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 73 records · Page 4Linked to original sources
PubMedDate not supplied

Platelet aggregation and reversible platelet aggregates in type I-diabetes staged by retinal fluorescein angiography.

In 70 patients with juvenile-onset, insulin-dependent (type I) diabetes and 75 age- and sex-matched controls the reversible platelet aggregates expressed as platelet count ratio (PCR) and the ADP-induced platelet aggregation were studied. Retinal microangiopathy was staged by retinal fluorescein angiography. The mean PCR of the patients (0.82 +/- 0.02) was statistically significantly lower than that of the controls (0.97 +/- 0.01). However, in different stages of retinopathy no significantly different PCR could be observed. ADP-induced platelet aggregation (0.5 and 1.0 micromol/l) exhibited a higher reactivity of diabetic platelets, but with the exception of tangent alpha (see later), the differences were not statistically significant in comparison to the controls. After collagen-induced platelet aggregation (0.5 and 1 microgram/ml) the lag time in diabetics was significantly (p less than 0.001) lower than in the controls, whereas the other quantitative parameters exhibited higher platelet reactivity in general, though not statistically significant. No relationship between PCR and the in vitro induced aggregation was found. The degree of retinopathy had no significant influence on platelet aggregation. In general, the data demonstrate an increase in sensitivity of platelets in juvenile-onset diabetics, whereas no influence of stage of microangiopathy could be detected.

Adenosine Diphosphate↗
PubMed1988

Effects of three beta-blockers with different pharmacodynamic properties on platelet aggregation and platelet and plasma cyclic AMP.

The effects of three different types of beta-adrenoceptor blocking agents on platelet aggregation and on platelet and plasma cyclic AMP content have been studied in 14 patients with mild hypertension given each drug in turn for two weeks. The drugs were a non-selective blocking agent with high intrinsic sympathomimetic activity, pindolol, the nonspecific blocking agent propranolol, and the beta 1-selective metoprolol. The threshold values of ADP and adrenaline for irreversible platelet aggregation were significantly higher for pindolol and metoprolol than for propranolol. The cyclic AMP content of platelets was higher during pindolol and metoprolol than during propranolol treatment. Pindolol produced a substantial increase in plasma cyclic AMP relative to the other two drugs. Thus, platelet aggregation and cyclic AMP formation are influenced by beta-adrenoceptor blockade in proportion to intrinsic sympathomimetic activity and affinity for different beta-adrenoceptor subtypes.

Adenosine Diphosphate↗
PubMed1987

Human plasma kallikrein: effect on the induced platelet aggregation.

Platelet aggregation induced by ADP, collagen and adrenaline is increased by low concentrations of human plasma kallikrein, which does not cause aggregation by itself and inhibits the aggregation induced by arachidonic acid and Thrombofax in platelet rich plasma, and the aggregation induced by thrombin in washed platelets. At higher concentrations however, plasma kallikrein inhibits the aggregation induced by all the agents tested with platelet rich plasma and also causes a decrease in the aggregation induced in whole blood.

Adenosine Diphosphate↗
PubMed1981

The effect of phospholipase inhibitor mepacrine on platelet aggregation, the platelet release reaction and fibrinogen binding to the platelet surface.

We have examined whether inhibition by mepacrine or freeing of arachidonic acid from platelet phospholipids inhibits platelet aggregation to collagen, thrombin or ADP, and the release reaction induced by thrombin or collagen. Loss of arachidonic acid was monitored by measuring the amount of 14C feed from platelets prelabelled with 14C-arachidonic acid. Mepacrine inhibited 14C loss by more than 80% but did not inhibit thrombin-induced platelet aggregation and had a small effect on release. ADP-induced platelet aggregation did not cause 14C loss. Mepacrine inhibited ADP-induced platelet aggregation by inhibiting the association of fibrinogen with platelets during aggregation. The effect of mepacrine on fibrinogen binding could be considerably decreased by washing the platelets but the inhibition of 14C loss persisted. Platelets pretreated with mepacrine and then washed show restoration of aggregation to collagen. Thus, mepacrine has two effects; 1. it inhibits phospholipases, 2. it inhibits fibrinogen binding. Freeing of arachidonic acid is not necessary for platelet aggregation or the release reaction.

Adenosine Diphosphate↗
PubMed1981

Glucose-6-phosphate dehydrogenase deficiency in human platelets and its effect on platelet aggregation.

Platelets from patients with known red blood cell G-6-PD deficiency were investigated to find out whether this genetic defect is associated with changes in platelet aggregation. The enzyme defect in platelets could be verified by a decreased G-6-PD activity which was as low as 15% compared to control subjects. The decreased enzyme activity was reflected by lowered levels of NADPH and GSH and by a diminished maximum capacity of the hexose monophosphate shunt. Aggregation measurements in platelet-rich plasma from deficient patients revealed an enhanced dose response to ADP which was higher by about one order of magnitude compared to controls. The same effect was observed in a smaller degree in arachidonic acid induced aggregation.

Blood Platelets↗
PubMed1988

In vivo effects of a low molecular weight heparin fragment on platelet aggregation and platelet dependent hemostasis in dogs.

Plasma defibrinogenated dogs were used to study the influence of conventional heparin and a low molecular weight heparin fragment (Fragmin, mean MW 5,000 d) on platelet dependent hemostasis. The heparins were given intravenously in gravimetrically equal doses. The bleeding from standardized skin flap wounds and platelet aggregation (ADP and thrombin) was studied. In comparison, higher doses of the fragment than of heparin were required to increase the bleeding. ADP-induced aggregation in defibrinogenated platelet rich plasma (after addition of normal dog plasma) was potentiated by both heparins. After injection of heparin or the fragment, ADP induced platelet aggregation without prior addition of normal plasma to the test-tube. In conclusion the heparin fragment affected bleeding to a less extent than conventional heparin. One explanation might be a weaker inhibition of thrombin-induced platelet aggregation.

Animals↗
PubMed1985

A modification of the Wu and Hoak method for the determination of platelet aggregates and platelet adhesion.

The Wu and Hoak method for determining circulating platelet aggregates has poor reproducibility; problems have been reported with the composition of the buffer systems, haemolysis, the effects of blood collection technique and a divergence of the platelet aggregate ratio in blood for healthy donors from the theoretical value of 1. Our investigations suggest that the original technique is highly operator-dependent, especially the collection of blood and the method of counting platelets after centrifugation. We describe an improved modification of the Wu and Hoak technique; a new buffer system has been developed and the proportion of blood in the buffered EDTA and buffered EDTA-formalin solutions has been altered to obtain platelet rich plasma. The platelet aggregate ratio (PAR) by this modified method for healthy donors in two different studies was 0.97 +/- 0.02 and 0.98 +/- 0.01 respectively. Finally, the principle of Wu and Hoak was used to measure accurately platelet adhesion, without the role of platelet-platelet interactions (aggregation). Platelet adhesion and aggregation were then used to evaluate the thrombogenicity of various artificial surfaces, including silicone rubber and polytetrafluoroethylene (PTFE) vascular grafts.

Blood Specimen Collection↗
PubMed1991

Effects of dietary fish oil supplementation on platelet aggregability and platelet membrane fluidity in normolipemic subjects with and without high plasma Lp(a) concentrations.

The purpose of this study was to compare the relative effect of n-3 fatty acids on plasma lipids and platelet function in normolipemic subjects (n = 8) with plasma Lp(a) levels greater than 30 mg/dl and normolipemic subjects (n = 7) without detectable plasma Lp(a) concentrations. Six weeks of dietary supplementation (3.8 g EPA and 2.9 g DHA/d) significantly reduced (P less than 0.005) plasma TGs in both groups whereas no changes of plasma TC, LDL-C, HDL-C, and Lp(a), respectively, were found. Collagen- or thrombin-stimulated platelet aggregation and collagen- or thrombin-induced TXB2 generation from platelets decreased by approx. 45% in Lp(a)-negative and Lp(a)-positive platelet donors after a 6 week dietary intake. Four more weeks without n-3 supplementation restored the pretreatment values of TGs, platelet aggregability and TXB2 release. The biophysical properties of platelets from normolipemics with and without high plasma Lp(a) concentrations revealed a similar structural order of platelets at 37 degrees C using DPH, TMA-DPH, or 6-AS as fluorescent probes. Also similar temperature-dependent changes in platelet fluidity from 37 degrees C to 17 degrees C were observed in platelet preparations from Lp(a)-positive and Lp(a)-negative subjects. However, no subtle changes in the structural order of platelets due to nutrient intakes were found in all subjects (n = 15, 19-28 yrs) using fluorescence polarization technique. The present data suggest a similar in vitro platelet behaviour from normolipemic subjects with and without high plasma levels of Lp(a) (which is considered a risk for premature atherosclerosis) in contrast to platelet aggregability and platelet fluidity in certain hyperlipidemic stages.

Adult↗
PubMed2004

A template-assembled synthetic protein surface mimetic of the von Willebrand factor A1 domain inhibits botrocetin-induced platelet aggregation.

Platelet adhesion, the initial step of platelet activation, is mediated by the interaction of von Willebrand factor (VWF) with its platelet receptor, the GPIb-IX complex. The binding of VWF to GPIb-IX is induced either by increased shear stress or by exogenous modulators, such as botrocetin. At a molecular level, this interaction takes place between the A1 domain of VWF and the GPIb alpha chain of the GPIb-IX complex. We report here the design and functional characteristics of a VWF template-assembled synthetic protein (TASP), a chimeric four-helix-bundle TASP scaffold mimicking the surface of the A1 domain. Twelve residues located on helices alpha 3 and alpha 4 in the native A1 domain were grafted onto a surface formed by two neighboring helices of the TASP. VWF TASP was found to inhibit specifically botrocetin-induced platelet aggregation and to bind both botrocetin and GPIb alpha. However, in contrast to the native A1 domain, VWF TASP did not bind simultaneously to both ligands. Modeling studies revealed that the relative orientation of the alpha helices in VWF TASP led to a clash of bound botrocetin and GPIb alpha. These results demonstrate that a chimeric four-helix-bundle TASP as a scaffold offers a suitable surface for presenting crucial residues of the VWF A1 domain; the potential of the TASP approach for de novo protein design and mimicry is thereby illustrated.

Binding Sites↗
PubMed1995

Investigations of platelet aggregation and platelet counts from stored canine whole blood.

The effects of the long term storage of canine blood at 4 to 6 degrees C in PVC-bags containing CPDA-1 as a stabiliser on platelet aggregation and platelet counts were investigated. Aggregation induced by collagen, adenosine diphosphate or a calcium ionophore was preserved well during the first six hours, but there was then a decrease of 24 to 46 per cent in the ability of the platelets to aggregate, after which during the next three to four weeks of storage there was no further decrease in their aggregation properties. The formation of aggregates of platelets reduced the numbers of platelets counted as single thrombocytes by more than 30 per cent during the first four days. The numbers of platelets recorded varied widely with the counting method used (counting chamber or automatically) and with the ethylenediamine tetra-acetic acid content of the dilution fluid.

Adenine↗
PubMedDate not supplied

Reorganization of contractile systems and protein tyrosine phosphorylation in platelet aggregation.

Platelet aggregation is accompanied with reorganization of contractile systems. This event involves tyrosine phosphorylation of various proteins. When tyrosine phosphorylation is induced by an intracellular trigger as vanadate, a phosphorylated cytosolic 60 Kd protein acts as a nucleating center on which new actin filaments grow. When aggregation is induced by an extracellular signal as ristocetin, actin filaments of the membrane-associated skeleton and the 60 Kd protein bound to this structure migrate toward the cytosol and only in this soluble state the 60 Kd protein undergoes tyrosine phosphorylation and consequently triggers reorganization of contractile systems.

Actins↗
PubMed2003

Direct demonstration of involvement of protein kinase Calpha in the Ca2+-induced platelet aggregation.

Platelets play critical roles in hemostasis and thrombosis through their aggregation following activation of integrin alphaIIbbeta3. However, the molecular mechanism of the integrin activation inside platelets remains largely unknown. Pharmacological experiments have demonstrated that protein kinase C (PKC) plays an important role in platelet aggregation. Because PKC inhibitors can have multiple substrates and given that non-PKC-phorbol ester-binding signaling molecules have been demonstrated to play important roles, the precise involvement of PKC in cellular functions requires re-evaluation. Here, we have established an assay for analyzing the Ca2+-induced aggregation of permeabilized platelets. The aggregation of platelets was inhibited by the addition of the arginine-glycine-aspartate-serine peptide, an integrin-binding peptide inhibitor of alphaIIbbeta3, suggesting that the aggregation was mediated by the integrin. The aggregation was also dependent on exogenous ATP and platelet cytosol, indicating the existence of essential cytosolic factors required for the aggregation. To examine the role of PKC in the aggregation assay, we immunodepleted PKCalpha and beta from the cytosol. The PKC-depleted cytosol lost the aggregation-supporting activity, which was recovered by the addition of purified PKCalpha. Furthermore, the addition of purified PKCalpha in the absence of cytosol did not support the aggregation, whereas the cytosol containing less PKC supported it efficiently, suggesting that additional factors besides PKC would also be required. Thus, we directly demonstrated that PKCalpha is involved in the regulation of Ca2+-induced platelet aggregation.

Blood Platelets↗
PubMed1985

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.

Type IIB von Willebrand disease is characterized by enhanced ristocetin-induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.

Adult↗
PubMed1995

Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation.

Platelet stimulation by thrombin leads to the activation of phosphoinositide 3-kinase (PI 3K) and to the production of the D3 phosphoinositides, phosphatidylinositol 3,4-bisphosphate (PdtIns-3,4P2) and 3,4,5-trisphosphate (PdtIns-3,4,5-P3). Because changes in the levels of these phosphoinositides correlate with the kinetics of actin assembly, they have been proposed to mediate actin assembly, causing cell shape changes. Wortmannin and LY294002, two unrelated inhibitors of PI 3-K, were used to investigate the role of PI 3-K in platelet actin assembly and aggregation. Both PI 3-K inhibitors abrogated the production of PdtIns-3,4-P2 and PdtIns-3,4,5-P3 in thrombin receptor-activating peptide (TRAP)-stimulated cells. However, neither wortmannin nor LY294002 altered the kinetics of actin assembly or the exposure of nucleation sites in TRAP-stimulated cells. In contrast, PI 3-K inhibitors showed a specific inhibitory pattern of cell aggregation, characterized by a primary phase of aggregation followed by progressive disaggregation. Flow cytometry analysis with the PAC1 monoclonal antibody or with FITC-labeled fibrinogen indicated that wortmannin inhibited the maintenance of the platelet integrin GPIIb-IIIa in its active state. Wortmannin also inhibited, in a dose-dependent manner, platelet aggregation induced by the binding of the monoclonal antibodies P256 and LIBS-6 to GPIIb-IIIa. LIBS Fab-induced aggregation also led to the production of PdtIns-3,4-P2. Platelet secretion, as evidenced by the release of preloaded 14C-5-hydroxy-tryptamine secretion or P-selectin up-regulation, was not affected by PI 3-K inhibition. These results demonstrate that the generation of D3 phosphoinositides is not required for actin assembly in TRAP-activated platelets. However, PI 3-K stimulation is necessary for prolonged GPIIb-IIIa activation and irreversible platelet aggregation. PI 3-K stimulation downstream of GPIIb-IIIa engagement may provide positive feedback required to sustain active GPIIb-IIIa.

Actins↗
PubMed1997

Activation status of platelet aggregates and platelet microparticles shed in sheared whole blood.

The role of temperature and shear rate in the activation status of aggregating platelets and platelet microparticles (MPs) was investigated in a modified concentric-cylinder rotational viscometer. Whole blood anticoagulated with citrate was exposed to a range of shear rates typical of cardiopulmonary bypass circuits (0, 1000, 2000 and 4000 s(-1)) over four temperatures spanning hypothermic to mildly hyperthermic conditions (24, 30, 37 and 42 degrees C) for short durations (100 s). Aliquots of blood were double-stained for CD41 (platelet GPIIb/IIIa) and CD62 (P-selectin). Platelets, platelet aggregates, MPs and red blood cell-platelet and -MP aggregates were identified by flow cytometry by acquiring only CD41-positive particles and differentiating on a plot of CD41 versus forward light scatter. The activation status of each particle was quantified by measuring CD62 expression (alpha-granule release). A degree of correlation between the shedding of MPs and the formation of platelet-platelet aggregates was observed for the data as a whole (r=0.85 for p<0.01), although this trend was not observed for a shear rate of 4000 s(-1). The mean expression of CD62 on both platelets and MPs was maintained at a very low level for all temperature and shear rate combinations. There was, however, a number of very highly activated MPs associated with red blood cells at high shear rates.

Journal Article↗
PubMed1990

Pharmacological studies on the mechanism of pressure inhibition of human platelet aggregation.

Platelet shape change and aggregation in response to adenosine diphosphate (ADP), epinephrine, collagen, thrombin, ristocetin, and phorbol myristate acetate (PMA) were studied photometrically at 1 ATA air and 35 ATA helium (He). Pressure inhibited aggregation in response to all agents except PMA. Dose response curves were constructed for ADP and epinephrine at 1 ATA and 35 ATA in the presence of acetylsalicyclic acid (ASA) 2.5 . 10(-4) M, which prevents aggregation due to released ADP and other granular constituents thus allowing study of the effect of the added stimulus alone. Pressure inhibited aggregation and yielded a shallower dose response curve. Pharmacologically, this would be interpreted as non-competitive blockade or reduced availability of receptors. All of the agonist agents inhibited by pressure are dependent upon extracellular Ca2+ for their function. All unmask other receptors (integrins) for adhesive proteins, principally fibrinogen. These integrins incorporate Ca2+ to become active. In contrast, PMA-induced aggregation, and shape change, are independent of extracellular Ca2+ and were unaffected by pressure. It is proposed that pressure may distort Ca2(+)-dependent surface glycoprotein receptors in a manner that reduces ligand affinity and hence inhibits platelet aggregation. The possibility that other calcium-mediated cell processes are affected by pressure cannot be discounted.

Adenosine Triphosphate↗
PubMed1990

Recombinant human erythropoietin increases blood pressure, platelet aggregability and platelet free calcium mobilisation in uraemic children: a possible link?

Recombinant human erythropoietin was administered to 10 uraemic children on chronic haemodialysis, all of whom responded by correcting their haemoglobin. In addition, they showed an increase in blood pressure; platelet aggregations, subnormal before therapy, improved during treatment. The intracellular free calcium concentration in platelets after thrombin stimulation also increased significantly during erythropoietin administration. We hypothesize that the effect of erythropoietin on platelet aggregability and on blood pressure may be due to an increase in the intracellular free calcium mobilisation in platelets and possibly in smooth muscle cells respectively.

Adolescent↗
PubMed1986

Glycoproteins IIb and IIIa and platelet thrombospondin in a liposome model of platelet aggregation.

Platelet membrane glycoproteins IIb and IIIa and platelet thrombospondin were incorporated onto phosphatidylcholine liposomes, by freeze thawing and sonication. Protein orientation on the liposomes was confirmed by susceptibility to neuraminidase cleavage and binding to lentil lectin-Sepharose (GPIIb-IIIa liposomes) and to heparin-Sepharose (thrombospondin liposomes). Glycoproteins IIb-IIIa bound 125I-fibrinogen with Kd of 7.5 X 10(-7)M. Binding was reversible and calcium-dependent. IIb-IIIa liposomes underwent fibrinogen-dependent aggregation in the presence of 10 mM CaCl2. Maximal aggregate formation was observed with a combination of IIb-IIIa liposomes and thrombospondin liposomes. This aggregation was partially inhibited by preincubation with monoclonal antibodies to the IIb-IIIa complex. Addition of EDTA caused complete reversal of aggregates. Thrombospondin liposomes also underwent fibrinogen and calcium dependent aggregation, however, this aggregation was less than that observed with the GPIIb-IIIa liposomes. Maximal aggregate formation was observed with a mixture of IIb-IIIa liposomes and thrombospondin liposomes. These studies demonstrate that GPIIb-IIIa and thrombospondin can be incorporated into phospholipid vesicles with preservation of function. Direct evidence is provided to demonstrate that glycoprotein IIb and IIIa and fibrinogen are sufficient for platelet aggregation and to demonstrate that thrombospondin may also contribute to platelet aggregation.

Binding Sites, Antibody↗