Effect of the PlA2 alloantigen on the function of β3-integrins in platelets

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3093-3099 ◽  
Author(s):  
Joel S. Bennett ◽  
Francesca Catella-Lawson ◽  
Andrew R. Rut ◽  
Gaston Vilaire ◽  
Weiwei Qi ◽  
...  
Keyword(s):  
Risk Factor ◽  
B Lymphocytes ◽  
Statistical Difference ◽  
Thrombus Formation ◽  
Coronary Thrombosis ◽  
Fibrinogen Binding ◽  
Β3 Integrin ◽  
Platelet Thrombus ◽  
Adhesion Of Platelets ◽  
Dissociation Constant Kd

Abstract The polymorphism responsible for the PlA2 alloantigen on the β3-component of β3-containing integrins is reported to be a risk factor for coronary thrombosis. This study examined the effect of PlA2 on the function of β3-integrins using platelets from subjects homozygous and heterozygous for PlA1 and PlA2. There was overlap in the distribution of the dissociation constant (Kd) and maximum fibrinogen binding (Bmax) values for fibrinogen binding to αIIbβ3 on platelets from PlA1 and PlA2 homozygotes and PlA1/PlA2 heterozygotes. However, whereas there was no statistical difference in these values for the PlA1homozygotes and PlA2 heterozygotes, the Kd for the PlA2 homozygotes was significantly lower than that for the PlA1/PlA2 heterozygotes, but was not statistically different from that for the PlA1 homozygotes. No differences were detected in ADP sensitivity between platelets from PlA1 homozygotes and PlA1/PlA2heterozygotes, in the IC50 for RGDS inhibition of fibrinogen binding to αIIbβ3, in the αvβ3-mediated adhesion of platelets to osteopontin and vitronectin, and in the phorbol ester-stimulated adhesion to fibrinogen of B lymphocytes expressing αIIbβ3 containing either the PlA1 or the PlA2 polymorphism. Finally, no differential effects of PlA2 on turbidometric platelet aggregation, platelet secretion, or platelet thrombus formation were found as measured in the PFA-100. Because no differences were detected in the ability of β3-integrins to interact with ligands based on the presence or absence of the PlA2 polymorphism, the results suggest that factors unrelated to β3-integrin function may account for the reported association of the PlA2 allele with coronary thrombosis.

Platelet thrombus formation by upstream activation and downstream adhesion of platelets in a microfluidic system

2020 ◽  
Vol 165 ◽  
pp. 112395 ◽  
Author(s):  
Sihui Xu ◽  
Jinxiang Piao ◽  
ByoungKwon Lee ◽  
ChaeSeung Lim ◽  
Sehyun Shin
Keyword(s):  
Thrombus Formation ◽  
Microfluidic System ◽  
Platelet Thrombus ◽  
Adhesion Of Platelets

scholarly journals Morphologic Platelet Changes During Thrombus Formation in the Rat

1977 ◽  
Author(s):  
R. Wiedemann ◽  
W. Weichert ◽  
K. Breddin
Keyword(s):  
Vessel Wall ◽  
Thrombus Formation ◽  
Vascular Lesions ◽  
Mesenteric Vessels ◽  
Platelet Thrombus ◽  
Adhesion Of Platelets ◽  
Damaged Vessel ◽  
Morphologic Changes

The film presents observations in small mesenteric vessels (diameter 10-20 μm) of the rat using high power Nomarski optics. Under stasis conditions platelets appear as flat discs. Leucocytes are often seen creeping slowly along the intact vessel wall. Vascular lesions are produced with a focused laser beam (Hadron 513 biolaser). Immediately after the lesion platelets stick to the site of the microburn either in their native disc like shape without apparent morphologic changes or with protrusions. Within seconds these platelets swell and form protrusions. After 3-10 min, depending on the size of the lesion the vessel is occluded by a platelet thrombus. Platelets undergo further swelling. Later the thrombus is partially or completely swept away and the vessel is recanal i zed. Irreversible fusion of platelets is rarely observed. . New, usually smaller thrombi form at the damaged vessel wall. The morphologic platelet changes observed differ markedly from the changes observed during aggregation in vitro. After injection of a new antithrombotic substance (Bay G 7565) the adhesion of platelets to the damaged area is remarkably diminished. The few platelets which adhere to the site of injury show the same swelling and transformation like in untreated animals. The film demonstrates that it is possible to investigate morphologic changes of single platelets during thrombus formation. It seems possible to adapt this model for the in vivo study of antithrombotic drugs.

Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo

2008 ◽  
Vol 99 (01) ◽  
pp. 190-195 ◽  
Author(s):  
Ildiko Konrad ◽  
Susanne Sauer ◽  
Lena Orschiedt ◽  
Maria Koellnberger ◽  
Reinhard Lorenz ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Atherosclerotic Plaque ◽  
Thrombus Formation ◽  
Atherosclerotic Lesion ◽  
Platelet Thrombus ◽  
Prevention Of Atherosclerosis ◽  
Adhesion Of Platelets ◽  
Deficient Mice

SummaryAcetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8–12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by ∼50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8–12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.

Inhbition of Platelet Thrombus Formation by Chlorpromazine Acting to Diminish Haemodynamically Induced Haemolysis

1979 ◽  
Author(s):  
G.V.R. Born ◽  
A. Uehmeier
Keyword(s):  
Platelet Aggregation ◽  
Human Blood ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Coronary Thrombosis ◽  
Internal Diameter ◽  
Novel Approach ◽  
Platelet Thrombus ◽  
Free Haemoglobin ◽  
Polyethylene Tubing

The idea that drugs capable of counter-acting hypotonic haemolysis (Seeman, 1972, Pharmacol Rev., 24, 583) might diminish the activating effect of erythrocytes on platelets (Gaarder et al., 1961, Nature, Lond., 192, 531) was suggested by one of us (GVRB) as a novel approach towards inhibiting their intravascular aggregation as thrombi. Indeed, chlorpromazine added to human blood in concentrations which diminish haemolysis but have no direct effect on platelet aggregation (Mills and Roberts, 1967, Nature, Lond., 213, 35) prolong the “bleeding time” from small holes in artificial vessels where extravasation is terminated, as in living arterioles, by aggregated platelets (Born, Bergquist and Arfors, 1976, Nature, Lond., 259, 235). Apyrase had a similar effect, suggesting that it was due to decreased plasma ADP. We now provide evidence that this ADP is released by haemolysis which is diminished by chlorpromazine. Human venous citrated blood at 37° was pumped continuously through polyethylene tubing 280 μm internal diameter. Chlorpromazine caused concentration-related increases in “bleeding times” from a standard cut and decreases in free haemoglobin. The observed haemolysis would provide enough ADP to initiate platelet aggregation. The results support the suggestion (Born et al., 1976) that drugs with this effect of chlorpromazine may prevent haemorrhage-induced, eg. coronary thrombosis.

In Vivo Antithrombotic Effect of Triflavin, an Arg-Gly-Asp Containing Peptide on Platelet Plug Formation in Mesenteric Microvessels of Mice

1994 ◽  
Vol 72 (04) ◽  
pp. 617-621 ◽  
Author(s):  
Joen-Rong Sheu ◽  
Seh-Huang Chao ◽  
Mao-Hsiung Yen ◽  
Tur-Fu Huang
Keyword(s):  
Thrombus Formation ◽  
Antithrombotic Agent ◽  
In Vivo Models ◽  
Occlusion Time ◽  
Fibrinogen Binding ◽  
Acute Pulmonary Thromboembolism ◽  
Platelet Thrombus ◽  
Mesenteric Microvessels ◽  
Plug Formation

SummaryTriflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. In this study, platelet thrombus formation was induced by irradiation of the mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. Electron microscopy reveals moderately damaged endothelial cells, as well as aggregates consisting almost exclusively of platelets with pseudopod formation, and degranulated appearance. Triflavin (10-20 µg/g) significantly prolonged the lag period of inducing platelet plug formation in mesenteric venules when it was intravenously infused. Triflavin (20 µg/g) prolonged the occlusion time about 2-fold (from control 112 ± 23 to 240 ± 47 s). Furthermore, PGE, briefly prolonged the occlusion time about 1.5-fold (from 105 ± 21 to 168 ± 20 s) when it was given by continuous infusion (40 µg/kg/min). On the other hand, triflavin was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at dose of 2-4 µg/g. Heparin (1.5 U/g) and indomethacin (200 µg/g) had no significant effect in prolonging the occlusion time or in reducing ADP-induced pulmonary embolism in mice. Therefore, triflavin is an effective antithrombotic agent in preventing the thromboembolism in these two in vivo models.

Thrombus formation on artificial surfaces: Correlative microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 840-841
Author(s):  
Quintin J. Lai ◽  
Stuart L. Cooper ◽  
Ralph M. Albrecht
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Low Voltage ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Polymer Surfaces ◽  
Flow Conditions ◽  
Transmission Electron ◽  
Adhesion Of Platelets ◽  
Microscopic Techniques

Thrombus formation and embolization are significant problems for blood-contacting biomedical devices. Two major components of thrombi are blood platelets and the plasma protein, fibrinogen. Previous studies have examined interactions of platelets with polymer surfaces, fibrinogen with platelets, and platelets in suspension with spreading platelets attached to surfaces. Correlative microscopic techniques permit light microscopic observations of labeled living platelets, under static or flow conditions, followed by the observation of identical platelets by electron microscopy. Videoenhanced, differential interference contrast (DIC) light microscopy permits high-resolution, real-time imaging of live platelets and their interactions with surfaces. Interference reflection microscopy (IRM) provides information on the focal adhesion of platelets on surfaces. High voltage, transmission electron microscopy (HVEM) allows observation of platelet cytoskeletal structure of whole mount preparations. Low-voltage, high resolution, scanning electron microscopy allows observation of fine surface detail of platelets. Colloidal gold-labeled fibrinogen, used to identify the Gp Ilb/IIIa membrane receptor for fibrinogen, can be detected in all the above microscopies.

Physico-Chemical Explanation of Blood Cell Adhesion in Thrombus Formation

1976 ◽  
Vol 36 (02) ◽  
pp. 430-440 ◽  
Author(s):  
A Marmur ◽  
E Ruckenstein ◽  
S. R Rakower
Keyword(s):  
Blood Cells ◽  
Thrombus Formation ◽  
Experimental Information ◽  
Deposition Surface ◽  
Physico Chemical ◽  
Quantitative Results ◽  
Energy Of Interaction ◽  
Induced Aggregation ◽  
Adhesion Of Platelets ◽  
Hydrodynamic Factors

SummaryA model is suggested which assumes that the rate of deposition of cells is determined both by hydrodynamic factors and by Brownian motion over the potential barrier caused by London and double-layer forces in the immediate vicinity of the deposition surface. The height of the barrier in the potential energy of interaction between blood cells and various surfaces is analyzed in relation to the physical properties of the cells, surfaces, and solutions. Based on this analysis, the adhesion of platelets to injured blood vessel walls and to non-biologic materials, the lack of adhesion of red blood cells under the same conditions, the mechanism of ADP induced aggregation and the interaction with blood flow are explained. The qualitative predictions of the model are substantiated by available experimental information. Quantitative results are presented in terms of a time constant, which typifies a period of contact with a surface, during which appreciable deposition occurs.

An Electron Microscopic Study of Platelet Thrombus Formation in the Rabbit with Particular Regard to 5-Hydroxytryptamine Release

1967 ◽  
Vol 18 (03/04) ◽  
pp. 592-604 ◽  
Author(s):  
H. R Baumgartner ◽  
J. P Tranzer ◽  
A Studer
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Endothelial Damage ◽  
Electron Microscopic ◽  
Rabbit Ear ◽  
Basement Lamina ◽  
Platelet Thrombus

SummaryElectron microscopic and histologic examination of rabbit ear vein segments 4 and 30 min after slight endothelial damage have yielded the following findings :1. Platelets do not adhere to damaged endothelial cells.2. If the vessel wall is denuded of the whole endothelial cell, platelets adhere to the intimai basement lamina as do endothelial cells.3. The distance between adherent platelets as well as endothelial cells and intimai basement lamina measures 10 to 20 mµ, whereas the distance between aggregated platelets is 30 to 60 mµ.4. 5-hydroxytryptamine (5-HT) is released from platelets during viscous metamorphosis at least in part as 5-HT organelles.It should be noted that the presence of collagen fibers is not necessary for platelet thrombus formation in vivo.

The Effect of Agents which Modify Platelet Behaviour and of Magnesium Ions on Thrombus Formation In Vivo

1979 ◽  
Vol 42 (02) ◽  
pp. 603-610 ◽  
Author(s):  
J H Adams ◽  
J R A Mitchell
Keyword(s):  
Thrombus Formation ◽  
Cerebral Arteries ◽  
Magnesium Ions ◽  
Body Formation ◽  
Inflammatory Agent ◽  
Platelet Thrombus ◽  
Magnesium Salts ◽  
Higher Doses ◽  
Do So

SummaryThe ability of potential anti-thrombotic agents to modify platelet-thrombus formation in injured cerebral arteries in the rabbit was tested. Low doses of heparin were without effect, while higher doses produced variable suppression of white body formation but at the expense of bleeding. Aspirin did not inhibit white body formation but another non-steroid anti-inflammatory agent, flurbiprofen was able to do so, as was the anti-gout agent, sulphinpyrazone. Magnesium salts both topically and parenterally, suppressed thrombus formation and increased the concentration of ADP which was required to initiate thrombus production at minor injury sites.

scholarly journals Obesity as a Risk Factor for Severe COVID-19 and Complications: A Review

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 933
Author(s):  
Fien Demeulemeester ◽  
Karin de Punder ◽  
Marloes van Heijningen ◽  
Femke van Doesburg
Keyword(s):  
Risk Factor ◽  
Disease Severity ◽  
Viral Entry ◽  
Thrombus Formation ◽  
Clinical Findings ◽  
High Risk Group ◽  
Therapeutic Interventions ◽  
Cytokine Storm ◽  
Negative Consequences ◽  
Major Complications

Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.

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