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 127 records · Page 7Linked to original sources
PubMed1983

Platelet aggregation in platelet suspensions from Mongolian gerbils (Meriones unguiculatus).

Blood obtained from Mongolian gerbils (Meriones unguiculatus) by cardiac puncture was used to develop a method for preparing platelet suspensions suitable for biochemical and aggregometric studies. The aggregation responses of gerbil platelet suspensions to 10 microM adenosine diphosphate and to 0.2 U/mL thrombin were immediate and irreversible. In addition, thrombin produced a short lag period. Bovine acid-soluble collagen (1:800) produced a long lag period coupled with an irreversible aggregation. Indomethacin (10 microM) significantly depressed adenosine diphosphate--induced aggregation but had no effect on thrombin-induced aggregation. Indomethacin significantly prolonged the lag period and reduced the rate of collagen-induced aggregation. Our results strongly indicate that platelet suspensions from the Mongolian gerbil, an animal which is responsive to hypercholesterolemic diets, may be useful in studying dietary lipid factors which influence platelet aggregation.

Adenosine Diphosphate↗
PubMed2000

Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction.

Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilintrade mark) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 microM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 microg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.

Cohort Studies↗
PubMed1990

Iloprost and tissue-type plasminogen activator differentially affect platelet aggregation in platelet-rich plasma and in whole blood.

Platelet aggregation in platelet-rich plasma (PRP) is more sensitive to agonists and more resistant to antagonists than that in whole blood. In this study, we show that the presence of neutrophils in whole blood accounts at least in part for diminished platelet aggregation in whole blood. The platelet-inhibitory effect of neutrophils relates to the release of nitric oxide and not to elastase or adenosine. Furthermore, two unrelated platelet inhibitors, iloprost and tissue-type plasminogen inhibitor, decrease platelet aggregation to a greater extent in whole blood than in PRP. However, these agents exert cumulative or synergistic inhibitory effects with neutrophils on platelet aggregation in PRP. Thus, the inhibition of platelet aggregation in vivo may relate to the interaction between neutrophils and platelet-inhibitory agents.

Blood Physiological Phenomena↗
PubMed1982

High performance liquid chromatography (HPLC) determination of endogenous serotonin released from aggregating platelets.

High performance liquid chromatography with electrochemical detection was developed for the determination of serotonin (5-hydroxytryptamine) in rabbit platelet and plasma. A peak from tissue extract (peak a) was identified as serotonin based on retention time on the chromatogram, using a potential that gave limiting current on both a current-potential curve and gas chromatography-mass spectrum, as compared with that of authentic serotonin. For the assay of serotonin, 5-hydroxy-N-methyltryptamine was used as an internal standard and the extraction recovery of the serotonin added to the platelet-rich plasma was almost total. Furthermore, using this highly sensitive method, it has been demonstrated that the release of endogenous serotonin from rabbit platelets occurs during collagen-induced platelet aggregation but not during adenosine diphosphate-induced platelet aggregation. The procedures described should prove to be simple and useful for pharmacological and physiological investigations on the relationship between platelet aggregation and release reaction.

Animals↗
PubMed1973

Plasmin-induced platelet aggregation and platelet release reaction. Effects on hemostasis.

Trypsin-activated pig plasmin and human plasmin activated by streptokinase (SK) caused aggregation of a suspension of washed platelets from human, rabbit, or pig blood. The platelet aggregation was reversible, but it was accompanied by a significant release of adenine nucleotides, serotonin, and platelet fibrinogen. Platelet fibrinogen was eventually digested. The effect of plasmin on platelets was inhibited by soybean trypsin inhibitor, epsilon aminocaproic acid, Persantin, prostaglandin E(1), and phenylbutazone. Short treatment of platelets with plasmin enhanced their sensitivity to ADP; however, this sensitivity was lost during longer incubation with plasmin. This enzyme also made platelets less sensitive to collagen and thrombin. Injecting SK into rabbits (10,000 U/kg body weight) caused a transitory drop of platelet count. These platelets lost part of their serotonin and fibrinogen. The administration of Persantin or of epsilon aminocaproic acid to rabbits before the injection of SK protected platelets from the loss of serotonin. Pretreatment with Persantin also resulted in partial protection of platelet fibrinogen in rabbits injected with SK. Platelets obtained from rabbits that had received both Persantin and SK were much more reactive with collagen than platelets obtained from rabbits injected with SK alone. Rabbits pretreated with Persantin did not show prolongation of the primary bleeding time that occurred after SK injection to control rabbits. It is suggested that plasmin generated after SK injection causes platelet release reaction in vivo. This may contribute to the hemostatic defect occurring during thrombolytic therapy or during systemic activation of fibrinolysis due to the other factors.

Adenine Nucleotides↗
PubMed2002

Effects of different thrombolytic treatment regimen with abciximab and tirofiban on platelet aggregation and platelet-leukocyte interactions: a subgroup analysis from the GUSTO V and FASTER trials.

BACKGROUND: Due to considerably high rates of reocclusion under standard thrombolytic therapy GP IIb/IIIa inhibitors have been combined with thrombolytics to improve therapeutic outcomes. Potential reasons for arterial reocclusion may be increased platelet activation, interaction of platelets with other cell types such as leukocytes and inadequate drug dosing due to lack of ideal platelet monitoring. We compared combination therapy regimens consisting of GP IIb/IIIa inhibitors and thrombolytics with respect to platelet inhibition and platelet-leukocyte interactions. METHODS AND RESULTS: From the GUSTO V trial (standard rPA vs. reduced dose rPA and abciximab) and the FASTER trial (standard TNK-tPA vs. reduced dose TNK-tPA and tirofiban) 15 patients were monitored by platelet aggregometry, rapid platelet function assay (RPFA) and flow cytometry (FC). rPA alone (n = 5) caused initial increases in platelet aggregation. However, platelet aggregation was significantly (p < 0.05) and sufficiently (>80%) inhibited by abciximab/rPA (n = 5) and tirofiban/TNK-tPA (n = 5). The platelet inhibitory effect of tirofiban/TNK-tPA was more pronounced compared to abciximab/rPA with a significant difference after 2 h (p < 0.05). Tirofiban/TNK-tPA and abciximab/rPA caused decreases in platelet-leukocyte aggregates as well as in binding of specific antibodies to the platelet vitronectin receptor and P-selectin (p < 0.05, respect.). No differences among the treatment groups were seen with respect to antibody binding to MAC-1 and CD154/CD40 ligand. CONCLUSIONS: Taken together, GP IIb/IIIa inhibitors overcome the platelet activating effect of thrombolytics resulting in sufficient platelet inhibition. RPFA is a suitable monitoring tool to accurately assess platelet inhibition. Within the given combination treatment regimen tirofiban appears to be more effective compared to abciximab and to exert effects beyond the inhibition of GP IIb/IIIa.

Abciximab↗
PubMed2002

Platelet aggregation and activation under complex patterns of shear stress.

Arterial stenosis results in a complex pattern of blood flow containing an extremely fast flow in the throat of stenosis and a post-stenosis low flow. The fast flow generates high shear stress that has been demonstrated in vitro to activate and aggregate platelets. One potential problem of these in vitro studies is that platelets are invariably exposed to a high shear stress for a period that is significantly longer than they would have experienced in vivo. More importantly, the role of the post-stenosis low flow in platelet activation and aggregation has not been determined. By exposing platelets to a shear profile that contains both high and low shear segments, we found that platelets aggregate when they are exposed to a high shear stress of 100 dyn/cm(2) for as short as 2.5 s, a period that is significantly shorter than those previously reported (30-120 s). Platelet aggregation under this condition requires a low shear exposure immediately after a high shear pulse, suggesting that post-stenosis low flow enhances platelet aggregation. Furthermore, platelet aggregation under this condition is not activation-dependent because the CD62P expression of sheared platelets is significantly less than that of platelets treated with ADP. Based on these findings, we propose that shear-induced platelet aggregation may be a process of mechanical crosslinking of platelets, requiring minimal platelet activation. This process may function as a protective mechanism to prevent in vivo irreversible platelet activation and aggregation under temporary high shear.

Adenosine Diphosphate↗
PubMed2000

Disaggregation of aggregated platelets by apyrase from the tick, Ornithodoros savignyi (Acari: Argasidae).

Apyrase, secreted by ticks during feeding, is a platelet aggregation inhibitor that functions as a regulator of the host's hemostatic system. This present study concerns the disaggregation effect of salivary gland apyrase from the tick Ornithodoros savignyi. Secondarily aggregated platelets, disaggregated by apyrase, exhibited a reversal of shape from a spherical (aggregated) form to a discoid form, reminiscent of reversible aggregation at low ADP concentrations in citrated platelet-rich plasma. However, they showed a dilatory open canaliculary system and an absence of granules indicating disaggregation after degranulation had taken place. In contrast, disaggregation by the fibrin(ogen)olytic enzyme, plasmin, showed that platelets degranulated, but retained a spherical form with numerous extended pseudopods. While thrombin had no effect on aggregation or clotting of platelets disaggregated with plasmin, it did activate those platelets disaggregated with apyrase and clotted the plasma. This is the first study to describe the disaggregating effects of tick derived apyrase on aggregated platelets. It also shows that apyrase can disaggregate platelets even after secondary aggregation and degranulation of platelets has taken place. Platelet aggregation is one of the main barriers encountered by ticks during feeding and counteraction of this process by ticks is an important factor for successful feeding.

Animals↗
PubMed2003

Effects of plumbagin on platelet aggregation and platelet-neutrophil interactions.

The effects of plumbagin were investigated on platelet aggregation in vitro and ex vivo, on the binding of thrombin-stimulated platelets to neutrophils, and platelet aggregation induced by intact neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF) activated neutrophils, by use of the methods of Hamburger, McEver and Born, respectively. The results showed that plumbagin in vitro significantly inhibited adenosine diphosphate (ADP)-, arachidonic acid (AA)-, or platelet activating factor (PAF)-induced platelet aggregation, in a concentration-dependent manner. The medium inhibitory concentrations (IC 50 ) were 39.4, 82.7 and 38.1 microM, respectively. Intragastric plumbagin at 10 mg/kg markedly suppressed platelet aggregation induced by ADP, AA, or PAF. Plumbagin decreased the binding between thrombin-stimulated platelets and neutrophils with an IC 50 of 62.9 microM. Plumbagin significantly inhibited washed platelet aggregation stimulated by fMLP- or PAF-activated neutrophils. The IC 50 values were 54.3 and 47.6 microM, respectively. On the other hand, plumbagin and aspirin increased the inhibition of intact neutrophils on AA-induced platelet aggregation. It is suggested that plumbagin inhibited platelet aggregation in vitro and ex vivo, suppressed the binding of activated platelets to neutrophils, inhibited platelet aggregation induced by activated neutrophils, and increased inhibition of intact neutrophils on platelet reactivity. Abbreviations. DMSO:dimethyl sulphoxide fMLP: N-formyl-methionyl-leucyl-phenylalanine ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet activating factor

Adenosine Diphosphate↗
PubMed1984

Influence of the pure synthetic PAF (platelet aggregating factor) on clot retraction and platelet aggregation.

Pure synthetic platelet aggregating factor (PAF) (1-O-Hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) induces a dose-dependent platelet aggregation in platelet-rich plasma (PRP) and in gel-filtered platelets. Irreversible platelet aggregation was observed at final concentrations of PAF higher than 2 X 10-(7) mol/l, while reversible or two-wave aggregation was obtained with lower final concentrations. The second wave was inhibited by acetylsalicylic acid, indomethacin, dipyridamole, EDTA, EGTA, theophylline, caffeine, PGE1 and verapamil. PAF does not induce reptilase clot retraction (RCR); however, it does not inhibit RCR induced by ADP or thrombin. Since all substances known to activate platelets also induce RCR, the lack of this activity by PAF would support the existence of a third pathway in platelets.

Animals↗
PubMed1991

Platelet aggregation in platelet-rich plasma and whole blood in 120 patients with myeloproliferative disorders.

In vitro platelet aggregation in platelet-rich plasma (PRP) and in whole blood (WB) was assessed in 31 patients with idiopathic myelofibrosis, 32 with essential thrombocytosis, 23 with polycythemia vera, and 34 with chronic myelogenous leukemia. In PRP most subjects showed normal or reduced platelet aggregation, whereas in WB the majority of patients showed increased platelet function. Spontaneous platelet aggregation (SPA) was observed frequently in WB, whereas it was seldom observed in PRP. SPA in WB was inhibited by in vitro addition of aspirin and apyrase, and SPA was only partially dependent on high platelet count because it also occurred in samples with normal platelet content (at variance with 13 subjects with reactive thrombocytosis, in which SPA was observed only in samples with high platelet concentration). Platelets from patients with idiopathic myelofibrosis had the highest tendency to undergo SPA.

Adenosine Diphosphate↗
PubMed1991

Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets.

The existence and role of an L-arginine:nitric oxide (NO) pathway in two human colorectal adenocarcinoma cell lines, SW-480 and SW-620, were investigated. Both cell lines, which derive from the same patient, SW-480 from the primary tumor and SW-620 from its metastatic lesion, were shown to have a cytosolic, Ca(2+)-independent, NADPH-dependent NO synthase, the activity of which was lower in the cytosol of SW-620. These cells were more potent inducers of platelet aggregation. In contrast, SW-480, which had more NO synthase activity, were less potent inducers of platelet aggregation. Pretreatment of both cell lines with NG-monomethyl-L-arginine, an inhibitor of NO synthase, potentiated their proaggregating effect and made them equally active. Exogenous L-arginine, NO, and related nitrovasodilators all inhibited platelet aggregation induced by SW-620. The antiaggregating activity of NO was further potentiated by prostacyclin and by M&B22948, a selective inhibitor of cyclic GMP phosphodiesterase. We propose that the generation of NO by tumor cells inversely correlates with their metastatic potential. Furthermore, we show that the lower activity of NO synthase in metastatic cells is due to the presence in these cells of a low molecular weight inhibitor of the NO synthase. In addition, agents which modulate platelet function by a cyclic GMP-dependent mechanism may be useful in the prevention of tumor metastasis.

Adenocarcinoma↗
PubMed1976

Factor VIII and human platelet aggregation. I. Evience that the platelet aggregating activity of bovine factor VIII is a property of its 'carrier protein' subunit.

Bovine factor VIII is a potent inducer of aggregation of human platelets. Upon gel filtration of five-thousand-fold purified material in 0.5 M CaCl2, bovine factor VIII is separated into high and low molecular weight components; the former contains both a 'carrier protein' and platelet aggregating activity, the latter the procoagulant activity (low molecular weight factor VII, LMW-FVIII). Upon removal of Ca2+ ions, LMW-F VIII recombines with the 'carrier protein'. LMW-F VIII modifies aggregation by 'carrier protein', but not aggregation by undissociated bovine factor VII, adenosine-5'-diphosphate or adrenaline. This finding indicates that the platelet aggregating activity in indeed a property of the 'carrier protein'.

Animals↗
PubMed1985

Botrocetin- and polybrene-induced platelet aggregation in platelet-type von Willebrand disease.

It has been reported that botrocetin, a Bothrops venom factor, induces platelet aggregation dependent on von Willebrand factor (vWF), and that platelet aggregation induced by Polybrene, a synthetic polycation, is enhanced by vWF. This report describes the platelet aggregability on stimulation with botrocetin and Polybrene in four patients with platelet-type von Willebrand disease (vWD) who showed increased platelet aggregation with low concentrations of ristocetin as the result of a platelet abnormality. Enhanced platelet aggregability with botrocetin was observed in platelet-rich plasma (PRP) from the patients. Platelet aggregation induced by botrocetin in a mixture of normal washed platelets and patient plasma was either decreased or normal, being dependent on the amount of plasma vWF. In contrast with ristocetin and botrocetin, Polybrene did not cause increased aggregation of patient PRP. Polybrene aggregated normal washed platelets less extensively in the presence of patient plasma than normal plasma. These studies demonstrated that botrocetin induced heightened interaction between platelets and vWF, but Polybrene did not, in platelet-type vWD, and that the enhanced responsiveness of patient platelets to botrocetin is related to an intrinsic platelet abnormality.

Crotalid Venoms↗
PubMed1988

Alterations of phospholipid asymmetry in the membrane of spontaneously aggregated platelets in diabetes.

The changes of asymmetric distribution of anionic phospholipids of human platelets in diabetic patients were studied by fluorescent and freeze fracture cytochemistry, using merocyanine 540 (MC 540) and polymyxin B (PxB) as specific markers. The membrane anionic phospholipids were detected with PxB, a membrane nonpermeant probe, used either in native form for freeze fracture electron microscopy or as dansylated or iodinated derivative for fluorescence microscopy or gamma counting, respectively. MC 540 is a naturally fluorescent probe which reportedly inserts into less packed bilayer domains. Both in platelet rich plasma and in washed platelets obtained from diabetic patients, some small platelet aggregates were observed, their number being generally dependent on the level of hyperglycemia. In contrast with single platelets, the aggregated ones bind PxB as revealed by all assay methods. The fluorescence microscopic studies with dansyl PxB and MC 540 displayed a strong binding of the fluorescent markers to aggregated platelets. The electron microscopic examination of freeze fracture replicas showed the appearance of characteristic PxB-induced deformations in the plasmalemma of aggregated platelets. The gamma counting of 125I-PxB incubated samples indicates significant differences on the platelets of diabetic patients as compared to those obtained from healthy subjects. Our data provide evidence that in diabetic patients, the spontaneous aggregated platelets are a result of the appearance of the anionic phospholipids in the outer half of plasmalemma. These changes may enhance the procoagulant activity and should represent a determinant of activated platelet recognition and their removal from circulation by splenic macrophages.

Anions↗
PubMed2004

Decreased platelet aggregation of platelet concentrate during storage recovers in the body after transfusion.

BACKGROUND: Previous reports have shown that storage decrease the ability of PLTs to aggregate in the form of PLT concentrate (PC). Nevertheless, there are few reports that have studied the PLT function in blood samples obtained from recipients after PLT transfusion. In this study, this issue was addressed by examining the ability of PLTs to aggregate after being transfused into the blood stream. STUDY DESIGN AND METHODS: PC was transfused to the patients with extremely low PLT counts resulting from chemotherapy. The maximum extent of PLT aggregation and size of the aggregates were compared between PLT in stored PC before transfusion with the PLT-rich plasma (PRP) from the recipients after transfusion and with PRP from patients with moderate decrease in PLT counts after chemotherapy. RESULTS: The maximum extent of PLT aggregation was significantly higher in PRP collected from the patients after transfusion compared to the extent obtained before transfusion. There were no significant differences in the maximum extents of PLT aggregation between the PRP collected from the recipients after PC transfusion and, in the same patients, when PLT counts were moderately low. CONCLUSION: These results suggest that the observed decreased in PLT aggregation after storage can improve in the body after transfusion, and transfused PLTs have similar aggregation ability compared to the PLTs derived from the patient.

Adenosine Diphosphate↗
PubMed1997

Proteolytic activation of a putative receptor leading to vasoconstriction and platelet aggregation.

Submandibular enzymatic vasoconstrictor (SEV), a member of the kallikrein family of enzymes, elicits biological effects by a proteolytically mediated mechanism. We studied 1) whether SEV is able to aggregate platelets and 2) whether SEV may activate a receptor other than the cloned thrombin receptor. SEV (10(-8)M) aggregated platelets, released ATP and increased intracellular Ca2+. Elastase treatment rendered human platelets unresponsive to SEV and thrombin (TH), but not to cathepsin G. In desensitization experiments performed with gamma-TH, after two successive additions of approximately 50 nM gamma-TH, a third dose elicited 15.8 +/- 3.4% of the initial response (n = 4), but platelets responded to approximately 20 nM SEV by 33.8 +/- 7.2% of control (p < 0.03 vs last response to gamma-TH). After desensitization to SEV (n = 4), the response to a third dose was 4 +/- 1.3% of control, but gamma-TH still induced 37.7 +/- 12.4% aggregation (p < 0.02 vs last response to SEV). Incubation of washed rabbit platelets with alpha-TH digested with elastase (10(-10) M TH added to 7 micrograms/ml elastase for 1 min) rendered them unresponsive to additional challenges with TH, but they still responded to an equipotent dose of SEV (2.7 x 10(-9) M) by 86 +/- 48% of control. In isolated rabbit aortic rings contracted with 10(-6) M norepinephrine (NE) to 42 +/- 3% of maximum. SEV (2.8 x 10(-8) M) caused further contraction to 87 +/- 4%. In contrast, alpha-TH (1.6 x 10(-7) M) tended to relax both NE- and SEV-contracted rings by 14 +/- 2 and 16.2 +/- 2%, respectively (n = 3 each). We concluded that part of the platelet-aggregating effect of SEV may be mediated by activation of a receptor(s) different from that of TH.

Animals↗