Disease relevance of Platelet Aggregation

• We have found that infusion of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]), an agent used in the treatment of von Willebrand's disease, causes platelet aggregation and thrombocytopenia in patients with Type IIB disease [1].
• Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand's disease [1].
• Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension [2].
• Platelet membrane glycoprotein IIb-IIIa (gpIIb-IIIa; alpha IIb-beta 3), the most prominent member of the integrin family of adhesion receptors on these cells, mediates platelet aggregation by binding fibrinogen and is critical in thrombosis and haemostasis [3].
• Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency [4].

Psychiatry related information on Platelet Aggregation

• Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase [5].
• The first wave of platelet aggregation, which is independent of platelet release products, is enhanced while the latency period for the occurrence of release reaction and prostaglandin biosynthesis is shortened [6].

High impact information on Platelet Aggregation

• Human platelet aggregation induced by vWF or low-dose thrombin was inhibited by PKG inhibitors but enhanced by cGMP [7].
• In contrast, inhibition of serum thromboxane B(2) formation and platelet aggregation by aspirin was blocked when a single daily dose of ibuprofen was given before aspirin, as well as when multiple daily doses of ibuprofen were given [8].
• Nitric oxide, however, inhibits platelet aggregation and may contribute to bleeding from an ulcer [9].
• Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation [10].
• The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate [11].

Chemical compound and disease context of Platelet Aggregation

• Prostacyclin (PGI2) is a powerful inhibitor of platelet aggregation, but its role in the pathogenesis of arterial thrombosis is uncertain [12].
• Platelet aggregation in response to 5-HT in migraine patients taking oral contraceptives [13].
• Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis in platelet aggregation [14].
• At 0.1 and at 0.2 mg/kg body weight, 74% and 92% of the glycoprotein IIb/IIIa receptors were blocked, respectively; adenosine-diphosphate-induced platelet aggregation was inhibited by 84% and 100% at these same doses [15].
• Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcer-associated changes in serum levels of VEGF and endostatin [16].

Biological context of Platelet Aggregation

• Thromboxane A2 (TxA2), an arachidonic acid metabolite causing vasoconstriction and platelet aggregation, is a putative mediator of coronary-artery vasospasm [17].
• These properties include the reduction of systemic blood pressure without changing heart rate, the lowering of coronary vascular and total peripheral resistance, the inhibition of platelet aggregation and the concomitant formation of thromboxane B2, and the reduction of the release of lysosomal enzymes [18].
• Activation is key to integrin function in processes as diverse as cell migration, the organization of the extracellular matrix and platelet aggregation [19].
• Nitric oxide provokes vasodilation and inhibits platelet aggregation [20].
• These observations suggest that the GPIIb-GPIIIa macromolecular complex on the platelet surface acts under the proper physiologic circumstances as the fibrinogen binding site required for normal platelet aggregation [21].

Anatomical context of Platelet Aggregation

• Endothelial cells in culture can modulate platelet aggregation and vascular tone, in part by producing prostacyclin (PGI2), a powerful vasodilator and inhibitor of platelet aggregation, but also by their ecto-ADPase activity, which initiates the conversion of pro-aggregating ADP to adenosine, a potent vasodilator and platelet inhibitor [22].
• ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen [23].
• Prostacyclin (prostaglandin I2, PGI2), produced by the blood vessel wall is the most potent known inhibitor of platelet aggregation induced by such stimuli as ADP and thrombin [24].
• Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation [25].
• Using a turbidimetric technique, we determined 1.7 micrometer adenosine diphosphate--induced platelet aggregation and disaggregation at 37 degrees C in the platelet-rich plasmas of two groups of men with coronary artery disease [26].

Associations of Platelet Aggregation with chemical compounds

• Moreover, the defective platelet aggregation and thromboxane formation observed in the patients were not corrected by estrogens [27].
• The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean +/- SEM of 4.7 +/- 0.6 to 3.7 +/- 0.6 microM (P less than 0.01) for ADP and from 3.7 +/- 0.8 to 1.8 +/- 0.5 microM (P less than 0.01) for epinephrine [28].
• Platelet aggregation was demonstrated when heparin (0.5 U per milliliter) was incubated with the patients' citrated platelet-rich plasma or with normal platelet-rich plasma in the presence of the patients' serum [29].
• Thus, platelets obtained from diabetic patients possess increased activity of the prostaglandin synthetase system, and this characteristic may be related to the increased platelet aggregation associated with the disease [30].
• Platelet cholesterol content and platelet aggregation [31].

Gene context of Platelet Aggregation

• Gas6 amplified platelet aggregation and secretion in response to known agonists [32].
• The physiological role of the platelet-secreted protein thrombospondin (TSP) is poorly understood, although it has been postulated to be involved in platelet aggregation and cellular adhesion [33].
• Deletion of the gene encoding Akt2 impaired platelet aggregation, fibrinogen binding, and granule secretion, especially in response to low concentrations of agonists that activate the G(q)-coupled receptors for thrombin and thromboxane A(2) [34].
• Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation [35].
• Platelets isolated from the TNF-alpha-treated mice showed a marked decrease in fibrinogen binding and P-selectin expression as well as reduced platelet aggregation in response to various agonists [36].

Analytical, diagnostic and therapeutic context of Platelet Aggregation

• In rats, intravenous infusion of three NO donors, glyceryl trinitrate, sodium nitroprusside, or 3'-morpholinosydnonimine, the stable metabolite of molsidomine, released 6-keto PGF1alpha (the stable metabolite of PGI2) and inhibited ex vivo human platelet aggregation to adenosine diphosphate by at least 80% [37].
• We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia [38].
• A biopsy specimen of her vein did not generate PGI2, as measured both by platelet-aggregation inhibition and radioimmunoassay of 6-keto-PGF1 alpha [39].
• Ex vivo platelet aggregation in response to 20 mumol/L ADP and 4 micrograms/mL collagen was measured over time after the first dose of either xemilofiban (5, 10, 15, or 20 mg) or placebo (ticlopidine) administered 8 to 18 hours after termination of abciximab and again after 1 week of twice-daily oral administration of study drug [40].
• This dose of bitistatin caused an immediate inhibition of platelet aggregation; however, between 4 and 24 hours of perfusion, platelets of bitistatin-treated animals were more responsive to ADP (p < 0.0001) compared with platelets in control animals [41].

References