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At least 451 records · Page 25Linked to original sources
PubMed2003

Is platelet aggregation a more important contributor than platelet adhesion to the overall platelet-related primary haemostasis measured by PFA-100?

BACKGROUND: Platelet-related primary haemostasis (PRPH), measured in PFA-100 as a closure time (CT), reflects platelets' combined ability to adhere and aggregate under higher shear stress. The inputs of platelet aggregation and platelet adhesion into the real values of CT remain unknown, and this poor discrimination results in the complexity of the PFA-100 measurement. OBJECTIVE: To estimate the particular contributions of two physiological phenomena, platelet aggregation and adhesion, and the importance of various membrane receptors underlying platelets' capability of the plug formation in PFA-100 cartridges. MATERIALS AND METHODS: Effects of various blockers antagonizing ligands binding to platelet surface membrane receptors (antagonists of GPIIb-IIIa complex, collagen receptors and purinoreceptors), and aurintricarboxylic acid (ATA), the antagonist of GPIb-von Willebrand factor (vWF) interaction, were monitored in 47 healthy donors with the use of PFA-100 and whole blood electrical aggregometry (WBEA). RESULTS: PFA-100 collagen/ADP CT was the most sensitive in probing the effect of platelet membrane receptor antagonists acting via the blockade of GPIIb-IIIa complex and those antagonizing GPIb-vWF interaction (GR144053F, Integrilin, ATA), whereas the other blockers, acting on collagen receptors or purinoreceptors, remained much less efficient. For the examined GPIIb-IIIa and GPIb antagonists, the overall variability in WBEA explained a very significant part (30-60%) of the overall variability in PFA-100 CT. CONCLUSIONS: GPIIb-IIIa-mediated platelet aggregation and von Willebrand factor interactions with GPIb and/or GPIIb-IIIa seem to be the major determinants of PFA-100 CT. On the contrary, other platelet receptors participating in platelet aggregation and/or platelet adhesion are of secondary importance and minor significance in blood flow at higher shear stress monitored in PFA-100.

Adult↗
PubMed1990

Shear-induced platelet aggregation.

Two platelet mechanisms contribute to haemostasis and thrombosis. (1) Compounds such as thrombin activate glycoprotein IIb/IIIa; fibrinogen is the ligand. The cyclooxygenase pathway is involved and so this process is aspirin sensitive. (2) Shearing forces alone activate a different domain on glycoprotein IIb/IIIa; von Willebrand's factor is the ligand. This process is probably non-enzymatic and is aspirin insensitive. The prevention of shear-induced platelet activation may prove to be more rewarding therapeutically than inhibition of aspirin sensitive pathways.

Blood Circulation↗
PubMed2005

Intraplatelet signaling mechanisms of the priming effect of matrix metalloproteinase-2 on platelet aggregation.

OBJECTIVE: Platelets contain and release some matrix metalloproteinases (MMPs), enzymes involved in the degradation of extracellular matrix, and one of these (MMP-2) exerts a proaggregatory effect. We explored the signal transduction mechanisms activated by MMP-2 in human blood platelets. METHODS AND RESULTS: Recombinant, human MMP-2, added before stimulation with subthreshold doses of different agonists, potentiated platelet activation, calcium influx, IP3 formation, and pleckstrin phosphorylation. Wortmannin and LY29400, two PI3-K inhibitors, suppressed the potentiating effects of MMP-2 and preincubation with MMP-2 enhanced the thrombin-induced association of the p85alpha PI3-K subunit with the cytoskeleton and increased the phosphorylation of PKB. Protein tyrosine kinase inhibitors, MAP kinase inhibitors, PLA2 inhibitors, cyclooxygenase inhibitors and antagonists of the P2Y1 and P2Y12 receptors did not affect the potentiating activity of MMP-2 on platelets. CONCLUSION: Our data show that MMP-2, at a concentration released by activated platelets, facilitates platelet activation acting at the level of a second messenger system common to different agonists and related to the activation of PI3-K. Platelet-released MMP-2 may contribute to platelet activation in vivo.

Androstadienes↗
PubMed1983

A potent platelet aggregation inducer from Trimeresurus gramineus snake venom.

A potent platelet aggregation inducer (platelet aggregoserpentin) was purified from Trimeresurus gramineus snake venom by DEAE-Sephadex A-50 and Sephacryl S-300 column chromatography. It was homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It elicited dose-dependently platelet aggregation and serotonin release reaction in rabbit platelet-rich plasma and platelet suspension. Exogenous calcium was required for its activity. Creatine phosphate/creatine phosphokinase and apyrase showed no significant inhibitory effect on aggregoserpentin-induced platelet aggregation in platelet suspension. Aggregoserpentin induced aggregation in ADP-refractory platelet-rich plasma. It caused no detectable malonic dialdehyde formation in the process of platelet aggregation. Indomethacin did not inhibit aggregoserpentin-induced platelet aggregation. Mepacrine abolished preferentially its aggregating activity, while prostaglandin E1 completely blocked both aggregoserpentin-induced aggregation and release reaction. Furthermore, platelet aggregoserpentin lowered basal and prostaglandin E1-stimulated cAMP levels in platelet suspension. Nitroprusside inhibited both its aggregating and releasing activity, while verapamil preferentially blocked its aggregating activity. It is concluded that aggregoserpentin activated platelets through lowering cAMP levels or the activation of endogenous phospholipase A2, resulting in the formation of platelet activating factor, but not of prostaglandins.

Adenine Nucleotides↗
PubMed1999

AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes.

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Acute Disease↗
PubMed1995

Dystrophin-related protein in the platelet membrane skeleton. Integrin-induced change in detergent-insolubility and cleavage by calpain in aggregating platelets.

The platelet membrane is lined with a membrane skeleton that associates with transmembrane adhesion receptors and is thought to play a role in regulating the stability of the membrane, distribution and function of adhesive receptors, and adhesive receptor-induced transmembrane signaling. When platelets are lysed with Triton X-100, cytoplasmic actin filaments can be sedimented by centrifugation at low g-forces (15,600 x g) but the membrane skeleton requires 100,000 x g. The present study shows that DRP (dystrophin-related protein) sediments from lysed platelets along with membrane skeleton proteins. Sedimentation results from association with the membrane skeleton because DRP was released into the detergent-soluble fraction when actin filaments were depolymerized. Interaction of fibrinogen with the integrin alpha IIb beta 3 induces platelet aggregation, transmembrane signaling, and the formation of integrin-rich cytoskeletal complexes that can be sedimented from detergent lysates at low g-forces. Like other membrane skeleton proteins, DRP redistributed from the high-speed pellet to the integrin-rich low-speed pellet of aggregating platelets. One of the signaling enzymes that is activated following alpha IIb beta 3-ligand interactions in a platelet aggregate is calpain; DRP was cleaved by calpain to generate an approximately 140-kDa fragment that remained associated with the low-speed detergent-insoluble fraction. These studies show that DRP is part of the platelet membrane skeleton and indicate that DRP participates in the cytoskeletal reorganizations resulting from signal transmission between extracellular adhesive ligand and the interior of the cell.

Amino Acid Sequence↗
PubMed1994

Effect of naloxone on platelet aggregation in rats.

The effect of naloxone on aggregation of blood platelets was investigated. Naloxone in millimolar concentrations dose-dependently inhibited collagen (20 mu g/ml)-induced platelet aggregation in rats PRP. For comparison with IC50 values on a molar basis, the ability of naloxone against platelet aggregation is similar to aspirin, but about 7-8 fold smaller than verapamil. In anesthetized spontaneously hypertensive rats (SHR), naloxone did not significantly alter the pressure response whereas administration of prazosin caused diminution of mean arterial pressure (MAP) related to dose. Naloxone did not interfere with the hematological parameters (i.e., WBC, RBC, PLT, HGB, HCT ... etc.) in Sprague-Dawley (SD) rats. The present study shows naloxone to be effective in obviating platelet aggregation, and seems to be reasonable in prevention of pulmonary platelet trapping (PPT), which is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS).

Animals↗
PubMed1990

Endothelin-1 inhibits platelet aggregation in vivo: a study with 111indium-labelled platelets.

1. A non-invasive technique for the scintigraphic determination of 111indium-labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 micrograms kg-1 i.v.), collagen (100 micrograms kg-1 i.v.), platelet-activating factor (PAF, 0.1 microgram kg-1 i.v.) or thrombin (18 iu kg-1 i.v.) was used to investigate the platelet-inhibitory effects of endothelin 1 (ET-1) in anaesthetized rabbits in vivo. 2. ET-1 (1 nmol kg-1 i.v.) inhibited ADP-stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide. 3. ET-1 (1 nmol kg-1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin-induced platelet aggregation. 4. Indomethacin (5 mg kg-1 i.v.) abolished the ET-1-induced inhibition of ADP-stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET-1. 5. In conclusion, the data demonstrate that ET-1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti-aggregatory cyclo-oxygenase product, presumably prostacyclin, into the circulation.

Adenosine Diphosphate↗
PubMed1993

Contribution of plasmin to sex differences in platelet aggregation in the rat.

Platelet aggregation was induced more strongly in male than in female 5, 12, and 45 week-old rats by both collagen and arachidonic acid. This is in agreement with our previous reports which suggested that the sex differences in platelet aggregation may be a primary characteristic of rat platelets. In plasma, plasmin-like activity was higher in male than in female rats. Plasmin alone induced aggregation, and low concentrations of plasmin synergistically enhanced collagen-induced aggregation in both male and female rats. Platelets potentiated plasmin generation by plasminogen activator at various Ca2+ concentrations in both male and female rats. Platelets from males displayed more efficient plasmin generation in 2 mM extracellular Ca2+ than those from females. If platelets were activated by abnormal causes in plasma, generated plasmin could make a greater contribution to the potentiated effect of platelet aggregation in male than in female rats. This study suggests that plasmin may be a partial cofactor in sex differences in platelet aggregation in the rat.

Animals↗
PubMed1988

The effect of fish oil consumption on platelet aggregation responses in washed human platelet suspensions.

Although the biochemical mechanisms relating to the inhibitory action of eicosapentaenoic acid on platelet function have previously been investigated in washed platelet suspensions, there is little existing evidence in washed platelet suspensions to indicate that dietary fish oil consumption reduces platelet aggregation responses. In the present work, eight healthy male volunteers consumed 20 fish oil capsules (MaxEPA) per day for a period of six weeks followed by a six week "dry-out" period during which no fish oil was consumed. Washed platelet suspensions were prepared and aggregation responses to collagen, platelet activating factor (PAF), and thrombin were assessed initially at week 0 and subsequently at 3, 6, 9, and 12 weeks of the experimental period. Three weeks of fish oil consumption did not produce any marked alterations in aggregation responses; however, six weeks of dietary fish oil supplementation resulted in decreased maximum aggregation responses to collagen and PAF by 50.1% and 27.2%, respectively. These results provide evidence, in washed platelet suspensions, that dietary fish oil consumption significantly diminishes platelet responses to collagen and PAF. The significance of these observations remains to be explored and interpreted.

Adult↗
PubMed1989

[Effect of dauricine on rat and human platelet aggregation and metabolism of arachidonic acid in washed rat platelets].

Dauricine (Dau), an isoquinoline alkaloid extracted from the roots of Menispermum dauricum D. C. and used as an antiarrhythmic agent in China recently, was shown to inhibit rat platelet aggregation induced by arachidonic acid (AA) and ADP, as well as human platelet aggregation induced by AA, ADP and adrenaline (Adr) in vitro in a dose-dependent manner. The concentration of Dau required for 50% inhibition (IC50) of rat platelet aggregation induced by AA and ADP was 26 and 37 mumol/L, respectively. For human platelet aggregation induced by AA, ADP and Adr the IC50 of Dau was found to be 39, 55 and 43 mumol/L, respectively. Dau inhibited the cyclooxygenase pathway metabolites of AA (TXB2 and HHT) in washed intact rat platelets. The production of TXB2 and HHT was reduced by 26% and 19%, respectively, when the Dau concentration was 50 mumol/L and by 46 and 45%, respectively, when the concentration of Dau was 100 mumol/L. The formation of 12-HETE was also inhibited at 100 mumol/L of Dau. The inhibitory effect of Dau on AA metabolism may be one of the mechanisms related to its inhibition of platelet aggregation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗