scholarly journals Antiprothrombin antibodies induce platelet activation: a possible explanation for anti‐FXa therapy failure in patients with antiphospholipid syndrome?

2021 ◽  
Author(s):  
Walid Chayoua ◽  
Phillip L.R. Nicolson ◽  
Joost C.M. Meijers ◽  
Caroline Kardeby ◽  
Lourdes Garcia‐Quintanilla ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Therapy Failure ◽  
Antiprothrombin Antibodies

Antibodies Against Platelet Glycoprotein Target Antigens in Antiphospholipid Syndrome (APS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3973-3973 ◽  
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Carlos Bidot ◽  
Lawrence L. Horstman ◽  
Vincenzo Fontana ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Endothelial Activation ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
Positive Group ◽  
Platelet Antibodies ◽  
Platelet Microparticles

Abstract Introduction: Antiphospholipid syndrome (APS) is characterized clinically by thrombotic events and the presence of antiphospholipid antibodies (aPLA) and/or lupus anticoagulant (LA). It is frequently associated with thrombocytopenia and anti-platelet antibodies have been implicated by some. However the roles of anti-platelet antibodies in APS have not been elucidated. We previously reported that platelet activation, but not endothelial activation, was associated with thrombosis in aPLA+ patients [Blood, 104:143a, 2004] but the cause of platelet activation was not addressed. In the present study, we investigated the prevalence of anti-platelet antibodies in APS patients, as well as platelet and endothelial activation. Material and Methods: We evaluated 47 patients with primary APS. Anti-platelet antibodies against GP IIb/IIIa (CD41b), GP Ib/IX (CD 42b) and GP IV (CD36) for IgG and IgM class were measured by PAICA assay [Thromb Haemost76:1820, 1996]. We also measured platelet and endothelial activation markers by flow cytometry: CD62P on platelets, CD31+/CD42+ platelet microparticles (PMP), and CD31+/CD42- endothelial microparticles (EMP). Results: Of the 47 patients, 34 (72%) were positive for at least one anti-platelet antibody. Looking first at IgG, 18/34 (53%) were positive for GP IV; 17/34 (50%) for GP IIb/IIIa; and 16/34 (47%) for GP Ib/IX. IgM antibodies were 47% (14/30) for GP Ib/IX, 38%(13/34) for GP IIb/IIIa, and 24% (8/33) for GP IV. Platelet and endothelial markers were significantly more common in the anti-platelet antibodies positive group: 40% vs. 21% for CD62P, 40% vs. 28.5% for EMP, and 23% vs. 5% for PMP, respectively. We found that CD62P associated significantly with IgM anti-GP IIb/IIIa (p< 0.05), and PMP with IgM anti-GP IIb/IIIa (p< 0.05), and IgM anti-GP IV (p< 0.05). Conclusions: Anti-platelet antibodies are common in APS, confirming previous reports. We found that anti-platelet antibodies IgM anti-GP IIb/IIIa, and IgM anti-GP IV were often associated with platelet activation, suggesting that these antibodies may activate platelets to play an important role in the thrombogenesis of APS. These antibodies were also associated with endothelial activation. It remains to be determined which antibodies, APLA and/or anti-platelet antibodies, play a dominant role in the activation of platelet or endothelial cells and contibute most to the pathogenesis of thrombosis in APS.

AB0218 Plasma heparanase levels are elevated in patients with antiphospholipid syndrome and correlate with platelet activation

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 650.1-650
Author(s):  
K.-J. Kim ◽  
S.-J. Park ◽  
J.-Y. Kim ◽  
I.-W. Baek ◽  
C.-H. Yoon ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome

scholarly journals Characterization of Plasma-Derived Small Extracellular Vesicles Indicates Ongoing Endothelial and Platelet Activation in Patients with Thrombotic Antiphospholipid Syndrome

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1211
Author(s):  
Ula Štok ◽  
Elizabeta Blokar ◽  
Metka Lenassi ◽  
Marija Holcar ◽  
Mojca Frank-Bertoncelj ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Study Groups ◽  
Surface Expression ◽  
Biological Properties ◽  
Endothelial Damage ◽  
Biologically Active ◽  
Systemic Autoimmune Disease ◽  
Cellular Origin

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL), which drive endothelial injury and thrombophilia. Extracellular vesicles (EVs) have been implicated in endothelial and thrombotic pathologies. Here, we characterized the quantity, cellular origin and the surface expression of biologically active molecules in small EVs (sEVs) isolated from the plasma of thrombotic APS patients (n = 14), aPL-negative patients with idiopathic thrombosis (aPL-neg IT, n = 5) and healthy blood donors (HBD, n = 7). Nanoparticle tracking analysis showed similar sEV sizes (110–170 nm) between the groups, with an increased quantity of sEVs in patients with APS and aPL-neg IT compared to HBD. MACSPlex analysis of 37 different sEV surface markers showed endothelial (CD31), platelet (CD41b and CD42a), leukocyte (CD45), CD8 lymphocyte and APC (HLA-ABC) cell-derived sEVs. Except for CD8, these molecules were comparably expressed in all study groups. sEVs from APS patients were specifically enriched in surface expression of CD62P, suggesting endothelial and platelet activation in APS. Additionally, APS patients exhibited increased CD133/1 expression compared to aPL-neg IT, suggesting endothelial damage in APS patients. These findings demonstrate enhanced shedding, and distinct biological properties of sEVs in thrombotic APS.

SAT0241 PLATELET INDICES COULD BE SIMPLE RELIABLE PREDICTORS OF THROMBOTIC EVENTS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1063.1-1063
Author(s):  
J. Zhao ◽  
M. LI ◽  
Q. Wang ◽  
X. Tian ◽  
X. Zeng
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Mean Platelet Volume ◽  
Platelet Distribution Width ◽  
Platelet Volume ◽  
Distribution Width ◽  
Platelet Indices ◽  
Logistic Analysis ◽  
Large Platelet ◽  
Pathogenic Process

Background:Platelet activation is considered as a pivot pathogenic process to be responsible for thromboembolism in antiphospholipid syndrome (APS). severalstudies shown that platelet indices including platelet distribution width (PDW), mean platelet volume (MPV), large platelet rate (P-LCR) are associated with platelet activation.Objectives:This study aims to determine the correlation between platelet indices and thrombotic events in patients with APS.Methods:Platelet activation is considered as a pivot pathogenic process to be responsible for thromboembolism in antiphospholipid syndrome (APS). severalstudies shown that platelet indices including platelet distribution width (PDW), mean platelet volume (MPV), large platelet rate (P-LCR) are associated with platelet activation.Results:A total of 207 patients [135(65.2%) female, 72(34.8%) male], medianage 35(IQR 10)] was classified into thrombotic group (n=150,72.5%) and non-thrombotic group(n=57,27.5%). PDW, MPV, P-LCR were significantly higher in thrombotic group than non-thrombotic group (13.0±3.4 vs. 11.2±7.3)p<0.001, 10.7±1.4vs.10.0±3.0,p<0.001, 30.25±11.6vs. 25.1±10.4 p<0.001, respectively]. No differences in age, WBC count, hsCRP and C3 were observed between groups. Also, HGB was found to be notably higher in thrombotic group than non-thrombotic group (143±29 vs. 132±15, p=0.001).Upon univariate logistic analysis, PDW (OR 1.554, 95%CI 1.289-1.873, p<0.001), MPV (OR 1.772, 95%CI 1.268-2.476, p=0.001), P-LCR (OR 1.089, 95%CI 1.040-1.140, p<0.001) were all significantly associated with the occurrenceof thrombosis. In multivariate logistic analysis, only PDW and positive LAwere identified to be risk factors of thrombotic events (Table 1). The ROC curve showed that PDW combinedwith positive LAwas a reliable indicator of thrombotic events with an AUC of 0.796 (95%CI 0.728-0.864). The optimal cut-off value for PDW was 12.4fl with a sensitivity of 72.0% and specificity of 77.2%.Conclusion:This study confirmed that PDW, P-LCR and MPV (especially PDW) were significantly associated with thrombotic events in APS patients, which could support the theory of platelet activation being a crucial factor of thrombosis inAPS. Caution should be raised when patients with positive LA has relatively high PDW level.Disclosure of Interests:None declared

Platelet activation in patients with antiphospholipid syndrome

1998 ◽  
Vol 9 (7) ◽  
pp. 653-658 ◽  
Author(s):  
Y. Shechter ◽  
Y. Tal ◽  
A. Greenberg ◽  
B. Brenner
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome

An in vitro model to mimic the thrombotic occlusion of small vessels in catastrophic antiphospholipid syndrome (CAPS)

Lupus ◽  
2019 ◽  
Vol 28 (14) ◽  
pp. 1663-1668
Author(s):  
E Pontara ◽  
C Cheng ◽  
M G Cattini ◽  
E Bison ◽  
M Pelloso ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Anticardiolipin Antibodies ◽  
Platelet Surface ◽  
Small Vessels ◽  
Function Analyzer ◽  
Vitro Model

Platelet activation and decrease in platelet count characterize the development of the most feared form of antiphospholipid syndrome (APS), i.e. catastrophic APS (CAPS). We aimed to assess if immuno-affinity purified anti-β2-glycoprotein I (aβ2GPI) antibodies enhance platelet activation inducing a significant flow obstruction in a platelet function analyzer (PFA). Affinity purified aβ2GPI antibodies were obtained from 13 triple positive patients with a strong lupus anticoagulant (LA) and high titers of IgG anticardiolipin antibodies (aCL) and IgG aβ2GPI. Platelet activation stimulated by adenosine diphosphate (ADP) in the presence or absence of aβ2GPI was measured by the expression of P-selectin on platelet surface using flow cytometry. P-selectin expression remained close to baseline when normal whole blood was incubated with aβ2GPI alone. When stimulated using aβ2GPI combined with ADP, P-selectin expression (28.42 ± 5.15% vs. 20.98 ± 3.94%, p = 0.0076) was significantly higher than ADP alone. Closure time of normal whole blood passed through the PFA was significantly shorter using affinity purified aβ2GPI than control IgG both in Col/ADP (160.1 ± 62.1 s vs. 218.6 ± 43.8 s; p = 0.021) and Col/EPI cartridges (149.5 ± 26.7 s vs. 186.9 ± 45.5 s; p = 0.030). Thus, platelet activation is enhanced by aβ2GPI antibodies with a consequent premature closure in a PFA, possibly resembling that in microcirculation in patients with CAPS.

Systemic Endothelial Cell Markers in Primary Antiphospholipid Syndrome

2000 ◽  
Vol 84 (11) ◽  
pp. 742-746 ◽  
Author(s):  
Frances M. Williams ◽  
Kiran Parmar ◽  
Graham R. Hughes ◽  
Beverley Hunt
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Primary Antiphospholipid Syndrome ◽  
Cell Of Origin ◽  
Intercellular Adhesion Molecule 1

SummaryThe pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.

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