scholarly journals Haemodynamic flow conditions at the initiation of high-shear platelet aggregation: a combined in vitro and cellular in silico study

2020 ◽  
Vol 11 (1) ◽  
pp. 20190126 ◽  
Author(s):  
B. J. M. van Rooij ◽  
G. Závodszky ◽  
A. G. Hoekstra ◽  
D. N. Ku
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Platelet Rich Plasma ◽  
High Shear ◽  
Shear Rates ◽  
Flow Simulations ◽  
In Silico Study ◽  
Platelet Aggregates

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compared with in vitro platelet aggregation experiments performed with porcine whole blood (WB) and platelet-rich-plasma (PRP). We studied whether the cell-depleted layer in combination with high shear and high platelet flux can account for the distribution of platelet aggregates. High platelet fluxes at the wall were found in silico . In WB, the platelet flux was about twice as high as in PRP. Additionally, initial platelet aggregation and occlusion were observed in vitro in the stenotic region. In PRP, the position of the occlusive thrombus was located more downstream than in WB. Furthermore, the shear rates and stresses in cell-based and continuum simulations were studied. We found that a continuum simulation is a good approximation for PRP. For WB, it cannot predict the correct values near the wall.

Vigorous exercise acutely changes platelet and B-lymphocyte CD39 expression

2005 ◽  
Vol 98 (4) ◽  
pp. 1414-1419 ◽  
Author(s):  
Antonino Coppola ◽  
Ludovico Coppola ◽  
Liliana dalla Mora ◽  
Francesco M. Limongelli ◽  
Antonio Grassia ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
B Lymphocytes ◽  
Platelet Activation ◽  
Critical Role ◽  
Strenuous Exercise ◽  
Platelet Glycoprotein ◽  
Vigorous Exercise ◽  
Platelet Aggregates

CD39/ATP diphosphohydrolase is expressed on B lymphocytes, cytotoxic T lymphocytes, monocytes, platelets, and endothelial cells, and it has a critical role in the inhibition of platelet responsiveness. To determine whether strenuous exercise could acutely change expression of CD39 in platelets and lymphocytes, eight healthy sedentary men, 34 yr old (SD 7), and eight physically active men, 34 yr old (SD 6), performed graded upright cycle ergometry to volitional exhaustion. Blood samples collected both at baseline and after exercise test were employed to measure CD39 expression in platelets and lymphocytes. The percentage of circulating platelet-platelet aggregates, the “in vitro” ADP and collagen-induced platelet aggregation, and the expression of both platelet glycoprotein IIb-IIIa (PAC-1) and P-selectin (CD62) were also considered markers of platelet activation. After strenuous exercise, all subjects demonstrated significant platelet activation as judged by the increased percentage of platelet-platelet aggregates. The in vitro ADP-induced platelet aggregation and the expression of CD62P on ADP-stimulated platelets significantly increased in sedentary but not in active subjects. After exercise, all of the subjects showed a significant reduction of CD39 expression in platelet [sedentary: from 2.2 (SD 0.8) to 1.1% (SD 0.8), P = 0.008; active: from 0.6 (SD 0.2) to 0.35% (SD 0.1), P = 0.009] and an increase of CD39 expression in B lymphocytes [sedentary: from 47 (SD 13) to 60% (SD 11), P = 0.0039; active: from 46 (SD 11) to 59% (SD 11), P = 0.0038]. Taken together, these findings confirm the critical role of this ADPase in inhibition of platelet responsiveness, also suggesting a possible role of B lymphocytes in thromboregulation mechanism.

Influence of Fibrinogen Split Products on Platelets

1967 ◽  
Vol 17 (01/02) ◽  
pp. 078-098 ◽  
Author(s):  
M. I Barnhart ◽  
D. C Cress ◽  
R. L Henry ◽  
J. M Riddle
Keyword(s):  
Platelet Aggregation ◽  
Plasma Concentration ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Platelet Response ◽  
Transient Nature ◽  
Platelet Morphology ◽  
Platelet Aggregates

SummaryBreakdown products of fibrinogen and fibrin can play a role in hemostasis and also may be of consequence in thrombosis. β2 fibrinogen derivative D is an electropositive terminal proteolysis product of fibrinolysis which has the ability to aggregate platelets. The normal plasma concentration of such nonclottable fibrinogen relatives is 0.2 mg/ml. During fibrinolysis this concentration may reach 5 mg/ml plasma. Addition of β 2 fibrinogen D (raising the plasma concentration 0.1 to 5 mg/ml) either in vivo or in vitro induced platelet aggregations. Moreover, alterations in platelet morphology occurred which were obvious by electron microscopy.Platelet depletion was a consistent response to the infusion of purified β2 fibrinogen D (8 to 55 mg/kg body weight) into dogs. Circulating platelets decreased as much as 85% but were only temporarily aggregated and reappeared in the circulation within 1 to 5 hrs. Small platelet aggregates circulated while large aggregates were trapped in the microcirculation. Thrombin was not responsible for the platelet aggregations as neither prothrombin nor clottable fibrinogen were changed significantly. The transient nature and morphological features of the platelet response according to microscopic criteria were prominent during and after infusion of β2 fibrinogen D.In vitro studies included 3 systems; washed platelets, platelet rich plasma and whole blood. Positive results were obtained with all, but platelets in whole blood were most responsive. The magnitude of platelet aggregation and morphology correlated with the concentration of β2 fibrinogen D. Platelet aggregation induced by ADP (10~5 mg/ml) was compared with that induced by β2 fibrinogen D (0.09 to 0.72 mg/ml). With either reagent aggregates were of dendritic forms. Combination of the 2 reagents was additive but did not further change the morphology. Additional factors seem necessary for development of viscous metamorphosis.

scholarly journals Pharmacologic inhibition of thromboxane synthetase and platelet aggregation: modulatory role of cyclooxygenase products

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1460-1466
Author(s):  
V Bertele ◽  
A Falanga ◽  
M Tomasiak ◽  
C Chiabrando ◽  
C Cerletti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Gas Chromatography Mass Spectrometry ◽  
Thromboxane Synthetase ◽  
High Resolution Gas Chromatography ◽  
Pharmacologic Inhibition

Dazoxiben , an imidazole-derived selective inhibitor of thromboxane A2 (TxA2) synthetase, prevented TxB2 synthesis in vitro in platelet-rich plasma from 16 normal subjects. Inhibition of TxB2 synthesis was accompanied by increased generation of PGE2, PGF2 alpha, and PGD2, as shown by radioimmunoassay, thin-layer radiochromatography, and high- resolution gas chromatography-mass spectrometry. Even at dazoxiben concentrations (40–80 microM) above those inhibiting TxB2 synthesis, platelet aggregation induced by threshold concentrations of arachidonic acid was inhibited in only 4 of 16 subjects, referred to as responders. The remaining 12 individuals were defined as nonresponders. The aggregating effect of arachidonic acid and of the prostaglandin- endoperoxide analog U-46619 was potentiated by PGE2 and prevented by PGD2 at concentrations within the range of those detected in dazoxiben - treated platelet-rich plasma. The antiaggregating effect of dazoxiben was counteracted by PGE2 (in responders) and was potentiated by PGD2 (in nonresponders). Platelets from responders and nonresponders did not differ in the amount of immunoreactive PGE2 material or in their sensitivity to U-46619 or PGD2. It is concluded that inhibition of thromboxane synthetase does not per se prevent platelet aggregation. The functional result of thromboxane suppression appears to be modulated by an interplay of the prostaglandin-endoperoxides, PGE2 and PGD2, which are formed in excess.

scholarly journals Biorheology of occlusive thrombi formation under high shear: in vitro growth and shrinkage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Britt J. M. van Rooij ◽  
Gábor Závodszky ◽  
Alfons G. Hoekstra ◽  
David N. Ku
Keyword(s):  
Platelet Rich Plasma ◽  
Lag Time ◽  
Flow Chamber ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Dependent Behavior ◽  
Platelet Aggregate ◽  
Contraction Angle

Abstract Occlusive thrombi formed under high flow shear rates develop very rapidly in arteries and may lead to myocardial infarction or stroke. Rapid platelet accumulation (RPA) and occlusion of platelet-rich thrombi and clot shrinkage have been studied after flow arrest. However, the influence of margination and shear rate on occlusive clot formation is not fully understood yet. In this study, the influence of flow on the growth and shrinkage of a clot is investigated. Whole blood (WB) and platelet-rich plasma (PRP) were perfused at high shear rates (> 3,000 s−1) through two microfluidic systems with a stenotic section under constant pressure. The stenotic section of the two devices are different in stenotic length (1,000 vs 150 μm) and contraction angle of the stenosis (15° vs 80°). In all experiments, the flow chamber occluded in the stenotic section. Besides a significantly increased lag time and decreased RPA rate for PRP compared to WB (p < 0.01), the device with a shorter stenotic section and steeper contraction angle showed a shear-dependent occlusion and lag time for both PRP and WB. This shear-dependent behavior of the platelet aggregate formation might be caused by the stenotic geometry.

scholarly journals Reversible platelet aggregation in the presence of calcium ions: mechanisms and potential value

2019 ◽  
Vol 18 (3) ◽  
pp. 120-129
Author(s):  
A. A. Filkova ◽  
M. A. Panteleev ◽  
A. N. Sveshnikova
Keyword(s):  
Platelet Aggregation ◽  
Calcium Ions ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Reversible Aggregation ◽  
Blood Clots ◽  
Platelet Concentration ◽  
Irreversible Aggregation ◽  
Platelet Aggregates

Disorders in the functions of platelets – blood cells responsible for the blood clots formation and prevention – are observed as independent diseases, as a complication of cancer and hematological diseases or as a result of a therapy. Nowadays, a test of platelet aggregation by aggregometry is the only diagnostic method for assessing the platelets functions. There are several varieties of aggregometry, which differ both in the method of recording the formation of platelet aggregates and in the method of preparing platelets for the experiment. In most laboratories, it is customary to conduct aggregometry in platelet-rich plasma in the presence of citrate ions. In this case, the concentration of calcium ions in plasma decreases, it prevents the thrombin formation and the plasma coagulation. On the other hand, it has long been known that platelet aggregation in response to ADP in the presence of calcium ions (in blood plasma collected in heparin or hirudin tubes, also blocking plasma clotting) is reversible: after 1-5 minutes after the addition of the activator, the disaggregation begins until the light transmission of the solution (platelet concentration) returns to its original level. This phenomenon is called "reversible” platelet aggregation. Reversible aggregation (“disaggregation”) is sometimes observed in aggregometry of citrate plasma, especially in pediatric patients. However, it is usually not considered normal and is considered a sign of platelet dysfunction. This review considers the known mechanisms of disaggregation in the presence or absence of calcium ions in the medium. The role of secondary activation of platelets as a potential cause of irreversible aggregation is discussed, as well as possible versions for explaining the results of aggregometry, when reversible platelet aggregation is observed.

Clumping of Blood Platelets by Heat Aggregated Gamma-Globulin

1969 ◽  
Vol 21 (01) ◽  
pp. 065-075 ◽  
Author(s):  
R. B Davis ◽  
G. C Holtz
Keyword(s):  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Gamma Globulin ◽  
Platelet Rich Plasma ◽  
Blood Platelets ◽  
Electron Microscopic ◽  
Rabbit Blood ◽  
Platelet Aggregates

SummaryThe influence of heat-aggregated γ-globulin on the in vitro clumping of rabbit blood platelets was investigated in detail. Clumping was found to be dependent on the amount of γ-globulin added to the system. Clumping began within 60 sec, and was influenced by the amount of heparin in the system. Incubation of platelet-rich plasma with adenosine prior to the addition of heat-aggregated γ-globulin reduced the extent of platelet aggregation but did so only after aggregation was well under way, 150 sec after addition of γ-globulin. The extent of platelet clumping by aggregated γ-globulin was significantly increased by non-aggregating quantities of epinephrine, nor-epinephrine, and 5-hydroxytryptamine in the system; however, bradykinin and histamine were without effect. Electron microscopic observations of platelet aggregates showed that variable destructive changes were present in platelet aggregates, with loss of organelles and platelet hyaloplasm. Marked pseudopod formation was observed in platelet aggregates formed by epinephrine and aggregated γ -globulin. The significance of the findings in relation to the problem of arterial thrombosis is discussed.

scholarly journals Pharmacologic inhibition of thromboxane synthetase and platelet aggregation: modulatory role of cyclooxygenase products

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1460-1466 ◽  
Author(s):  
V Bertele ◽  
A Falanga ◽  
M Tomasiak ◽  
C Chiabrando ◽  
C Cerletti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Gas Chromatography Mass Spectrometry ◽  
Thromboxane Synthetase ◽  
High Resolution Gas Chromatography ◽  
Pharmacologic Inhibition

Abstract Dazoxiben , an imidazole-derived selective inhibitor of thromboxane A2 (TxA2) synthetase, prevented TxB2 synthesis in vitro in platelet-rich plasma from 16 normal subjects. Inhibition of TxB2 synthesis was accompanied by increased generation of PGE2, PGF2 alpha, and PGD2, as shown by radioimmunoassay, thin-layer radiochromatography, and high- resolution gas chromatography-mass spectrometry. Even at dazoxiben concentrations (40–80 microM) above those inhibiting TxB2 synthesis, platelet aggregation induced by threshold concentrations of arachidonic acid was inhibited in only 4 of 16 subjects, referred to as responders. The remaining 12 individuals were defined as nonresponders. The aggregating effect of arachidonic acid and of the prostaglandin- endoperoxide analog U-46619 was potentiated by PGE2 and prevented by PGD2 at concentrations within the range of those detected in dazoxiben - treated platelet-rich plasma. The antiaggregating effect of dazoxiben was counteracted by PGE2 (in responders) and was potentiated by PGD2 (in nonresponders). Platelets from responders and nonresponders did not differ in the amount of immunoreactive PGE2 material or in their sensitivity to U-46619 or PGD2. It is concluded that inhibition of thromboxane synthetase does not per se prevent platelet aggregation. The functional result of thromboxane suppression appears to be modulated by an interplay of the prostaglandin-endoperoxides, PGE2 and PGD2, which are formed in excess.

scholarly journals Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

2015 ◽  
Vol 54 (9) ◽  
pp. 1936-1941 ◽  
Author(s):  
Madhusudan M. ◽  
Farhan Zameer ◽  
Akhilender Naidu ◽  
Nagendra Prasad M. N. ◽  
Bhadrapura Lakkappa Dhananjaya ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Withania Somnifera ◽  
In Silico Study ◽  
Inhibitory Potential
Sign in / Sign up

Export Citation Format

Share Document