, the potential mechanistic role of VD in APS protection was discussed, highlighting the potential effects of VD as a promising adjuvant treatment option for APS.

Infections are an important cause of hospital admission in systemic lupus erythematosus (SLE) due to the immunosuppressed state of these patients. Although cryptococcal meningitis is the most common fungal infection in SLE, it is relatively rare and thus often diagnosed late, causing considerable morbidity and mortality. The management of SLE in the setting of cryptococcal meningitis becomes difficult, as immunosuppressive agents used in SLE lead to difficulty in eradicating the infection. Here, we present a case report of a patient with SLE, lupus nephritis, and antiphospholipid syndrome (APS) who developed cryptococcal meningitis and was successfully managed., (© Journal of The Association of Physicians of India 2025.)

BACKGROUND Lupus anticoagulants (LA) can interfere with routine coagulation tests such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The international normalized ratio (INR) is derived from PT and is used to monitor warfarin therapy. A positive LA result is one of the laboratory criteria of the 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria. We report a case in which LA interfered with INR measurement in an APS patient. CASE REPORT Our patient was a 45-year-old man who had experienced multiple episodes of thromboembolism. His INR was consistently high, despite not being on any anticoagulant. Our laboratory used a recombinant PT reagent, Siemens Healthineers Dade® Innovin® on a fully automated coagulometer, the Sysmex CS-2500. PT measurements were repeated using 2 different analyzers, the Sysmex CA-104 and Werfen ACL Top 550 CTS. The PT results were 40.5 s (reference range (RR): 9.3-10.8 s) and 56 s, using Sysmex CS2500 and CS104, respectively. However, the PT was 13.4 s (RI: 10.3-12.7 s) using Werfen ACL Top 550 CTS. We retested the sample using Thromborel® S, a tissue-derived PT reagent, and PT was found to be within the reference range. The patient tested positive for LA, anti-cardiolipin, and anti-beta2 glycoprotein I antibodies. CONCLUSIONS LA can falsely prolong the PT when a recombinant PT reagent is used. When we retested the plasma using a tissue-derived PT reagent - Thromborel® S - PT was within normal limits. Thus, it is important to acknowledge that LA can react differently with different PT reagents.

Introduction: Anzi Tiaochong Fang (ATF) is a traditional Chinese medicine (TCM) Fangji widely used to treat antiphospholipid syndrome-related recurrent pregnancy loss (APS-RPL). This study aimed to identify the quality markers and elucidate the mechanisms of ATF in treating APS-RPL., Methods: Chemical, network pharmacology, and in vitro verification were employed to identify quality markers and mechanisms of ATF. HPLC-MS/MS was used to identify and quantify ATF compounds. APS-RPL targets were identified using databases such as HERB, similarity ensemble approach, PharmMapper, Swiss Target Prediction, Gene Expression Omnibus, Genecards, and DisGeNET. GO and Reactome analyses were conducted using KOBAS-i. In vitro verification was performed using CCK-8, FDA staining, and ELISA., Results: This study identified 23 compounds and 942 targets, including 132 APS-RPL targets and 42 targets between ATF and APS-RPL. GO analysis demonstrated significant enrichment in cytokine-mediated signaling pathway, positive regulation of angiogenesis, response to hypoxia, inflammatory response, and platelet degranulation. Reactome analysis indicated significant enrichment in Immune System, Cytokine Signaling in the Immune system, Signaling by Interleukins, Platelet activation, signaling and aggregation, and Signaling by VEGF. Core targets identified included VEGFA, ALB, TNF, IL-6, and STAT3, with liquiritigenin, nobiletin, ginsenoside Rb1, and astragalin identified as quality markers. In vitro experiments demonstrated that ATF promoted HTR-8/SVneo cell viability, significantly reduced TNF-α and IL-1β levels, and upregulated IL-6., Conclusions: These findings contribute to the identification and quantification of potential quality markers and elucidate the molecular mechanisms of ATF, thereby supporting its therapeutic potential in the treatment of APS-RPL., Competing Interests: Declarations. Ethical approval: This study does not contain any studies with human participants or animals performed by any of the authors. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: To determine the number of patients that met classification for antiphospholipid antibody syndrome (APS) after applying the 2023 American College of Rheumatology and the European Alliance for Associations of Rheumatology (ACR/EULAR) classification criteria, to identify reasons patients did not meet the new criteria, and determine the number of patients who were single, double, or triple positive based on laboratory criteria., Methods: A single center, retrospective chart review of patients with APS on anticoagulation managed by ambulatory care clinical pharmacists. Data collected included patient demographics, type of anticoagulation, and clinical and laboratory criteria for APS as defined by the 2023 ACR/EULAR criteria. Data is presented using descriptive statistics., Results: A total of 51 patients previously diagnosed with APS were included. There were 42 patients on warfarin (82.3%), 4 patients on direct oral anticoagulants (19%), 3 patients on low molecular weight heparin (5.8%), and 2 patients on fondaparinux (3.9%). Of the 51 patients, 12 (23.5%) met classification criteria, 33 (64.7%) did not meet classification criteria and 6 (11.7%) had insufficient data. Of the 27 patients that did not meet criteria, 13 patients did not meet the laboratory criteria (39.4%), 6 patients did not meet the clinical criteria (18.2%) and 14 patients did not meet both laboratory and clinical criteria (42.4%). Of the 12 patients that met classification criteria, 2 patients were triple positive (16.7%), 3 were double positive (25%), and 7 were single positive (58.3%)., Conclusions: Results from this study indicate that APS continues to be a complex disease state with challenges in diagnosis and classification. Since only a small number of patients in our clinic continued to meet the classification criteria, opportunities for patient re-evaluation of management strategies at our institution could be considered., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Systemic lupus erythematosus is a multi-organ autoimmune disorder that is treated by immunosuppressive agents that weaken the immune defense against opportunistic pathogens and latent infections such as strongyloidiasis. Herein, we report the case of a 43-year-old woman known to have systemic lupus erythematosus who presented with gastrointestinal symptoms, edema, and bone pain 2 months after receiving immunosuppressive treatment., Case Presentation: A 43-year-old Iranian female known to have systemic lupus erythematosus and antiphospholipid syndrome presented with abdominal pain, nausea, vomiting, and generalized edema. She was on CellCept, prednisolone, and hydroxychloroquine. The vital signs were within the normal range. On physical examination, no rash was observed on the skin. There was only a mild tenderness in epigastric region. The results of blood analysis revealed hypochromic microcytic anemia, normal leukocyte count with mild eosinophilia. Liver enzymes as well as renal function tests were within the normal range. Stool examination was negative for trophozoites, ova, or cysts of parasites. Endoscopic findings included a generalized nodular appearance of duodenum with an infiltrative mucosa in the wall of duodenum, suggesting lymphoma. The pathology report determined the diagnosis of strongyloidiasis. Cap albendazole 400 mg was administered twice a day for 2 weeks. Abdominal pain was completely relieved 1 week after starting the treatment. The patient was eventually discharged after 10 days., Conclusion: The significance of this case report is the necessity to send complete blood count and serologic assays to screen latent strongyloidiasis before receiving immunosuppressive agents in patients with systemic lupus erythematosus., Competing Interests: Declarations. Ethics approval and consent to participate: This study has been approved by the ethics committee of Hormozgan University of Medical Science (IR.HUMS.REC.1402.459) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by the presence of β 2-glycoprotein I ( β 2-GPI)-targeting antiphospholipid antibodies (aPLs) and vascular thrombosis or obstetrical complications. One of its severe manifestations is nephropathy. Methods: To examine the role of type I interferon (IFN) and therapeutic potential of tyrosine kinase 2 (Tyk2) inhibition, we administered BMS-986202, a novel Tyk2 inhibitor, in a mouse model of APS nephropathy. We administered BMS-986202 to BALB/c mice at a dose of 2 mg/kg. Biochemical and histological characteristics of APS nephropathy were then determined. The type I IFN signature in the kidney was also evaluated by real-time polymerase chain reaction (PCR). Results: The Tyk2 inhibitor reversed the elevation of blood urea nitrogen (BUN) and microalbuminuria in the murine model of APS nephropathy. In addition, the Tyk2 inhibitor reversed the pathological vascular changes in the kidney as judged in electron microscopy (EM), and fibrin and C3 deposition as revealed in immunohistochemistry (IHC). An increased expression levels of IFN signature (IFN regulatory factor 7 (IRF7) and Mx1) in the kidneys of APS mice were found. Tyk2 inhibition reversed such an upregulation. Conclusion: Our results demonstrated the key role of type I IFN in the pathogenesis of APS nephropathy. Furthermore, the therapeutic efficacy of Tyk2 inhibition was demonstrated in a murine model of APS nephropathy. Our results could provide a new treatment strategy for this debilitating disease., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Kuo-Tung Tang et al.)

Aims: Some patients with Obstetric Antiphospholipid Syndrome (OAPS) still experience miscarriage and placental dysfunction after routine treatment, which is related to an abnormal increase in neutrophil extracellular traps (NETs). The labeling of statins has been revised to remove the contraindication for use during pregnancy. Our aim is to investigate the effect of Simvastatin on pregnancy outcomes in OAPS and its correlation mechanisms with NETs., Main Methods: The effect of Simvastatin on pregnancy outcomes was observed. The effect of simvastatin on the function and apoptosis of neutrophils has evaluated. The effect of Simvastatin to NETs and the changes in oxidative stress levels were observed. Different groups of NETs were extracted to intervene the HTR8-Svneo.RNA-seq analysis of the mechanism of which Simvastatin reduces NETs. Seahorse experiment detected the effect of Simvastatin on neutrophil glycolysis levels. Fluorescence co-localization and flow cytometry and Co-IP were used to verify relevant mechanisms., Key Findings: In the OAPS mice, Simvastatin can reduce embryo absorption rate, reshape placental blood flow perfusion. Simultaneously reducing the production of NETs both in vivo and vitro, remolding oxidative stress. Simvastatin can improve neutrophil dysfunction caused by aPL-IgG. The reduction of NETs improved HTR8-Svneo's dysfunction. The intervention of Simvastatin on neutrophils under the stimulation of aPL-IgG showed a signature in glycolytic. The key rate limiting enzyme PKM2 in glycolysis interacts with Cit-H2b and PI3K/AKT signaling pathway., Significance: Our study providing basic theoretical support for the treatment of OAPS with Simvastatin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 by The American Society of Hematology.)

Anticoagulation is central to the management of antiphospholipid syndrome (APS), an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL; ie, 1 or more of lupus anticoagulant [LA], anticardiolipin, anti-beta-2- glycoprotein I, IgG, or IgM antibodies). The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Accurate assessment of anticoagulation intensity underpins optimal anticoagulant dosing for thrombus treatment or primary/secondary prevention. In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between LA and the thromboplastin reagent used in the INR determination. In this review, we summarize the use of warfarin/VKA in patients with APS, along with venous and point-of-care INR monitoring. We also discuss the role and monitoring of LMWH/UFH, including in the anticoagulant refractory setting and during pregnancy., (Copyright © 2024 by The American Society of Hematology.)

Background: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare autoimmune condition characterized by acquired prothrombin (FII) deficiency associated with antiphospholipid syndrome (APS) and life-threatening bleeding. We present the case of a 34-year-old woman with heavy menstrual bleeding (HMB), positive Lupus anticoagulant (LA) test, and high titer anticardiolipin antibodies Immunoglobulin G (ACA IgG) and anti-β2 glycoprotein I antibodies IgG (antiB2GPI IgG). Severe iron deficiency anemia necessitated recurrent blood transfusions and intravenous iron infusions from 2018 to 2021., Results: In January 2022, she was admitted to our clinic. Von Willebrand disease screening and platelet function analysis (PFA100) were normal. FII and FIX deficiencies were detected, without factor IX inhibitors. Anti-phosphatidylserine/prothrombin antibodies were confirmed by Padua University lab. To reduce antibody titers and menstrual bleeding, immunosuppressive therapy (Rituximab 375 mg/m2 weekly ×4 weeks) and hormonal therapy (desogestrel 75 mcg/day) were initiated., Conclusion: After 1-year, complete remission of clinical symptoms was achieved, with normalization of FII and FIX values and moderate reduction of aPS/PT titers, especially IgM isotype., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Cerebral venous sinus thrombosis (CVST) is a rare but serious manifestation of venous thrombosis in patients with antiphospholipid syndrome (APS). This study investigated the risk factors, clinical characteristics and prognosis of CVST in APS patients., Methods: This retrospective cohort study included all thrombotic APS (tAPS) patients from Peking Union Medical College Hospital (PUMCH) from April 2005 to August 2023. Demographic characteristics, laboratory data and thrombotic risk factors were compared between tAPS-CVST group and tAPS-non-CVST group. Kaplan-Meier survival analysis was utilized to compare the recanalization rate and the recurrence rate., Results: A total of 453 APS patients were enrolled, and 40 (8.8%) APS patients were with CVST. The median age of the APS-CVST patients was 27 (21.25, 32.75) years, and 72.5% were females. In 50% of these patients, CVST was the initial symptom of APS, with headache being the most prevalent clinical symptom (95%). Involvement of more than two venous sinuses were observed in 79.5% of patients, with the transverse sinus (79.5%) and sigmoid sinus (74.4%) being the most commonly affected sites. Oral contraceptives, intracranial infections and malignancy were identified as risk factors of APS-CVST. There were no statistically significant differences in baseline characteristics or the distribution of antiphospholipid antibodies profiles between the two groups. After a median follow-up of 24 (12, 52) months, 21 patients (52.5%) experienced recanalization, and 13 patients (32.5%) had a thrombotic recurrence. Survival analysis indicated that adequate anticoagulant therapy significantly contributed to recanalization (HR 6.27, 95% CI 2.616-15.02, P = 0.003), while continuous anticoagulant therapy was highly effective in reducing the recurrence of thrombotic events (HR 0.14, 95% CI 0.0447-0.4328, P = 0.0007)., Conclusion: CVST should be considered in APS patients who experience sudden onset headaches, particularly those with thrombotic risk factors, such as the use of oral contraceptives, intracranial infections and malignancy. Continuous and adequate anticoagulant therapy is pivotal and beneficial for achieving recanalization and prevention of recurrence. Key Points • The prevalence of CVST in patients with APS may be underestimated. • APS-CVST is associated with special risk factors, including pregnancy, intracranial infection, oral contraceptives and tumors. • Long-term and adequate anticoagulation therapy can increase the vascular recanalization rate and reduce thrombosis recurrence., Competing Interests: Declarations. Conflicting interests: All authors declare that there are no conflicts of interest., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy., Competing Interests: Disclosure of interest Dr. Emmerich reports he has no conflicts of interest. Dr. Zuily reports he has no conflicts of interest. Dr. Gouin-Thibault reports board membership or symposia from BMS, Bayer, Leo Pharma, Stago, Viatris. Dr. Couturaud reports having received research grant support from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, GlaxoSmithKline, Chiesi and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, Leo Pharma, Sanofi, Chiesi. Dr. Morange reports having research grant support from Bristol-Myers Squibb and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer and Sanofi. Dr. Huisman reports no conflicts of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: This study evaluates the endometrial receptivity of obstetric anticardiolipin syndrome (OAPS) patients using various ultrasound indicators and the efficacy of low-dose aspirin (LDA) treatment., Methods: This retrospective study recruited patients from Shanghai Ren Ji Hospital, China from January 2022 to December 2023. Doppler parameters of the endometrium and uterine artery blood flow were recorded to assess the endometrial receptivity of OAPS patients compared with normal pregnant women and an other immune diseases group. The receiver operating characteristic curve was used to predict the risk of OAPS patients. Doppler parameters of OAPS patients were conducted repeatedly after a 2-month period of treatment with LDA., Results: Compared with normal pregnant women, the OAPS group showed remarkably increased endometrial perfusion resistance (PI, RI, S/D) and uterine artery perfusion resistance (RI and S/D) (P < 0.001) and had good predictive values (area under the curve = 0.806, 0.976, 0.942, 0.902, and 0.901, respectively). The endometrial thickness of the OAPS group was much thinner than that of the normal group (P < 0.001). Uterine blood flow impedance PI showed no difference in both groups (P = 0.68). In comparison to other autoimmune diseases, the OAPS group also showed an increasing trend in the resistance of endometrium and uterine artery blood flow. After LDA treatment, there was an obvious improvement in the endometrial blood flow perfusion in the OAPS group (P < 0.01)., Conclusion: Compared with the normal group and other autoimmune diseases, the resistance of endometrial and uterine artery blood flow in the OAPS group was increased significantly. The Doppler index showed the predictive value of OAPS, and it was confirmed that LDA could enhance blood perfusion among OAPS women., (© 2024 International Federation of Gynecology and Obstetrics.)

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., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Antiphospholipid syndrome (APS) encompasses a range of clinical conditions, particularly thrombotic or obstetrical manifestations, associated with the presence of antiphospholipid antibodies. Managing thrombotic APS in daily clinical practice can be challenging and requires thorough risk stratification and tailored treatment strategies. Primary prophylaxis focuses on correcting the traditional thrombotic risk factors and, in certain situations, may include low‑dose aspirin and / or prophylactic anticoagulants (eg, low‑molecular‑weight heparin). Treatment of thrombotic APS primarily involves long‑term anticoagulation with vitamin K antagonists (VKAs). In some cases, a combination of VKAs and low‑dose aspirin, increased doses of VKAs with an international normalized ratio target greater than 3, or a switch to therapeutic doses of low‑molecular‑weight heparin might be employed. The use of hydroxychloroquine is essential in patients with secondary systemic lupus erythematosus and may be considered in individuals with recurrent thrombosis. In other selected situations, the use of immunomodulatory agents can be considered.

Rationale: Antiphospholipid antibody syndrome and protein S/C deficiency are diseases that are sometimes complicated by thrombus, and heparin-induced thrombosis (HIT) has also been reported., Patient Concerns: A male patient in his 60s with elevated D-dimer and superior mesenteric thrombus and portal vein thrombus underwent partial small intestine resection and thrombectomy. After administration of heparin, aortic thrombosis and pulmonary embolism occurred along with rapid thrombocytopenia., Diagnosis: The patient was diagnosed with HIT combined with protein S deficiency and antiphospholipid antibody syndrome., Interventions and Outcomes: Heparin administration was discontinued, and plasma exchange with fresh frozen plasma replacement and argatroban administration were started. These treatments reduced D-dimer, restored platelet counts, and improved thrombosis., Lessons: Although HIT alone can cause severe arteriovenous thrombosis, our case suggests that it is important to search for the underlying procoagulant factors., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Antiphospholipid syndrome (APS) is a state of hypercoagulability due to persistent antiphospholipid antibodies (aPLs) in the blood. Catastrophic APS (CAPS) is a severe form with higher morbidity and mortality in which there occurs widespread thrombosis in multiple organs and hence warrants early diagnosis and aggressive management. We report a case of pediatric CAPS with extensive cutaneous involvement precipitated by infection successfully treated with the combination of high dose systemic corticosteroids, antibiotics, long-term anticoagulation, and wound care., (© 2024 Wiley Periodicals LLC.)

Introduction: Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting., Materials and Methods: We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records., Results: 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding ( p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding ( p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009)., Conclusions: We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment., Case Report: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage., Conclusion and Importance: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage., Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3., Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I 2 = 46%, 95% CI [0.58-5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I 2 = 52%, 95% CI [1.04-7.90]), because it reduced the number of miscarriages (OR = 0.35, I 2 = 52%, 95% CI [0.13-0.96])., Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yuan et al.)

Introduction: Systemic Lupus Erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which manifests as recurrent thrombotic events or obstetric complications in presence of antiphospholipid antibodies. Hereby we present a case of a child who presented with low grade fever, superficial thrombophlebitis with mucosal bleeding and was diagnosed as Lupus Anticoagulant Hypoprothrombonemia Syndrome (LAHS)., Case: A 7-year-old girl was hositalized with complaints of fever and spontaneous bleeding from gums and epistaxis. On examination, she had multiple small tender nodular lesions with greenish hue of overlying skin suggesting superficial thrombophlebitis and mild non-tender hepatosplenomegaly. Her coagulogram revealed normal platelet counts and deranged PT and APTT. ESR and CRP were raised. Serology for viral infections, blood and urine cultures were negative. Patient had persistent coagulopathy, mucosal bleeding and low-grade fever despite supportive treatment. She was tested for anti-nuclear antibodies (ANA) in view of suspicion of autoimmune process. ANA was positive in high titer with speckled pattern on indirect immunofluorescence. Mixing studies showed correction of PT and non-correction of APTT. PT based factors were normal except for prothrombin (FII) which was low and remained low despite dilution. APTT based factors (FVIII and FIX) were low but corrected on dilution. This was suggestive of prothrombin deficiency and a presence of a nonspecific inhibitor of APTT pathway (likely lupus anticoagulant). Presence of antiprothrombin antibodies established the diagnosis of LAHS. ENA profile was positive for SmD1, Ro60 and Ku. Complement levels were low. Direct Coomb's test was positive but there was no evidence of hemolysis. Lupus anticoagulant by DRVVT and anti-cardiolipin antibodies by ELISA were positive. Patient was diagnosed as Systemic Lupus Erythematosus with Lupus Anticoagulant Hypoprothrombinemia Syndrome. She was treated with IV methylprednisolone. Patient showed significant improvement in form of resolution of fever, mucosal bleeding, correction of deranged INR and reversal of hypocomplementemia. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering doses of prednisolone. On follow up, child was doing well and her prothrombin time and complement levels had normalized. Low dose aspirin was aspirin was added for thromboprophylaxis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: This review offers an overview of the most important recent articles on pediatric APS., Recent Findings: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe characteristics of published research on the safety and efficacy of vitamin K antagonists (VKA) for pregnant patients with antiphospholipid antibodies (aPL), including their methodological characteristics and knowledge gaps., Methods: This study followed the Joanna Briggs Institute methodology for scoping reviews and used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol system. Studies were primarily identified through searching electronic databases including MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. Study characteristics and outcomes were reported and described using customized charting tables., Results: Of 1528 publications, 17 remained in the final analysis. These reported up to 190 VKA-treated aPL-positive pregnancies diagnosed as antiphospholipid syndrome (APS); pregnancy cases were likely overlapping in some publications. In the 17 reports, there were 723 individuals in comparison groups, including healthy pretreatment pregnancies and women with APS treated with standard therapies without VKA. However, only 4 (23.5%) of the 17 publications stated a study objective focusing on VKA use, of which only one was a full-length article. In addition, information on VKA doses, disease diagnostic criteria, and the long-term outcomes of offspring were largely absent., Conclusion: The current evidence is insufficient to assess VKA efficacy and safety profiles in aPL-positive pregnant patients. Studies with a defined focus on VKA use in this population are lacking, and reporting of key information is not consistent. The relative lack of knowledge of VKA use in pregnant women with APS is concerning, and efficacy and safety questions remain., (Copyright © 2024 by the Journal of Rheumatology.)

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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Patients with thrombotic antiphospholipid syndrome (APS) are at high risk for recurrent thrombosis, and indefinite anticoagulation is recommended. Patients with APS merit indefinite anticoagulation, and vitamin K antagonists (VKAs) have historically been the standard treatment. Direct oral anticoagulants (DOACs) present an appealing alternative to VKAs. Due to their pharmacokinetic and pharmacodynamic characteristics, DOACs offer advantages over VKAs, namely the lack of need for laboratory monitoring, the usage of a fixed dosage, and the absence of significant interaction with dietary components and drugs. The efficacy and safety of DOACs in patients with APS have been studied in four phase II/III clinical trials (three with rivaroxaban and one with apixaban). These studies showed DOACs' inferiority compared to VKAs in preventing recurrent thrombosis. Recurrence was significantly greater in patients with arterial thrombotic events and a triple positivity for antiphospholipid antibodies. No differences were observed in the incidence of venous thromboembolism between both groups. Major bleeding was similar in patients treated with DOACs or VKAs. Several observational studies have reported similar results. This review aims to analyse the existing evidence on the efficacy and safety of DOACs for secondary prevention in patients with APS.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Carrara, Mataj, Gastoldi, Ruggenenti, Sciascia and Roccatello.)

Antiphospholipid syndrome (APS) is an autoimmune disorder that presents with hypercoagulability and results in a lab artifact of prolonged PTT. The most severe form is catastrophic antiphospholipid antibody syndrome (CAPS), which manifests as rapidly progressing thromboses in multiple organ systems leading to multi-organ ischemia. The mainstay management CAPS is anticoagulation and systemic corticosteroids. Antifibrinolytic agents have previously been thought to be relatively contraindicated in CAPS due to the pro-thrombotic nature of the disease; the complex coagulation profile of CAPS can make it difficult to assess the risks and benefits of antifibrinolytic therapy. Also, should a patient with CAPS require cardiopulmonary bypass (CPB) for surgery, it poses a unique challenge in providing appropriate anticoagulation in the setting of prolonged ACT. We present a case of a 32-year-old postpartum female with CAPS requiring heart transplant who safely received intraoperative antifibrinolytic therapy and was successfully anticoagulated during CPB after perioperative plasmapheresis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Beta 2 glycoprotein I (β2GPI) is the major autoantigen in the antiphospholipid syndrome, an autoimmune disorder characterized by thrombotic and obstetric complications. The autoantibodies that target beta 2 glycoprotein I are pathogenic and contribute to disease pathogenesis. The β2GPI molecule is composed of 5 domains that are numbered 1 through to 5. Autoantibodies bind mainly to domain 1 whereas the majority of the biological functions of the β2GPI molecule in diverse processes such as apoptotic cell clearance, complement regulation, lipopolysaccharide clearance and anticoagulation have been localised to domain 5 and its unique biochemistry, reviewed in this article. The role of purified domain 5 peptide as a potential therapeutic agent in APS and ischemia reperfusion injury is discussed., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy., Case Presentation: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications., Conclusion: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Thrombotic manifestations, mainly venous thromboembolism (VTE) and stroke, are the most common and potentially life-threatening presentations of antiphospholipid syndrome (APS). The management of APS requires the assessment of the antiphospholipid antibodies (aPL) profile, of concurrent systemic lupus erythematosus or other systemic autoimmune diseases and the presence of risk factors for cardiovascular disease and bleeding. Anticoagulation with vitamin K antagonists (VKA) remains the cornerstone of therapy for thrombotic APS. As platelets play a central role in APS, low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers, and also plays a role as combination therapy with VKAs in arterial thrombosis. Treatment with direct oral anticoagulants (DOACs) could be considered in certain low-risk situations, although they are not recommended in patients with arterial thrombosis or triple positive aPL. Adjuvant therapies such as hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding. In this article, we review the evidence and the recommendations of the guidelines for the treatment of APS, and provide a critical and practical approach of its management from our clinical perspective., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by recurrent venous or arterial thrombosis and pregnancy complications, with persistent antiphospholipid autoantibodies. APS is often found in conjunction with other autoimmune diseases, such as systemic lupus erythematosus (SLE). SLE-associated APS patients may require dental procedures like tooth extractions. Due to the complex nature of this autoimmune disorder, perioperative management requires a comprehensive approach involving various medical specialists.These patients are frequently taking medications like anticoagulants, antiplatelet drugs, disease-modifying drugs and immunosuppressants. This medication regimen can increase their risk of postoperative complications, including bleeding, thrombosis, delayed healing and postoperative infections. Currently, there are no established guidelines for performing tooth extractions in individuals with SLE-associated APS.We report a case of SLE-associated APS with pericoronitis requiring surgical extraction. The purpose of this report is to offer practical recommendations for the perioperative management of dental procedures and alteration in medications used in such cases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis., (© 2024. The Author(s).)

Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and APS., Methods: We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e. NETosis) and venous thrombosis in lupus and APS., Results: At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production and large-vein thrombosis., Conclusion: Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban., Competing Interests: A. Undas received lecture honoraria from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, and Sanofi-Aventis. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) were significantly upregulated. Here, we found that neutrophils from patients with APS used glycolysis more avidly than neutrophils from people in the healthy control group, especially when the neutrophils were from patients with APS with a history of microvascular disease. In vitro, inhibiting either glycolysis or the PPP tempered phorbol myristate acetate- and APS IgG-induced NETosis, but not NETosis triggered by a calcium ionophore. In mice, inhibiting either glycolysis or the PPP reduced neutrophil reactive oxygen species production and suppressed APS IgG-induced NETosis ex vivo. When APS-associated thrombosis was evaluated in mice, inhibiting either glycolysis or the PPP markedly suppressed thrombosis and circulating NET remnants. In summary, these data identify a potential role for restraining neutrophil glucose flux in the treatment of APS.

Introduction: Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple-positive antiphospholipid syndrome (APS)., Methods: Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents., Results: Ninety seven of 116 (83.6%) were dRVVT- and APTT-positive, 85/97 (87.6%) of which were TSVT/ET-positive, 9/116 (7.8%) were dRVVT-positive only, 6 of which were TSVT/ET-positive, and 10/116 (8.6%) were APTT-positive only, 5 of which were TSVT/ET-positive. 96/116 TSVT/ET-positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti-β 2 -glycoprotein I antibody titres for all three LA assays., Conclusions: TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS., (© 2024 John Wiley & Sons Ltd.)

Antiphospholipid antibody syndrome is an autoimmune condition with clinical manifestations of vascular thrombosis and adverse pregnancy outcomes including recurrent miscarriage, fetal loss, growth restriction and pre-eclampsia with persistent antiphospholipid antibodies on laboratory examination. Treatment is targeted at preventing recurrent thrombosis and improving pregnancy outcomes. Commonly, treatment includes aspirin and anticoagulation, however, newer immunomodulatory treatments may also improve outcomes. The case describes a patient with a history of multiple miscarriages and pregnancy losses, fetal growth restriction and pre-eclampsia, and pulmonary embolism. Because of her significant adverse pregnancy outcomes, she was treated with certolizumab with a successful delivery at 33 weeks and 6 days. She also developed acute pancreatitis in the postpartum period. This is a rare condition, affecting 1-14/10 000 births. The pancreatitis resolved with conservative management, and she had an uncomplicated interval cholecystectomy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombosis is one of the many signs of antiphospholipid syndrome (APS) and COVID-19 infection. Although the mechanisms contributing to thrombosis in APS and COVID-19 are relatively similar, this remains an open subject. Even now (when the COVID-19 pandemic has subsided), there is no conclusive solution to APS and COVID-19 co-occurrence. The presence of newly generated antiphospholipid antibodies (aPLs) in COVID-19 infection may or may not be connected to the diagnosis of APS. The prevalence of aPLs is substantial in severe COVID-19 but not related to thrombosis or a worse outcome. Adequate monitoring of antibody positivity over time is recommended for APL diagnosis. On the other hand, thrombosis and thrombocytopenia can rarely occur with vaccination with mRNA vaccines. Some studies have shown that COVID-19 immunization is well tolerated among APS patients who are triple-positive for aPL, which may comfort patients and referring physicians and lessen hesitation in unvaccinated APS/aPL-positive patients. In this narrative review, we will give an overview of the interaction between aPL-APS-COVID-19-thrombosis and related diagnostic insights learned during the pandemic., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aβ2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: There were no conflicts of interest for Dr. Bakow and Lisa Yanek. Dr. Chaturvedi has received honoraria for consulting or advisory board participation from Alexion, Sanofi Genzyme, Sobi, Takeda, and UCB pharmaceuticals. Her institution has received research funding on her behalf from Takeda. She has also received honoraria/royalties from UpToDate.com and Dynamed,com. In the last 36 months, Dr. Crowther has received Personal Funding or has sat on Advisory Boards for Astra Zeneca, Hemostasis Reference Laboratories, Syneos Health, and Eversana. He has prepared educational materials and/or presented talks for Bayer, Pfizer, and CSL Behring. He has participated in various medicolegal activities relating to thrombosis, anticoagulant drugs, or other aspects of hematological practice. He has also worked with multiple for-profit and not-for-profit entities such as Up To Date and medical communication companies. He holds the Leo Pharma Chair in Thromboembolism, endowed at McMaster University., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antiphospholipid syndrome nephropathy includes a variety of histological lesions, including thrombotic microangiopathy, which is not included among the diagnostic criteria of antiphospholipid syndrome. Whereas in secondary antiphospholipid syndrome, e.g. to systemic lupus erythematosus, there is emerging evidence of a benefit from complement blockade with eculizumab, optimal treatment of primary antiphospholipid syndrome-associated thrombotic microangiopathy is currently unknown. We report the case of a 36-year-old male patient with primary antiphospholipid syndrome-associated thrombotic microangiopathy, presenting with a clinical picture of atypical hemolytic-uremic syndrome with frequent relapses, treated with eculizumab (four 900 mg weekly doses followed by 1200 mg fortnightly infusions) leading to resolution of hemolysis, long-term remission and partial kidney function recovery (peak serum creatinine 3.8 mg/dL, decreased and stabilized around 2.5 mg/dL) over a follow up period of over 2 years., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice., Objectives: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups., Patients/methods: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model., Results: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01)., Conclusion: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation., Competing Interests: Declaration of competing interest Authors had no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The objective of the study was to compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment., Methods: We conducted a single-arm, open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e. heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for 5 days) was added to conventional treatment. The primary outcome was a live birth ratio of >30 weeks of gestational period, and the secondary outcome included improving pregnancy outcomes compared to previous pregnancy., Results: Twenty-five per cent of patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG., Conclusions: This clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome characterised by diffuse arterial and venous thrombosis, in the presence of positive antiphospholipid antibodies. The multiple sites of thrombosis in small, medium and large vessels progress to multiorgan failure, accounting for the high mortality rate associated with CAPS. Unregulated complement activation is increasingly recognised as critical to the pathogenesis of CAPS. Early diagnosis is essential to initiate prompt life-saving treatment with the triple therapy of anticoagulation, immunosuppression and either plasmapheresis or intravenous immunoglobulin. Among other immunosuppressive agents, eculizumab, a complement inhibitor has demonstrated efficacy in treatment-resistant cases.We report an instructive case of a woman presenting with both clinical and laboratory findings consistent with primary CAPS, resistant to initial treatment and responsive to eculizumab, with emphasis on genetic testing and implications for future therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)