RESUMEN

Key Clinical Message: Recurrence of valvular involvement may occur after Libman-Sacks endocarditis surgery, emphasizing the need for frequent multivalvular evaluations with echocardiography or more sensitive methods to optimize surgical outcomes. Abstract: This report presented a 32-year-old woman, complaining of recurrent fever and chills. Physical examination revealed the presence of a third heart sound (S3), a pan-systolic murmur (III/VI) at mitral and tricuspid foci, tachycardia, and fine pulmonary crackles. Transesophageal echocardiography (TEE) revealed severe mitral regurgitation (MR) and moderate tricuspid regurgitation (TR) with vegetations on the mitral valve. Initially, intravenous antibiotic therapy was started simultaneously with diagnostic studies. Despite a positive TEE, negative blood cultures on three separate occasions precluded meeting the diagnostic criteria outlined in the modified Duke criteria. Moreover, the patient's condition continued to deteriorate after antibiotic therapy, leading to the diagnosis of Libman-Sacks endocarditis. The patient was considered a candidate for mitral valve surgery. All vegetations were completely debrided and then the mitral valve was reconstructed. Follow-up post-surgery echocardiography revealed the absence of MR and mitral stenosis (MS). Four months later, the patient presented again complaining of fatigue, dyspnea, lower extremity edema, and ascites with evidence of pulmonary hypertension and right heart failure on physical examination. TEE was performed, which revealed severe MR, severe TR, detached artificial chordae, and blood leak from the perforated pericardial patch. Therefore, she was necessitated for valvular surgery and underwent mitral and tricuspid valve surgery. The mitral ring and perforated pericardial patch were removed, and a mitral prosthetic valve was implanted. In addition, the tricuspid valve was repaired. Follow-up post-surgery echocardiography revealed the absence of MR and TR. To our knowledge, this is the first case of LSE recurrence with multi-valvular involvement.

RESUMEN

BACKGROUND: Antiphospholipid syndrome (APS) is a chronic autoimmune disease characterized by venous or arterial thrombosis, pregnancy morbidity and a variety of other autoimmune and inflammatory complications. Here, we report a case of APS associated with multiple coronary thromboses. CASE SUMMARY: The patient, a 28-year-old male, suffered from recurrent coronary thromboses over a period of 31 months. Despite undergoing interventional coronary procedures, thrombolytic therapy, and anticoagulation treatment, the condition persisted intermittently. An extensive search for underlying thrombogenic factors revealed a diagnosis of APS. Accurate adjustment of the medication regimen led to the absence of further acute coronary syndrome (ACS) episodes during the subsequent 20-month follow-up. Although the patient occasionally experiences chest tightness, no further symptoms of distress have been reported. CONCLUSION: APS can manifest as ACS. Screening for rheumatologic and immunological conditions is essential when encountering patients with multiple coronary thromboses. Treatment strategy should include symptomatic relief and a targeted and aggressive approach to address the underlying pathophysiology.

RESUMEN

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.

RESUMEN

Psychiatric disorders are reported to be associated with systemic inflammatory conditions and autoimmune diseases. Antiphospholipid syndrome (APS) is a rare condition with poorly understood prevalence and incidence in the general population. Case reports have described co-occurrences of psychiatric conditions and APS. Previous case reports have indicated that patients with APS can have comorbid psychosis, anxiety, depression, and other psychiatric conditions. The association between APS and psychiatric illness, however, remains under-investigated in longitudinal studies. In this report, we present the case of a woman in her 40s who was voluntarily admitted to the psychiatric inpatient unit for treatment of auditory hallucinations within the context of borderline personality disorder. She reported a rather extensive medical and psychiatric history of several previous illnesses, musculoskeletal injuries, and hospitalizations. Due to the significant social stress and multiple comorbidities, she may be at increased vulnerability to acute exacerbations of both APS and brief psychotic episodes. In this case report, the patient had a history of three hypercoagulability incidents that were shortly followed by psychiatric admissions. This report highlights the importance of considering systemic conditions such as APS in patients presenting with psychiatric illness. Patients with APS and concomitant psychosis may benefit from screening for APS flares in the case of a psychotic break.

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) that predispose individuals to thrombotic events and pregnancy-related complications. APS can occur as a primary condition or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Catastrophic APS (CAPS) is a rare, severe variant of APS, marked by rapid-onset, widespread thrombosis leading to multi-organ failure, often triggered by infections, surgical procedures, or cessation of anticoagulation therapy. Both APS and CAPS present significant clinical challenges due to their potential for severe morbidity and mortality. This comprehensive review aims to provide a detailed overview of the pathogenesis, clinical features, diagnostic criteria, and management strategies for APS and CAPS. The review highlights the immunological mechanisms underlying APS, including the role of aPLs, complement system activation, and endothelial cell dysfunction in developing thrombosis. It also outlines the clinical manifestations of APS, such as venous and arterial thrombosis, pregnancy morbidity, and neurological symptoms, along with the diagnostic criteria based on clinical and laboratory findings. The review delves into its pathogenesis, clinical presentation, and diagnostic challenges in the context of CAPS, emphasizing the need for immediate and intensive therapy to manage this life-threatening condition. Current management strategies for APS, including anticoagulant therapy, immunomodulatory treatments, and specific interventions for pregnancy-related complications, are discussed. The review highlights the importance of a multidisciplinary approach for CAPS, combining anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. The review also addresses the prognosis and long-term outcomes for patients with APS and CAPS, underlining the necessity for ongoing monitoring and follow-up to prevent recurrent thrombotic events and manage chronic complications. Finally, future directions in research are explored, focusing on emerging therapies, biomarkers for early diagnosis, and the need for clinical trials to advance the understanding and treatment of these complex syndromes. By enhancing the understanding of APS and CAPS, this review aims to improve diagnosis, treatment, and patient care, ultimately leading to better health outcomes for those affected by these conditions.

RESUMEN

Objective: The signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) syndrome (STAT3-GOF) is an inborn error of immunity (IEI) characterized by diverse manifestations of immune dysregulation that necessitate systemic immunomodulatory treatment. The blockade of the interleukin-6 receptor and/or the inhibition of the Janus kinases has been commonly employed to treat diverse STAT3-GOF-associated manifestations. However, evidence on long-term treatment outcome, especially in the case of adult patients, is scarce. Methods: Clinical data, including laboratory findings and medical imaging, were collected from all seven patients, diagnosed with STAT3-GOF, who have been treated at the Hannover University School, focusing on those who received a Janus kinase (JAK) inhibitor (JAKi). Previously published cases of STAT3-GOF patients who received a JAKi were evaluated, focusing on reported treatment efficacy with respect to diverse STAT3-GOF-associated manifestations of immune dysregulation and safety. Results: Five out of seven patients diagnosed with STAT3-GOF were treated with a JAKi, each for a different indication. Including these patients, outcomes of JAKi treatment have been reported for a total of 41 patients. Treatment with a JAKi led to improvement of diverse autoimmune, inflammatory, or lymphoproliferative manifestations of STAT3-GOF and a therapeutic benefit could be documented for all except two patients. Considering all reported manifestations of immune dysregulation in each patient, complete remission was achieved in 10/41 (24.4%) treated patients. Conclusions: JAKi treatment improved diverse manifestations of immune dysregulation in the majority of STAT3-GOF patients, representing a promising therapeutic approach. Long-term follow-up data are needed to evaluate possible risks of prolonged treatment with a JAKi.

Asunto(s)

RESUMEN

BACKGROUND: Ovulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear. MATERIALS AND METHODS: A retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared. RESULTS: 121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive ß-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle. CONCLUSION: Ovarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation.

RESUMEN

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.

RESUMEN

Catatrophic antiphospholipid syndrome (CAPS), a rare variant of antiphospholipid syndrome (APS), is associated with rapid multiorgan failure. While APS is associated with single medium-to-large blood vessel occlusions, CAPS is most often associated with several, concurrent vascular occlusions of small vessels, commonly of the kidneys, heart, skin and brain. We present a case of a 21-year-old female patient with a history of immune thrombocytopenia purpura and APS, who eventually developed concurrent cerebral venous sinus thrombosis, diffuse alveolar haemorrhage, renal thrombotic microangiopathy, and a necrotic, vasculitic wound on her forearm. Despite hospitalisation and treatment, her condition worsened and the patient eventually died after succumbing to suspected CAPS.

Asunto(s)

RESUMEN

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.

RESUMEN

OBJECTIVES: This study aims to evaluate the utility of the 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria in identifying primary APS patients at high risk of complications. METHODS: In this single-center study, primary APS patients were classified according to both the revised Sapporo criteria and the 2023 ACR/EULAR criteria. The risk of complications was assessed using the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). RESULTS: Forty-five patients (73% females, median age 49 years) were included. Thirty-six patients met the 2023 ACR/EULAR criteria, all of whom also fulfilled the revised Sapporo criteria. Additionally, four out of nine patients not meeting the 2023 ACR/EULAR criteria satisfied the revised Sapporo criteria. Agreement rate between the two classification criteria was 91%, with a Cohen's kappa index of 0.66. Patients meeting the 2023 ACR/EULAR criteria had significantly higher aGAPSS scores compared to those who did not (13, 8-13 vs. 3, 0-5; p = 0.005). Furthermore, 55% of patients meeting the 2023 ACR/EULAR criteria were categorized as high risk based on aGAPSS scores, while those not meeting the criteria were predominantly categorized as low risk (77%). Interestingly, patients not meeting the 2023 ACR/EULAR criteria but fulfilling the revised Sapporo criteria had significantly higher aGAPSS scores compared to those not meeting either set of criteria (7, 5-13 vs. 0, 0-1.5; p = 0.015). CONCLUSION: The 2023 ACR/EULAR criteria effectively identify primary APS patients at increased risk of complications, as indicated by the aGAPSS score. Key Points • Identifying primary APS patients at high risk of complications remains a significant challenge. • The 2023 ACR/EULAR criteria show a correlation with the aGAPSS score, exhibiting the highest correlation with laboratory domains and minimal correlation with clinical domains. • The 2023 ACR/EULAR classification criteria are effective in identifying primary APS patients at high risk of complications.

RESUMEN

IMPORTANCE: Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations. OBSERVATIONS: This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation. CONCLUSIONS AND RELEVANCE: The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

Asunto(s)

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians' understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.

Asunto(s)

RESUMEN

INTRODUCTION: The gut microbiome is recognized as a factor that could potentially contribute to the persistent antibodies of antiphospholipid syndrome (APS). Gut microbial interventions can both induce and mitigate APS in mice. In human APS patients, anti-beta-2-glycoprotein I (ß2GP-1) titers correlate with antibody titers against a gut commensal protein homologous to ß2GP-1. AIM: To  investigate the effect of the intestinal microenvironment on human APS. Methods We cross-sectionally compared intestinal microbiota composition quantified by shotgun sequencing; fecal short chain fatty acids (SCFAs), bacterial metabolites known to affect autoimmune processes; and fecal calprotectin, an intestinal inflammatory marker, in APS patients and healthy controls. RESULTS: Neither alpha nor beta diversity of the gut microbiota differed between APS patients (n = 15) and controls (n = 16) and no taxa were differentially abundant. Moreover, fecal SCFAs and fecal calprotectin, did not differ between the groups. CONCLUSION: Gut microbiome effects on the APS phenotype are likely not driven by bacterial overabundance, SCFA production or intestinal inflammation.

RESUMEN

Castleman disease (CD) comprises a rare spectrum of disorders characterized by benign lymphoepithelial proliferation, classified into unicentric and multicentric forms. The idiopathic multicentric Castleman disease (iMCD) subtype, specifically, is challenging to diagnose and treat due to its variable manifestations and unpredictable disease course. We report a case of a 23-year-old female with a history of iron deficiency anemia presenting with concurrent antiphospholipid syndrome (APS) and human herpesvirus-6 (HHV-6) positivity. Investigations revealed a gastric mass, with a biopsy suggestive of the plasma cell variant of CD. This case report aims to understand the possible association of HHV-6 positivity with CD and the significance of diagnosing APS early in patients with the disease. Treatment with siltuximab and tocilizumab proved effective, highlighting the role of interleukin 6 (IL-6) in the elusive etiology of this condition.

RESUMEN

Posterior reversible encephalopathy syndrome (PRES) is a neurological disease characterized by a variety of neurological findings, in accordance with radiological characteristics. PRES is commonly secondary to elevated BP and/or conditions such as autoimmune patients receiving immunosuppressive drugs. Our case involves a 36-year-old female with a history of autoimmune hepatitis (AIH), who presented with sudden onset headaches from 3 weeks prior, and a single episode of seizure attack the morning before admission. In the initial examination she had highly elevated blood pressure (BP) (190/116). Her neurological examination revealed decline in force of limbs in addition to mild paresthesia. After primary stabilization, she underwent brain magnetic resonance imaging. Due to the clinical and radiological findings, the patient was diagnosed with PRES. In the following work-up of BP elevation, abdominopelvic sonography and subsequent computed tomography scan, multiple lesions were observed in spleen and both kidneys consistent with infarction. In further evaluation, Lupus-like anticoagulants were found to be elevated, which, in conjunction with the confirmed antiphospholipid syndrome (APS), suggested a possible role for APS-nephropathy as the missing link between PRES and APS. However, despite the role of an autoimmune disease in increasing the risk of developing other autoimmune conditions, APS and AIH have been rarely observed together. Our study indicates that developing APS in the context of AIH is a rare occurrence. However, APS could serve as a critical intermediary, potentially facilitating the onset of PRES despite lower BP.

RESUMEN

Antiphospholipid syndrome is an immunopathologic disorder that should be considered in all patients with recurrent and/or unexplained thromboembolic events. Antiphospholipid antibodies are diagnostic markers, and anticoagulation therapy is the therapeutic and preventive strategy. Long-term anticoagulation therapy is necessary, with careful attention to potential bleeding complications.

RESUMEN

Background The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. Objective To evaluate whether the gut microbiome affects disease activity in human APS. Methods This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. Results A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( p = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( p = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.

RESUMEN

OBJECTIVE: Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time, kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects. METHODS: We performed RNA-sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n = 4) SLE (n = 5), and control (n = 3) individuals, differential gene expression analysis (DGEA), and enrichment analysis using gene ontology (GO), and CORUM, KEGG and Reactome pathway databases. RESULTS: Two-dimensional projection showed a distinct gene profile in primary APS vs control kidneys samples, but similar to SLE. DGEA in APS vs controls returned 276 upregulated and 217 downregulated genes, while the comparison between APS and SLE identified 75 upregulated and 111 downregulated genes. In 276 upregulated genes, enriched GO terms were (innate) immune response, inflammatory response, leucocyte and lymphocyte activation, cytokine production and T cell activation. CORUM and KEGG revealed complement-related genes (C3, C4A, C4B). Expression levels showed logFC values of 2.25 (p= 1.58e-05) for C3, 2.17 (p= 2.69e-06) for C4A, and 2.135 (p= 3.7e-06) for C4B in APS vs controls, without differences between APS and SLE. Interferon (IFN) alpha/beta signalling was revealed by Reactome. Expression levels of nine IFN-regulated genes found upregulated in APS vs control kidneys (p-values ≤ 0.001 for all). Examining neutrophil-extracellular traps (NETs)-related gene expression, 13 of 15 upregulated NETs-related genes exhibited higher expression in APS vs controls but not vs SLE. CONCLUSION: Complement, interferon and NETs-related genes are highly expressed in APS kidney tissues, similarly to SLE, pointing out the role of innate immunity in APS nephropathy pathogenesis and potential treatment targets.

RESUMEN

Background: Life-long vitamin K antagonist (VKA) therapy is recommended as a standard of care in antiphospholipid syndrome (APS) patients with thrombosis. Concerns have been raised about the validity of international normalized ratio (INR) measurements in lupus anticoagulant (LA)-positive APS patients because LA may interfere with phospholipid-dependent coagulation tests and could elevate INR measurements. Objectives: Here, we aimed to determine the interference of antigen-specific monoclonal and isolated patient antibodies with LA activity on INR measurements. Methods: Pooled normal plasma and control plasma from patients on VKA (without LA) were incubated with monoclonal and isolated patient immunoglobulin G antiprothrombin and anti-beta-2-glycoprotein I antibodies that express LA activity. INR was determined before and after addition using 3 laboratory assays (Owren STA-Hepato Prest, Quick STA-NeoPTimal, and Quick STA-Neoplastine R) and 1 point-of-care test device (CoaguChek Pro II). Results: Antiprothrombin and anti-beta-2-glycoprotein I antibodies with LA activity interfered with recombinant human thromboplastin reagents (Quick STA-Neoplastine R and CoaguChek Pro II), particularly when added to plasma of VKA-treated controls. This effect was most evident on point-of-care test INR measurements, while the recombinant Quick reagent exhibited a lesser degree of interference. In contrast, tissue-derived thromboplastin reagents (Owren STA-Hepato Prest and Quick STA-NeoPTimal) remained largely unaffected by these antibodies, both in pooled normal plasma and VKA anticoagulated control plasma. Among these reagents, the Owren INR reagent exhibited the lowest sensitivity to the influence of LA antibodies. This observed difference in sensitivity is independent of the plasma dilution factor or the presence of factor V or fibrinogen in Owren reagent. Conclusion: INR reagents that utilize recombinant human thromboplastin are more sensitive to the presence of monoclonal and patient-derived antibodies with LA activity. Consequently, APS patients positive for LA should be monitored using tissue-derived thromboplastin reagents, given its reduced susceptibility to interference by LA-causing antibodies.