Antiphospholipid Antibodies In Patients Research Articles

Investigating the Status of Antiphospholipid Antibodies in Patients with Mild COVID-19

Background and Objective: COVID-19 disease has various manifestations, such as fever, sore throat, shortness of breath, body pain, and loss of consciousness. This disease may cause coagulation disorders and therefore an increase in thromboembolic events in these patients. This study examines the status of anti-phospholipid antibodies (aPL) in such patients, as one of the factors of increased coagulability. Materials and Methods: This case-control study examined anti-phospholipid antibodies (including lupus anticoagulant, anti-cardiolipin antibody, and anti-beta-2 glycoprotein antibody) in 60 patients with definite mild COVID-19. Patients were included in the study if they met the inclusion criteria. The blood samples of the studied subjects were analyzed in the unit's laboratory. The patients' sample results were compared to those of 60 healthy individuals who were matched in terms of age and gender. Results: The mean age scores of the case and control groups were 48.54±15.29 and 46.91±16.71 years, respectively (P=0.57). In case group, the Anti-β2GPI (IgG and IgM) test was positive in two patients (P=0.578 and P=0.346). The LAC test was positive in 3 patients and 2 controls (P=0.57). Anti-cardiolipin antibodies was positive in 4 patients (IgG in 1 patient and IgM in 3 patients), compared to the control group in 1 patient (P=0.004). Conclusion: According to the results of this study, the prevalence of aPL was higher in patients with mild COVID-19 than in healthy individuals. Considering the role of aPL in thrombosis, it may increase the coagulability conditions in these patients.

Profile and clinical relevance of non-criteria antiphospholipid antibodies in patients diagnosed with or highly suspected of APS.

This study investigates the positivity and relevance of non-criteria aPLs with clinical phenotypes in patients highly suspected of or diagnosed with APS. Outpatient cases were included from a prospectively maintained database, and patients were grouped into APS (n = 168), seronegative APS (SNAPS, n = 9), those meeting the diagnostic criteria for clinical events without laboratory results (only-event, n = 15), those that had aPL positivity without clinical manifestations (asymptomatic APA, n = 39), and healthy controls (n = 88). Criteria aPL results and APS-related clinical features were extracted. Sixteen non-criteria aPLs were tested and analysed. LA, aCL and anti-β2 glycoprotein-I were positive in 84.5%, 61.3% and 74.4% of APS patients, and 61.5%, 59.0% and 74.4% of asymptomatic APA patients, respectively. In patients negative for criteria serological tests, 23 out of 24 were positive for at least one non-criteria aPL. Triple-positive patients also had significantly higher tests of some aPLs in comparison with other groups. Stroke was associated with anti-phosphatidyl-inositol (aPI) IgG and anti-phosphatidyl-glycerol (aPG) IgG. Late embryonic loss correlated with aPI IgM, and premature birth/eclampsia was associated with aPI IgG and aPG IgG. There were also positive associations between heart valve lesions and anti-phosphatidylserine-prothrombin (aPS/PT) IgM, APS nephropathy and anti-phosphatidyl-choline IgG or aPS/PT IgG, and livedo reticularis and anti-phosphatidyl-ethanolamine IgM. The prevalence of non-criteria aPLs differed from diagnostic biomarkers in patients diagnosed with or suspected of APS. Detection of aPLs provided additive value in the evaluation of APS-related clinical manifestations.

Antiphospholipid antibodies in patients with stroke during COVID-19: A role in the signaling pathway leading to platelet activation.

Several viral and bacterial infections, including COVID-19, may lead to both thrombotic and hemorrhagic complications. Previously, it has been demonstrated an "in vitro" pathogenic effect of "antiphospholipid" antibodies (aPLs), which are able to activate a proinflammatory and procoagulant phenotype in monocytes, endothelial cells and platelets. This study analyzed the occurrence of aPL IgG in patients with acute ischemic stroke (AIS) during COVID-19, evaluating the effect of Ig fractions from these patients on signaling and functional activation of platelets. Sera from 10 patients with AIS during COVID-19, 10 non-COVID-19 stroke patients, 20 COVID-19 and 30 healthy donors (HD) were analyzed for anti-cardiolipin, anti-β2-GPI, anti-phosphatidylserine/prothrombin and anti-vimentin/CL antibodies by ELISA. Platelets from healthy donors were incubated with Ig fractions from these patients or with polyclonal anti-β2-GPI IgG and analyzed for phospho-ERK and phospho-p38 by western blot. Platelet secretion by ATP release dosage was also evaluated. We demonstrated the presence of aPLs IgG in sera of patients with AIS during COVID-19. Treatment with the Ig fractions from these patients or with polyclonal anti-β2-GPI IgG induced a significant increase of phospho-ERK and phospho-p38 expression. In the same vein, platelet activation was supported by the increase of adenyl nucleotides release induced by Ig fractions. This study demonstrates the presence of aPLs in a subgroup of COVID-19 patients who presented AIS, suggesting a role in the mechanisms contributing to hypercoagulable state in these patients. Detecting these antibodies as a serological marker to check and monitor COVID-19 may contribute to improve the risk stratification of thromboembolic manifestations in these patients.

Extra-criteria antiphospholipid antibodies in patients with small vessel brain lesions and clinical manifestations associated with antiphospholipid syndrome

ObjectivesNeurological manifestations compatible with small vessel brain lesions (SVBL), such as migraine, cognitive impairment, seizures, and transverse myelitis, may be related to antiphospholipid syndrome (APS) and patients could need APS therapies even though they do not fit into thrombosis or obstetric morbidity. Furthermore, extra-criteria antiphospholipid antibodies (aPL) provide an increase in sensitivity in patients with clinical manifestations related to APS but negative for IgG/IgM anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GPI), and lupus anticoagulant, which are the antibodies included in the classification criteria for APS. MethodsWe determined extra-criteria aPL in 65 SVBL patients with neurological traits and Magnetic Resonance Imaging suggestive of APS but negative for APS classification criteria, 47 of whom were prospectively followed and tested over three years. A group of 95 patients with autoimmune diseases (AD) but without clinical traits of APS was also studied. ResultsA persistent presence of extra-criteria aPL was detected in 27.7% of patients: 12.77% IgM anti- prothrombin (PT), 6.38% IgG anti-PT, 6.38% IgM anti-phosphatidylethanolamine (PE), 4.26% IgA aβ2GPI, 2.13% IgG anti-phosphatidylserine/prothrombin (PS/PT) and 2.13% IgM anti-PS/PT.There was a tendency towards a higher prevalence of these aPL in SVBL patients than in AD – especially for IgA aβ2GPI – and a lack of IgG aPS/PT positivity in the AD group. We found no SVBL patient positive for IgA aCL, IgG anti-PE, annexin V, or aβ2GPI domain I. ConclusionsExtra-criteria aPL can improve sensitivity for APS diagnosis in patients with SVBL, especially IgA aβ2GPI and IgG anti-PS/PT antibodies.

Association of Antiphospholipid Antibodies with Clinical Manifestations in Children with Systemic Lupus Erythematosus.

The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE). We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group. Values of aPLA were defined in reference laboratories. The disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, whereas tissue damage degree was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR DI; SDI; DI). Research in our center showed that patients with cSLE often had hematological, cutaneous, and non-thrombotic neurological manifestations. Antiphospholipid antibodies may be present transiently or permanently. A significant change in the titer value was observed in the IgG isotype of aCLA. The presence of higher values of IgM β2GP1 at the beginning indicates that higher disease activity can be expected. Higher disease activity correlates with greater tissue damage. Additionally, it has been shown that aPLA positive patients have two and a half times higher risk of tissue damage than aPLA negative ones. Our study shows that the presence of antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus may indicate a higher risk of tissue damage, but since it is a rare disease in childhood, prospective and multicenter studies are necessary to assess the importance of the presence of these antibodies.

The Presence of Antineutrophil Cytoplasmic Antibodies and Antiphospholipid Antibodies in Patients with Severe Acute Respiratory Syndrome Coronavirus 2: A Case-Control Study among Sudanese Patients.

Patients infected with COVID-19 are at an increased risk for thrombosis, suggesting a possible role of COVID-19 in the induction of coagulopathy. This study aimed to investigate the presence of prothrombotic antineutrophil cytoplasmic antibodies (ANCA) and antiphospholipid antibodies (aPLs) in the course of COVID-19 infection and to correlate these markers with severity and fatality, suggesting that COVID-19-induced autoimmune thrombosis is a possible axis in the inflammatory circuit of this infection. To investigate this, we conducted a case-control study which included patients with a positive reverse transcription-polymerase chain reaction (RT-PCR) test of COVID-19 and a control group with negative COVID-19 PCR and antibody (IgG-IgM and IgA nucleoprotein) ELISA results. An indirect immunofluorescence assay using granulocyte biochips (Aesku slides from AESKU DIAGNOSTICS, Germany) was used to detect ANCA (IgG), as well as multiplex ELISA for the detection of antiphospholipid antibodies for all patients with COVID-19 and for the control group. The results revealed the detection of antiphospholipid antibodies (IgG) in one patient out of the 45 patients in the case group. 1/45(2.2%) and 7/45(15.6%) tested positive for ANCA. Five were men and two were females, with one case revealed to be positive for both aPL and ANCA. A cytoplasmic reaction on the eosinophil granulocytes was observed in 2 cases; both were positive for ANCA. Other markers (CRP, APTT, PT, INR, ESR, and neutrophil and lymphocyte counts) were included in the study, along with demographic data. No aPL or ANCA reactions were detected for any of the control groups. These findings suggest that aPL and ANCA may be induced during the course of inflammation in COVID-19 and possibly contribute to the disease's severity and mortality.

Prevalence of Antiphospholipid Antibodies in Patients with Bad Obstetric History of unknown Etiology and Its Association with Clinical Parameters

Prevalence of Antiphospholipid Antibodies in Patients with Bad Obstetric History of unknown Etiology and Its Association with Clinical Parameters

Risk of livedo with antiphospholipid antibodies in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Livedo is a well-known skin condition in patients with systemic lupus erythematosus (SLE) which correspond to small vessels involvement. The influence of antiphospholipid antibodies (aPL) on the occurrence of livedo is controversial. The aim of our study was to estimate the risk of livedo associated with aPL in patients with SLE. We conducted a systematic review and meta-analysis of the literature from 1977 to 2021 to estimate the risk of livedo in SLE patients according to different aPL profiles. Data sources were PubMed, Embase, Cochrane Library, hand search, and reference lists of studies. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcome (livedo). Two independent investigators assessed study eligibility, quality, and extracted patient characteristics from each study as well as exposure (aPL) and outcome (livedo). Risk estimates were pooled using random effects models and sensitivity analyses. For all stages of the meta-analysis, we followed the PRISMA guidelines. PROSPERO registration number: CRD42015027377. Of the 2,355 articles identified, 27 were included with a total of 4,810 SLE patients. The frequency of livedo was 25.5% in aPL-positive patients and 13.3% in aPL-negative patients. The overall Odds Ratio (OR) for livedo in aPL-positive patients compared to aPL-negative patients was 2.91 (95% CI; 2.17-3.90). The risk of livedo was significantly increased for most of aPL subtypes, including lupus anticoagulant (LA) (OR = 4.45 [95% CI; 2.21-8.94]), IgG anticardiolipin (OR = 3.95 [95% CI; 2.34-6.65]), and IgG anti-β2-glycoprotein 1 (OR = 3.49 [95% CI; 1.68-7.27]). We demonstrated in this meta-analysis an excess risk of livedo in aPL-positive SLE patients compared to aPL-negative patients. For daily practice, in patients with SLE, livedo associated with aPL could correspond to a peculiar group of patients with small vessel disease. Livedo could be a good candidate for inclusion in future classification criteria for antiphospholipid syndrome.

Antiphospholipid antibodies in patients with calcific aortic valve stenosis.

The antiphospholipid syndrome is defined by antiphospholipid antibodies (aPL) together with arterial and/or venous thromboembolism and/or obstetric morbidities. aPL are overrepresented in SLE and acute myocardial infarction, but it is unknown whether aPL are associated with calcific aortic valve stenosis (CAVS) in the general population. The prevalence of aPL and other SLE-associated autoantibodies and their impact on aortic valve transcriptomics were therefore determined. A total of 233 tricuspid CAVS cases (median age 74, 69% male) and an age- and sex-matched control population were included. aPL were measured as anti-cardiolipin and anti-β2Glycoprotein-I of IgG/M/A isotypes. Resilient, thickened and calcified aortic valve (AV) tissue derived from five aPL positive and five matched aPL negative CAVS patients undergoing surgical aortic valve replacement were analysed by microarrays. The prevalence of positivity for any aPL (IgG/M/A) in patients with CAVS was 6.4% (95% CI 3.6% - 10.4%: n = 233). aPL IgG was significantly more prevalent in CAVS cases vs controls (4.6% vs 0.6%, P = 0.04). AV tissue from aPL IgG/IgM-positive patients was negatively enriched in pathways related to interferon signalling. One hundred differentially expressed genes could predict local AV CAVS progression with supervised machine learning algorithms. aPL IgG was more common in CAVS patients compared with matched controls and aPL positivity was associated with altered AV transcriptomics related to local disease progression and interferon pathways. Further studies should aim to establish aPL as a possible risk marker and/or causal factor for CAVS and could offer new precision therapeutic targets.

Proliferative Vasculopathy Associated With Antiphospholipid Antibodies in Patients With Neurological Symptoms.

BackgroundProliferative vasculopathy (PV) associated antiphospholipid syndrome (APS) in the central nervous system is a rare un(der)recognized form of extra-criteria manifestations of APS. This study investigated the angiographic characteristics of cerebral and cervical arteries in patients with PV associated with antiphospholipid antibodies (aPLs).MethodsPatients with aPLs, neurologic symptoms and diffuse luminal narrowing on brain or neck magnetic resonance angiography were selected from electronic medical records. Vascular wall and intraluminal pathology were examined by high-resolution vessel wall MR imaging (VW-MRI).ResultsA total of 11 patients (six men and five women) with PV-aPL, of median (interquartile range) age 42 (34–61) years, were included. Median anticardiolipin antibodies IgG titer was 78.9 (28.2–134.0) units and anti-beta 2 glycoprotein I antibodies (aB2GPIs) IgG titer was 227.2 (0.0–1012.1) units. All patients had diffuse luminal narrowing in the carotid basilar and/or cerebral arteries, five in the internal carotid artery (ICA); two each in the middle cerebral artery (MCA) and vertebral artery; and one each in the basilar artery (BA) and posterior cerebral artery. On VW-MRI, four patients showed concentric thickening of the vascular walls of the ICA and/or MCA and two showed mild eccentric wall thickening of the ICA or BA. All patients received antithrombotic treatment. In two patients with extremely high aB2GPIs titer, diffuse narrowing progressed despite treatment with antithrombotic agents on follow-up imaging.ConclusionsThis study suggests that PV-aPL might be a distinct extra-criteria manifestation of APS that can manifest as long-segmental diffuse stenosis of cerebral and cervical arteries. It should be considered in relatively young patients with neurologic symptoms and aPLs.

Impact of Antiphospholipid Antibodies on Intracytoplasmic Sperm Injection Outcome

Introduction and Aim: The effect of antiphospholipid syndrome on pregnancy is extensively discussed but the debate is still ongoing. This debate increased when the association was examined after assisted reproductive techniques for infertility. The current work aimed to evaluate the influence of Antiphospholipid antibodies in patient undergo first cycle of intracytoplasmic sperm injection.
 Subjects and Methods: The study comprised 130 of infertile females, who were scheduled for the first ICSI cycle. Before protocol selection, basal hormonal assay was performed and included FSH, LH, E2, prolactin and AMH. Plasma concentration of anti-phospholipids (APAs) was measured. Then, females were categorized into groups according to APAs (positive and negative groups). After ICSI, the clinical pregnancy was confirmed by presence the gestational sac or sac with positive pulsation. Ongoing pregnancy was recognized if the pregnancy continued after 12 weeks of the gestation and clinical miscarriage if pregnancy terminated before 12 weeks of gestation.
 Results: All females were in their reproductive age (18- 40 years). Their fertility duration ranged between 1 and 7 years, and it was of primary type among 96 women. The long agonist protocol was used for 72 women and the antagonist protocol done for 58 women. The Antiphospholipid antibodies were positive among 27 females (20.8%), and there was no significant difference between APL positive and negative groups regarding pregnancy results (either chemical, clinical, incidence of abortion or ongoing pregnancy after 12 weeks) for all females. However, in women with positive clinical pregnancy, the rate of abortion was significantly increased in patients with APL- positive than negative females (66.7% vs 26.7%).
 Conclusion: The presence of APA was associated with higher significant abortion rate after the first cycle of ICSI. Thus, screening for APA in women with infertility scheduled for assisted reproduction is recommended.

Antineutrophil cytoplasmic antibody-associated vasculitis in presence of positive antiphospholipid antibody: a case report\xa0

BackgroundAntineutrophil cytoplasmic antibody-associated vasculitis is dominated by inflammatory occlusion of small vessels, causing tissue ischemia in various organs. This disorder has rarely been associated with vasculopathy, such as antiphospholipid syndrome.Case presentationWe report a case of a 48-year-old Persian male presenting with distal digital gangrene along with inflammatory arthralgia. High titers of anti-proteinase 3 and antiphospholipid antibodies (anticardiolipin antibody) were detected in laboratory evaluation. Therefore, a diagnosis of antineutrophil cytoplasmic antibody-associated vasculitis and antiphospholipid syndrome was made and treated with anticoagulant along with monthly pulses of cyclophosphamide and a daily dose of 1 mg/kg prednisolone.ConclusionOur case, along with other reports, illustrates that these two entities can coexist. Therefore, monitoring antiphospholipid antibodies in patients with antineutrophil cytoplasmic antibody-associated vasculitis with or without clinical evidence of any thrombosis and ruling out thrombosis in cases that do not respond to proper treatment of vasculitis may be relevant to prevent irreversible or fatal organ damage.

Epidemiology of Antiphospholipid Syndrome in the General Population.

Purpose of ReviewThe epidemiology of antiphospholipid syndrome (APS) is poorly understood. Here, we review the current understanding of the epidemiology of antiphospholipid syndrome in the general population and the frequency of antiphospholipid antibodies in the general population in patients with obstetric morbidity, arterial events, and venous thromboembolism.Recent FindingsThere have been few population-based studies that estimated the prevalence and incidence of APS. The estimated incidence and prevalence among most these studies ranged between 1 and 2 cases per 100,000 and 40 and 50 cases per 100,000 respectively. The prevalence of antiphospholipid antibodies in patients with obstetric morbidity was 6–9%, while in arterial events and venous thromboembolism is 9–10%. However, this data remains limited. Mortality of patients with APS is 50–80% higher than the general population.SummaryThe epidemiology of APS has been difficult to elucidate. Population-based studies patients with diverse age, racial, and ethnic backgrounds are needed.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

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-β2glycoprotein-1 (β2GP1) 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.

Abstract 13625: Association of Antiphospholipid Antibodies With Venous Thromboembolism in COVID-19

Introduction: Coagulation abnormalities leading to arterial and venous thrombotic events have been described in patients with COVID-19 and studies have reported an overall pooled incidence of venous thromboembolism (VTE) of 17%, however little is known regarding VTE association with antiphospholipid antibodies in patients with COVID-19. Hypothesis: Antiphospholipid antibodies are associated with VTE events in COVID-19. Methods: This is a retrospective cohort study of COVID-19 patients hospitalized at the University of Virginia Medical Center (UVA). Serum samples were collected and stored in the UVA COVID-19 biorepository. Anti-cardiolipin (aCL) and anti-b2glycoprotein1(ab2GLP1), IgM/IgG titres, were measured from stored samples, using the enzyme-linked immunosorbent assay (ELISA). Specimens were analysed at two distinct time-points/days during the patient’s hospitalization for COVID-19. VTE incidence was collected retrospectively by chart review. The study was approved by the Institutional Review Board at UVA. Two-tailed Mann-Whitney two-sample rank-sum tests were conducted to examine whether there were significant differences in APS antibody levels, and mean change in APS levels between the two time points analysed, and VTE events. Additionally, logistic regression models were constructed to examine whether APS antibody levels and mean change in APS levels had a significant effect on the odds of observing a case of VTE. Results: There were 53 patients included in the study. The mean age of participants was 57.2 years (SD 13.9). VTE did not corelate with the levels of APS at studied time points, or the mean change in APS levels during the disease course. aCL IgM (p = 0.24), aCL IgG (p = 0.92), ab2GLP1 IgM (p = 0.79), and ab2GLP1 IgG (p = 0.79). Changes in the APS antibody levels during the course of the disease were not predictive of the odds of having VTE. Similarly, these changes did not predict the need for ICU care. Conclusions: This study shows that neither the presence of antiphospholipid antibodies nor the change in APS levels during the course of COVID-19 correlated with VTE events.

Extra criterial antiphospholipid antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data)

The role of antiphospholipid antibodies (aPL), which are not included in the classification criteria, in antiphospholipid syndrome (APS) andsystemic lupus erythematosus (SLE) is not well understood.Objective: to determine the frequency of detection of IgG antibodies to domain 1 of β2-glycoprotein 1 (IgG-aβ2GP1-D1), IgA antibodiesto cardiolipin (aCL) and IgA antibodies to β2-glycoprotein 1 (IgA-a β2GP1) in patients with primary APS and APS in combination withSLE.Patients and methods. The study included 63 patients in whom IgG/IgM-aCL and IgG/IgM-aβ2GP1 were detected by enzyme-linkedimmunosorbent assay (ELISA) and IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GP1 and IgG-aβ2GP1-D1 by chemiluminescence analysis (CLA).Results and discussion. The detection rate of IgG-aβ2GP1-D1 was 76%, IgA-aCL – 56%, IgA-aβ2GP1 – 48%. Isolated positivity for IgA-aCL,IgA-aβ2GP1, IgG-aβ2GP1-D1 was not observed. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with high positivity forIgG/IgM-aCL and IgG/IgM-aβ2GP1. There was a statistically significant relationship between IgA-aCL/IgA-aβ2GP1 and the standard aPLprofile, as well as IgG-aβ2GP1-D1, IgG-aCL and IgG-aβ2GP1.Conclusion. A high detection rate of IgG-aβ2GP1-D1, IgA-aCL, IgA-aβ2GP1 was found in patients with APS. A statistically significant relationshipwas found between IgA-aCL/IgA-aβ2GP1 and the standard aPL profile, as well as IgG-aβ2GP1-D1 with IgG-aCL and IgG-aβ2GP1.

ACUTE MULTIPLE TERRITORIES STROKE IN AN ANTICOAGULATED COVID-19 PATIENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The complications of coronavirus disease 2019 (COVID-19) involve the nervous system, including acute stroke, which is currently linked to the hypercoagulable state associated with COVID-19 [1]. CASE PRESENTATION: Our patient is a 70-year-old man with past medical history of hypertension and diabetes mellitus who presented to the emergency department with shortness of breath and fatigue for five days duration. Vitaly was stable, except for saturating 88% on the room air. He was alert and oriented on physical exam, lung exam was remarkable for bibasilar rales. He had no focal neurological deficits. Lab Work showed elevated COVID-19 markers. Chest x-ray showed left-sided infiltrates. He was admitted to the respiratory care unit and was started on dexamethasone, remdesevir, ceftriaxone, azithromycin, and enoxaparin prophylactic dose. His oxygen requirement continued to increase, and on the ninth day, he was placed on a nasal high-flow oxygen device with 60 liters FiO2 of 90%. On the eleventh day, the patient developed right facial droop, aphasia and right-sided weakness. The National Institutes of Health Stroke Scale was 16. Code stroke was called, and a brain computed tomography scan without contrast revealed cortical infarct in the high left parietal cerebral hemisphere without hemorrhage. Computed tomography angiography (CTA) of the head and neck showed mild narrowing within the middle cerebral artery. Magnetic resonance imaging, later on, showed left medial frontoparietal infarct in ACA territory. Cardiology workup confirmed no cardiac pathology. The neurology team decided not to start the tissue plasminogen activator (tPA) because he was out of the tPA window, and as no large vessel occlusion was found, a thrombectomy was not performed. DISCUSSION: COVID-19 infection is considered a highly coagulable status, especially the severe form of the disease. The pathophysiology behind this is not well understood yet. However, Severe COVID-19 is associated with cytokine activation, which activates endothelial cells and mononuclear cells with expression of tissue factor leading to coagulation cascade activation [2]. It has also been observed that COVID-19 can induce Antiphospholipid antibodies, which might play a role in thrombosis in those patients [3]. Our case confirms that COVID-19 induced acute stroke can occur in multiple territories despite the patient being well anticoagulated. CONCLUSIONS: Acute stroke should be suspected in COVID-19 patients with acute neurological changes even if the patient is on prophylactic anticoagulation. Frequent screening neurological examination can lead to early detection and treatment of acute stroke. REFERENCE #1: Verstrepen, K., Baisier, L. & De Cauwer, H. Neurological manifestations of COVID-19, SARS and MERS. Acta Neurol Belg 120, 1051–1060 (2020). https://doi.org/10.1007/s13760-020-01412-4 REFERENCE #2: Beyrouti R, Adams ME, Benjamin L, et alCharacteristics of ischaemic stroke associated with COVID-19Journal of Neurology, Neurosurgery & Psychiatry 2020;91:889-891. REFERENCE #3: Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C, Zhao J, Sun X, Tian R, Wu W, Wu D, Ma J, Chen Y, Zhang D, Xie J, Yan X, Zhou X, Liu Z, Wang J, Du B, Qin Y, Gao P, Qin X, Xu Y, Zhang W, Li T, Zhang F, Zhao Y, Li Y, Zhang S. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr 23;382(17):e38. doi: 10.1056/NEJMc2007575. Epub 2020 Apr 8. PMID: 32268022;PMCID: PMC7161262. DISCLOSURES: No relevant relationships by Abdul Rahman Al Armashi, source=Web Response No relevant relationships by Ameed Bawwab, source=Web Response No relevant relationships by Arthur Boyd, source=Web Response No relevant relationships by Kanchi Patell, source=Web Response No relevant relationships by Keyvan Ravakhah, source=Web Response No relevant relationships by Francisco Somoza-Cano, source=Web Response

Antiphospholipid antibodies in patients with Graves' orbitopathy: preliminary data.

Graves' orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (-) subgroups of GO patients. Study included consecutive patients with GO (66 with Graves' (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations.

Neurologic Manifestations of COVID-19 in Children: Emerging Pathophysiologic Insights.

The COVID-19 pandemic has affected mortality and morbidity across all ages, including children. Neurologic manifestations of coronavirus disease 2019, ranging from headaches to cerebrovascular stroke, may involve the CNS or peripheral nervous system. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19. Knowledge about mechanisms of neurologic disease and immunologic response to severe acute respiratory syndrome coronavirus 2 is scarce but rapidly growing. Here, we concisely review experimental and clinical data relevant to pathophysiologic hypotheses regarding neurologic manifestations of coronavirus disease 2019. We highlight important knowledge gaps in differences between adults and children in their response to coronavirus disease 2019.