Case report on postoperative coagulation abnormalities.

RATIONALE: Intracranial aneurysm (IA) is defined as a localized dilation of cerebral arteries. With the continuous development of modern medical technology, surgery is still one of the main treatment methods. Although there are various postoperative complications, abnormal coagulation function is rare, especially those caused by lupus antibodies after surgery. The patient not only experienced postoperative abnormalities in coagulation function, but also discovered the presence of lupus anticoagulants in their body. Is the patient suffering from coagulation dysfunction caused by lupus anticoagulants, how is lupus anticoagulant produced, and what's special about treatment. With these questions in mind, we reviewed the entire treatment process of the patient. PATIENT CONCERNS: A 69-year-old woman presented with "headache and dizziness with neck pain" and was eventually diagnosed with IA hemorrhage. The patient underwent craniotomy under general anesthesia, and provided targeted support and treatment. Postoperative symptoms such as coma and intermittent fever occurred, and coagulation indicators were generally normal. After symptomatic support treatment, such as anti-infection treatment, the patient's temperature was gradually controlled. However, the abnormal clotting index and the efficacy of symptomatic therapeutic support, such as supplementation with coagulation factors, were not good. After further examination, the lupus anticoagulant was found, which provided us with a new treatment idea. DIAGNOSES: Coagulation disorders, postoperative IA, hypertension grade 3 (extremely high risk), coronary atherosclerotic atheropathy, and type 2 diabetes. INTERVENTIONS: The patient developed abnormal coagulation function after craniotomy, and symptomatic support treatment with coagulation factor supplementation and plasma infusion was ineffective. Finally, the lupus anticoagulant was found after a series of relevant examinations. After timely adjustment of the treatment plan, the patient's coagulation indices gradually improved. OUTCOMES: In this report, we present the case of a patient with abnormal coagulation function caused by the lupus anticoagulant after IA surgery. LESSONS: The coagulation function of the patient was abnormal after craniocerebral operation. After coagulation factor supplementation, the coagulation index of the patient was still not well improved. After further examination, the lupus anticoagulant was found. The treatment plan was actively adjusted, and the patient's condition gradually improved. Early recognition can allow doctors to provide appropriate therapy to patients.

The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

BACKGROUND: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. METHODS: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI) and lupus anticoagulant (LA) was then calculated. RESULTS: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-ß2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. CONCLUSIONS: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.

Risk factors for cardiovascular diseases in patients with systemic lupus erythematosus: an umbrella review.

Cardiovascular disease in patients with systemic lupus erythematosus (SLE) remains one of the most common causes of death and is caused by several factors, including both traditional and disease-specific risk factors. We aimed to systematically appraise the evidence of cardiovascular disease risk factors focusing on the SLE population. The protocol for this umbrella review is registered in PROSPERO (registration no. CRD42020206858). A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library from database inception to June 22, 2022, for systematic reviews and meta-analyzes that examined cardiovascular disease risk factors in patients with SLE. Two reviewers independently extracted data and assessed the quality of the included studies using the "Assessing the Methodological Quality of Systematic Reviews 2 (AMSTER 2)" tool. Of the 102 identified articles, nine systematic reviews were included in this umbrella review. All included systematic reviews were assessed as critically low quality according to the AMSTER 2 tool. The traditional risk factors identified in this study were older age, male sex, hypertension, dyslipidemia, smoking, and a family history of cardiovascular disease. SLE-specific risk factors were long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. This umbrella review identified some cardiovascular disease risk factors in patients with SLE; however, the study quality of all included systematic reviews was critically low. Key Points • We examined the evidence of cardiovascular disease risk factors focusing on patients with systemic lupus erythematosus. • We found that long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant, were cardiovascular disease risk factors among patients with systemic lupus erythematosus. • The review indicates the need for well-validated and high-quality future reviews that assess major adverse cardiovascular events as an outcome in patients with systemic lupus erythematosus.

The impact of antiphospholipid antibodies in Takayasu arteritis.

BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies.

Tumor-selective viruses are a novel therapeutic approach for treating cancer. Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are tumor-selective adenoviral vectors designed to express immunomodulatory transgenes. Prolonged activated partial thromboplastin time (aPTT), associated with the presence of antiphospholipid antibodies (aPL), has been observed in patients with viral infections, and following administration of adenovirus-based medicines. aPL may be detected as lupus anticoagulant (LA), anti-cardiolipin (aCL) and/or anti-beta 2 glycoprotein antibodies (aß2GPI). No subtype alone is definitive for development of clinical sequalae, however, patients who are 'triple positive' have a greater thrombotic risk. Additionally, isolated aCL and aß2GPI IgM do not appear to add value in thrombotic association to aPL positivity, rather IgG subtypes must also be present to confer an increased risk. Here we report induction of prolonged aPTT and aPL in patients from eight Phase 1 studies who were treated with adenoviral vectors (n = 204). Prolonged aPTT (≥ Grade 2) was observed in 42% of patients, with a peak at 2-3 weeks post-treatment and resolution within ~ 2 months. Among patients with aPTT prolongation, LA, but not aCL IgG nor aß2GPI IgG, was observed. The transience of the prolongation and discordance between positive LA and negative aCL/aß2GPI IgG assays is not typical of a prothrombotic state. Among the patients with prolonged aPTT there was no evidence of an increased rate of thrombosis. These findings elucidate the relationship between viral exposure and aPL in the context of clinical trials. They suggest a framework in which hematologic changes can be monitored in patients receiving similar treatments.Clinical trial registration:NCT02028442, NCT02636036, NCT02028117, NCT03852511, NCT04053283, NCT05165433, NCT04830592, NCT05043714.

Lupus Anticoagulant-Hypoprothrombinemia Syndrome and Pseudotumor Cerebri as an Initial Presentation of Systemic Lupus Erythematosus in a 16-Year-Old Male Patient: A Case Report and Literature Review.

BACKGROUND Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is an exceptionally rare disease caused by prothrombin antibodies, resulting in reduced factor II levels. This disease can present with significant bleeding and is usually associated with autoimmune disorders, particularly systemic lupus erythematosus (SLE). There are currently no guidelines for the treatment of LAHPS, and corticosteroids remain the criterion standard therapy. Pseudotumor cerebri is a disease that involves an idiopathic rise in intracranial pressure in association with papilledema. The coexistence of pseudotumor cerebri with SLE is rare, with an overall incidence of 0.7%. CASE REPORT A 16-year-old male initially presented to our hospital with nausea, headaches, and decreased visual acuity. He was diagnosed with pseudotumor cerebri based on the findings of papilledema and a raised opening pressure on lumbar puncture. Three months later, he presented with macroscopic hematuria and persistent epistaxis. Further investigation revealed a prolonged activated partial thromboplastin time and prothrombin time, along with positive LA and reduced Factor II levels, resulting in a diagnosis of LAHPS. The patient received a dose of 1 mg/kg/day of prednisolone along with hydroxychloroquine, and he had a complete recovery with cessation of bleeding and normalization of laboratory parameters. CONCLUSIONS We are reporting a case of pseudotumor cerebri with a further presentation of LAHPS in a patient found to have SLE. As both associations are rare in the presence of SLE, it is vital to recognize them early to initiate adequate management and intervention to avoid life-threatening complications.

A case report of secondary synchronous diagnosis of multiple myeloma and systemic lupus erythematosus after breast cancer treatment: A CARE-compliant article.

INTRODUCTION: Breast cancer (BC) is the most diagnosed cancer worldwide. Multiple myeloma (MM) is a hematologic malignancy characterized by the overproduction of monoclonal antibodies in the bone marrow. Systemic lupus erythematosus (SLE) is distinguished by the aberrant activity of the immune system with heterogeneous clinical manifestations. The coexistence of more than one major illness in a patient can present a diagnostic challenge for clinical physicians, especially when the comorbid diseases share a similar clinical presentation. Herein, we report an unusual case of secondary synchronous diagnosis of MM and SLE after BC treatment. PATIENT CONCERNS: A 69-year-old female patient with breast cancer experienced severe skin itching and rashes on the face, anterior chest wall, back, and trunk for two days before admission. She had high levels of immunoglobulin and anti-nuclear antibodies; low levels of complements 3 and 4; positive anti-cardiolipin-IgM, anti-beta 2 glycoprotein-1 (anti-ß2GP1) antibodies, and lupus anticoagulant results at serological testing. DIAGNOSIS: The postoperative pathology report showed ductal carcinoma in situ in the right breast. SLE was confirmed based on the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria. IgG-κ type multiple myeloma was confirmed by bone marrow biopsy, and the patient was synchronously diagnosed with SLE and MM after BC treatment. INTERVENTIONS: Glucocorticoids and immunosuppressive agents, including intravenous hydrocortisone (5 g every 8 hours) and oral hydroxychloroquine (Plaquenil) (200 mg twice daily) were administered to treat SLE. One capsule of thalidomide 50 mg was administered orally every night at bedtime for MM. OUTCOMES: The patient died two days later, shortly after the administration of drugs, due to multiple organ failures secondary to pneumonia and respiratory failure. CONCLUSION: This is a case of MM and SLE after BC treatment. The present challenge was the early detection and accurate diagnosis of the secondary major illnesses, as the clinical manifestations were similar and non-specific between these two diseases. Awareness and prompt recognition of the common clinical symptoms of SLE and MM should be considered by clinical physicians to avoid delayed diagnoses and facilitate early treatment for a better prognosis.

Left ventricular size and function in patients with systemic lupus erythematosus associate with lupus anticoagulant: An echocardiographic follow-up study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. PURPOSE: We aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. METHODS: We included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7-21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. RESULTS: During follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e' ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). CONCLUSION: Presence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated.

Increased risk of acute and chronic microvascular renal lesions associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Microvascular renal lesions have been described in patients with antiphospholipid antibodies (aPL), however their association with aPL is inconsistent among studies. Therefore, our objective was to investigate associations between microvascular renal lesions and aPL among systemic lupus erythematosus (SLE) patients. METHODS: Studies were selected if they included SLE patients with and without aPL positivity with a description of kidney biopsy identifying acute and/or chronic microvascular renal lesions as well as lupus nephritis. Data sources were Pubmed, Embase, Cochrane Library, hand search, congress abstracts, and reference lists of studies, without language restrictions. Risk estimates were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the Mantel-Haenszel method (random effects). RESULTS: Of 1860 identified records obtained between 1991 and 2021, 35 published studies (10 cohorts, 7 case-control, 18 cross-sectional) met inclusion criteria, including 3035 SLE patients according to American College of Rheumatology criteria and 454 cases of microvascular renal lesions. Frequency of microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 31.3% vs. 10.4%, respectively. The overall pooled odds ratios (OR) for microvascular renal lesions in aPL-positive vs. aPL-negative SLE patients was 3.03 (95% confidence interval [CI], 2.25-4.09). The risk of microvascular renal lesions was the highest for lupus anticoagulant (OR = 4.84 [95% CI, 2.93 to 8.02]) and IgG anticardiolipin antibodies (OR = 3.12 [95% CI,1.08-9.02]) while the association with anti-ß2-glycoprotein I antibodies (OR = 1.88 [95% CI, 0.25-14.14]) did not reach statistical significance. Furthermore, aPL were not associated with any classes of lupus nephritis. CONCLUSION: In SLE patients, aPL-positivity is associated with a significant 3- to 5-fold increased risk for specific microvascular renal lesions. This risk is mainly driven by lupus anticoagulant and IgG anticardiolipin antibodies. Our results support the inclusion of microvascular renal lesions as new criteria for definite antiphospholipid syndrome.

Cardiovascular disease risk in antiphospholipid syndrome: Thrombo-inflammation and atherothrombosis.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL) (lupus anticoagulant, anticardiolipin antibodies and anti-beta2glycoprotein I (anti-ß2GPI) antibodies) and a plethora of macro- and micro-vascular manifestations, affecting predominantly young adults. Cardiovascular events are the leading causes of morbidity and mortality in APS. APL-mediated thrombo-inflammation and atherothrombosis are emerging pathogenetic mechanisms of cardiovascular disease (CVD) in APS, involving endothelial cell and monocyte activation, cytokines and adhesion molecules expression, complement and neutrophils activation, neutrophil extracellular traps formation, platelet cell activation and aggregation, and subsequent thrombin generation, in parallel with an oxidized low-density lipoprotein (oxLDL)-ß2GPI complex induced macrophage differentiation to foam cells. High risk aPL profile, especially the presence of lupus anticoagulant and triple aPL positivity (all three aPL subtypes), co-existence with Systemic Lupus Erythematosus (SLE), as well as traditional risk factors such as smoking, hypertension, hyperlipemia and obesity are associated with both subclinical atherosclerosis and cardiovascular events in APS. Increased awareness of CVD risk by the physicians and patients, regular assessment and strict control of traditional risk factors, and lifestyle modifications are recommended. Use of low-dose aspirin should be considered for cardiovascular prevention in asymptomatic aPL carriers or SLE patients with high-risk aPL profile. The role of older agents such as hydroxychloroquine and statins or new potential targeted treatments against immuno- and athero-thrombosis has been demonstrated by experimental and some clinical studies and needs to be further evaluated by randomized controlled studies. This review summarizes the available evidence about the pathogenetic mechanisms and prevalence of cardiovascular events and subclinical atherosclerosis, the interrelationship between traditional and disease-related CVD risk factors, and the cardiovascular risk assessment and management in APS.

Cardiac manifestations in primary antiphospholipid syndrome and their association to antiphospholipid antibodies' types and titers-cross-sectional study of Serbian cohort.

OBJECTIVES: Antiphospholipid syndrome (APS) is multisystem autoimmune coagulopathy with antiphospholipid antibodies (aPL) in its ground, manifested as a primary disease (PAPS) or in the setting of other conditions, most commonly systemic lupus erythematosus. The objective of this cross-sectional study was to investigate various cardiac manifestations and their possible relation to aPL type and titer in a Serbian cohort of PAPS patients. METHODS: A total of 360 PAPS patients were analyzed and aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and lupus anticoagulant (LA). Cardiac manifestations investigated were valvular lesions (comprehending valvular thickening and dysfunction not related to age and pseudoinfective endocarditis), coronary artery disease (CAD) with specific insight for myocardial infarction (MI), chronic cardiomyopathy (CMP), and acute decompensated heart failure (ADHF) as well as pulmonary hypertension (PH) and intracardiac thrombus presence. RESULTS: The prevalence of cardiac manifestations overall was 19.6%. There was a strong association between age and the majority of cardiac manifestations, as well as standard atherosclerotic risk factors. aCL IgG-positive patients had a higher prevalence of valvular lesions (p = 0.042). LA presence was significantly related to MI (p = 0.031) and PH (p = 0.044). CMP and ADHF were significantly related to higher titers of aCl IgG (p = 0.033, p = 0.025 respectively). Age and smoking were independent risk predictors for MI in PAPS with meaningful risk for LA positivity (OR 2.567 CI 0.671-9.820 p = 0.168). CONCLUSIONS: Certain cardiac manifestations in PAPS were related to certain aPL type and/or titer levels, imposing confirmation in prospective studies. Preventive actions, comprehending proper anticoagulant/antithrombotic therapy, and intense action against standard atherosclerotic risk factors are of utmost importance in this group of patients. Key Points • In Serbian patients with primary antiphospholipid syndrome (PAPS), prevalence of non-criteria cardiac manifestations was 19.6% and they were significantly related to certain antiphospholipid antibodies and titers. • Lupus anticoagulant was a meaningful predictor of myocardial infarction, enabling possible risk stratification and proper preventive and therapeutical strategies in this subgroup of PAPS patients. • Patients with high titers of aCL IgG are more prone to acute decompensated heart failure occurence, imposing careful follow-up of these patients • Based on the analysis of the Serbian PAPS cohort, even being non-criterial, cardiology manifestations are significantly present and inclusion of cardiologists in treatment and follow-up of these patients should be implied from the diagnosis establishment.

Angiogenic markers could predict adverse pregnancy outcomes.

Adverse pregnancy outcomes (APOs) have been a devastating actuality in clinic. However, the pre-onset risk factors, that correlated with pregnancy failure, including antiphospholipid antibodies (APLs) and angiogenic factors, remain unclear. A retrospective study was performed in this research, and data from 145 pregnant women were collected during their pregnancy. Patients were finally divided into non-APO group (n = 89) and APO group (n = 56) according to their pregnancy outcomes. The associations among their characteristics, laboratory tests, therapies, and outcomes were analyzed. Univariate analysis demonstrated that patients with APOs showed significant prevalence of lupus anticoagulant (LAC) positive (P < 0.001), antiphospholipid syndrome (P = 0.030), and heparin prior to pregnancy (P = 0.041). LAC positive was correlated with shorter gestational age (P = 0.043) and gestational weeks of pre-term delivery (P = 0.011). Increased ratio of soluble vascular endothelial growth factor receptor-1/placental growth factor in pregnancies with APLs was correlated with the APOs and worse neonatal outcomes, including gestational age (P = 0.028), fetal death (P = 0.011), gestational weeks of pre-term delivery (P = 0.002), and birth weight percentile (P = 0.016). Angiogenic markers in pregnancies with APLs were correlated with the incidence of APOs.

Hypercoagulability in patients with indirect carotid cavernous fistulas.

BACKGROUND: To assess patients with indirect carotid-cavernous fistulas (CCF) for evidence of hypercoagulable state (HS) by combination of comprehensive medical questionnaire and laboratory testing. METHODS: Patients with confirmed diagnosis of CCF treated between 2003 and 2019 were included and administered a questionnaire screening for HS risk factors and undergone laboratory investigations which included complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody titres), Factor V Leiden, prothrombin, protein C, protein S, antithrombin III, homocysteine, prothrombin G20210, CALR and JAK2 mutation screening. Participants with abnormal laboratory testing and/or past history of ischemic stroke, atrial fibrillation, cancer or hypercoagulability-associated hereditary disorders were deemed to have HS. RESULTS: Twenty-two patients were enrolled. Seventeen were women and the mean age at diagnosis was 60. Fourteen (64%) had evidence of HS: six on medical history, three with laboratory evidence and five with both. Eight (36%) had current abnormal hypercoagulability markers. One had a diagnosis of Klippel-Trenaunay Syndrome, but no others had evidence of hereditary thrombophilia. Nine were on anti-coagulation initiated after diagnosis of stroke or atrial fibrillation discovered on average 5.5 years after the diagnosis of CCF. CONCLUSION: A total of 64% percent of patients with previous indirect CCF had evidence of underlying HS indicating that hypercoagulability might play a role in the pathogenesis of CCF. The results support need for comprehensive testing for underlying HS in patients with indirect CCFs to better identify, manage, and prevent further thromboembolic events.

Central Retinal Vein Occlusion Presumably Associated with Lupus Anticoagulant Induced by SARSCoV-2.

PURPOSE: To report a case of unilateral central retinal vein occlusion (CRVO) and macular edema presumably associated with lupus anticoagulant (LA) induced by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). METHOD: Case report. RESULTS: A 32-year-old male patient presented to the emergency department with a 5-day history of blurry vision. He was diagnosed with a CRVO and macular edema. The only pathological finding was positive LA which could have been induced by his recent confirmed SARS CoV-2 infection. The patient's evolution was satisfactory after two injections of Intravitreal dexamethasone (Ozurdex®), with improvement in macular edema and visual acuity. CONCLUSION: COVID-19 may be associated to retinal vascular occlusive disorders. Transient virus-induced LA might play a role in the pathogenesis of the thrombotic event.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Síndrome antifosfolipídico en pediatría: a propósito de un caso / The antiphospholipid antibody syndrome in pediatrics: a case repor

El síndrome antifosfolipídico (SAF) es infrecuente en la edad pediátrica (3 %) y se presenta como eventos trombóticos de lechos vasculares y/o abortos espontáneos, asociado a la presencia de anticuerpos antifosfolipídicos (aFL). Este síndrome puede ser primario o asociado a alguna enfermedad sistémica subyacente. Se presenta el caso de una niña de 12 años con hemiparesia faciobraquiocrural derecha y alteración en la marcha de aparición aguda, en la cual se confirma un accidente cerebrovascular (ACV) isquémico por trombosis de la arteria cerebral media asociado a aFL positivos (anticuerpo anticardiolipina, anticoagulante lúpico y anticuerpo anti-ß2-glicoproteína). Cumple con los criterios para realizar diagnóstico de síndrome antifosfolipídico. Luego de iniciar el tratamiento, la paciente evoluciona de manera favorable. Se trata de una patología infrecuente y de presentación variable, por lo que requiere un alto sentido de alerta por parte del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento, y disminuir su morbimortalidad

Antiphospholipid syndrome (APS) is infrequent at pediatric age (3 %) and is characterized by venous or arterial thrombosis and/or spontaneous abortions. APS occurs either as a primary condition or in the setting of an underlying disease. This is a case of a 12-year-old girl with a right hemiparesis and acute disturbance in gait, in which an ischemic cerebrovascular accident (CVA) due to middle cerebral artery thrombosis associated with positive antiphospholipid antibodies is confirmed (anticardiolipin antibody, lupus anticoagulant and anti-ß2-glycoprotein antibody), fulfilling the criteria for the diagnosis of antiphospholipid syndrome . After starting treatment accordingly, the patient evolves favorably. As this pathology is infrequent and of variable presentation, it requires a high sense of alert from the health team to avoid delays in diagnosis and treatment

[Influencing factors of thrombosis besides antiphospholipid antibodies in patients with antiphospholipid syndrome].

Objective: To identify the influencing factors of thrombosis besides antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). Methods: The 169 patients diagnosed with APS were enrolled according to the current APS classification criteria from January 2003 to August 2017 in Peking University People's Hospital. There were 23 males and 146 females with a mean age of (41±15) years. Antiphospholipid antibodies, including anticardiolipin (aCL), anti-ß2glycoprotein-1 (ß2GP1) antibodies and antibodies to the phosphatidylserine-prothrombin complex (aPS/PT), were determined by enzyme-linked immunosorbent assay (ELISA) methods. Lupus anticoagulant (LA) was identified using the STA Compact coagulation testing system. The differences of clinical and laboratory characteristics between patients with and without thrombosis were analyzed (100 cases and 69 cases, respectively). The influencing factors for thrombosis in patients with APS were determined using binary logistic regression. Results: Compared with patients without thrombosis, patients with thrombosis were older and had a longer disease duration ((45±17) years vs (35±9) years and M(Q1, Q3) 12.0(3.8, 84.0) months vs 48.0(12.0, 108.0) months, both P<0.05). The percentage of male, primary APS, smoking, low blood platelet count, hypertension, and diabetes in patients with thrombosis were significantly higher than those in patients without thrombosis (all P<0.05). Similarly, the rates of antinuclear antibodies positive, aCL positive, aPS/PT-IgM positive, and aPS/PT-IgG positive in patients with thrombosis were significantly higher than those in patients without thrombosis (all P<0.05). The levels of D-dimer in patients with thrombosis were significantly higher than that in patients without thrombosis (P<0.05). There was significant difference in global anti-phospholipid syndrome score (GAPSS) between patients with and without thrombosis (P<0.05). The GAPSS score was also significantly higher in patients with arterial thrombosis than that in patients with venous thrombosis (P<0.05). Smoking and D-dimer levels were independent influencing factors for thrombosis in patients with APS (smoking: OR=11.222, 95%CI:1.119-112.544, P=0.040, D-dimer levels: OR=1.002, 95%CI: 1.000-1.003, P=0.037). Conclusions: Thrombotic APS patients are older and have a longer suffering duration, a higher ratio of male, primary APS, smoking, hypertension, lower blood platelet count, diabetes, higher GAPSS scale, and higher D-dimer levels. Smoking and D-Dimer levels may be independent risk factors for thrombosis in patients with APS.

Coronavirus-disease-2019-induced antiphospholipid-like syndrome: a case report.

BACKGROUND: This paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events. CASE DESCRIPTION: The patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019. CONCLUSION: According to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis.

Association of antiphospholipid antibodies with clinical activity and renal pathological activity in patients with lupus nephritis.

OBJECTIVES: This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). METHODS: Levels of anticardiolipin () antibodies, anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS: A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p < 0.001; r = -0.39, p = 0.003, respectively). The level of IgM- was significantly correlated with SLEDAI, and serum levels of C3 and C4 (r = 0.27, p = 0.014; r = -0.22, p = 0.041; r = -0.23, p = 0.035, respectively). CONCLUSIONS: Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.