Antiphospholipid Syndrome Research Articles

RISCO OBSTÉTRICO ASSOCIADO ÀS TROMBOFILIAS ADQUIRIDAS: UMA REVISÃO BIBLIOGRÁFICA

Introduction: Acquired thrombophilias, particularly antiphospholipid syndrome (APS), are conditions associated with a significant increase in obstetric morbidity. These conditions have been correlated with a range of pregnancy complications, including recurrent miscarriages, preeclampsia, intrauterine growth restriction, stillbirths, and thromboembolic complications. Understanding acquired thrombophilias is crucial for the appropriate management of affected pregnant women, aiming to reduce maternal and fetal risks. Objective: The objective of this study is to review recent literature on the relationship between acquired thrombophilias, with an emphasis on antiphospholipid syndrome, and adverse pregnancy outcomes. Additionally, the study aims to evaluate the most commonly used diagnostic methods for identifying these conditions, as well as discuss available therapeutic approaches, including the use of anticoagulants and other clinical interventions. Methodology: This is a literature review conducted from publications indexed in the PubMed database, focusing on the years 2020 to 2025. Studies specifically addressing pregnancy in women with acquired thrombophilia, particularly APS, were included, excluding those related to hereditary thrombophilias or non-pregnant populations. The selection of articles considered the most relevant clinical, diagnostic, and therapeutic aspects. Results: The results of the analysis indicate that the combination of low-dose aspirin and heparin is one of the most effective therapeutic approaches, being associated with better live birth rates in pregnant women with APS. Moreover, comorbid factors such as obesity, immune alterations, and a history of thrombosis may exacerbate the negative effects of thrombophilias, increasing the risk of obstetric complications. Studies also highlight the importance of continuous monitoring and early diagnosis, which are essential for proper management. Conclusion: Early diagnosis of acquired thrombophilias, combined with a multidisciplinary therapeutic approach, can significantly contribute to reducing risks for both the mother and the fetus. Preventive strategies, such as the combined use of anticoagulants and careful monitoring during pregnancy, are key to improving obstetric outcomes. A review of clinical practices and the personalization of treatment are essential elements for therapeutic success.

Effects of telitacicept in SLE patients with antiphospholipid antibody positivity: a retrospective self-controlled case series.

Antiphospholipid antibody (aPL) is closely related to the manifestation of antiphospholipid syndrome (APS) and an increased risk of thrombosis in systemic lupus erythematosus (SLE) patients. Telitacicept is a new dual B cell inhibitor which has been approved in China to treat SLE, but its application in APS or aPL-positive patients is still lacking. This study aimed to observe the effects of telitacicept in SLE patients with aPL positivity. It is a retrospective self-controlled case series study on SLE patients with aPL positivity who received telitacicept at a Chinese medical center during June 2021 to March 2023. Demographical information, clinical and immunological characteristics, and aPL profiles were gleaned from the electronic medical records system, and response of aPL profiles to telitacicept treatment was analyzed. Sixteen SLE patients were included. Eight of them were definite APS, and the other eight patients were aPL carriers. After 6months of telitacicept administration, significant improvements were observed in parameters representing SLE disease activity, including SLEDAI-2K, anti-dsDNA antibody levels, and complement levels. Meanwhile, we observed significant decreases in aPL levels that had not been previously reported. LAC normalized ratios significantly decreased from baseline after telitacicept treatment for 6months (dRVVT: 1.86 (1.24, 2.80) vs. 1.44 (1.11, 1.94), P = 007; SCT: 1.76 (1.28, 3.23) vs. 1.36 (1.06, 2.01), P = 0.010). The titer of aCL IgG decreased from 196.6 (54.58, 328.85) to 90.20 (15.6, 202.20) CU, and anti-β2GPI IgG decreased from 828.70 (51.60, 2490.80) to 211.10 (18.40, 422.50) CU after 6months of telitacicept treatment (P-value 0.005 and 0.013, respectively). Interestingly, a rebound tendency in aPL titers was observed after telitacicept withdrawal. No thrombosis events or pregnancy morbidities occurred, and no serious adverse events or death happened during treatment. Telitacicept may be an effective and safe option for patients with persistent aPL. Further well-designed prospective cohort studies are needed to confirm these findings. Key Points • Telitacicept is effective to lower aPL titers and promote aPL seroconversion, which may provide potential for the application of telitacicept in APS by reducing aPL-related events. • No thrombosis events and serious adverse events happened in aPL-positive patients during telitacicept treatment.

Brain atrophy is associated with antiphospholipid antibody syndrome with and without vascular pathology.

Brain atrophy is associated with antiphospholipid antibody syndrome with and without vascular pathology.

Investigating the association between antiphospholipid syndrome and ovarian reserve: A systematic review and meta-analysis of the literature.

BackgroundAutoimmune diseases can reduce ovarian reserves. Women in reproductive ages are susceptible to an autoimmune disorder known as antiphospholipid syndrome (APS). The aim of this study is to investigate the association between APS and ovarian reserve (OR).MethodPubMed, Scopus, Web-of-Science, Science Direct, and the Google scholar search engine were searched (22 June 2024) for studies that investigated the effect of APS on OR. Literature screening, data extraction, and assessment of the risk of bias of the included studies were conducted by two reviewers independently. Mean differences were computed using a random effects model. Heterogeneity was assessed by I2%.ResultsFour cross-sectional studies were included in this meta-analysis. None of the studies had a high risk of bias. There was no significant association identified between primary (MD = -0.27, 95% CI, -1.42 to 0.87, p = 0.639) and secondary APS (SMD = -0.38, 95% CI, -2.46 to 1.69, p = 0.717) with antimullerian hormone amounts. The antral follicle count (AFC) was investigated in two studies revealed lower levels of AFC in women with primary APS. Regarding the levels of gonadotropins and estradiol in the participants' serum, the results are contradictory.ConclusionsThe results of this meta-analysis identified there is no relationship between primary and secondary APS with the reduction of ovarian reserves in women with APS. This issue should be considered in the reproductive health of women with APS, who can have children at the right time by consulting a rheumatologist and reproductive health specialist.

Clinical significance of the determination of antibodies to the NR2 subunit of glutamate N-methyl-D-aspartate receptors (aNMDAR) in patients with systemic lupus erythematosus and antiphospholipid syndrome

The aim – to determine the clinical significance of hyperproduction of antibodies to the NR2 subunit of glutamate N-methyl-D-aspartate receptors (aNMDAR) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).Material and methods. The study included 66 patients with reliable diagnoses of SLE and APS (SLE – 24 patients; SLE+APS – 18 patients, primary APS – 24 patients). Young women (35.5±10.2 years) prevailed (72.7%). All patients were examined according to the standards recommended by the Association of Rheumatologists of Russia, and also examined by a psychiatrist. Neuropsychiatric syndromes, mainly psychiatric, were detected in 62 (93.9%) patients. aNMDAR was determined in all patients and 20 healthy donors, matched by gender and age, by enzyme immunoassay in blood serum.Results. The concentration of aNMDAR in patients with neurological manifestations of SLE and APS did not exceed the threshold value, but was significantly higher than in healthy donors (4.32±2.0 versus 2.96±1.44 ng/ml, respectively; p=0.042). Patients with elevated aNMDAR concentrations had a statistically significantly higher (p<0.05) probability of detecting neurological manifestations such as acute/transient cerebrovascular accident/epilepsy (odds ratio (OR) – 9.0), as well as bipolar affective disorder (OR=14.0), and statistically not significantly – schizotypal disorder (OR=3.8) and moderate cognitive impairment (organic type) (OR=2.15). The probability of detecting APS in patients with elevated aNMDAR values was 1.7 times higher, the risk of thrombosis according to the GAPSS (Global Anti-Phospholipid Syndrome Score) was 4.28 times higher, and aPL positivity (aCL, aß2GP-1, aFs/Pt) and a-ds-DNA – 2.5–6.73 times (the differences were not statistically significant).Conclusion. aNMDAR may play an important role in the development of certain neuropsychiatric manifestations in patients with SLE and APS. It is advisable to conduct larger-scale studies aimed at confirming the need to identify aNMDAR as a biomarker for the diagnosis and monitoring of the progression of neuropsychiatric manifestations of SLE and APS.

Pediatric antiphospholipid syndrome: expanding our understanding of antiphospholipid syndrome in children.

Antiphospholipid syndrome (APS) is an autoimmune, thromboinflammatory disease, which affects children and adults. There are particular features of the disease and nuances to diagnosis and management in a pediatric population, which must be appreciated to improve clinical care. Pediatric-specific epidemiological studies highlight that pediatric APS is quite rare with incidence in some populations of 0.2 per 100 000. There are new classification criteria in APS, which include a wider range of clinical features increasingly identified in registry data and case series of pediatric APS, though validation in pediatric APS is still needed. There is a particularly high proportion of pediatric APS patients with noncriteria antiphospholipid antibodies (aPL). Recurrent thrombosis is especially common in pediatric APS, highlighting the difficulty of management of this disease with high morbidity in children. Recent research has enhanced understanding of pediatric-specific APS epidemiology, laboratory findings, the wide variety of clinical features, and challenges in successful treatment. Future directions could include evaluation of potentially unique features in pediatric pathophysiology, an evaluation of the new APS classification criteria in children, broader prospective data on clinical and laboratory features, and a continued search for treatment beyond committing young patients to lifelong anticoagulation.

Diagnostic, research, and real-life effect of the 2023 EULAR-ACR classification criteria for antiphospholipid syndrome.

Diagnostic, research, and real-life effect of the 2023 EULAR-ACR classification criteria for antiphospholipid syndrome.

Who are we bridging? Description of warfarin patients receiving injectable bridging therapy.

Who are we bridging? Description of warfarin patients receiving injectable bridging therapy.

Myocardial infarction in a young patient with antiphospholipid syndrome: A case report

Myocardial infarction in a young patient with antiphospholipid syndrome: A case report

RETINAL VASCULITIS IN A PATIENT WITH HANSEN DISEASE.

Hansen disease is endemic in over 140 countries worldwide and a potentially blinding condition. The authors describe a case of retinal vasculitis in a patient with Hansen disease with concomitant positive antiphospholipid antibody serology, a potentially underreported complication in this setting. A 37-year-old Brazilian man systemically stable on triple therapy (clofazimine, rifampin, and dapsone) for Hansen disease presented for a comprehensive ophthalmic evaluation. Dilated examination revealed diffuse peripheral intraretinal hemorrhages in his right eye. Fluorescein angiography showed peripheral nonperfusion, abnormal shunt vessels and leakage from the retinal veins in the right eye, and peripheral nonperfusion and vascular leakage in the fellow eye, consistent with vasculitis. Laboratory workup was notable for positive antiphospholipid antibodies (lupus anticoagulant, anticardiolipin immunoglobulin M (IgM), and anti-beta-2 glycoprotein 1 IgM) and normocytic anemia. As antiphospholipid antibodies are present in a large proportion of patients with Hansen disease, it is possible that retinal vasculitis may be more common than previously thought. The extent to which retinal vasculitis occurs in patients with Hansen disease remains uncertain and possibly underestimated due to the frequency of anterior segment scarring, which impedes retinal evaluation. Heightened surveillance for potential retinal vascular complications is warranted.

S-hydroxychloroquine prevents the antiphospholipid thrombogenic complexes for antiphospholipid syndrome treatment.

S-hydroxychloroquine prevents the antiphospholipid thrombogenic complexes for antiphospholipid syndrome treatment.

An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies: reply

An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies: reply

Cognitive dysfunction in systemic lupus erythematosus: Its relationship with intracerebral volumes and antiphospholipid antibody profile. Case series

Cognitive dysfunction in systemic lupus erythematosus: Its relationship with intracerebral volumes and antiphospholipid antibody profile. Case series

ASIA syndrome masked as recurrent angioedema: can development be predicted by genetic screening

Background: ASIA – autoimmune/inflammatory syndrome induced by adjuvants. Symptoms can be multifacial and the recurrent angioedema (AE) is one of the dominant. Genetic screening is discussed as a preemptive option. HLA type II (DRB1*0301 or in combination with HLA-B*08, DRB1*01, and DRB4), as well as the Arg620Trp polymorphism in the PTPN22 are discussed as a causative reason responsible for the development of autoimmune diseases, including ASIA syndrome [1,2]. Methods: A single center observation of 16 patients with ASIA syndrome and 10 controls. Genetic screening was performed in 14 patients from the ASIA group and 10 patients from the control group. Results: All patients with ASIA are women, potential triggers included hyaluronic acid fillers 10/16, including in combination with breast silicone implants 1/16, follicle-stimulating hormone and human chorionic gonadotropin supplementation 1/16, arthroplasty with shoulder joint replacement 1/16, face hyaluronic acid injections 5/16 and calcium hydroxyapatite 1/16. The sites of AE localization were face 15/16, larynx (1/16), upper (2/16) and lower extremities (1/16). There were arthralgia, myalgia, muscle weakness - 1/16, hypocomplementary urticarial vasculitis, lymphocytic colitis - 1/16, arthralgia combined with lymphadenopathy - 1/16, chronic spantaneous and solar urticaria - 1/16, fixed erythema of skin, antiphospholipid syndrome - 1/16, normocomplementemic urticarial vasculitis - 1/16, Still's disease - 1/16. Autoimmune response was presented by autoantibodies in 10 of 16 patients. 10 patients received non-sedating antihistaminic drugs (5 in isolation, 1 with filler removal, 1 with hydroxychloroquine(HC), 3 with HC and omalizumab), 1 - tranexamic acid, 1 - danazol, 1 - HC, and 3 patients received no therapy. A combination of two genetic factors was detected in 3 patients: DRB1*0301, B1*08 (in two with Arg620Trp polymorphism). Isolated Arg620Trp polymorphism was detected in 6 patients. Conclusion: Genetic factors were found in 9 out of 16 patients and none in control group. Further studies are needed to create reliable diagnostic and treatment algorithm.

Thrombophilia assessment: Experience of the hematology laboratory of IBN ROCHD AMC of Casablanca

Thrombophilia is a condition characterized by an increased tendency to thrombosis. It results from various etiologies often intertwined and involving both hereditary and acquired risk factors. In Morocco, there is a lack of data concerning thrombophilia at the national level and the declaration is not mandatory, the real prevalence of this pathology is impossible to determine. This study concerned patients who presented with thrombosis and whose thrombophilia assessments were carried out at the Hematology Laboratory of AMC Ibn Rochd in Casablanca. 80 assessments were compiled: The main indication that motivated the request for a thrombophilia assessment was DVT in 23 patients (28.75%), followed by ICVA in 20 patients (25%). The results were positive in 51.25% of cases: protein S deficiency was the most frequent (36.25%), anti-phospholipid antibodies were discovered in 2 patients. The diagnosis of venous thrombosis was made in 50 patients (62.5%), and the diagnosis of arterial thrombosis was made in 30 patients (37.5%), of which 20 patients (66.7%) had an ICVA. In our study, the predominant risk factor was PS deficiency unlike literary data in other Western countries which note APCR as the most frequent risk factor. This may be due to ethnic variability, hence the need for a larger multicenter study to confirm these results.

Clinical characteristics of ischemic stroke in Japanese young adults.

Background and Purpose There is limited data on the characteristics of stroke in young adults in East Asia including Japan. We aimed to clarify the clinical characteristics of ischemic stroke in Japanese young adults. Methods We prospectively enrolled ischemic stroke patients aged 18 to 50 years old who were admitted to 5 high-volume stroke centers within 14 days after onset between February 2018 and January 2023. We collected clinical and imaging data based on the study protocol and analyzed them for conventional and specific stroke risk factors, stroke etiology, and clinical outcome. Results We enrolled 275 subjects (median age, 46 years; men, 71%; full time workers, 75%; median NIHSS score at admission, 2 points). The major risk factors were dyslipidemia (59%), hypertension (49%), and smoking (32%). Hyperhomocysteinemia, migraine, and antiphospholipid syndrome were found in 21%, 11% and 5%, respectively. The RNF213 p.R4810K variant was identified in 4.5%. The most common stroke etiologies were small vessel occlusion (26%) and arterial dissection (25%; intracranial in 20% and extracranial in 5%). The stroke recurrence rate was 5% at 3 months. Modified Rankin scale 0-1 at 3 months was observed in 76%, whereas 61% were able to return to their previous full-time work and 31% exhibited symptoms of depression. Conclusions The leading stroke etiologies in young adults in Japan were small vessel occlusion and intracranial arterial dissection, which differs from those observed in Western countries. Most young stroke patients had a favorable outcome, but some of them encountered problems relating to employment or mental health after their stroke.

Systemic Lupus Erythematosus with Refractory Immune Thrombocytopenia Progressing to Catastrophic Anti-Phospholipid Syndrome During Thrombopoietin Receptor Agonist Therapy: A Case Report

Background/Objectives: Autoimmune thrombocytopenia is a common manifestation of systemic lupus erythematosus (SLE). Its main treatments are glucocorticoids, intravenous immunoglobulin, and immunosuppressants, but thrombopoietin mimetics may be considered with refractory to conventional treatment. Romiplostim, a thrombopoietin receptor agonist, has been approved for increasing platelet counts in corticosteroid-refractory chronic immune thrombocytopenia. However, data on its long-term safety and efficacy in patients with SLE are still lacking. Case Presentation: We present the case of a 55-year-old woman with SLE and refractory immune thrombocytopenia who developed bilateral adrenal hemorrhage and progressed to fatal catastrophic anti-phospholipid syndrome while using romiplostim.

Acute Symmetric Arterial Thrombosis of the Four Extremities Associated with Pregnancy: Case Report

During the normal process of pregnancy, there is a procoagulant state derived from the alteration of all the components of the Virchow Triad. Multiple biochemical and structural changes lead to an increased risk of thromboembolic events. Although venous embolic events are more common, arterial thrombosis generally leads to devastating outcomes. Anticoagulation in pregnant patients has very specific indications, primarily in patients with a history of thromboembolism or poor obstetric history. There are multiple drugs used for venous or arterial thrombosis, some of which are associated with teratogenic effects, the most commonly used being low molecular weight heparin. In cases of valve prosthesis and antiphospholipid syndrome, antiplatelet drugs should be added. Shock is the main cause of admission and mortality in intensive care units. In the absence of myocardial dysfunction, hypotension is primarily caused by hypovolemia and the physiological inability to self-regulate and adequately perfuse. In these cases, there are guidelines for the use of vasopressors, aimed at maintaining adequate perfusion to essential organs. However, the use of these drugs may be associated with adverse effects, including the possibility of ischemia in some anatomical regions. In this article, we present the case of a multi-pregnant patient with the presence of several etiopathogenic factors that triggered distal necrosis of all four extremities, requiring amputation.

Secondary Immunodeficiency in Marginal Zone Lymphoma and Impact of Bruton Tyrosine Kinase Inhibitor

Secondary immunodeficiencies are clinically challenging and emphasize the need for a multidisciplinary approach. Our case underscores the importance of understanding the potential impact of B cell–targeting therapies, such as Bruton tyrosine kinase (BTK) inhibitors, on immune function, opportunistic infection prophylaxis, and clinical management. A 55-year-old male with a history of systemic lupus erythematosus (SLE) on hydroxychloroquine, antiphospholipid antibody syndrome on warfarin, anal cancer s/p resection, long-standing splenomegaly, and lymphadenopathy with unremarkable core needle biopsy in 2018 was diagnosed with marginal zone lymphoma via excisional lymph node biopsy in 2023. His clinical course was complicated by a hospitalization for septic shock secondary to Streptococcus agalactiae bacteremia and during this admission he was found to have significant immunodeficiency characterized by low T-lymphocyte counts (in cells/μL): CD3+ 141, CD4+ 65, and CD8+ 65, as well as low IgG levels 510 mg/dL (CD19 counts not obtained). Of note, he had persistent lymphopenia (0.06 to 0.49 cells/μL) and intermittent neutropenia (1.26-1.72 cells/μL) since 2009. After starting rituximab for lymphoma, he developed severe neutropenia (0.47 cells/μL), Candida esophagitis (requiring transient PEG tube placement), and a left ethmoid and sphenoid sinus abscess and orbital cellulitis due to Aspergillus fumigatus. Given the severe side effects and disease progression after rituximab, he was transitioned to a selective BTK inhibitor, zanubrutinib. For Pneumocystis jiroveci (PCP), antiviral and antifungal prophylaxis, he receives dapsone, acyclovir, and voriconazole, respectively. He has remained infection free since initiating zanubrutinib despite persistent lymphopenia (in cells/μL: CD3+ 147-183, CD4+ 74-108, CD8+ 48-62, CD19+ 8). His IgG levels improved to 700-800 mg/dL. His most recent PET scan showed stable disease. Notably, genetic testing was nondiagnostic. Our patient’s secondary immunodeficiency is multifactorial from SLE, lymphoma, and rituximab. The impact of selective BTK inhibitors on immune function is not well studied. Ibrutinib, a first-generation BTK inhibitor, improves T cell exhaustion with treatment of B cell lymphomas; similar findings were not observed for zanubrutinib, although studies are limited. Furthermore, recommendations on opportunistic infection prophylaxis often rely on data from HIV patients, yet it is unclear if the immune dysfunction is similar in individuals with non-HIV immunodeficiencies.

Clinical and immunological Characteristics of 10 X-linked Chronic Granulomatous Disease Female Carriers

Background and Aims Chronic granulomatous disease (CGD) is a rare inherited disorder with affected neutrophil “respiratory burst” due to defective NADPH-oxidase function. The most common form, X-linked CGD, is associated with disease manifestations also in female carriers. Increased susceptibility to infections is observed in females with skewed X-chromosome inactivation. Additionally, carriers have increased risk of autoimmunity. Methods We analyzed clinical manifestations, evaluated respiratory burst on neutrophils (%burst), and performed lymphocytes immunophenotyping in a cohort of 10 CGD carriers (aged 26-46 years, median = 41 years). Results Autoimmune disorders and infections observed in 3/10 and 2/10 females, correspondently. Discoid lupus, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome were described. 6/10 were asymptomatic; 1 female has both infections and autoimmune complications. %Burst varies from 16% to 90% (median = 38.5%): 18-72% in females with autoimmunity, 18-22 with infections, and 16-90% asymptomatic. Thus, all carriers with infections have decreased %burst, but %burst decrease does not necessarily lead to infectious manifestations. %Burst correlates with the number of switched (CD19+CD27+IgD-) and non-switched (CD19+CD27+IgD+) memory B cells (r = 0.75 and 0.68, p = 0.0001 and 0.0009), DN B cells (CD19+CD27-IgD-), and CD21 low CD38 low B cells (r = -0.76, p = 0.0001). Carriers with autoimmunity have decreased NKT cells (p = 0.04) and have a tendency to increase naïve CD4 (CD4+CD45RA+CCR7+) and CD8 (CD8+CD45RA+CCR7+) T cells and RTE (CD4+CD45RA+CD31+) (statistical significance was not reached due to small sample size). However, lymphocyte subsets usually associated with autoimmune disorders in PID (Tregs, activated/memory T cells, and CD21 low B cells) did not differ in carriers with autoimmunity from those in asymptomatic careers. Conclusions Increased susceptibility to infections and B-memory cells differentiation in X-CGD female carriers are concerned with a % of neutrophils with normal NADPH-oxidase function.