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 1,153 records · Page 64Linked to original sources
PubMed2002

Combined effects of eptifibatide and anticoagulants: differences between LMWH and UH or rH in thrombin generation inhibition but not in platelet aggregation inhibition.

Aim of our study was to investigate effects of eptifibatide and anticoagulants on platelet aggregation and thrombin generation under low and high coagulant challenge in tissue factor-activated platelet rich plasma using a model allowing simultaneous determination of the time course of platelet aggregation and thrombin generation. Eptifibatide exerted a dose-dependent anti-aggregating effect under both high and significantly stronger under low coagulant challenge. Combination of eptifibatide and anticoagulants resulted in significant additive prolongation of the lag phase until the onset of platelet aggregation, more pronounced under low coagulant challenge. Under high, but not under low coagulant challenge combination of eptifibatide and anticoagulants had a significant synergistic inhibitory effect on platelet aggregation. Under low coagulant challenge combination of eptifibatide with LMWH, but not with UH, or rH, resulted in significantly reduced thrombin potential, F 1+2 generation, and FXa formation compared to measurements in the absence of eptifibatide. We demonstrate a synergistic effect of eptifibatide and anticoagulants on platelet aggregation inhibition and an additional inhibitory effect of LMWH and eptifibatide on thrombin generation. Our results support the notion that combination of eptifibatide and anticoagulants might be beneficial in atherosclerotic disease to palliate the thrombogenic potency of ruptured atherosclerotic plaques.

Anticoagulants↗
PubMed1983

A species difference in platelet aggregation induced by tumour cells.

Ehrlich ascites tumour cells (EATC) induced the aggregation of human platelets but not of sheep or rabbit platelets in native platelet-rich plasma. Aggregation was initiated by the interaction of EATC with a component(s) of human plasma, possibly related to the complement system, which led to the release of cellular ADP, a potent platelet aggregating agent. EATC previously incubated with human platelet-poor plasma induced immediate aggregation in platelet-rich plasma from all three species. The species difference in platelet aggregation by EATC is therefore related to the activity or availability of plasma component(s) responsible for release of cellular ADP rather than to intrinsic differences in platelet responsiveness to the tumour cells.

Animals↗
PubMed1988

Effects of repeated oral doses of fenflumizole on platelet aggregation and thromboxane formation in man ex vivo.

Anti-platelet effects of fenflumizole, a new cyclo-oxygenase inhibitor, were studied in man ex vivo. Fenflumizole was given to male volunteers at the oral doses of 25, 50 or 100 mg per day, each dose for a period of seven days. The formation of thromboxane B2 (TXB2) during whole blood clotting, platelet aggregation induced by arachidonic acid and ADP, the formation of TXB2 during aggregation as well as serum concentration of fenflumizole were measured repeatedly during drug administration and for a fortnight after drug discontinuation. TXB2 formation during whole blood clotting was decreased dose-dependently by fenflumizole. The degree of inhibition of TXB2 formation was proportional to fenflumizole concentration in serum within each individual. The lag phase of platelet aggregation induced by arachidonic acid was prolonged and the formation of TXB2 during aggregation decreased by fenflumizole. No total inhibition of either TXB2 synthesis or platelet aggregation was caused by the fenflumizole doses used. The results show that the degree of inhibition of platelet thromboxane forming capacity by repeated doses of fenflumizole is closely related to the concentration of the drug in blood. Platelet aggregation however is less sensitive to changes in fenflumizole levels and cannot be assessed solely on the basis of cyclo-oxygenase activity.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Comparative effects of recombinant staphylokinase and streptokinase on platelet aggregation.

Recombinant staphylokinase (RSTA) has been shown to offer promise as a thrombolytic agent. In contrast to streptokinase (SK), few studies have been devoted to possible effects of RSTA on platelets. We have compared the capacity of RSTA and SK to trigger platelet aggregation and to modify ADP (2.5 microM) response in platelet-rich plasma (PRP) of 125 healthy subjects. Thus, exposure of PRP to SK (40 to 50 micrograms/ml) induced platelet aggregation in 6 out of 25 subjects. However, under the same conditions, RSTA failed to induce platelet aggregation in all cases (25 out of 25 subjects). In contrast to RSTA, SK (0.4 to 50 micrograms/ml) greatly reduced ADP-induced platelet aggregation in 12 out of 25 subjects. Preincubation of plasma with SK is associated with a decrease in the fibrinogen concentration. Furthermore, there was a good correlation between SK-induced fibrinogenolysis and SK-induced platelet aggregation defect (r2 = 0.9; p = 0.001). No fibrinogenolysis was observed when different amounts of RSTA (0.4 to 50 micrograms/ml) were incubated in plasma for one min. However, there was a marked decrease in fibrinogen level (about 50%) when the plasma was incubated for five min with a very high concentration of RSTA. SK markedly enhanced the platelet response to ADP in 13 out of 25 subjects. In PRP of 6 out of 25 subjects, SK induces platelet aggregation and potentiates platelet response to ADP, however in PRP of 7 out of 25 subjects, SK caused only the increase of platelet response to ADP. The monoclonal antibody anti-Fc gamma RIIa1, I-3 (2 micrograms/ml), abolished SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation. In all cases (25 out of 25 subjects), RSTA failed to potentiate platelet response to ADP. These findings confirm that RSTA has a lesser fibrinogenolytic ability than SK and suggest its negligible effect on platelet function.

Adenosine Diphosphate↗
PubMed2002

An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates.

BACKGROUND: The ability of abciximab to prevent fibrinogen binding to activated platelets indicates it may also promote dissolution of platelet-rich thrombi. The present study examined the capacity of abciximab to reverse platelet aggregation in vitro. METHODS AND RESULTS: Experiments were performed on blood from healthy non-medicated donors. Platelet aggregate formation and disaggregation were monitored turbidimetrically. Platelet-bound fibrinogen was measured by flow cytometry. For disaggregation studies, platelets were first stimulated with either ADP or the 11-mer thrombin receptor activating peptide (TRAP), then varying amounts of abciximab were added at periodic intervals after agonist addition. Platelet disaggregation was detected by comparing the extent of light transmittance at 4 min after addition of either abciximab or saline to PRP. ATP release was simultaneously monitored by chemi-luminescence. When added 1 min after low concentrations of ADP, abciximab rapidly (< 1 min) dispersed platelet aggregates in a dose-dependent manner, with complete disaggregation observed with 6.25 microg/mL of the beta3 antagonist. In contrast, equivalent concentrations of abciximab did not induce appreciable disaggregation to platelets stimulated with TRAP (10 microM). Platelet counts of samples that had undergone complete disaggregation, as assessed by aggregometry, were equivalent to baseline, indicating dispersal of aggregates to single cells. Concentrations of abciximab that produced complete disaggregation induced partial displacement of platelet-bound fibrinogen (52 +/- 8% inhibition of fibrinogen binding at 12.5 microg/ml abciximab). The disaggregation effectiveness of abciximab decreased as the time between ADP and subsequent abciximab addition widened, and as the amount of both dense granule release and agonist stimulation increased. However, pre-treatment of platelets with acetylsalicylic acid (ASA) did not potentiate platelet disaggregation induced by abciximab. CONCLUSIONS: These data indicate that abciximab facilitates the dispersal of newly formed platelet aggregates in vitro, by partially displacing fibrinogen from activated GPIIb/IIIa receptors. In vivo, abciximab may destabilize coronary thrombi by preventing aggregate formation and dispersing mural thrombi.

Abciximab↗
PubMed2003

Effects of proteins from hen egg yolk on human platelet aggregation and blood coagulation.

We studied the effect on both platelet aggregation and blood coagulation, known to be major risk factors in thrombogenesis, of proteins from hen egg yolk (EP). EP potently inhibited collagen-induced human platelet aggregation in a dose-dependent manner. Furthermore, EP has a synergistic effect on the inhibition of human platelet aggregation with both molsidomine, an inhibitor of cGMP-specific phosphodiesterase, and theophylline, an inhibitor of cAMP-specific phosphodiesterase. These results indicate that the active mode of EP might be involved in elevation of the levels of both cGMP and cAMP. Prothrombin time and activated partial thromboplastin time were potently prolonged by EP. These data suggest that EP prolongs the time interval between the conversion of fibrinogen to fibrin. Accordingly, these findings demonstrate that EP might have antithrombotic effects by inhibiting platelet aggregation and fibrin formation.

Animals↗
PubMed2005

[Study on the relationship of plasma fibrinogen, platelet aggregation rate and peripheral arterial occlusive disease].

OBJECTIVE: To detect the relationship of plasma fibrinogen, platelet aggregation rate and peripheral arterial occlusive disease (PAOD) in the elderly. METHODS: Cross-sectional survey for PAOD was implemented. Two thousands one hundred twenty-one subjects aged 60 - 89 years, male 941, female 1180, means aged 68.51 +/- 4.83 years, were randomly selected out of 20 411 elderly residents within 94 residential communities on the Wanshoulu area, Beijing. Case group involved 232 subjects, including 73 males and 159 females, with mean age 70.97 +/- 6.46 years, were randomly selected from the PAOD group on the PAOD cross-sectional study. 464 subjects were involved in the control group, including 217 males and 247 females, with mean age of 68.63 +/- 5.29, were randomly selected beyond the PAOD group on the PAOD cross-sectional study. Plasma fibrinogen level and platelet aggregation rate were determined in both groups. T test between the two groups was performed. The factors contributing to PAOD in this study (including: age, gender, smoking, obesity, family history of hypertension, diabetes, coronary artery disease, stroke and triglycerides, cholesterol, high density lipoprotein, low density lipoprotein, plasma fibrinogen, platelet aggregation rate) were performed using logistic regression analysis by diagnostic criteria of PAOD in this study. Stepwise selection was also used in this multivariate regression analysis. RESULTS: Plasma fibrinogen level (435.45 mg/dl +/- 115.25 mg/dl), was higher in the PAOD group than in the control group (360.96 mg/dl +/- 93.52 mg/dl, P = 0.001). Platelet aggregation rate at 3 minute (48.76% +/- 23.90%) in the PAOD group was higher compared with the control group (43.50% +/- 26.76%) with P = 0.012. Logistic regression analysis showed that factors, as plasma fibrinogen (OR = 0.994, 95% CI: 0.992 - 0.994), platelet aggregation rate at 3 minute (OR = 0.578, 95% CI: 0.403 - 0.829) were independent risk factors contributing to PAOD in this study. CONCLUSION: Plasma fibrinogen level and platelet aggregation rate were higher in the older patients of PAOD. It is possible for clinical physicians to inhibit platelet aggregation and reduce plasma fibrinogen level in the PAOD patients.

Aged↗
PubMed1975

Cardiopulmonary bypass. Microembolization and platelet aggregation.

Particulate microemboli and in vitro platelet aggregation were studied in blood of patients during cardiac operations with an electronic particle size analyzer. A small gradient of microemboli developed on passage of blood through a bubble oxygenator but not through a membrane oxygenator. However, with both types of oxygenators, there was a sustained increase in the volume of microemboli in cardiotomy return blood which was much greater than in aterial blood. After cardiopulmonary bypass with both oxygenators, there was a comparable reduction in the volume of circulating platelets which exceeded that of the hemoglobin concentration, indicating platelet loss exceeded that that expected from hemodilution alone. However, the total volume and mean size of platelet aggregates induced in blood of patients after membrane oxygenation was significantly greater than similar measurements after bubble oxygenation. This study shows that membrane oxygenation reduces particulate microembolization and preserves platelet function in patients undergoing cardiac operations when compared to bubble oxygenation.

Adenosine Diphosphate↗
PubMed2006

Synergistic effect of cilostazol and dipyridamole mediated by adenosine on shear-induced platelet aggregation.

INTRODUCTION: The Cilostazol Stroke Prevention Study found that cilostazol, a phosphodiesterase 3 inhibitor, can reduce the risk of subsequent stroke in Japanese patients with cerebral infarction. Here, we measured the effects of cilostazol in vitro on shear-induced platelet aggregation, an important mechanism of thrombosis at arterial bifurcations or stenotic lesions. We also evaluated the influences of intrinsic adenosine on the ability of cilostazol to inhibit shear-induced platelet aggregation by investigating the effect of dipyridamole, an inhibitor of cellular adenosine reuptake, in combination with cilostazol in vitro. MATERIALS AND METHODS: We measured platelet aggregation induced by a shear rate of 10,800 s(-1) in whole blood and in platelet-rich plasma from healthy volunteers using a cone-plate streaming chamber. RESULTS: Both cilostazol and adenosine dose-dependently inhibited shear-induced platelet aggregation in platelet-rich plasma samples. Adding a low concentration of adenosine (0.3 microM) did not inhibit shear-induced platelet aggregation, but significantly enhanced the inhibitory effect of cilostazol in platelet-rich plasma. Dipyridamole dose-dependently inhibited shear-induced platelet aggregation in whole blood and significantly enhanced the inhibitory effect of cilostazol on shear-induced platelet aggregation, but did not affect shear-induced platelet aggregation in platelet-rich plasma. The inhibitory effects of cilostazol combined with dipyridamole in whole blood were almost completely reversed by adenosine deaminase. CONCLUSIONS: Dipyridamole appears to synergistically enhance the inhibitory effect of cilostazol on shear-induced platelet aggregation by maintaining high plasma levels of adenosine.

Adenosine↗
PubMed2004

Relative effects of GAL+ and GALlow/- porcine hematopoietic cells on primate platelet aggregation and endothelial cell activation: implications for the induction of mixed hematopoietic chimerism in the pig-to-primate model.

BACKGROUND: The induction of porcine hematopoietic cell chimerism in preconditioned baboons has been hampered by the development of thrombotic microangiopathy. As pigs that lack expression of Gal alpha 1,3 Gal (Gal) may become available in the near future, we have explored the effects of porcine hematopoietic cells that express low or no Gal (Gal(low/-)) on baboon platelet aggregation and on human umbilical vein endothelial cell (HUVEC) activation. METHODS: Porcine mobilized peripheral blood progenitor cells (PBPC; Gal(+)) and bone marrow mononuclear cells (BM; Gal(+) or Gal(low/-)) were investigated for their potential to (i) induce aggregation of baboon platelets, and (ii) to activate endothelial cells as measured by increased expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin on HUVEC. alpha-Galactosidase-treated PBPC were also investigated for their effect on platelet aggregation. RESULTS: Gal(+) PBPC and Gal(+) BM cells (10(7)) induced aggregation of baboon platelets by 42 and 31%, respectively, whereas Gal(low/-) BM cells did not induce any platelet aggregation. alpha-Galactosidase-treated PBPC induced less platelet aggregation than untreated PBPC. Gal(+) PBPC and Gal(+) BM cells (10(7)) increased expression of VCAM-1, ICAM-1 and E-selectin on HUVEC, whereas Gal(low/-) BM cells did not. CONCLUSIONS: In contrast to Gal(+) PBPC or BM, Gal(low/-) BM cells do not induce aggregation of baboon platelets or activate HUVEC. The induction of tolerance through mixed hematopoietic cell chimerism may be facilitated when alpha-galactosyltransferase-knockout pigs become available.

Animals↗
PubMed1975

The release of prostaglandin-like substances during platelet aggregation and pulmonary microembolism.

During pulmonary microembolism subsequent to induced platelet aggregation in vivo, a pressor response is elicited in the lungs due to the release of vasoactive substances. During the prefusion of isolated cat lungs with whole blood, platelet aggregation induced by collagen released prostaglandin-like substances (PG-LS), and a rabbit aorta contracting substance (RCS) as measured by continuous biosassay of the venous effluent. This release occurred in parallel to the pulmonary pressor response. The same amount of PG-LS and RCS was released when the lungs were replaced by a blood filter to trap platelet aggregates. Apparently PG-LS and RCS are released from platelets during their aggregation. As E- and F-type PGs are rapidaly inactivated in the pulmonary circulation, there must either be an equal generation of PGs in the lungs themselves, or rather, the release of PGs from platelets must occur distal to the inactivation mechanism without any additional PG-release from the lungs. The exact role of PGs in the lung responses to intravascular platelet aggregation is not clear.

Animals↗
PubMed1980

[Effect of Complamin on fibrinolysis and platelet aggregation in the aged].

Investigated were the behaviour of platelet aggregation and fibrinolytic activity of the blood, under the influence of different doses of Complamin, and its effect in vitro on platelet aggregation. We have shown that platelet aggregation diminished only slightly after intravenous injection of Complamin, but the ADP-and collagen-induced aggregation in vitro were inhibited. Except that, fibrinolytic activity in the blood had been induced, but the degree and continuance of fibrinolysis were limited depending on the patient. There was no significant modifications of examined tests after prolonged intravenous infusion of the drug.

Aged↗
PubMedDate not supplied

Increased platelet aggregation response in Cavalier King Charles Spaniels with mitral valve prolapse.

Mitral valve prolapse (MVP) is a fundamental feature of myxomatous mitral valve disease in the dog. In humans, primary MVP is associated with increased platelet reactivity. In Cavalier King Charles Spaniels (CKCS), a breed predisposed to myxomatous mitral valve disease, there is a high prevalence of hypomagnesemia and platelet anomalies, such as thrombocytopenia and macrothrombocytosis. The objective of this study was to evaluate platelet aggregation responses in CKCS and to determine the relationship between the platelet aggregation response and serum magnesium concentration, MVP, mitral regurgitation (MR), and platelet count. In 19 CKCS with MVP and 7 control dogs (not CKCS), the platelet aggregation response to 3 different agonists was compared. The CKCS with >100,000 platelets/microL (n = 10) had a significantly higher maximum aggregation response with regard to all tested agonists than the CKCS with <100,000 platelets/microL (n = 9) and control dogs (n = 7). The CKCS with <100,000 platelets/microL had a platelet aggregation response similar to the control dogs. There was no correlation between degree of MVP and platelet aggregation response. Platelet diameter increased (P = .006) and serum magnesium concentration decreased (P = .04) with lower platelet concentration. In conclusion, CKCS with MVP appeared to separate into 2 groups--1 group with <100,000 platelets/microL, normal platelet aggregation, low serum magnesium concentration, and enlarged platelets, and another group with >100,000 platelets/microL, increased platelet aggregation, and normal serum magnesium concentration and platelet size.

Animals↗
PubMed1992

The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans.

The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

Adult↗
PubMed2006

Recombinant P-selectin glycoprotein-ligand-1 delays thrombin-induced platelet aggregation: a new role for P-selectin in early aggregation.

1. P-selectin is involved, with P-selectin glycoprotein (GP)-ligand-1 (PSGL-1), in platelet/leukocyte interactions during thrombo-inflammatory reactions; it also stabilizes platelet aggregates. Its antagonism accelerates thrombolysis and enhances the anti-aggregatory effects of GPIIb-IIIa inhibitors. This study was designed to investigate the mechanisms of P-selectin-mediated platelet aggregation. 2. In freshly isolated human platelets, P-selectin translocation after thrombin stimulation increased rapidly to 48, 72, and 86% positive platelets after 60, 120, and 300 s, respectively. Platelet aggregation at 60 s post-stimulation averaged 46.7 +/- 1.9% and its extent followed closely the kinetics of P-selectin translocation. 3. Pre-treatment of platelets with P-selectin antagonists, a recombinant PSGL-1 (rPSGL-Ig) or a blocking monoclonal antibody, significantly delayed platelet aggregation in a dose-dependent manner. At 100 microg ml(-1) of rPSGL-Ig, platelet aggregation was completely inhibited up to 60 s post-stimulation and increased thereafter to reach maximal aggregation at 5 min. The second phase of platelet aggregation, in the presence of rPSGL-Ig, was completely prevented by the addition of a GPIIb-IIIa antagonist (Reopro) at 60 s, whereas its addition in the absence of rPSGL-Ig was without any significant effect. 4. Combination of rPSGL-Ig with Reopro or with an inhibitor of Pi3K (LY294002), which reduces GPIIb-IIIa activation, showed to be more effective in inhibiting platelet aggregation, in comparison to the effects observed individually. 5. rPSGL-Ig blocks P-selectin, whereas Reopro and LY294002 block GPIIb-IIIa and its activation, respectively, without a major effect on the percentage of platelets expressing P-selectin. 6. In summary, platelet P-selectin participates with GPIIb-IIIa in the initiation of platelet aggregation. Its inhibition, with rPSGL-Ig, delays the aggregation process and increases the anti-aggregatory potency of Reopro. Thus, combination of P-selectin and GPIIb-IIIa antagonism may constitute a promising therapeutic option in the management of thrombotic disorders.

Blood Platelets↗
PubMed1989

A new index for collagen induced platelet aggregation.

In this paper, we propose a new index of platelet aggregation for optical aggregometry, the "R" value. This represents the rate of change in the half time for platelet aggregation (T1/2) induced by collagen with changes in the platelet concentration and expresses the degree of platelet sensitivity to collagen. The "R" value has been shown to reflect the aggregability of platelets due to activation of the contact factors. The "R" values were significantly different in the acute and chronic phases of occlusive arterial disease, while ordinary platelet aggregation parameters did not change. A decrease in the "R" value appears to indicate a platelet hyperfunction and hypercoagulable state, in other words a prethrombotic state.

Adenosine Diphosphate↗
PubMed1985

Platelet aggregation and glaucoma.

In this study platelet aggregation was determined in 79 patients with primary open angle glaucoma (POAG) and 81 patients suspected of having glaucoma (ocular hypertension). There is a positive association between high age and the presence of vascular diseases (p less than 0.01). An age dependent association between spontaneous platelet aggregation (SPA) and the presence of POAG was also observed (p less than 0.05). This indicates that the incidence of SPA in the elder group of patients with POAG is higher than in the elder glaucoma suspect group and in the group of younger patients. The association between vascular diseases and SPA and between vascular diseases and the presence of POAG were not significant at the 5% level. The incidence of SPA is not influenced by sex distribution, by the presence of diabetes, smoking or the use of timolol maleate topically.

Age Factors↗
PubMed1996

Effects of cocaine on human platelet aggregation in vitro.

BACKGROUND: A temporal relationship has been established between cocaine ingestion and myocardial infarction, and a cocaine-induced increase in platelet aggregation has been suggested as a possible explanation. However, the mechanisms of cocaine associated coronary thrombosis have yet to be completely elucidated. For this reason, we examined the in vitro effect of cocaine and its metabolites on platelet aggregation. METHODS: Platelet aggregation was tested by obtaining platelet rich plasma from 42 healthy volunteers and incubating the platelet rich plasma in six concentrations of cocaine (ranging from 1.47 to 2940 nmol) for 10 minutes prior to aggregation with ADP 1 microM. The same procedure was used to test the effect of two cocaine metabolites, benzoylecgonine and ecgonine methyl ester, on platelet aggregation. Abnormal results were confirmed by inducing aggregation with ADP at higher concentrations (2.4 and 10 microM) and with arachidonic acid (624 microM). RESULTS: At increasing concentrations, cocaine progressively inhibited ADP and arachidonic acid induced platelet aggregation. No effect was seen with benzoyl ecgonine or ecgonine methyl ester as compared to saline. CONCLUSIONS: These data suggest that under certain conditions cocaine may negatively affect hemostasis by decreasing platelet aggregation.

Adenosine Diphosphate↗