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 847 records · Page 47Linked to original sources
PubMed2000

On the mechanism of plasmin-induced platelet aggregation. Implications of the dual role of granule ADP.

Plasmin-induced platelet aggregation has been considered to be a cause of reocclusion after thrombolytic treatment with plasminogen activators. However, little is known regarding the mechanism and regulation of plasmin-induced platelet aggregation. In this study, we demonstrated that plasmin causes the degranulation of platelets, and that ADP released from granules plays a crucial role in the induction of platelet aggregation. This conclusion is supported by results showing that both ADP antagonists and ADPase can inhibit the effect of plasmin on platelets. We also demonstrated that pretreatment of platelets with ADP makes the platelets more sensitive to plasmin, and plasmin-induced platelet aggregation is, therefore, observed at lower concentrations where no aggregation occurs in quiescent platelets. In other words, it is thought that ADP potentiates the plasmin-induced aggregation. The effect of ADP was inhibited by N(6)-[2-(methylthio)-ethyl]-2-(3,3, 3-trifluoropropyl)thio-5'-adenylic acid, monoanhydride with dichloromethylenebisphosphonic acid (AR-C69931), a selective antagonist for the P2T(AC) subtype of P2 receptor, but not by the P2Y1 receptor-selective antagonist adenosine 3'-phosphate 5'-phosphosulfate (A3P5PS). The P2X1 receptor agonist alpha, beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) did not mimic the action of ADP. These data indicate that ADP potentiates plasmin-induced platelet aggregation via the P2T(AC) receptor. In addition, epinephrine, a typical G(i) agonist against platelets, could potentiate the plasmin-induced platelet aggregation, suggesting that the signal via the G(i) protein is involved in potentiating the plasmin-induced platelet aggregation, ADP is secreted from platelet granules, and concomitantly works in conjunction with plasmin in a P2T(AC) receptor-mediated manner.

Adenosine Diphosphate↗
PubMed1980

Effects of prostacyclin on platelet aggregation as studied with "filter-loop" technique in the flowing blood of the dog.

Using Hornstra's "filter loop" technique for determination of platelet aggregation in the circulating blood, the role played by prostaglandin I2 (PGI2) in platelet aggregation was studied in the canine heart-lung preparation (HLP) supported by a donor. A dose-related aggregation of platelet was induced by close injection of ADP into the "filter loop". PGI2 induced a marked suppression of ADP-induced platelet aggregation. After indomethacin, ADP-induced platelet aggregation became very much protracted, but was promptly terminated by PGI2. Bradykinin produced an inhibition of platelet aggregation, while it produced an increase in the coronary blood flow (CBF). After indomethacin, the increase in CBF and the inhibition of ADP-induced platelet aggregation produced by bradykinin was greatly attenuated. Essentially similar results were obtained in the anesthetized closed-chest dogs. These findings strongly suggest that the transient nature of ADP-induced platelet aggregation in the flowing blood is due to the intervention of antiaggregatory PGI2.

Adenosine Diphosphate↗
PubMed2000

Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation.

UNLABELLED: Activation of endothelial cells and platelet sequestration play major roles in rejection of xenografts. The histopathology of both hyperacute and acute vascular or delayed rejection of vascularized discordant xenografts is characterized by interstitial hemorrhage and intravascular thrombosis. Agents that prevent platelet activation and consequent microthrombus formation have proven beneficial in xenograft rejection but do not fully preclude vascular thrombosis. Recently, several new anti-platelet therapies have undergone extensive clinical testing for atherosclerotic thrombotic vascular disorders; other putative therapies are undergoing pre-clinical evaluation. We have investigated the effect of several of these novel agents on platelet aggregation in baboons in order to screen for future potential in xenograft rejection models. METHODS: Drugs tested in these experiments were aurintricarboxylic acid (ATA, von Willebrand Factor-GPIb inhibitor), fucoidin (a selectin-inhibitor), 1-benzylimidazole (1-BI, thromboxane synthase antagonist), prostacyclin (PGI2, endothelial stabilizer), heparin (thrombin antagonist), nitroprusside sodium or nicotinamide (NPN or NA, both NO-donors), and eptifibatide (EFT, GPIIb/IIIa receptor antagonist). These were infused intravenously to nine baboons. Coagulation parameters and platelet counts were monitored and baboons were observed for adverse side-effects. The efficacy of these agents in inhibiting platelet aggregation was assayed in a platelet aggregometer. RESULTS: Treatment with ATA and fucoidin resulted in complete inhibition of platelet aggregation but also in major perturbation of coagulation parameters. 1-BI and PGI2 had no effect when administered alone, but in combination resulted in moderate inhibition of aggregation without disturbance in PT or PTT. NPN and NA had no substantive effects on platelet aggregation. Heparin resulted in specific inhibition of thrombin-induced platelet aggregation and, as anticipated, was associated with moderate prolongation of PTT. Importantly, EFT caused complete inhibition of platelet aggregation without changes in coagulation. Platelet counts, fibrinogen levels, and fibrinogen degradation products remained within the normal ranges in all experiments. CONCLUSIONS: Although excellent inhibition of platelet activation was obtained with ATA and fucoidin, clinical use may be precluded by concomitant disturbances of coagulation. Combinations of heparin and EFT may prove beneficial in preventing the thrombotic disorders associated with xenograft rejection while maintaining adequate hemostatic responses. These agents are to be evaluated in our pig-to-primate xenotransplantation models.

Animals↗
PubMed1992

Heparin potentiation of collagen-induced platelet aggregation is related to the GPIIb/GPIIIa receptor and not to the GPIb receptor, as tested by whole blood aggregometry.

To determine whether heparin potentiation of platelet aggregation is related to platelet GP IIb/IIIa and GP Ib receptors, four series of experiments were performed on blood from normal volunteers. In the first experiment pretreatment with the monoclonal antibody 7E3 (MAb 7E3), which antagonizes at the GP IIb/IIIa receptor, potently inhibited the collagen-induced platelet aggregation (p less than 0.001). With heparin added to blood pretreated with MAb 7E3, the aggregation increased (p less than 0.005) to an extent similar to that when only saline was used for pretreatment. In the second experiment, monoclonal antibody 10E5 (MAb 10E5) and peptide RGDS, substances which also antagonize at the GP IIb/IIIa receptor, decreased collagen-induced platelet aggregation to an extent similar to that after pretreatment with MAb 7E3. Following pretreatment with RGDS, heparin increased platelet aggregation (p less than 0.03), while after pretreatment with antibody MAb 10E5 heparin did not enhance platelet aggregation. In the third experiment aurin, an inhibitor of von Willebrand factor and its interaction with the platelet GPIb receptor, decreased platelet aggregation dose-dependently. In the fourth experiment heparin enhanced platelet aggregation to a similar extent (p less than 0.005), regardless of pretreatment of the blood with saline, aurin or monoclonal antibody 6D1 (MAb 6D1), the latter an antagonist at the GP Ib receptor. In conclusion, the potentiation of collagen-induced platelet aggregation by heparin was not inhibited by MAb 7E3, RGDS, aurin or MAb 6D1, but was abolished by MAb 10E5, implying that the heparin effect is related to activation of the platelet GP IIb/IIIa receptor complex.

Adult↗
PubMed2001

The activation of platelet aggregation by human cholangiocarcinoma cells is mediated through thrombin receptor.

Tumor cell induced platelet aggregation (TCIPA) played an importance role in early state of thrombosis in cancer patients. In addition, TCIPA was recognized as one important step in metastatic cascade. Cholangiocarcinoma, one of the most common cancers in the north-eastern part of Thailand, associated with thrombosis was reported. The authors investigated the effects of cholangiocarcinoma cells on platelet function as measured by platelet aggregation. Primary human cholangiocarcinoma (HuCCA) cells were established in our laboratory. Cells were cultured as standard techniques and grown to confluence until used, after which cells were replaced with fresh medium (Dulbeco Modified Eargle's Medium, DMEM) without serum for 24, 48 and 72 h. Then, the conditioned medium (CM) was collected. CM (24, 48 and 72 h) from HuCCA failed to induce platelet aggregation, whereas, HuCCA pellets induced platelet aggregation and potentiated platelet aggregation induced by submaximal concentration of thrombin. Interestingly, platelet aggregation induced by HuCCA was inhibited by hirudin (thrombin receptor antagonist; 10, 20 and 40 U) in a dose dependent manner. Thus, cholangiocarcinoma cells can induce platelet aggregation in a direct tumor cell-platelet contact via thrombin receptor. Therefore, the use of antiplatelet agents especially via thrombin receptors may help to prevent TCIPA or metastasis by CCA.

Adult↗
PubMed1994

Purification and characterization of platelet aggregation inhibitors from snake venoms.

Proteins that inhibit glycoprotein (GP) IIb/IIIa mediated platelet aggregation have been purified from the venom of two snake species. A small platelet aggregation inhibitor (p1.AI), multisquamatin (Mr = 5,700), was purified from Echis multisquamatus venom by hydrophobic interaction HPLC and two steps on C18 reverse phase HPLC. A larger p1.AI, contortrostatin (Mr = 15,000), was purified by a similar HPLC procedure from the venom of Agkistrodon contortrix contortrix. Both p1.AIs inhibit ADP-induced human, canine and rabbit platelet aggregation using platelet rich plasma (PRP). Multisquamatin has an IC50 of 97 nM, 281 nM and 333 nM for human, canine and rabbit PRP, respectively. Contortrostatin has an IC50 of 49 nM, 120 nM and 1,150 nM for human, canine and rabbit PRP, respectively. In a competitive binding assay using 125I-7E3 (a monoclonal antibody to GPIIb/IIIa that inhibits platelet aggregation) both contortrostatin and multisquamatin demonstrated GPIIb/IIIa specific binding to human and canine platelets. The IC50 for contortrostatin displacement of 7E3 binding to human and canine GPIIb-/IIIa is 27 nM and 16 nM, respectively and for multisquamatin it is 3 nM and 63 nM, respectively. Our results indicate that both p1.AIs inhibit platelet aggregation by binding with high affinity to GPIIb/IIIa.

Animals↗
PubMed1996

Inhibition of platelet aggregation by endocardial endothelial cells.

We assessed the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after brief interaction with EECs isolated from the right ventricles of porcine hearts. Platelet aggregation in response to thrombin was significantly inhibited by brief incubation of platelet suspensions over EEC monolayers. Pretreatment of EECs with indomethacin restored platelet reaction but that with L-NAME and hemoglobin (Hb) did not. The PGI2 content of platelet suspensions after interaction with cultured EECs was significantly correlated with the inhibition of platelet aggregation. These results suggest that EECs inhibit platelet aggregation by releasing PGI2.

Animals↗
PubMed1983

A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases.

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.

Adenocarcinoma↗
PubMed1986

The in vitro and in vivo effects of isoflurane and nitrous oxide on platelet aggregation.

In view of the possible antiaggregation effects of newer general anesthetics we investigated the in vitro and in vivo effects of isoflurane and nitrous oxide on platelet aggregation. Platelets obtained from 18 healthy volunteers, were exposed in vitro for 30 min in a closed chamber to oxygen-carbon dioxide (90%, 5%) (control), oxygen-carbon dioxide-nitrous oxide (80%), or oxygen-carbon dioxide-isoflurane (1.5%) with or without nitrous oxide (80%). Samples were tested in ADP- and collagen-induced aggregation tests. Both nitrous oxide and isoflurane produced statistically significant inhibition of ADP-induced aggregation. Inhibition of collagen-induced aggregation was not statistically significant. In 18 patients who received nitrous oxide (3 L/min) and isoflurane (1-2%) during anesthesia, platelet aggregation was reduced significantly. We conclude that both nitrous oxide and isoflurane cause moderate but statistically significant inhibition of platelet aggregation that may be clinically important in some patients.

Adenosine Diphosphate↗
PubMed1985

Aspirin and other platelet-aggregation inhibiting drugs.

The biochemistry of platelets is surprisingly complex, and offers the opportunity for numerous platelet-aggregation inhibiting ("antiplatelet") drugs to interfere with different aspects of their metabolism and function. Thus, aspirin inhibits platelet aggregation by irreversibly inactivating cyclo-oxygenase, a key enzyme in platelet prostaglandin metabolism, while the other nonsteroidal anti-inflammatory drugs and sulphinpyrazone cause reversible and dose-dependent inhibition of the same enzyme. Dipyridamole can inhibit both platelet adhesion and aggregation by raising the platelet cyclic AMP level through phosphodiesterase inhibition. The use of aspirin, sulphinpyrazone, and dipyridamole as antithrombotic agents has now been extensively evaluated. In general, treatment with these drugs has been more likely to prevent arterial than venous thromboembolism, and aspirin or the combination of aspirin and dipyridamole has been more effective in this respect than has sulphinpyrazone. Recent evidence strongly suggests that aspirin reduces the risk of non-fatal myocardial infarction in patients with unstable angina, and that the administration of aspirin in combination with dipyridamole significantly improves graft patency after aortocoronary bypass. Aspirin also appears to reduce the likelihood of stroke or death in men with transient cerebral ischaemic attacks.

Aspirin↗
PubMedDate not supplied

Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles.

Murine 15091A mammary adenocarcinoma cells and membrane vesicles spontaneously shed from these tumor cells in culture can induce aggregation of washed human platelets. A spectrum of proteinase inhibitors was tested for their ability to inhibit 15091A induced platelet aggregation. Of the inhibitors tested the most effective were those selective for cysteine proteinases. The effect of the spectrum of proteinase inhibitors on 15091A induced platelet aggregation was compared to the effect on cathepsin B-like cysteine proteinase activity in homogenates of 15091A tumor cells and their spontaneously shed vesicles. The results suggest that there is a correlation between activity of a cathepsin B-like proteinase in 15091A cells and vesicles and the ability of these cells and vesicles to induce aggregation of washed human platelets.

Adenocarcinoma↗
PubMed1985

Action mechanism of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.

Platelet aggregation inducer and inhibitor were isolated from Echis carinatus snake venom. The venom inducer caused aggregation of washed rabbit platelets which could be inhibited completely by heparin or hirudin. The venom inducer also inhibited both the reversibility of platelet aggregation induced by ADP and the disaggregating effect of prostaglandin E1 on the aggregation induced by collagen in the presence of A23187, arachidonate, ADP and platelet-activating factor (PAF) with an IC50 of around 10 micrograms/ml. It did not inhibit the agglutination of formaldehyde-treated platelets induced by polylysine. In the presence of indomethacin or in ADP-refractory platelets or thrombin-degranulated platelets, the venom inhibitor further inhibited the collagen-induced aggregation. Fibrinogen antagonized competitively the inhibitory action of the venom inhibitor in collagen-induced aggregation. In chymotrypsin-treated platelets, the venom inhibitor abolished the aggregation induced by fibrinogen. It was concluded that the venom inducer caused platelet aggregation indirectly by the conversion of prothrombin to thrombin, while the venom inhibitor inhibited platelet aggregation by interfering with the interaction between fibrinogen and platelets.

Adenosine Diphosphate↗
PubMedDate not supplied

Increased platelet aggregates in patients with transient ischemic attacks.

In order to evaluate the pathogenetic importance of platelet aggregates in cerebrovascular disease, a platelet count ratio method was used to study 66 patients with transient ischemic attacks (TIAs). Thirty normal subjects and 22 patients without thromboembolic disorders were also included as controls. The mean platelet aggregate ratio of the TIA group was 0.75 +/- 0.03 SEM which was significantly lower than that of normal subjects (0.90 +/- 0.02) or patients controls (0.88 +/- 0.01) (P less than 0.01). Seventeen patients with TIA were then treated with aspirin (1,200 mg) and dipyridamole (200 mg) daily. The platelet aggregate ratios were normalized in 13 patients. Of four patients who did not respond to this regimen, one did respond to sulfinpyrazone. When sulfinpyrazone was discontinued, recurrence of symptoms was preceded by an increase in platelet aggregates. These findings suggest that platelet aggregates may play an important role in the pathogenesis of cerebrovascular insufficiency. The determination of platelet aggregates appears useful in selecting patients for antiplatelet therapy.

Adult↗
PubMed2004

[Purification and characterization of platelet aggregation inhibitor component from venom of agkistrodon halys pallas].

Snake venom proteins,particularly from the viper and elapid families, have been known to contain a number of platelet active components including what cause platelet aggregation or inhibit platelet aggregation. Some of them have potential clinical usefulness for the treatment of human hemorrhagic or thrombotic disease. Agkistrodon halys pallas belonging to viper family is only growing in China. The aim of this study was to purify a human platelet aggregation inhibitor from venom of Agkistrodon halys pallas and determine its biochemical character. Whether a component could inhibit human platelet aggregation was act as a method to follow the tracks of the protein. Crude venom of Agkistrodon halys pallas was loaded onto a DEAE-Sepharose CL-6B chromatography column could gain 6 peaks. A platelet inhibitor with molecular mass of 65 kD on SDS-PAGE, was purified from peak 2 by Sephadex G-75 gel filtration and SP-Sepharose, Mono Q on FPLC. It could inhibit human platelet aggregation induced by ADP, collagen without activities of phospholipase A2, esterase, fibrinogenolytic. It is concluded that a platelet inhibitor can be isolated and purified from venom of Agkistrodon halys pallas and its inhibition of platelet aggregation is does-dependent.

Crotalid Venoms↗
PubMed1988

Platelet aggregation and vasopressin receptors in patients with diabetes mellitus.

Plasma vasopressin, vasopressin-induced platelet aggregation, and platelet vasopressin receptors were investigated in 10 normal subjects and 14 diabetic patients free of microangiopathy. Basal plasma vasopressin concentration was identical in two groups. Platelet aggregation induced by vasopressin as well as by epinephrine was not significantly altered in the diabetic patients. However, exploration of platelet V1-vasopressin receptors revealed in the diabetic group a dramatic reduction in the number of binding sites without alteration of the receptor affinity for tritiated vasopressin. Thus vasopressin-induced platelet aggregation in uncomplicated diabetes mellitus remains normal despite a decrease in the number of vasopressin receptors presumably due to alterations of the platelet membrane structure.

Adult↗
PubMed1978

Thromboxane generation and platelet aggregation in survivals of myocardial infarction.

Arachidonic acid (AA)-induced platelet aggregation was studied in platelet-rich plasma of 30 male patients who survived myocardial infarction and in 30 healthy men of similar age. Mean platelet aggregation thresholds to AA were 746 +/- 62 micrometer, and 869 +/- 57 micrometer, respectively. Only in 2 healthy subjects, but in 12 patients, irreversible platelet aggregation was induced consistently with low concentrations of AA, under 500 micrometer. The rate of conversion of AA to thromboxane A2 (TXA2) by platelets of these patients was augmented. Furthermore, less endogenous TXA2 was required to trigger aggregation of their platelets as compared to the controls. We have also shown that in platelet-poor plasma of these patients with "hyperreactive" platelets there exists a transferable factor which makes platelets of healthy subjects more prone to aggregatory action of AA. It is proposed that the assessment of platelet aggregability with AA provides a tool for identifying a subgroup of patients with coronary heart disease who might substantially benefit from the secondary preventive treatment with aspirin and with other antiplatelet drugs which inhibit the generation of TXA2 in platelets.

Adult↗
PubMed1989

[The effects of ligustrazine, aspirin and beta-histine on platelet aggregation in patients with acute ischemic stroke].

With a auto-balanced terbidimeter, the effects of ligustrazine, aspirin and betahistine on platelet aggregation were studied in 45 patients with acute ischemic stroke. The adopted parameters were: 1) the maximal aggregation (Amax), 2) the maximal aggregation velocity (Vmax), 3) the effective disaggregation rate in 5 minutes (DA 5), 4) the inhibition rate of aggregation given by drugs (IR), and 5) the concentration causing 50% inhibition of aggregation (IC 50). The results indicated that these three drugs could inhibit platelet aggregation both in vivo and in vitro. Aspirin could promote the aggregated platelets disaggregation in vivo and ligustrazine, in vitro. Regarding the effects on inhibiting platelet aggregation in vitro, ligustrazine was the most noticeable among the 3 drugs and aspirin was more effective than betahistine. The IC50 of ligustrazine, aspirin and betahistine were 0.568 mg/ml, 1,286 mg/ml and 1.722 mg/ml respectively. The authors considered that all three drugs possessed anti-platelet effects but they showed some differences among them.

Aged↗
PubMed2005

[Isolation and purification of an inhibitor on platelet aggregation from Ixodes sinensis].

OBJECTIVE: To study the bioactive components in ticks which inhibit platelet aggregation, and to understand the molecular mechanism of tick-host interaction. METHODS: Sephadex G-50 gel filtration and high performance liquid chromatography (HPLC) were used to purify the platelet aggregation inhibitor from lxodes sinensis. Its molecular weight and purity were checked by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Platelet-rich plasma (PRP) of rabbit was used to examine the function of platelet aggregation inhibitor. RESULTS: A purified platelet aggregation inhibitor was identified from L. sinensis with a molecular weight of 8 065. It inhibited platelet aggregation induced by ADP with strong potency. The inhibition of platelet aggregation reached over 90% under a concentration of 10 microg/ml. CONCLUSION: An inhibitor of platelet aggregation from L. sinensis was identified, which may play an important role for ticks to successfully get blood meal from their hosts.

Animals↗