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PubMed2002

[Effect of vitamin C on platelet aggregation in smokers and nonsmokers].

BACKGROUND: Epidemiologic studies suggest a protective effect of regular intake of vitamin C and vitamin E as antioxidant in the manifestation of coronary heart disease. Cigarette smoke contains a large amount of radicals and reactive oxygen-derived substances enhancing aggregation of platelets. We investigated the effect of vitamin C as an important antioxidant in human plasma on the aggregation of human platelets in smokers and nonsmokers. TEST PERSONS AND METHOD: Overall 40 persons (mean age: 28 +/- 9 years) were randomized. The groups of chronic smokers (21 +/- 9 "packyears") and nonsmokers consisted of 20 persons, respectively. In each group ten persons were treated with intravenous infusion of 3 g vitamin C or 100 ml 0.9% saline solution (placebo). The maximal aggregation was measured with an aggregometer after 0, 3, 6, and 24 hours with collagen concentrations of 0.5 microgram/ml and 1.0 microgram/ml, respectively. RESULTS: In smokers with vitamin C application the group comparison by Wilcoxon's rank test demonstrated a significant decrease of platelet aggregation after 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.05), whereas nonsmokers with vitamin C application revealed a significant decrease of platelet aggregation after 3 and 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.03). The comparison between smokers and nonsmokers regarding the effect of vitamin C on platelet aggregation for both collagen concentrations demonstrated no significant difference (3 hours: p = 0.84 and p = 0.97; 6 hours: p = 0.81 and p = 0.59; and 24 hours p = 0.57 and p = 0.06, not significant, respectively). CONCLUSION: These findings suggest that vitamin C exerts an unknown inhibitory effect on collagen-induced platelets aggregation. These observations may represent a further protective effect of vitamin C in the development of coronary heart disease.

Adult↗
PubMed2000

Effect of laparoscopic cholecystectomy on platelet aggregation.

The purpose of this study was to investigate the effect of laparoscopic cholecystectomy on platelet function. We operated on 40 women with symptomatic gallbladder stone, 20 of whom (study group) underwent laparoscopic cholecystectomy and 20 of whom (control group) open cholecystectomy. Patients with a history of bleeding, abnormal platelet count, or systemic disorders and those who were on salicylates, heparin, or oral anticoagulants were excluded. Blood parameters were checked at the beginning and the end of the operation, including platelet aggregation using adenosine 5'-diphosphate (ADP), collagen, and ristocetin in a whole-blood aggregometer. Platelet aggregation was evaluated by percent aggregation. Platelet aggregation due to collagen and ristocetin increased significantly at the end of the operation in the study group (p < 0.001). Aggregation due to ADP did not differ significantly from the start to the end of the operation. Control group results did not show any differences. Although the clinical findings of aggregated platelet are not frequently observed in practice, we suggest that laparoscopy increases platelet aggregation.

Abdomen↗
PubMedDate not supplied

Platelet aggregation abnormalities in idiopathic scoliosis.

Platelet aggregation studies were performed in 22 adolescent girls with idiopathic scoliosis. Impaired ADP-induced platelet aggregation was found in washed platelets of the 22 patients with idiopathic scoliosis when compared with the controls (76.5% of control values; p less than 0.01). Furthermore, platelets from patients with progressive curves showed a greater degree of abnormality than platelets from those with nonprogressive curves, e.g., 57.6 +/- 22% of control values (p less than 0.001). No significant differences in aggregation could be detected when platelets were aggregated with the ionophore A-23187 in either the absence or the presence of calcium. Platelet aggregation studies in patients with other spinal deformities did not differ from the healthy controls. Because platelets share similar contractile proteins as muscles, the present study suggests that a muscle disorder may play an important pathogenic role in idiopathic scoliosis.

Adenosine Diphosphate↗
PubMed1995

Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets.

BACKGROUND: Relaxin, a peptide hormone of ovarian origin, has been shown to cause a striking dilatory action on microvessels in different organs. In our recent studies, relaxin has been shown to stimulate the production of nitric oxide, a powerful vasodilatory agent, in several targets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function. EXPERIMENTAL DESIGN: The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with relaxin at different concentrations and then stimulated with collagen or thrombin. Aggregation and intracellular levels of cGMP and Ca2+ were determined. In some experiments, inhibitors or potentiators of nitric oxide activity were also used to clarify whether the mechanism of action of relaxin involves the L-arginine-nitric-oxide pathway. Electron microscopy of platelets treated and not treated with relaxin was also carried out. RESULTS: Preincubation of the platelets with relaxin before stimulation with proaggregants resulted in a significant, concentration-dependent inhibition of platelet aggregation, accompanied by an elevation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through nitric oxide. Ultrastructurally, relaxin was shown to hinder the conformational changes and granule exocytosis usually occurring in platelets during aggregation. CONCLUSIONS: This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive activities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic and hypertensive disorders of pregnancy and cardiovascular diseases.

Adult↗
PubMed1986

Effects of 2-indolecarbohydrazides on thromboxane synthetase activity and on in vitro and ex vivo blood platelet aggregation. New selective inhibitors.

Platelet antiaggregatory action of 42 synthetic 2-indolecarbohydrazides was studied observing their actions on arachidonic acid (AA) and adenosine-5-diphosphate (ADP) induced platelet aggregation. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on those compounds whose previous activities included inhibition of AA induced platelet aggregation and inhibition of the second wave of aggregation using ADP as the aggregating agent. Those compounds which demonstrated inhibition of TXB2 with increased PGE2 were subsequently tested with PGH2 as the aggregating agent. Results of this work demonstrate that 3 of the 42 compounds have specific inhibitory activity for thromboxane synthetase. The most active compounds were 1-methyl-5-hydroxyindole derivatives.

Arachidonic Acid↗
PubMed1996

Combination chemotherapy for breast carcinoma using a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) causes a platelet aggregation defect.

Various coagulation parameters including platelet aggregation were evaluated during the course of treatment in 25 patients with breast carcinoma receiving a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). No significant changes were found in whole blood clotting time (WBCT), prothrombin time (PT), kaolin cephalin clotting time (KCCT), platelet count (PC) and prothrombin consumption index (PCI). The CMF combination induced a significant reduction in platelet factor-3 (PF3) availability and reduction in platelet aggregation to ADP and adrenaline. These defects occurred without development of thrombocytopenia. The changes occurred on the 8th day of chemotherapy and a progressive suppression in platelet aggregation was noted during subsequent follow-up. This acquired abnormality in platelet aggregation and PF3 availability may be responsible for various hemorrhagic manifestations such as mucositis, epistaxis and hemorrhagic cystitis following CMF therapy. Further, these changes precede the onset of life-threatening complication of thrombocytopenia. The study of platelet aggregation should be considered besides platelet counting in patients on CMF combination to assess bleeding diathesis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Ticlopidine facilitates the deaggregation of human platelets aggregated by thrombin.

Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80-90% 14C-serotonin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5x the activity of thrombin) and PGE1 (10 mumol/l) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 mumol/l) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Adenosine Diphosphate↗
PubMed1994

A possible role for extracellular bicarbonate in U-46619-induced rat platelet aggregation.

U-46619, a thromboxane A2 agonist, has been believed not to induce aggregation of rat platelets. However, we have found that U-46619 evoked rat platelet aggregation when the cells were suspended in HCO3-containing medium, whereas it was inactive in medium lacking HCO3-. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS), selective inhibitor of the HCO3/Cl- exchanger, inhibited the aggregation of rat platelets induced by U-46619 as well as by collagen and ADP. Thrombin-induced aggregation was also inhibited by DIDS, although to a much lesser extent. Several inhibitors of anion transporters, such as phloretin, pyridoxal phosphate and ethacrynic acid, suppressed U-46619-induced aggregation. These observations indicate that HCO3-influx via an anion exchanger may be involved in the signal transduction pathway of U-46619 in rat platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Effects of aprotinin in platelet aggregation and cytosolic free calcium in swine platelets.

Aprotinin inhibited platelet aggregation induced by thrombin (0.25 U.ml-1) with IC50 200 kIU.ml-1, and inhibited the rise of cytosolic free calcium concentration in platelets stimulated by thrombin (0.1 U.ml-1) in the absence and in the presence of Ca2+ 0.5 mmol.L-1 (IC50 117 and 50 kIU.ml-1, respectively), but had no effect on the amounts of actin and myosin heavy chain associated with cytoskeletons. These suggest that aprotinin is an anti-platelet agent and may exert its action through inhibiting the Ca2+ flux.

Animals↗
PubMed2001

Augmented oxidative stress of platelets in chronic smokers. Mechanisms of impaired platelet-derived nitric oxide bioactivity and augmented platelet aggregability.

OBJECTIVES: We investigated whether impaired platelet-derived nitric oxide (PDNO) bioactivity and augmented platelet aggregability in chronic smokers are related to the imbalance of the intraplatelet redox state through increased oxidative stress. BACKGROUND: Chronic smoking impairs PDNO release and augments platelet aggregability. However, their mechanisms are unknown. METHODS: Collagen-induced PDNO release, platelet aggregation, plasma and intraplatelet vitamin C and reduced glutathione (GSH), intraplatelet cyclic guanosine 3',5'-monophosphate (cGMP) and intraplatelet nitrotyrosine production, which is a marker of the peroxynitrite formation, were measured in 11 chronic smokers and 10 age-matched nonsmokers. RESULTS: Release of PDNO and levels of intraplatelet cGMP were lower, and platelet aggregation was greater, in smokers than in nonsmokers. Intraplatelet vitamin C and GSH levels were lower in smokers than in nonsmokers. Intraplatelet nitrotyrosine production was greater in smokers than in nonsmokers. Next, we investigated the effects of oral vitamin C administration (2 g). After vitamin C administration, intraplatelet vitamin C levels were increased and not different at 2 h between the two groups. Then, PDNO release, intraplatelet cGMP levels and platelet aggregation in smokers were restored to the levels of nonsmokers. In smokers, PDNO release and consumption of GSH during platelet aggregation were inversely correlated, and consumption was much less after vitamin C administration. Vitamin C administration decreased intraplatelet nitrotyrosine production in smokers. CONCLUSIONS: Impaired PDNO bioactivity and augmented platelet aggregability may be caused by an imbalance of the intraplatelet redox state through increased oxidative stress in smokers.

Administration, Oral↗
PubMed1990

Temporal aggregate size distributions from simulation of platelet aggregation and disaggregation.

A modification of the Smoluchowski collision theory for platelet aggregation is proposed with additional kinetic terms to accommodate observed disaggregation behavior. This model, consisting of a set of coupled, nonlinear, first-order differential equations, approximates size distributions with time for normal human platelets in plasma after the addition of a stimulus. Parameters controlling the kinetics of the formation and breakup of aggregates are numerically investigated. The aggregation coefficient, predominant during the aggregation phase, is strongly dependent on both time and aggregating agent doses. For the disaggregation phase, the disaggregation rate constants are a function of aggregate size, with a time-dependent disaggregation coefficient. Numerical results generated by the model are compared with experimental volume-size distribution curves from the literature.

Humans↗
PubMed1991

Low levels of hydrogen peroxide enhance platelet aggregation by cyclooxygenase activation.

Platelet aggregation can be triggered by addition of exogenous arachidonate owing to its conversion to endoperoxides and thromboxane A2. The dose-response curve of arachidonate-induced platelet aggregation exhibited a very steep slope. Simultaneous addition of H2O2 (1-200 microM) significantly shifted this curve to the left. H2O2 alone did not induce aggregation up to a concentration of 1 mM; however, a reversible increase of cytoplasmic Ca2+ and a small increase of the thromboxane levels could be observed. In the presence of exogenous arachidonate H2O2 led to an increased formation of arachidonate metabolites. Our data demonstrate that at threshold levels of 20:4 H2O2 is able to promote conversion of 20:4 to proaggregatory prostaglandin endoperoxides, and subsequently platelet activation is facilitated. Thus we support the evidence for a role of H2O2 in the activation of cyclooxygenase possibly by providing an adequate peroxide tone.

Dose-Response Relationship, Drug↗
PubMed1998

Platelet-released ADP stabilizes PAF-induced rabbit platelet aggregation by stabilizing intracellular calcium.

AIM: To examine whether platelet-released adenosine diphosphate (ADP) would contribute to the stabilization of rabbit platelet aggregation induced by platelet activating factor (PAF). METHODS: Rabbit platelet aggregation induced by PAF was measured turbimetrically. ADP release from rabbit platelets stimulated by PAF was determined by HPLC. Intracellular Ca2+ was measured using Ca(2+)-sensitive fluorescent indicator Fura 2-AM. RESULTS: PAF > or = 1 nmol.L-1 induced full platelet aggregation, which did not deaggregate over 5 min after aggregation reached peak. Platelet aggregation was deaggregated in a concentration-dependent manner by subsequent addition of ADP scavenger ATP-diphosphohydrolase (apyrase) at 5-100 mg.L-1. PAF 3 nmol.L-1 stimulated release of ADP (29% vs 6% of control), and elicited a rapid rise in intracellular calcium ([Ca2+]i) which peaked at approximately 15 s. Then the [Ca2+]i gradually decayed from 585 +/- 80 nmol.L-1 within 100 s to a low level (364 +/- 82 nmol.L-1). Apyrase 100 mg.L-1, added 2 min after PAF, reduced [Ca2+]i to a lower level (171 +/- 29 nmol.L-1). CONCLUSION: Platelet-released ADP stabilizes PAF-induced rabbit platelet aggregation by stabilizing [Ca2+]i at elevated level.

Adenosine Diphosphate↗
PubMed1990

Inhibition of cyclooxygenase-independent platelet aggregation by low vitamin E concentration.

Platelet aggregation induced by threshold concentrations of agonists such as collagen, PAF or epinephrine was inhibited in vitro by 100 microM aspirin but was restored by stimulating platelets with high concentrations of collagen, PAF or by a combination of epinephrine and PAF. Incubating aspirin-treated platelets with 50-100 microM vitamin E or vitamin E acetate inhibited platelet aggregation by high concentrations of collagen and PAF and by the combination of epinephrine and PAF; platelet thromboxane A2 formation was less than 10% in samples incubated with 100 microM aspirin. Apyrase, added to aspirin-treated platelet, did not influence platelet aggregation induced by epinephrine and PAF. The present study suggests that concentrations of vitamin E as low as 50-100 microM inhibit cyclooxygenase-independent platelet aggregation when combined with an inhibitor of the arachidonate pathway.

Apyrase↗
PubMed1978

Platelet aggregation in diabetic retinopathy.

Platelet aggregation in diabetic retinopathy was investigated in a group of 25 patients. An enhanced activity induced by epinephrine and arachidonic acid was found in this group as compared with the controls, whereas in adenosine diphosphate (ADP) platelet aggregation no differences were observed. Spontaneous aggregation was found in 8% of the diabetic retinopathy cases.

Adenosine Diphosphate↗
PubMed1988

Interrelation of platelet aggregation, release reaction and thromboxane A2 production.

Aggregation of platelets, stimulated by different agonists, was inhibited by omitting sample stirring or by preincubation of platelets with a monoclonal antibody against glycoproteins IIb-IIIa or with a pentapeptide containing the sequence Arg-Gly-Asp-Ser. In platelets stimulated by collagen, ADP and epinephrine, the inhibition of aggregation paralleled a reduction of both release reaction and thromboxane A2 formation. When thrombin was the stimulus, ATP release and thromboxane A2 production were unaffected (or only slightly modified) by the inhibition of platelet aggregation. These data add further evidence to the hypothesis that aggregation supports the activation of platelets stimulated by weak agonists.

Adenosine Diphosphate↗
PubMed1981

Free fatty acid-induced platelet aggregation: studies with solubilized and nonsolubilized fatty acids.

The aggregation response of washed porcine platelets to the sodium salts of stearic, oleic, palmitic, and myristic acids was analyzed turbidometrically. The fatty acids were prepared as aqueous suspensions and as taurocholate- or albumin-solubilized systems. The final concentration of fatty acid in the platelet preparation varied between 70 and 600 microM. This range was within or below the normal physiological limits of 300-1200 microM. Platelet aggregation was observed with both the suspended and taurocholate-solubilized fatty acids. The extent of platelet aggregate formation increased with the fatty acid concentration and chain length. With the exception of stearate, the taurocholate-solubilized fatty acids were more active than the suspensions. Albumin-solubilized fatty acids were devoid of platelet aggregating activity. Particle-size analysis of the solubilized fatty acids indicated that fatty acid precipitation had occurred subsequent to the addition of taurocholate-solubilized fatty acids to the platelets. This precipitation did not occur with the albumin-solubilized systems, suggesting that the fatty acids must assume a particulate physical state to induce aggregation. Platelet aggregation induced by fatty acids was not inhibited by 80 nM epoprostenol, 75 microM alprostadil, or 150 microM indomethacin. This finding indicated that the fatty acid-induced platelet aggregation was independent of cyclic AMP-related calcium shift, cyclooxygenase-arachidonate, or granular nucleotide release mechanisms.

Adenosine Diphosphate↗
PubMed1986

Miconazole inhibition of platelet aggregation by inhibiting cyclooxygenase.

Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment.

Adenosine Diphosphate↗