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.

Anti-Platelet Glycoprotein Antibodies in Thrombocytosis Are Frequently Detected and Are Associated with Platelet Activation and Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3974-3974
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Loreta Bidot ◽  
Lawrence L. Horstman ◽  
Vincezo Fontana ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Antibodies ◽  
Myeloproliferative Disorders ◽  
Endothelial Activation ◽  
Platelet Glycoprotein ◽  
Negative Group ◽  
Positive Group ◽  
Activation Marker ◽  
Platelet Antibodies ◽  
Platelet Antibody

Abstract Introduction: Thrombosis is the major cause of morbidity and mortality in patients with thrombocytosis (TS) associated with myeloproliferative disorders (MPD), but predicting which patients are at risk has been challenging. We recently reported that antiphospholipid antibodies (APLA) and platelet activation are risk factors in TS [C Bidot et al; Hematology, 10:451, 2005]. To shed further light on the cause of platelet activation in TS, we here report on measuring anti-platelet antibodies in a group of these patients. Material and Methods: Thirty-three TS patients, 15 with clinical thrombosis and 18 without, were evaluated using PAICA method of L. Macchi et al [Thromb Haemost76:1020,1996]. We assayed anti-platelet antibodies against 3 target antigens, GPIIb/IIIa (CD41b), GP Ib/IX (CD42b) and GP IV (Cd36) for IgG and IgM. We also measured platelet activation marker CD62P, and microparticles from platelets (PMP, defined by CD31+/CD42+) and endothelial cells (EMP, defined by CD31+/CD42−) by flow cytometry. Results: At least one anti-platelet antibody was detected in 19/33 (57.5%) of TS patients. Considering first IgG in the19 who were anti-platelet antibodies positive, 14/19 (73.6%) were positive for CD36, 12/19 (63%) for CD41b and 8/19 (42.1%) for CD42b. For IgM in these 19 patients, incidences were 58.8% for CD41b, 38.8% for CD36 and 35% for CD42b. When we compared the anti-platelet antibody positive group with the negative group, we observed that activation marker CD62P was significantly higher in the former (p= 0.04), as were EMP levels (p= 0.02), but PMP levels were not different. Next, we compared results with incidence of thrombosis. None of the IgG results discriminated thrombosis from non-thrombosis. However, all three IgM results were significant in this regard: CD36 (p< 0.05), CD42b (p< 0.02), and most notably, CD41b (p< 0.0003). Conclusions: These results show that anti-platelet antibodies of IgM class, especially anti-CD41b, are associated with platelet activation, endothelial activation, and clinical thrombosis in TS. These findings parallel our previous report on APLA in TS. We suggest that IgM-CD41b may activate platelets, predisposing to hypercoagulable state in this disorder.

Atherosclerosis and the antiphospholipid syndrome: A link unravelled?

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 140-143 ◽  
Author(s):  
Y Shoenfeld ◽  
D Harats ◽  
J George
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Clinical Manifestations ◽  
Humoral Response ◽  
Arterial System ◽  
Glycoprotein I ◽  
Shock Proteins ◽  
Modified Forms ◽  
Progression Of Atherosclerosis

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to β2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.

scholarly journals Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction

2007 ◽  
Vol 98 (08) ◽  
pp. 420-426 ◽  
Author(s):  
Emilie Lanoy ◽  
Didier Tcheche ◽  
Laurent Feldman ◽  
Annie Bezeaud ◽  
Eduardo Anglès-Cano ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Platelet Activation ◽  
Plasminogen Activator Inhibitor ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
St Segment Elevation ◽  
St Segment ◽  
Circulating Microparticles ◽  
The Difference

SummaryWe tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST-segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1+2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P-selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47–84) ng/ml vs. 53 (44–63) ng/ml] and PAP [114(65–225) ng/ml vs. 88 (51–147) ng/ml].The difference persisted after adjustment for risks factors (p=0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation.

Biochemical Markers with Low-grade Inflammation as Predictors of Thrombotic Events in Antiphospholipid Syndrome

2017 ◽  
Vol 68 (7) ◽  
pp. 1586-1590
Author(s):  
Claudia Gavris ◽  
Vladimir Poroch ◽  
Laurentiu Simion ◽  
Adrian Baracan ◽  
Elena Toader ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Biochemical Markers ◽  
Cumulative Risk ◽  
Low Grade ◽  
Activation Markers ◽  
Acute Thrombosis ◽  
Markers Of Inflammation ◽  
Hs Crp ◽  
Low Grade Inflammation

The study aimed to test the inflammation hypothesis in antiphospholipid syndrome (APS) by assessing biochemical markers of inflammation and platelet activation. Forty one patients with APS were compared to 40 controls. High-sensitivity C-reactive protein (hs-CRP) (as inflammatory biomarker), P-selectin and soluble CD40L (sCD40L) (as platelet activation markers) were measured by ELISA at enrolment and after 12 months follow-up. Serum hs-CRP, P-selectin and sCD40L levels were significantly higher in patients with APS compared to controls. P-selectin was significantly higher in APS patients with recurrent or acute thrombosis compared to APS patients with no recurrent thrombotic events. Serum hs-CRP and anticardiolipin antibodies (aCL) and were independent predictors of thrombosis in APS. In conclusion, persistent increased hs-CRP titres demonstrated low-grade inflammation in APS. Serum biomarkers as aCL and hs-CRP were independent thrombotic cumulative risk predictors in patients with APS.

A Role of Platelet Activation in Lacunar Stroke?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1141-1141
Author(s):  
Nadine Ajzenberg ◽  
Philippa C Lavallee ◽  
Julien Labreuche ◽  
Dorothee Faille ◽  
marie-Genevieve Huisse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Endothelial Activation ◽  
Population Based ◽  
Vascular Risk ◽  
Lacunar Stroke ◽  
Activation Markers ◽  
Median Change

Abstract Abstract 1141 Lacunar stroke accounts for 25% of all ischemic strokes and is characterized by small infarcts located in the deep white matter, basal ganglia or pons resulting from the occlusion of deep branch arteries. In the last years, evidences about the role of endothelial dysfunction in lacunar stroke also named cerebral small vessel disease, have emerged. However platelet activation and aggregation are of major importance in acute thrombosis of atherosclerotic arteries, but their role and that of thrombus formation at sites of arteriolar injury as a precipitating event of lacunar stroke remains unclear. The aim of the present study was to determine platelet and endothelial activation in consecutive patients with recent lacunar stroke in comparison to population-based control subjects matched for age, sex and vascular risk factors. Methods— Platelet activation markers include activated glycoprotein (GP) IIbIIIa, P-selectin expression, platelet microparticles determined by flow cytometry, shear-induced platelet aggregation (SIPA), measured in a Sipagreg device that reproduces rheological conditions of stenotic or small arteries. We also studied endothelial activation markers including von Willebrand factor antigen (vWF), homocystein and high sensitivity C-reactive Protein (hsCRP). All these parameters were measured in 74 consecutive patients with recent lacunar stroke, in whom detectable large artery atherosclerosis or cardiac embolism have been ruled out, and in 74 population-based controls with no stroke history, matched for age, sex, hypertension, and diabetes. All patients were treated by anti-aggregant therapy, 15 (20%) were treated by clopidogrel (75 mg/d) and the remaining 59 cases received only acetylsalicylic acid (75 to 160 mg/d). Repeated blood samples were collected at one- and three-months after symptom onset. Results— One month after symptom onset, patients had similar levels of platelet activation compared to matched controls (p>0.40 for all-comparisons), including platelet membrane P-selectin with a median value of 1.3% and an interquartile range (IQR) (0.7–2.8) in patients and 1.1% (0.6–2.2) in controls, p=0.37), platelet activated GPIIbIIIa reached 2.9% (0.9–6.7) in patients and 2.8% (0.7–10.2) in controls, p=0.94. Platelet-derived microparticles were 5067/μL of blood (3720–7490) and 5035 (3530–8150) p=0.63l, in patients and controls, respectively. SIPA values at 4000 sec-1 were in the normal range in patients and controls, with no difference between the two groups: the median value of platelet aggregation was 22% (12–37%) in cases and 23% (7–45%) in controls (p=0.96), respectively. Endothelial activation parameters were increased in patients in comparison to controls (vWF p=0.002 and homocystein/creatinemia p=0.025) The median value of vWF antigen was 142% (114–182%) in cases and 122% (97–150%) in controls (p=0.002). The median value of ratio homocysteinemia/creatinemia was 0.151 (0.119–0.187) in cases and 0.134 (0.111–0.165) in controls (p=0.025). The median value of hsCRP was 2.7 mmol/l (1.5–6.0) in cases and 2.0 mmol/l (1.0–3.4) in controls (p=0.059). Level of hsCRP was slightly increased in patients compared to controls (p=0.059). At 3 months, significant decrease in vWF and hsCRP levels (median change in vWF=10%, p=0.004; median change in hsCRP=0.4 mg/L, p=0.02) was detected in patients. Homocystein level and all platelet parameters remained unchanged at this time compared to 1 month. Conclusions— Our results confirm that endothelial dysfunction is a major feature of lacunar stroke. One explanation could be an endothelial response to an acute systemic aggression by an unidentified agent. In contrast, chronic platelet activation, when compared to controls matched for age, sex and vascular risk factors, did not seem to play a central role in the pathophysiology of lacunar stroke. Disclosures: No relevant conflicts of interest to declare.

Clinical manifestations in patients with antiphospholipid antibodies: Beyond thrombosis and pregnancy loss

Lupus ◽  
2021 ◽  
pp. 096120332199524
Author(s):  
Irene Cecchi ◽  
Massimo Radin ◽  
Elena Rubini ◽  
Silvia G Foddai ◽  
Alice Barinotti ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Clinical Manifestations ◽  
Case Series ◽  
Clinical Spectrum ◽  
Prothrombotic State ◽  
Pregnancy Morbidity ◽  
Immunological Condition

The clinical spectrum of the antiphospholipid syndrome (APS) encompasses additional manifestations other than thrombosis and pregnancy morbidity, which may potentially affect every organ and system. The pathophysiology of APS indeed cannot be explained exclusively by a prothrombotic state and the “extra-criteria” manifestations of the syndrome should be attributed to other mechanisms, such as inflammation, complement and platelet activation. In this case-series, we report patients with uncommon clinical APS presentations, to highlight relevant peculiarities of the syndrome, potentially paving the way for a further update of clinical as well as laboratory manifestations of this complex immunological condition.

scholarly journals Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuela Velásquez ◽  
Luisa F. Peláez ◽  
Mauricio Rojas ◽  
Raúl Narváez-Sánchez ◽  
Jesús A. Velásquez ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Endothelial Activation ◽  
No Production ◽  
Endothelin 1 ◽  
New Therapies ◽  
Pregnancy Morbidity ◽  
Obstetric Aps

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases.

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