scholarly journals Immunogenicity, Safety and Antiphospholipid Antibodies After SARS-CoV-2 Vaccine in Patients With Primary Antiphospholipid Syndrome

2021 ◽  
Author(s):  
Flavio Signorelli ◽  
Gustavo Guimarães Moreira Balbi ◽  
Nadia Emi Aikawa ◽  
Clovis Artur Almeida Silva ◽  
Léonard de Vinci Kanda Kupa ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Neutralizing Antibodies ◽  
Thrombotic Event ◽  
Control Group ◽  
Blood Collection ◽  
Primary Antiphospholipid Syndrome ◽  
Increased Risk ◽  
Excellent Safety Profile ◽  
Induced Changes

Abstract Background: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). The recent reports of thrombosis associated with the adenovirus-based vaccines raises concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger a dysregulated immune response with possible clotting complications. Therefore, the objectives of this study were to assess immunogenicity, aPL production and safety of Sinovac-Coronavac in PAPS patients.Methods: This prospective controlled phase 4 study of SARS-CoV-2-naïve PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69. Safety and aPL production were also assessed. Results: Forty-four PAPS patients and 132 CG had comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092) and GMT [50.2(95%CI 34.5-73.2) vs. 61.7 (95%CI 52.8-72.3), p=0.249] as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity [64.3% (49.0-77.0) vs. 60.9% (45.6-81.3), p=0.689]. Of note, for D28, the antibody response was very low and also similar in both groups SC (25.8% vs. 30.6% p=0.609). Antiphospholipid levels remained stable throughout the study at D0 vs D28 vs D69 (IgG aCL, p=0.058; IgM aCL, p=0.091; IgG aβ2GPI, p=0.513 and IgM aβ2GPI, p=0.468). Thrombotic event up to 6 months or other moderate/severe side effects were not observed.Conclusions: We provide novel evidence that Sinovac-CoronaVac vaccine has a high immunogenicity and excellent safety profile in PAPS. We further demonstrated that this vaccine did not trigger thrombosis or induced changes in aPL-related antibodies production. Our findings strongly support the recommendation of SARS-CoV-2 vaccination for PAPS patients.Trial registration: ClinicalTrials.gov - Identifier: NCT04754698 first registered on February 8th, 2021.

scholarly journals Flare of Antiphospholipid Syndrome in the Course of COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e207-e210 ◽  
Author(s):  
Alexandre Thibault Jacques Maria ◽  
Isabelle Diaz-Cau ◽  
Jean-Marc Benejean ◽  
Anaïs Nutz ◽  
Aurélie Schiffmann ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Severe Acute Respiratory Syndrome ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Adrenal Glands ◽  
Primary Antiphospholipid Syndrome ◽  
Increased Risk ◽  
Risk For Thrombosis

AbstractWe report the case of a 48-year-old man followed since 2013 for primary antiphospholipid syndrome (APLS) revealed by venous thromboembolism in the presence of antiphospholipid antibodies (APL-Abs, anticardiolipin and anti-β-2-glycoprotein-1), who decompensated in the course of coronavirus disease (COVID-19). Despite efficient anticoagulation, he suffered bilateral adrenal glands hemorrhage and limb arterial ischemia. The tropism of severe acute respiratory syndrome coronavirus-2 for endothelium can lead to microangiopathy and increased risk for thrombosis. If APL-Abs positivity can be an epiphenomenon under inflammatory and prothrombotic conditions, COVID-19 was herein responsible for disseminated thrombosis and a threat of catastrophic APLS, despite efficient anticoagulation.

Analysis Of a Single Institutional Cohort Of 20,593 Patients Tested For Antiphospholipid Antibodies Indicates Significant Prospective Risk For Thrombosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2366-2366
Author(s):  
D. Yitzchak Goldstein ◽  
Jacob Rand ◽  
Lucia R Wolgast
Keyword(s):  
Information System ◽  
Antiphospholipid Antibodies ◽  
Thrombotic Event ◽  
Tertiary Care ◽  
Control Group ◽  
P Value ◽  
Care Organization ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Quantification of the risk associated with positive antiphospholipid (aPL) antibodies has been problematic since previous assessments have relied on observing relatively small study populations or meta-analyses of collected larger groups. There would be a significant benefit to a tool that would permit analysis of clinical outcomes of large patient cohorts. We applied a novel analytical information system, named “Clinical Looking Glass” (CLG), which aggregates clinical, diagnostic, therapeutic and outcomes data from a single large academic health care center to address this question. Methods CLG was employed to collect all patients at a large tertiary care institution for whom antiphospholipid antibodies including lupus anticoagulant (LAC), anticardiolipin (aCL) antibodies and anti- β2-glycoproteinI (aβ2GPI) were performed. The immunoassays were grouped by isotype and values of >30U/L (>99th percentile) were considered positive. An untested control group was derived from outcomes data on all institutional Pioneer Accountable Care Organization patients, a cohort, whose coordinated care is managed by a single institution, permitted accurate and robust follow-up data. We used the CLG to track patients for a period of 583 days (maximum data available for control group) following their individual test results to identify a predefined thrombotic outcome. The outcome was defined by any encounter (inpatient, outpatient or ED), subsequent to the initial lab value date, which demonstrated a new thrombotic event. Results Using CLG we were able to evaluate 20,593 unique patients who had some form of LA testing performed. The aCL assays were performed on the greatest number of patients (18,201) followed by the LAC (11,267) with the fewest number of patients tested for aβ2GPI (7,914). A total of 5,660 patients had testing for all three. Of all 11,267 patients having LAC testing performed, 754 patients had at least one positive result. Of these 25.9% went on to develop a thrombotic event during the follow-up period compared to 15.0% of LAC negative patients (p value <0.001) and only 1.64% of the ACO control group suffering an event (p value <0.001). The relative risk associated with LAC positivity over the control group was 14.75 (95% CI 13.6-19.1). All other APL antibodies also demonstrated statistically increased risk of thrombosis over the examined cohort control (RR ranging from 6.6-11.2), but each of these to a significantly lesser degree than when compared directly to the LAC (results summarized in adjoining table and graph). Conclusions This first large study of aPL assays with prospective data from a single clinical information system confirms previous observations from smaller studies that LAC is the most significant laboratory predictor of future thrombotic events. However, in contrast to previous studies, all aPL antibodies, including IgA, demonstrated a statistically increased risk over a control population with LAC positivity having statistically greater risk than all others. Interestingly, aCL IgM was the weakest predictor of a future thrombotic event. Additionally we demonstrate the utility of clinical analytical software tools to offer very powerful ways to test prior assumptions and obtain novel results on large cohorts of patients in “real world” settings. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical diagnosis in patients with positive antiphospholipid antibodies

2020 ◽  
Vol 105 (105(810)) ◽  
pp. 90-95
Author(s):  
P. Herreros Fernández-Arroyo ◽  
J. M. Urra-Ardanaz
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Thrombotic Event ◽  
Primary Antiphospholipid Syndrome ◽  
Clinical Environment ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Igm Antibodies ◽  
Coagulation Tests

Objective: To know the relationship between the presence of three antiphospholipid antibodies: lupus anticoagulant and the anticardiolipin of isotypes IgM and IgG with the development of thrombotic events and alterations in coagulation and also, study the clinical environment in which those antibodies appear. Material and methods: Cross-sectional descriptive study in which we have analyzed retrospectively, in 123 patients with positive results for at least one of the antiphospholipid antibodies under study, their alterations in coagulation, if they suffer or have suffered any thrombotic event and the clinical environment in which these antibodies appear and. Results: 52,1% of patients with positive lupus anticoagulant have some type of abnormality in coagulation tests, compared with 43,75% of patients with anticardiolipin of isotype IgG and 24,64% of patients with anticardiolipin of isotypes IgM. The most frequent antibody in patients with primary antiphospholipid syndrome is anticardiolipin of isotypes IgM, which appears in 75%, while in the case of patients with secondary antiphospholipid syndrome due to erythematosus systemic lupus, the most frequent antibody is anticardiolipin of isotypes IgG, which is detected in 46,7%. Among the patients who suffered thrombotic event, in 45,94% anticardiolipin of isotypes IgM was detected, compared with 43,24% with lupus anticoagulant, and only 16,22% with anticardiolipin of isotype IgG. Conclusions: The antiphospholipid antibodies that alters coagulation tests to a greater extent is the lupus anticoagulant. Anticardiolipin of isotype IgM antibodies are the most frequent in primary antiphospholipid syndrome while anticardiolipin of isotype IgG are associated in a greater degree with secondary antiphospholipid syndrome, especially in patients with erythematosus systemic lupus. Anticardiolipin of isotype IgM antibodies represent a higher risk of thrombotic events in patients with positive antiphospholipid antibodies.

The clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome

2020 ◽  
Author(s):  
Dong-mei Yin ◽  
Philip de Groot ◽  
Marisa Ninivaggi ◽  
Katrien M.J. Devreese ◽  
Bas de Laat
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Control Group ◽  
Domain I ◽  
Normal Controls ◽  
Better Than

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.

scholarly journals Case of an unusual diagnosis of primary antiphospholipid syndrome with multiple clinical complications

2020 ◽  
Vol 2020 (12) ◽  
Author(s):  
Stathis Tsiakas ◽  
Chrysanthi Skalioti ◽  
Paraskevi Kotsi ◽  
Ioannis Boletis ◽  
Smaragdi Marinaki
Keyword(s):  
Antiphospholipid Syndrome ◽  
Thrombotic Event ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Young Male ◽  
Multiple Organ ◽  
Systemic Autoimmune Disease ◽  
Antiphospholipid Antibody ◽  
Primary Antiphospholipid Syndrome ◽  
Wide Range

ABSTRACT Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by the presence of antiphospholipid antibodies in association with thrombotic events and/or obstetric complications. Renal involvement is not infrequent in both primary and secondary APS. Kidney manifestations comprise a wide range of clinical features, including hypertension, major renal vessel thrombosis or microvascular endothelial injury, also described as APS nephropathy. In the absence of a thrombotic event, clinical manifestations of APS are often non-specific. We recently encountered a case of primary APS in a young male with newly diagnosed hypertension and renal impairment. The diagnosis of APS was initially suspected by his kidney biopsy findings, when electron microscopy examination showed the features of chronic microangiopathy, and was later confirmed by a triple positive antiphospholipid antibody profile and multiple organ involvement.

Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome

2016 ◽  
Vol 65 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Entela Nuri ◽  
Mara Taraborelli ◽  
Laura Andreoli ◽  
Marta Tonello ◽  
Maria Gerosa ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Primary Antiphospholipid Syndrome

Adamts-13 Gene Mutations and Transcription Analysis in Primary Antiphospholipid Syndrome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1823-1823
Author(s):  
Veysel sabri Hancer ◽  
Reyhan Diz-Kucukkaya ◽  
Aysegul topal-Sarikaya
Keyword(s):  
Antiphospholipid Syndrome ◽  
Thrombotic Microangiopathy ◽  
Autoimmune Disorder ◽  
Control Group ◽  
Polymorphism Analysis ◽  
Primary Antiphospholipid Syndrome ◽  
Healthy Controls ◽  
Transcription Analysis ◽  
Cross Point ◽  
Female Ratio

Abstract Von Willebrand factor (vWF) is a large multimeric protein produced by endothelial cells and megakaryocytes. vWF mediates adhesion of plateletes at sites of vascular injury, and transports factor VIII. After secretion, vWF multimers are cleaved by ADAMTS-13 (A disintegrin –like and metalloprotease with thrombospondin type 1 motif 13) enzyme to smaller multimers. Decreased activity of ADAMTS-13 by autoantibodies, mutations and other etiologies causes thrombotic microangiopathy (intraluminal platelet thrombosis in the microvasculature, thrombocytopenia, and red blood cell fragmentation). Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis and fetal losses associated with elevated levels of antiphospholipid antibodies. The pathology of small vessel thrombosis in APS patients has been shown to be related with thrombotic microangiopathy. Recently, Austin et al reported that ADAMTS-13 activity was reduced in patients with APS. They also showed an increase of large vWF multimers in plasma of those patients. In this study, we aimed to investigate ADAMTS-13 mutations which decrease the activity of enzyme and the quantitative gene transcrition rates in patients with primary APS and healthy controls. We evaluated 70 primary APS patients (male to female ratio was 25/45), and age and sex matched healthy controls. Exons 10+11,12,13+14 of ADAMTS-13 gene were amplified with the PCR assay for 365del, Q449stop C508Y mutations and P475S polymorphism analysis. PCR products were cleaved with restriction digestion enzymes and genotyped. C508Y mutation was screened by a DNA sequencer system. Total RNA samples were extracted from peripheral blood and cDNA samples were synthesized with reverse transcriptase. Original primers and probes were designed for the target gene ADAMTS-13 and the reference gene HPRT- 1. cDNA amounts of target and reference genes in patient and healthy control groups were determined by real-time PCR. We did not find C365del, Q449stop mutations and P475S polymorphism in the control group and the patients with APS (Table1.) We used Pfaffl method for transcription analysis and found that mRNA amounts of ADAMTS-13 was significantly decreased in APS group compared to helathy controls (Table 1). Our results may suggest that ADAMTS-13 gene is down regulated at the transcription stage in patients with APS. Transcription factors or existence of other mutation(s) at promotor region may explain this effect. This study demonstrated that ADAMTS 13- vWF related mechanisms may have important role in the development of thrombosis in APS patients. Table 1. Data of transcription analysis and mutations which affect the activity of ADAMTS13. C365del Q449stop P475S C508Y ADAMTS13 CP* HPRT1 CP* ADAMTS13 mRNA ratio (PAPS/ Control) * Cross Point APS n=70 0 0 0 0 33,71 30,43 0,5 Control n=100 0 0 0 0 32,23 30,05

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