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.

SourceResearch connectionFrom yearThrough year

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

At least 937 records · Page 52Linked to original sources

PubMed1990

Platelet aggregation in septic shock. Effect of pentoxifylline.

In contrast to normal individuals, patients suffering from adult respiratory distress syndrome (ARDS) due to septic shock had increased platelet aggregation and circulatory platelet aggregates in blood. In vitro incubation with pentoxifylline (Trental) decreases platelet aggregates. This suggests that in addition to its platelet aggregation inhibitory effect, it also causes platelet disaggregation. Platelet aggregate patterns were shown to normalize two weeks after clinical recovery.

Adult↗

PubMed1991

Interactions between prostaglandin E2 and inhibitors of platelet aggregation which act through cyclic AMP.

Prostaglandin (PG) E2 potentiates platelet aggregation at low concentrations (10(-8)-10(-6) M). It also inhibits aggregation at a higher concentration (10(-5) M), probably by acting through cyclic adenosine 3',5'-monophosphate (cyclic AMP). The mechanism of this biphasic effect of PGE2 and its implications for thrombosis are not clearly understood. Using a sensitive cyclic AMP assay, in conjunction with platelet aggregation studies, we have examined the interactions between PGE2 and other inhibitors of platelet aggregation which act through cyclic AMP. Low concentrations of PGE2 reversed the inhibition of platelet aggregation and increase in cyclic AMP levels induced by PGI2, PGD2 and adenosine (which stimulate adenylate cyclase (AC) through separate and specific platelet receptors). In contrast, low concentrations of PGE2 added to the inhibition of platelet aggregation and increase in cyclic AMP levels induced by forskolin (which stimulates AC directly) and AH-P 719 and DN-9693 (which inhibit cyclic AMP phosphodiesterase (PDE]. These results suggest that the biphasic effect of PGE2 may be mediated by interaction with two separate platelet receptors. Low concentrations appear to potentiate aggregation by acting at a receptor which is directly coupled to an inhibitory guanine nucleotide-binding protein (Gi), possibly the putative PG endoperoxide receptor. High concentrations of PGE2 appear to inhibit aggregation by acting at an additional receptor, probably the PGI2 receptor. The ease with which PGE2 reverses the effects of PGI2, PGD2 and adenosine, but adds to the effects of AH-P 719 and DN-9693, suggests that PDE inhibitors might offer greater potential than these AC stimulators as an anti-thrombotic strategy.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Purification of a Class B1 platelet aggregation inhibitor phospholipase A2 from Indian cobra (Naja Naja) venom.

A platelet aggregation inhibitor phospholipase A(2) (NND-IV-PLA(2)) was isolated from Naja naja (Eastern India) venom by a combination of cation and anion exchange chromatography. NND-IV-PLA(2) is the most catalytically active enzyme isolated from the Indian cobra venom. The acidic PLA(2) profile of Eastern regional Indian cobra venom is distinctly different from that of the western regional venom. However the acidic PLA(2)s from both the regions follow the pattern of increasing catalytic activity with increase in acidic nature of the PLA(2) isoform. NND-IV-PLA(2) is a Class B1 platelet aggregation inhibitor and inhibits platelet aggregation induced by ADP, collagen and epinephrine. Modification of active site histidine abolishes both catalytic activity and platelet aggregation inhibition activities while aristolochic acid, a phospholipase A(2) inhibitor has only partial effect on the two activities.

Adenosine Diphosphate↗

PubMed1990

The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO-donors.

1. Full inhibition of thrombin-induced platelet aggregation was elicited by the least maximal platelet inhibitory concentrations of nitric oxide (NO; 7 +/- 1 microM) or NO-donors which included sodium nitroprusside (NaNp; 80 +/- 13 microM) 3-morpholinosydnonimine (SIN-1; 3 +/- 0.1 microM) or endothelial cells (EC; 2.36 +/- 0.12 x 10(5) added 1 min before thrombin. Oxyhaemoglobin (oxyHb; 10 microM) administered 30s to 10 min after stimulation with thrombin caused a time-dependent reversal of the inhibition induced by these agents. OxyHb was ineffective when these agents were co-incubated with the non-selective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 0.05 mM). 2. OxyHb did not reverse the platelet inhibition with IBMX (0.2 mM) or that caused by a selective guanosine 3'; 5'-cyclic monophosphate (cyclic GMP) phosphodiesterase inhibitor 2-O-propoxyphenyl-8-azapurin-6-one, (M & B 22948; 20 microM). In addition, oxyHb did not reverse the inhibition with iloprost (1 nM) which inhibits platelet aggregation through stimulation of adenylate cyclase. 3. The inhibition of platelet aggregation by NO (7 +/- 1 microM) or NaNp (80 +/- 13 microM) was accompanied by a 13 fold increase in cyclic GMP levels occurring within 15 s of addition of these agents. In the continued presence of NO or NaNp, the reversing effect of oxyHb given 1 min after thrombin was associated with a pronounced decrease in cyclic GMP levels. 4. We conclude that the inhibition of platelet aggregation by activators of guanylate cyclase depends in the first few minutes on continuous stimulation of the enzyme in order to maintain intracellular concentrations of cyclic GMP, except when its breakdown is inhibited. 5. The addition of agents such as oxyHb after the inhibition of platelet aggregation offers another way of investigating the biochemical changes involved in maintaining platelets in an inactive state.

1-Methyl-3-isobutylxanthine↗

PubMed1982

Studies of the effect of auranofin, a new antiarthritic agent, on platelet aggregation.

Auranofin (AF), at a concentration of 10 micrograms/ml, was found to be a potent inhibitor of ADP-, epinephrine-, or collagen-induced platelet aggregation utilizing platelet-rich plasma obtained from human blood. In contrast, aurothioglucose was less effective than AF in inhibiting epinephrine- or collagen- induced platelet aggregation. The inhibitory effect of AF was more evident on the second phase of aggregation. The inhibitory effect of AF was more evident on the second phase of aggregation and was a function of drug preincubation time. Compared to platelet-rich plasma, washed platelets were superior for detecting the inhibitory action of AF (greater than or equal to 0.1 microgram/ml) on ADP-induced platelet aggregation. This potent inhibitory action of AF on ADP-induced platelet aggregation was antagonized by dithioerythriol, a potent reducing agent. These results suggest that AF can inhibit both platelet release and aggregation mechanisms which may be relevant to its antiarthritic activity. Further studies are required to elucidate the cellular mechanism by which AF inhibits platelet aggregation.

Adenosine Diphosphate↗

PubMed1998

Inhibitory effects of nimodipine on platelet aggregation and thrombosis.

AIM: To study the inhibitory effects of nimodipine (Nim) on rat platelet aggregation and arterial thrombosis in vivo. METHODS: The aggregation rate of platelets induced by ADP and inhibition rate of Nim were measured by the change of light transmission. Effect of Nim on arterial occlusion time was measured by electric stimulation. Effect of Nim on the contents of 6-keto-PGF1 alpha and TXB2 in serum was measured by radioimmunoassay. RESULTS: Nim 4.5, 9, 18, and 36 mg.kg-1.d-1 ig for 4 d restrained the platelet aggregation. The IC50 (95% confidence limits) was 26 (9-44) mg.kg-1. Nim 4.5, 9, and 18 mg.kg-1.d-1 ig for 4 d markedly prolonged the time of thrombotic occlusion in carotid artery induced by electric stimulation. Nim 9 and 18 mg.kg-1.d-1 improved the imbalance of 6-keto-PGF1 alpha/TXB2 in serum after thrombosis. CONCLUSION: Nim was a potent inhibitor of platelet aggregation, which was partially concerned with the improved balance of 6-keto-PGF1 alpha/TXB2.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Inhibitory effects of beraprost on platelet aggregation: comparative study utilizing two methods of aggregometry.

We evaluated the inhibitory effects of beraprost, a stable prostacyclin analogue, on platelet aggregation, assessed by two methods of platelet aggregometry. The conventional aggregometry detects changes in light transmission (LT) of a platelet suspension, and a recently developed aggregometry based upon a particle counting principle detects light scattering (LS) generated by platelet aggregates. Since LS is more sensitive than LT in detecting platelet aggregates of small size, the minimal concentrations of agonists (ADP, epinephrine, collagen, and U46619) to induce detectable aggregate formation were consistently lower with LS (1/2 to 1/6) than with LT. The effects of beraprost were evaluated on platelet aggregation induced by the optimal concentrations of agonists thus determined for each sample. The IC50 values of beraprost on platelet aggregation, as assessed by LS, were 1/2 to 1/10 of those assessed by LT. In suppressing platelet aggregation assessed by LS, beraprost was especially potent with IC50 of 0.2-0.5 nM when platelets were activated by U46619, a thromboxane A2 analogue, or low concentrations of collagen which activates platelets through thromboxane A2 production. The IC50 values were 2-5 nM with ADP and epinephrine, which induce the formation of small aggregates independently of thromboxane A2 production. These findings suggest that LS can detect inhibitory effects of lower concentrations of antiplatelet agents, since it detects the formation of small aggregates induced by agonists in the lower concentration range than LT. It is also suggested that beraprost potently inhibits thromboxane A2-elicited initial signal transduction pathway, reflected by the formation of small aggregates.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1993

Aggregation and disaggregation kinetics of human blood platelets: Part III. The disaggregation under shear stress of platelet aggregates.

In the preceding two papers (1, 2), a population balance equation (PBE) mathematical model was developed, validated, and applied to the analysis of platelet aggregation kinetics under the influence of hydrodynamic shear stress. The present work involves the application of the model to the analysis of platelet reactions under shear stress in circumstances where disaggregation processes are of dominant importance: the disaggregation of aggregates formed in response to added agonists. Aggregation-disaggregation experiments were performed in the constant shear field of a rotational viscometer, and the evolution of the particle size distribution was determined by use of an electronic particle counter. The PBE model was used to simulate the experimental results. Exploratory calculations made it possible to reduce a rather complete, complex model to a more tractable form which retains the capability of simulating the experimental observations. For the experimental conditions studied, disaggregation by a splitting mechanism was found to be of dominant importance. The surface erosion mechanism can be neglected without significant impact on results. Physical reasoning confirmed by exploratory calculations showed that a discontinuous form of the breakage rate expression which incorporates a minimum friable particle size, gives significantly better results than a continuous expression. A simple step function void fraction parameter was found to be at least as successful as a more complicated, continuous function. The resulting simplified model has the potential of increasing our understanding of kinetics and mechanisms of platelet reactions, and of characterizing the state of platelet activity. Hence, it may be useful in efforts to understand thrombotic and hemostatic processes.

Adenosine Diphosphate↗

PubMed1975

The effect of heparin on platelet aggregation by common inductors and by ristocetin in congenital bleeding disorders due to factor VIII or fibrinogen defects.

Platelet aggregation by various inductors was studied in citrated and heparinized plasma of the following groups of subjects: Normal, hemophilia A, combined factor V and factor VIII deficiency, v. Willeprand's disease and congenital afibrinognemia. The results may be summarized as follows: A-platelet aggregation in citrated plasm 1) platelet aggregation by common inductors ADP, adrenalin and collagen was normal in all groups of subjects but for the patients with congential afibrinogenemia in whom adrenalin induced aggregation was absent or markedly refuced whereas ADP and collagen gave slightly reduced or near normal aggregation curves. 2) platelet aggregation by ristocetin was normal in all groups of subjects but for v. Willebrand's disease in which it was absent. B-platelet aggregation in heparized plasma. 1) platelet aggregation by common inductors resulted to be normal in all groups of subjects except in congenital afibrinogenemia. In this latter case the pattern was still mildly defective but here was an increased aggregation as compared to citrated plasma. These findings have been interpretemmon inductors. 2) platelet aggregation by ristocetin resulted to be absent in all groups of subjects investigated. The possible mechanism of action of the inhibitory effect exercised py heparin with regard to restocetin is discussed.

Adenosine Diphosphate↗

PubMed1980

Beta-thromboglobulin and platelet aggregates in glomerulonephritis.

Circulating platelet aggregate ratios (CPAR) and plasma beta-thromboglobulin (B-TG) concentrations were determined in 53 patients with chronic progressive glomerulonephritis [mesangiocapillary glomerulonephritis (15) and focal and segmental hyalinosis and sclerosis (38)] and compared with those from both normal subjects and patients with no evidence of renal disease. The mean B-TG concentration was higher in patient controls [32.6 +/- 6.2 ng/ml (SEM)] than in normal subjects [19.0 +/- 2.0 ng/ml (SEM)] but this did not reach significance (P < 0.10 > 0.05). Nephritic patients had markedly elevated levels [49.8 +/- 4.0 ng/ml (SEM)], but B-TG was significantly correlated with renal impairment. Elevated B-TG levels in patients with nephritis may thus reflect renal impairment or ill-health. The mean CPAR of the nephritic patients [0.75 +/- 0.02 (SEM)] was lower than that of both normal [0.86 +/- 0.03 (SEM), P < 0.001] and patient controls [0.87 +/- 0.02 (SEM), P < 0.001]. CPAR was not correlated with renal function or platelet concentration. Low CPAR in nephritic subjects provides further evidence for in-vivo activation of platelets in patients with glomerulonephritis.

Adult↗

PubMedDate not supplied

Effect of picotamide and aspirin, combined or alone, on platelet aggregation in patients with cerebral infarction.

After 7 and 90 days of treatment, we studied the effect of picotamide, a thromboxane synthase inhibitor (450 and 900 mg/day), aspirin (150 mg/day), and aspirin plus picotamide (150 and 450 mg/day respectively) on platelet aggregation, evaluated in platelet rich plasma of 48 patients affected by ischemic stroke. Platelet aggregation, induced by collagen (1.0 and 2.0 micrograms/ml) and adenosine diphosphate (1.0 and 10 micrograms/L), was significantly increased in patients in comparison with healthy controls. Aspirin (150 mg/day) reduced collagen-induced platelet aggregation (1.0 microgram/ml) after 7 days of treatment. Picotamide (450 mg/day) reduced platelet aggregation induced by both concentrations of collagen, while the higher dose (900 mg/day) had no significant effect. Aspirin plus picotamide reduced the aggregation induced by 1.0 microgram/ml collagen and by 10 mumol/L adenosine diphosphate after 90 days of therapy. This study has shown that patients during the acute phase of stroke are characterized by an increased in vitro platelet aggregation. Aspirin may be beneficial in the acute phase of the cerebral ischemic event. Picotamide and picotamide plus aspirin could be useful for reducing platelet aggregation in long term treatment.

Acute Disease↗

PubMed1991

Disseminated intravascular coagulation associated with Staphylococcus aureus septicemia is mediated by peptidoglycan-induced platelet aggregation.

Disseminated intravascular coagulation (DIC) may complicate severe septicemia caused by Staphylococcus aureus. S. aureus can induce spontaneous platelet aggregation in vitro, the rapidity and degree of which correlates with the severity of DIC in patients with sepsis. Purified peptidoglycan from DIC isolates aggregated human platelets in the presence of staphylococcal protein A with significantly shorter aggregation times than did peptidoglycan from non-DIC isolates. Purified teichoic acid from DIC and non-DIC isolates failed to aggregate platelets in vitro, or in vivo in guinea pigs but inhibited the peptidoglycan-induced aggregation in a dose-response manner. These studies suggest that peptidoglycan may mediate S. aureus-induced spontaneous platelet aggregation in vitro and DIC in vivo. The variability among strains of S. aureus to induce DIC and platelet aggregation may depend on the unique composition of their peptidoglycan and perhaps also the extent of exposure or availability of cell wall teichoic acid.

Animals↗

PubMed1986

Effect of heparin on platelet aggregation inhibited by PGI2, trifluoperazine and verapamil.

The enhancement of platelet aggregation by heparin in the presence of certain inhibitors of aggregation was investigated in an attempt to discern the mechanism through which heparin alters platelet function in plasma. These studies were performed by adding prostaglandin I2 (PGI2), verapamil, or trifluoperazine to platelet-rich plasma (PRP) in the presence or absence of heparin. Adenosine diphosphate (ADP), collagen, or arachidonic acid were used for induction of platelet aggregation. The inhibitory agents reduced platelet aggregation to 5 to 20% of control in the absence of heparin. When present in the reaction mixture along with the inhibitor, heparin restored aggregation to approximately 57 to 92% of control depending on the inhibitor and aggregating agent. This proaggregatory action of heparin was observed when heparin and PGI2 were preincubated together or separately for 20 min prior to the addition of PRP and ADP. Results were similar regardless of the sequence in which PGI2 and heparin were added to PRP, and irrespective of the time of incubation of platelets with PGI2. No suppression of platelet cyclic AMP concentration was observed with heparin alone. Heparin also failed to reduce the magnitude of platelet cyclic AMP accumulation promoted by PGI2, forskolin, or a mixture of PGI2 and forskolin. These observations suggest that heparin promoted platelet aggregation and partially overcame the effect of certain inhibitory agents by mechanism(s) that did not involve a reduction of platelet cyclic AMP.

Blood Platelets↗

PubMed1986

Effects of thromboxane A2 inhibition on osteogenic sarcoma cell-induced platelet aggregation.

There is evidence that tumors may stimulate platelet aggregation, causing release of thromboxane A2. Thromboxane A2 may potentiate tumor metastasis by stimulating tumor cell growth and proliferation and by enhancing platelet-tumor cell aggregate formation. Despite potential significance of thromboxane A2 in tumor metastasis, agents which inhibit thromboxane A2 synthesis have not been uniformly effective in reducing tumor metastasis. We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release. Osteogenic sarcoma cells added to platelet-rich plasma caused complete and irreversible platelet aggregation as well as thromboxane A2 release. Preincubation of platelet-rich plasma with SQ-29,548 (2 to 20 nM) decreased platelet aggregation induced by tumor cells, but it had no effect on thromboxane A2 release. In contrast, preincubation of platelet-rich plasma with OKY-046 (0.1 to 10 microM) had no effect on platelet aggregation despite a decrease in thromboxane A2 synthesis. These results suggest that thromboxane A2 receptor blockers, rather than synthetase inhibitors, may prevent tumor cell-induced platelet aggregation.

Blood Platelets↗

PubMed1985

Influence of platelet volume on the ability of prostacyclin to inhibit platelet aggregation and the release reaction.

The influence of mean platelet volume (MPV) and platelet count on in vitro platelet sensitivity to prostacyclin (PGI2) was studied with human size-dependent platelet subpopulations prepared by counterflow centrifugation. The original unfractionated platelet suspension and each of five size-dependent platelet fractions were suspended in buffer at a platelet count of 2 X 10(8)/ml. The percent decrease in the extent of platelet aggregation and adenosine triphosphate (ATP) release in response to 10 micrograms/ml collagen was determined over a range of PGI2 concentrations in a Lumi-Aggregometer. A significant positive correlation between MPV and the concentration required to give 50% inhibition for both platelet aggregation and ATP release (r = 0.99, p less than 0.001 and r = 0.99, p less than 0.001, respectively) was observed. In separate experiments, the effect of platelet count on the ability of a given dose of PGI2 to inhibit platelet aggregation and ATP release was determined, and a significant inverse correlation was noted (r = 0.99, p less than 0.01 and r = 0.98, p less than 0.01, respectively). Our data indicate that the sensitivity of human platelets to the inhibitory effects of PGI2 is dependent on both the platelet volume and the platelet count. Thus, the presence of a greater platelet mass, resulting from either an increased MPV or an increased platelet count, decreases the inhibitory effectiveness of PGI2 on both platelet aggregation and the release reaction.

Adenosine Triphosphate↗

PubMed1995

Effect of DC-015, a novel potent and selective alpha 1-adrenoceptor antagonist, comparison with prazosin on noradrenaline-induced platelet aggregation.

The antiplatelet activity of DC-015, a newly synthesized quinazoline derivative was determined in human platelet-rich plasma. From the binding studies, the Ki values of DC-015 for alpha 1-, alpha 2-adrenoceptors and 5-HT1, 5-HT2 receptors were about 0.21 (nM), 0.59 (microM), 0.16 (microM) and 0.38 (microM), respectivity. On the other hand, the Ki values of prazosin for alpha 1- and alpha 2-adrenoceptors were about 0.19 (nM) and 4.8 (microM), respectivity. Experimental results indicated that DC-015 dose-dependently inhibited noradrenaline (10 microM)-induced platelet aggregation in human platelet-rich plasma. At 20 microM, DC-015 would completely inhibit platelet aggregation induced by noradrenaline. A high concentration of prazosin (> 30 mM) caused sligh inhibition of aggregation. Furthermore, DC-015 (2 microM) significantly increased the cyclic AMP level in human platelet-rich plasma, whereas, prazosin significantly increased cyclic AMP level only at higher concentrations (100 microM). We can conclude that DC-015 inhibited noradrenaline-induced platelet aggregation mainly through binding to alpha 2-receptor on platelets, resulting in inhibiting platelet aggregation.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1998

Patients with venous stasis ulceration have increased monocyte-platelet aggregation.

PURPOSE: Leukocyte activation has been implicated in the pathogenesis of venous stasis ulceration, but the involvement of activated platelets and leukocyte-platelet aggregates has not been previously investigated. The purpose of this study was to determine whether patients with venous stasis ulceration have increased platelet activation and a propensity toward formation of leukocyte-platelet aggregates. METHODS: Blood was drawn from the superficial veins of the leg just proximal to a venous stasis ulcer and from an antecubital vein in 14 patients with venous stasis ulceration. Blood was also drawn from the antecubital vein of 14 volunteers without evidence of venous disease. Whole-blood flow cytometry was used to analyze the samples before and after activation with a panel of agonists for evidence of platelet activation and the formation of leukocyte-platelet aggregates. RESULTS: Patients with venous stasis ulceration had a greater number of monocyte-platelet aggregates in both the arm and leg samples than did the control subjects (p < 0.01). Furthermore, antecubital blood samples from patients with venous stasis ulceration stimulated with either thrombin-receptor agonist peptide, adenosine diphosphate, or phorbol myristate acetate formed more monocyte-platelet aggregates than did control samples (p < 0.05). No differences in platelet activation or neutrophil-platelet aggregate formation were noted among the three sample groups. CONCLUSIONS: Patients with venous stasis ulceration have an increase in the number of monocyte-platelet aggregates in systemic venous blood as well as in venous blood adjacent to a venous stasis ulcer, implicating the monocyte as the leukocyte involved in the pathogenesis of venous stasis ulceration. No association was identified between the presence of a venous stasis ulcer and either neutrophil-platelet aggregation or the activation of individual platelets. Because platelet activation is necessary for the formation of monocyte-platelet aggregates, these data also suggest that monocyte-platelet aggregation is a more sensitive marker for in vivo platelet activation than is the identification of individual activated platelets.

Adenosine Diphosphate↗

PubMed1978

Ionophore A-23187- and thrombin-induced platelet aggregation: independence from cycloxygenase products.

Stimulation of platelets labeled with [14C]-arachidonate by ionophore A23187 or thrombin produces rapid degradation of specific membrane phospholipids. This is also reflected by the release of [14C]archidonate, which is immediately transformed into products of the cycloxygenase and lipoxygenase enzyme systems, and by increased labeling of phosphatidic acid. Arachidonate metabolism can be effectively prevented by preincubation with indomethacin and eicosatetraynoic acid, but platelet aggregation induced by ionophore A23187 or trombin is not blocked under these conditions. Nevertheless, in the virtually total absence of metabolism of arachidonate, platelet aggregation still occurs concomitantly with phospholipid breakdown and with increased labeling of phosphatidic acid. Increased levels of cyclic AMP block both phospholipase activation and aggregation induced by ionophore A23187 and trombin. These data suggest that some early consequence of phospholipase activation, independent of a metabolic product of arachidonate but possibly related to the production of phosphatidic acid, may play a central, causative role in mediating platelet aggregation.

Animals↗