Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Platelet Aggregation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2001

Alterations of platelet aggregation kinetics with ultraviolet laser emission: the "stunned platelet" phenomenon.

Platelets, a major constituent of thrombus, play a crucial role in the pathogenesis of acute ischemic coronary syndromes. The effect of ultraviolet laser emission on platelets within thrombi is unknown. The effects of increasing levels of laser energy on platelets in whole blood were investigated. Blood samples were obtained by aseptic venipuncture and anticoagulated with 3.8% sodium citrate. Samples were exposed to increased levels (0, 30, 45, 60 mJ/mm2; 25 Hz) of ultraviolet excimer laser fluence (308 nm wave-length) and then tested for ADP and collagen induced platelet aggregation, platelet concentration, and for platelet contractile force (PCF) development. Scanning electron microscopy was used to detect laser induced morphologic changes of platelets and by flow cytometric analysis to detect changes in expression of platelet surface antigens p-selectin (CD 62) and glycoprotein IIb/IIIa (CD 43). Exposure to excimer laser energy produced dose dependent suppression of platelet aggregation and force development ("stunned platelets"). ADP aggregation decreased from 8.0+/-1.1 Ohms (mean+/-SEM) to 3.7+/-0.8 Ohms (p<0.001) to 2.7+/-0.6 Ohms (p <0.001) and to 1.8+/-0.5 Ohms (p <0.001) as the laser energy increased from 0 to 30 to 45 to 60 mJ/mm2, respectively. Collagen induced aggregation decreased from 21.4+/-1.4 Ohms to 15.7+/-1.2 Ohms (p <0.001) to 11.7+/-1.1 Ohms (p <0.001) and to 9.9+/-1.0 Ohms (p <0.001), in response to the same incremental range of laser energy. Platelet contractile forces declined from 34,500+/-3700 to 27.800+/-2700 dynes as laser energy increased from 0 to 60 mJ/mm2 (p <0.03). Platelet concentration did not change with increasing laser energy. The expression of platelet surface antigen p-selectin (CD 62) remained stable through increasing levels of laser energy exposures while the percentage of CD 43 positive platelets significantly increased with exposure to laser energy, yet the level of expression did not exceed 0.5% of cells. Thus, aggregation kinetics are altered in platelets exposed to ultraviolet laser energy as manifested by decreased platelet aggregation and reduction in platelet force development capability. The response is dose dependent and most pronounced at higher energy levels such as 60 mJ/mm2.

Adenosine Diphosphate↗
PubMed1999

Effects of prestorage white cell reduction on platelet aggregate formation and the activation state of platelets and plasma enzyme systems.

BACKGROUND: The introduction of prestorage white cell (WBC) reduction in random-donor platelet concentrates in Canada has increased the occurrence of particulate material in PCs. The effects of filtration on platelet activation state and the activation of plasma enzyme systems were assessed. STUDY DESIGN AND METHODS: Particulate material was examined by light microscopy, electron microscopy, protein electrophoresis, and biochemical analysis. Thirty PCs (10 unfiltered, 20 filtered) were examined during processing and 5-day storage for pH, platelet count and mean volume, morphology, activation marker expression, and hypotonic shock response. Complement activation, thrombin generation, and fibrinolysis were assessed by using specific enzyme immunoassays or chromogenic assays. RESULTS: By all analyses, the particulate material appeared to be platelet aggregates. Platelets exposed to WBC-reduction filters expressed a significantly higher level of activation markers CD62 and CD63, altered morphology, and increased platelet microparticles throughout the storage period than did unfiltered platelets. Complement activation at the C3 level was significantly increased in filtered units with little evidence of coagulation or fibrinolytic system activation. CONCLUSION: Exposure of platelets to filters during prestorage WBC reduction increased platelet activation and mildly increased complement activation over the levels during the storage period. These alterations can contribute to the formation of irreversible platelet aggregates during processing.

Antigens, CD↗
PubMed1989

Inhibition of platelet aggregation and arachidonate metabolism in platelets by procyanidins.

The effects of procyanidins on platelet aggregation and arachidonate metabolism in platelets were studied. Nine procyanidins were used in this investigation. Procyanidins B-2-S, EEC and C-1 significantly induced the inhibition of platelet aggregation, and the potency of inhibition was comparable with aspirin. Procyanidin B-2-S was used as a representative of procyanidins for further studies on the effect on arachidonate metabolism. In arachidonate metabolism by fatty acid cyclooxygenase pathway, B-2-S inhibited TXB2 and HHT formation by intact platelets treated with exogenous arachidonic acid. It also inhibited TXB2 formation measured by a specific radioimmunoassay when the cells were challenged with calcium ionophore A23187. In cell-free system, B-2-S inhibited both TXB2 and 12-HETE bioxynthesis in platelet microsome and cytosol, respectively. The inhibitory effect on thromboxane biosynthesis might explain the inhibitory effect of procyanidins on platelet aggregation.

Animals↗
PubMed1990

Influence of oryzanol on platelet aggregation in rats.

Platelet aggregation was measured using platelet rich plasma prepared from rats fed oryzanol in the control diet and those fed oryzanol in a 1 per cent cholesterol diet (HCD). Oryzanol with the control diet did not alter platelet aggregation induced by ADP and collagen. On the other hand, oryzanol fed along with HCD significantly inhibited platelet aggregation induced by ADP and totally inhibited aggregation induced by collagen.

Adenosine Diphosphate↗
PubMed1976

Isolation of intact megakaryocytes from guinea pig femoral marrow. Successful harvest made possible with inhibitions of platelet aggregation; enrichment achieved with a two-step separation technique.

Methods have been devised to harvest megakaryocytes from guinea pig femoral marrow and to isolate them in high yield. When marrow tissue was disaggregated the megakaryocytes underwent degenerative changes characterized by the loss of cytoplasmic granules and alterations in membrane topography, similar to the changes seen in aggregating platelets. These morphologic changes were interpreted to mean that megakaryocytes possessed functional attributes of platelets. The use of agents which inhibit platelt aggregation (0.38% sodium citrate. 10(-3) M adenosine, and 2 x 10(-3) M theophylline) in a medium free of bivalent cations prevented these changes. This solution resulted in both an excellent morphologic preservation and a significantly increased recovery of megakaryocytes from marrow tissue. A two-step purification of the intact megakaryocytes was carried out on the basis of their low density and large size, with equilibrium density gradient centrifugation followed by velocity sedimentation. This sequence gave approximately a 100-fold enrichment of megakaryocytes, significantly better than that achieved with either method alone. These techniques for harvesting and concentrating megakaryocytes make it possible for the first time to study megakaryocytes in vitro.

Adenosine↗
PubMed1987

Pharmacological properties of the novel anti-platelet aggregating agent 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid.

Various pharmacological properties of a new antiplatelet aggregating agent, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid (E-5510), were examined in order to elucidate its mode of action, Firstly, the inhibitory effect on in vitro aggregation of platelets from humans and various experimental animals was studied. E-5510 inhibited human platelet aggregation induced by collagen, arachidonic acid, adenosine diphosphate (ADP), platelet activating factor (PAF) and epinephrine. Thrombin-induced platelet aggregation, which was not inhibited by acetylsalicylic acid (ASA) or the thiazole drug, 4,5-bis(4-methoxyphenyl)-2-(trifluoromethyl) thiazole, was inhibited by E-5510. E-5510 inhibited collagen-induced platelet aggregation in platelet-rich plasma (PRP) from guinea pigs, beagle dogs and monkey to the same degree as in human PRP, but its effect was weaker in rat PRP. Human platelet adhesion to a collagen-coated plastic disk and thrombin-induced adenosine triphosphate (ATP) release from human platelets were also inhibited by this compound. Next, the ex vivo anti-platelet effect of E-5510 was examined in guinea pigs and beagle dogs. E-5510 was the most potent among the tested drugs (ticlopidine, ASA, cilostazol and the thiazole drug. The anti-platelet effect of this compound appeared within 1 h and lasted more than 8 h after oral administration. The above results suggest that E-5510 may antagonize platelet activation by inhibiting phospholipase C and/or A2, which results in suppression of both phosphatidylinositol breakdown and arachidonic acid release from phospholipids, as well as by inhibiting cyclooxygenase. E-5510 exerted its anti-platelet action without affecting prostaglandin I2 production in the blood vessels. It is considered that E-5510 has a highly potent anti-platelet aggregating effect and a unique multi-site mode of action. This compound is a promising candidate as an antithrombotic drug for clinical use.

Animals↗
PubMed1991

Antibodies to platelet-activating factor (PAF) inhibit PAF-induced platelet aggregation.

Platelet-activating factor (PAF) is the most potent platelet agonist known. PAF-induced platelet aggregation was blocked by pre-incubation of PAF with the immunoglobulin fraction from sheep or rabbit anti-PAF anti-serum. Inhibition was specific for PAF and was dependent upon immunoglobulin and PAF concentrations. Antibody-mediated inhibition of PAF-activity may be a valuable method for studying the biological effects of PAF in some systems.

Adenosine Diphosphate↗
PubMed1980

Demonstration of PGI2 production by isolated perfused rat lungs with platelet aggregation test.

Platelet aggregation test was used for PGI2 measurements. The use of 6 % CO2 in air stabilized human platelet rich plasma (PRP) so that it could be used for up to 7 hours in these measurements. The PGI2 caused inhibition of aggregation in response to ADP was concentration dependent in the range of 0.5 ng/ml to 50 ng/ml. Isolated perfused rat lungs released spontaneously 190 ng/min PGI2 and about 3 % of infused arachidonic acid potassium salt (equivalent to 25 microgram/min arachidonic acid) was converted to PGI2.

Adenosine Diphosphate↗
PubMed2005

Inability of probiotic bacterial strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 to induce human platelet aggregation in vitro.

Platelet aggregation contributes to the pathogenesis of infective endocarditis, and aggregation of platelets induced by lactobacilli is thought to be an important contributory factor in the development and progression of Lactobacillus endocarditis. The main purpose of this study was to examine the effect of immunity-enhancing probiotic strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 on the activation and aggregation of human blood platelets. Whole blood samples from healthy individuals were incubated in vitro with HN001 or HN019 and subsequently labeled with platelet-specific monoclonal antibodies, fluorescein isothiocyanate-conjugated anti-CD41a (expressed on normal platelets), and phycoerythrin-streptavidin-conjugated anti-CD62p (expressed on activated platelets) before analysis by flow cytometry. Platelet-rich plasma was used to assist the gating of the platelet cluster. ADP and epinephrine were used as the physiological platelet activation agonists. Platelet aggregation-inducing strain Streptococcus sanguis 133-79 was used as a positive control strain. The mean fluorescence intensity of phycoerythrin and the percentage of platelets expressing the CD62p marker were used to assess the degree of platelet activation. The percentage of CD62p-positive platelets and the light scatter profiles of the agonist-activated platelets were used to identify the occurrence and degree of platelet aggregation. HN001 and HN019 had no effect on spontaneous platelet activation and aggregation; they also failed to exacerbate the platelet aggregation activity induced by ADP and epinephrine. Therefore, these test probiotic strains HN001 and HN019 are less likely to participate in the pathogenesis of infective endocarditis or other thrombotic disorders with regard to platelet aggregation factors.

Antibodies, Monoclonal↗
PubMed1987

Free platelet count and size distribution during C1q inhibition of collagen-induced platelet aggregation.

Electronic free platelet counting was more sensitive than turbidimetry to detect collagen-induced platelet activation in human platelet-rich plasma. Purified human C1q exhibited a greater inhibitory effect on collagen-induced platelet aggregation in turbidimetry than free platelet counting. Because the change from small to large platelet aggregates is responsible for the continuing increase in light transmission, C1q was likely more capable of blocking the formation of large platelet aggregates than the formation of small aggregates from single platelets. The rate of change by collagen in light transmission and free platelet count was reduced in the presence of C1q but the timing of the peak response remained the same. Electronic platelet sizing revealed that the volume of single platelets transiently increased during the turbidimetric "lag phase". The mean, mode and median volume of the remaining free platelets then decreased, suggesting a selective loss of large, functionally more active platelets and/or platelet degranulation. C1q had no effect on the volume increment during the "lag phase", but reduced the subsequent fall in the volume of free platelets.

Adult↗
PubMed2005

Platelet aggregation and vasoconstriction related to platelet cyclooxygenase and 12-lipoxygenase pathways.

Many thrombotic angiopathies originate as a result of an abnormal interaction between platelets and blood vessel walls. The present study focused on the platelet activating factor (PAF)-induced platelet aggregation mechanism and was undertaken to clarify the association between platelet aggregation and vasocontractility. Vasoconstriction was examined in perfused artery segments dissected from the central ear artery of male rabbits. Autologous platelet rich plasma (PRP) was infused into the perfusion system. Vasocontractility was examined in response to PRP plus PAF or collagen. The vasocontractile response to noradrenaline (NA-R) on perfusion of PRP plus PAF was initially augmented, then gradually attenuated. The platelet aggregation in response to PAF was constant and longlasting and moderately inhibited by nordihydroguaiaretic acid, a 12-lipoxygenase (LOX) inhibitor, but was unaffected by indomethacin, a cyclooxygenase inhibitor. The attenuated responses disappeared and NA-R was returned to the initial level on pretreatment with tetrodotoxin which excluded neurogenic components from the arterial preparation. In contrast, a repetitive NA-R to PRP plus collagen gradually increased. Thus, it may be concluded that PAF-induced platelet aggregation participates in activation of the 12-LOX pathway and is accompanied by the release of vasodepressor nerve-stimulating substances from platelets.

Animals↗
PubMed1995

Effects of heparin and hirudin on thrombin generation and platelet aggregation after intrinsic activation of platelet rich plasma.

The effects of unfractionated heparin (UH) and recombinant hirudin (rH) on prothrombin activation, free thrombin generation, and platelet aggregation induced by endogenously generated thrombin after intrinsic activation of platelet rich plasma were compared. Free thrombin generation and platelet aggregation were assessed simultaneously by delaying fibrinogen polymerisation with GPRP. UH more effectively inhibited prothrombin activation and free thrombin generation than rH. Increasing concentrations of rH had hardly any effect on the peak amount of free thrombin, while in the presence of 400 nM UH only traces of free thrombin were detected. Comparison of TAT and THC (thrombin-hirudin complex) generated until the onset of platelet aggregation on a molar basis showed that much more thrombin was inactivated in the presence of rH than in plasma containing UH. The explosive generation of free thrombin in hirudinized plasmas was accompanied by a markedly steeper aggregation curve as compared to heparinized plasmas. The generation of thromboxane B2 was markedly delayed in the presence of UH but not influenced in the presence of rH. Our results suggest that UH is more effective than rH in inhibiting prothrombin activation after intrinsic activation of platelet rich plasma, while rH prevents clotting more by direct inactivation of already generated thrombin. The inability of even high concentrations of rH to prevent the explosive generation of free thrombin might contribute to the observed inefficiency of rH to inhibit platelet aggregation.

Blood Platelets↗
PubMedDate not supplied

Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments.

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 microM), a specific alpha(2)-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca(2+) mobilization in human platelets stimulated by collagen (1 microg/ml). Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E(1) (10 microM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 microM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 microM) in this study. The thrombin-evoked increase in pH(i) was markedly potentiated in the presence of morphine (1 and 5 microM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to alpha(2)-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na(+)/H(+) exchanger. This leads to increased intracellular Ca(2+) mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1985

N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin.

Platelet aggregation is currently felt to play an important role in the pathogenesis of ischemic vascular disorders. The smooth muscle relaxant, nitroglycerin, has been shown to inhibit platelet aggregation in vitro, but at concentrations that were felt to be unattainable in vivo. Because the in vivo action of nitroglycerin on smooth muscle cells has been shown to depend on the presence of reduced cytosolic sulfhydryl groups, the inhibitory effect of nitroglycerin on platelet aggregation was examined in the presence of the reduced thiol, N-acetylcysteine. Millimolar concentrations of N-acetylcysteine potentiated markedly the inhibitory effect of nitroglycerin on platelet aggregation induced by ADP, epinephrine, collagen, and arachidonate, decreasing the 50% inhibitory concentration (IC50) approximately 50-fold for each of these agents. Other guanylate cyclase activators inhibited ADP-induced aggregation similarly and this inhibition was likewise potentiated by N-acetylcysteine. Platelet guanosine 3',5'-cyclic monophosphate content increased fivefold in the presence of nitroglycerin and N-acetylcysteine 2 min before maximal inhibition of ADP-induced aggregation was achieved, while simultaneously measured cyclic AMP did not change relative to base-line levels. In the absence of N-acetylcysteine, nitroglycerin induced a marked decrease in platelet-reduced glutathione content as S-nitroso-thiol adducts were produced. The synthetic S-nitroso-thiol, S-nitroso-N-acetylcysteine, markedly inhibited platelet aggregation with an IC50 of 6 nM. These data show that N-acetylcysteine markedly potentiates the inhibition of platelet aggregation by nitroglycerin and likely does so by inducing the formation of an S-nitrosothiol adduct(s), which activate guanylate cyclase.

Acetylcysteine↗
PubMed1961

Effects of bacterial endotoxin on rabbit platelets. I. Platelet aggregation and release of platelet factors in vitro.

Incubation of platelet-rich rabbit plasma with E. coli endotoxin at 37 degrees C results in platelet aggregation and transfer of platelet 5-hydroxytryptamine to plasma. Release of 5HT is influenced by dose of endotoxin, type of anticoagulant, and temperature of incubation. A heat-labile plasma factor is necessary for the platelet-endotoxin interaction. Additional studies have shown that incubation of endotoxin with platelet-rich rabbit plasma also results in release of platelet phospholipid and bactericidins active against B. subtilis.

Animals↗
PubMed1990

SQ-27986 inhibition of platelet aggregation is mediated through activation of platelet prostaglandin D2 receptors.

SQ-27986, a oxabicycloheptane derivative, potently inhibits ADP-, collagen- and arachidonic acid-induced platelet aggregation in human platelet-rich plasma. Human platelet aggregation induced by ADP is inhibited by SQ-27986 (EC50 = 22nM), and the inhibitory action of SQ-27986 can be prevented with N-0164, a PGD2 antagonist. By comparison, ADP-induced rat platelet aggregation is unaffected by SQ-27986 (IC50 greater than 80 microM). Washed human platelets treated with SQ-27986 exhibit elevated cAMP levels and activated cAMP-dependent protein kinase. Elevation of platelet cAMP levels (greater than 4 fold basal) and activation of the cAMP-dependent protein kinase (greater than 4 fold) are observed with SQ-27986 concentrations above 100 nM. The SQ-27986-induced elevation of cAMP can be prevented by N-0164. Lysed platelets treated with SQ-27986 showed stimulated adenylate cyclase activity. SQ-27986 competes with [3H]prostaglandin D2 binding to isolated platelet membranes (EC50 for SQ-27986 is 20 nM, which was more potent than cold PGD2 itself). Radiolabeled Iloprost binding is virtually unaffected by SQ-27986 (EC50 greater than 100 microM), indicating that SQ-27986 does not interact with platelet prostacyclin receptors. These studies indicate that SQ-27986 inhibits platelet aggregation by activating platelet adenylate cyclase via stimulation of platelet PGD2 receptors.

Adenosine Diphosphate↗
PubMed2001

Spontaneous platelet aggregation with congenital giant platelet containing large granules and thick membrane.

Inherited giant platelet disorders are a heterogeneous group of disorders. In the current study, a patient was reported with moderate bleeding tendency, giant platelets, and spontaneous platelet aggregation, which were not affected by the administration of aspirin or ticlopidine. The electron microscopy of platelets showed a black and thick plasma membrane with crystal-like fine hairs in the exterior coat and more large and variously shaped granules in the cytoplasm. The expression of glycoprotein (GP) Ib, GP IIb, and GP IIIa on platelet surface was normal, and no mutations in genes for GP Ib alpha, GP Ib beta, and GP IX were detected. These phenomena are so distinguishable from those of Mondreal platelet syndrome and other hereditary giant platelet disorders, that we propose that this patient probably has a novel platelet disorder, which has not yet been reported.

Blood Platelet Disorders↗