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The Journal of Thoracic and... Aug 2004Platelet function plays a major role in the understanding of thromboembolic events in prolonged mechanical support. We studied the platelet activation, platelet...
BACKGROUND
Platelet function plays a major role in the understanding of thromboembolic events in prolonged mechanical support. We studied the platelet activation, platelet aggregation profile, and efficacy of aspirin in patients in whom an external ventricular assist device had been implanted.
PATIENTS AND METHODS
Fifteen patients were studied prospectively up to 6 weeks after implantation of the same type of ventricular assist device. Platelet function was studied weekly before daily aspirin administration. Aspirin efficacy was tested ex vivo by measuring platelet aggregation triggered by arachidonic acid. Flow cytometry was used to quantify the spontaneous and induced (adenosine diphosphate stimulation) expression of glycoproteins alphaIIbbeta3, Ibalpha, and CD62P on platelet membranes. The plasma levels of von Willebrand factor (von Willebrand factor activity and von Willebrand factor antigen) and fibrinogen were also determined.
RESULTS
Six of the 15 patients (26%) maintained an arachidonic acid-induced platelet aggregation despite daily aspirin treatment (250 mg). CD62P values remained increased during a 5-week postoperative period. Spontaneous levels of glycoproteins alphaIIbbeta3 and Ibalpha on platelet membranes remained within a normal range with a preserved reactivity. The plasma levels of fibrinogen and von Willebrand factor remained increased during the entire study period.
CONCLUSION
In patients with an implanted external ventricular assist device, the platelet activation profile displays a persistent activation with a preserved reactivity associated with a persistent high inflammatory state and endothelial activation.
Topics: Adolescent; Aspirin; Female; Heart-Assist Devices; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Time Factors
PubMed: 15282455
DOI: 10.1016/j.jtcvs.2003.11.059 -
Clinical and Applied... Aug 2011Platelet activation is crucial for wound healing at sites of endothelial cell injury and involves multiple factors that mediate platelet recruitment, adherence, and... (Review)
Review
Platelet activation is crucial for wound healing at sites of endothelial cell injury and involves multiple factors that mediate platelet recruitment, adherence, and aggregation. Platelet activation in response to atherosclerotic plaque rupture or endothelial cell detachment can result in pathologic thrombus formation and acute ischemic events. Current oral antiplatelet agents, aspirin and adenosine diphosphate (ADP) receptor antagonists, are effective but associated with bleeding as they target activation pathways critical for protective hemostasis and pathologic thrombosis. Each inhibits a single platelet activation pathway and does not impact activation by thrombin. The lack of complete inhibition of platelet function allows continued thrombus formation and recurrent thrombotic events. Inhibition of the protease-activated receptor 1 (PAR-1) stimulated by thrombin offers a rational strategy to achieve more comprehensive platelet inhibition when used in combination with standard-of-care, dual antiplatelet therapy. We expect that this new approach may mitigate bleeding risk, because PAR-1 is not essential for hemostasis.
Topics: Blood Platelets; Hemostasis; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Receptor, PAR-1; Thrombosis
PubMed: 20566574
DOI: 10.1177/1076029610373366 -
Lancet (London, England) Sep 1995
Topics: Hemorheology; Humans; Micropore Filters; Myocardial Ischemia; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Platelet Count; Pressure
PubMed: 7674762
DOI: 10.1016/s0140-6736(95)91653-9 -
Platelets 2019Purity, limited platelet activation, and preservation of platelet function are important stakes of preparation of platelet concentrates (PC) for clinical use. In fact,...
Purity, limited platelet activation, and preservation of platelet function are important stakes of preparation of platelet concentrates (PC) for clinical use. In fact, contaminating red blood cells and leukocytes, as well as activated and/or poorly functional platelets in PC, represents a risk of poor efficiency and adverse side effects during platelet transfusion. Therefore, optimization of preparation and storage of PC is still an active field of research. Shear-induced platelet activation is an unwanted side effect of the hard-spin (up to 5000g) step of centrifugation-based methods currently used in blood banks to prepare PC from whole blood samples. Here, we evaluated the effectiveness of an acoustic-based fractionation device for the isolation of human platelets from whole blood bags. The purity, activation status, and functionality of platelets isolated by acoustopheresis were compared with those of platelets isolated using a reference protocol known to produce limited platelet activation and consisting of two consecutive soft-spin centrifugations (120g and 1200g). Platelet concentration and purity were determined using an automated hematology analyzer. Platelet activation status and platelet reactivity to collagen and thrombin were assessed in flow cytometry by measurement of surface expression of P-selectin and activated integrin αIIbβ3. The ability of isolated platelets to incorporate into a thrombus when transfused to NOD/SCID mice was investigated by intravital microscopy using the ferric chloride-induced thrombosis model. Blood fractionation by acoustophoresis led to the elimination of more than 80% of red blood cells and leukocytes from the platelet fraction, whose mean purity was of 92.8 ± 12.8%. The activation status and reactivity to collagen and thrombin of acoustophoresis-isolated platelets were similar to those of platelets isolated by soft-spin centrifugation. Finally, acoustophoresis-isolated platelets were tethered, adhered to the vessel wall, and incorporated into a growing thrombus following ferric chloride-induced vascular injury. Together, our results indicate that acoustophoresis is a suitable method for the isolation of human platelets with minimal platelet activation and preservation of platelet function.
Topics: Animals; Blood Platelets; Humans; Mice; Platelet Activation; Platelet Transfusion
PubMed: 29211557
DOI: 10.1080/09537104.2017.1386296 -
Platelets Jun 2017Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We...
Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.
Topics: Aged; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Platelet Activation; Pulmonary Veins; Recurrence
PubMed: 27736274
DOI: 10.1080/09537104.2016.1227429 -
Anesthesiology Dec 2009
Topics: Humans; Milrinone; Perioperative Care; Phosphodiesterase Inhibitors; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 19934858
DOI: 10.1097/ALN.0b013e3181c155ee -
Platelets Sep 2000ADP plays a central role in platelet aggregation. Activation of platelets via ADP proceeds via three membrane receptor proteins, two of which are coupled to a G protein... (Review)
Review
ADP plays a central role in platelet aggregation. Activation of platelets via ADP proceeds via three membrane receptor proteins, two of which are coupled to a G protein and the third one constituting an ion channel mediating rapid Ca2+-influx. Via Ca2+-mobilization, the Gq-coupled P2Y1 receptor acts in concert with the Gi-coupled P2TAC receptor, which functions by lowering intracellular cAMP levels. The importance of Ca2+-influx via the P2X1 ion channel remains to be elucidated.
Topics: Animals; Humans; Platelet Activation; Platelet Aggregation; Receptors, Purinergic P2
PubMed: 11083454
DOI: 10.1080/09537100050144713 -
Journal of Thrombosis and Haemostasis :... Feb 2003The His131Arg polymorphism of platelet FcgammaRIIA affects the binding affinity of certain IgG subclasses. The Arg131 allele has been associated with (auto)immune...
The His131Arg polymorphism of platelet FcgammaRIIA affects the binding affinity of certain IgG subclasses. The Arg131 allele has been associated with (auto)immune thrombocytopenia and heparin-induced thrombocytopenia in some studies. Because FcgammaRIIA can transmit platelet activation signals, we studied platelet responsiveness from 73 healthy donors to determine if this polymorphism modulated platelet function. Platelet function was studied by agonist and shear-induced activation, and standard aggregation. FcgammaRIIA was genotyped by allele-specific PCR. Compared with His131, the Arg131 allele was associated with significantly greater binding of activation-dependent antibodies. This effect was most prominent for the receptor-induced binding site (RIBS) antibodies F26 (P < 0.0001) and RIBS1 (P = 0.0057), and the ligand-induced binding site antibody LIBS1 (P = 0.0367). Unexpectedly, Arg131-positive platelets did not show greater fibrinogen binding, platelet aggregation or shear-induced platelet activation. We considered whether enhanced Fc binding and FcgammaRIIA cross-linking were responsible for those discrepancies. The increased binding of the two RIBS antibodies to the Arg131 isoform was abolished by blocking FcgammaRIIA, and the FcgammaRIIA genotype effect on F26 IgG binding was lost when F26 F(ab')2 fragments were used. Furthermore, intact F26 and RIBS1 IgG directly and specifically induced P-selectin expression, and this effect was greatest in Arg131-positive platelets. We concluded that (a) the His131Arg polymorphism of FcgammaRIIA does not affect intrinsic platelet reactivity; (b) RIBS antibodies are able to cross-link FcgammaRIIA and activate platelets, and this activation has a modest effect on Arg131 platelets; and (c) flow cytometric based platelet assays may need to compensate for this FcgammaRIIA His131Arg effect on platelet activation.
Topics: Adult; Antibodies, Monoclonal; Antigens, CD; Base Sequence; Blood Platelets; DNA; Female; Fibrinogen; Genotype; Humans; Immunoglobulin G; In Vitro Techniques; Male; Platelet Activation; Platelet Aggregation; Polymorphism, Genetic; Receptors, IgG
PubMed: 12871511
DOI: 10.1046/j.1538-7836.2003.00054.x -
Seminars in Thrombosis and Hemostasis Oct 1991
Review
Topics: Diabetes Mellitus; Humans; Platelet Activation
PubMed: 1803512
DOI: 10.1055/s-2007-1002648 -
Seminars in Thrombosis and Hemostasis Nov 2018Regular exercise may reduce the risk of major cardiovascular thrombotic events. However, previous studies suggest that the risk of myocardial infarction or primary... (Review)
Review
Regular exercise may reduce the risk of major cardiovascular thrombotic events. However, previous studies suggest that the risk of myocardial infarction or primary cardiac arrest is transiently increased during exercise. Thus, on the one hand, exercise seems to be able to protect against cardiovascular disease, but on the other hand, it seems to provoke sudden cardiac death. As platelets play a key role in arterial thromboembolic disease, the effect of exercise on platelet function is of special interest. This systematic review summarizes the evidence of the influence of exercise on platelet function in patients with coronary artery disease, angina pectoris, hypertension, or peripheral arterial disease. We specifically investigated, (1) if platelet function was increased in patients prior to exercise compared with healthy controls, (2) if exercise influenced platelet function differently in patients compared with healthy controls, and finally (3) if exercise reduced the effect of aspirin (acetylsalicylic acid). We performed a literature search in PubMed, Embase, Scopus, and Cochrane Library. In total, 18 articles were included and grouped into studies including patients with coronary artery disease ( = 7), angina pectoris ( = 5), hypertension ( = 5), and patients with peripheral arterial disease ( = 2). One study included both patients with coronary artery disease and patients with hypertension, and this study was therefore included in both groups. All studies performed short-term exercise either using treadmill ( = 12), primarily following the Bruce protocol, or bicycle ergometer test ( = 6). Overall, patients did not differ from healthy controls in platelet aggregation or activation prior to exercise. After exercise, conflicting results were reported with some studies reporting intensified platelet aggregation and/or platelet activation, some studies found no difference, whereas a few studies reported a reduction in platelet aggregation after exercise when compared with controls. Exercise seemed to impair the effect of aspirin during or shortly after exercise. In conclusion, the studies reported contradictive results. However, this review indicates that strenuous short-term exercise induces increased platelet activation also implying a reduced effect of aspirin during short-term exercise. Controlled studies on the effect of regular long-term low-intensity exercise are needed to further clarify the influence of long-term exercise on platelet function.
Topics: Blood Platelets; Cardiovascular Diseases; Exercise; Exercise Test; Humans; Platelet Activation; Platelet Aggregation; Platelet Function Tests
PubMed: 30267393
DOI: 10.1055/s-0038-1673618