Platelet Prostaglandin Research Articles

Unbalanced plasma control of TxA2 and PGI2 synthesis in vitamin E-deficient rats.

Factors contributing to the antioxidant power of plasma may play a role in the control of arachidonic acid (AA) metabolism. The purpose of this study was to evaluate the possible effects of vitamin E deficiency on platelet and vascular prostaglandin synthesis. CD-COBS male rats were fed for 7 mo a diet containing either 1 or 75 mg/kg vitamin E. At the end of this period, serum levels of vitamin E were 0.4 +/- 0.1 and 10 +/- 0.6 micrograms/ml in the two groups, respectively. Malondialdehyde (MDA) generation by AA was significantly higher in platelet-rich plasma from vitamin E-deficient rats. Thromboxane B2 (TxB2) in serum from vitamin E-deficient rats increased about 16 times compared with controls, whereas 6-keto-PGF1 alpha levels increased only 3 times. The ratio between TxB2 and 6-keto-PGF1 alpha, increased therefore manyfold in vitamin E-deficient animals. MDA formation and [14C]AA metabolism in washed platelets were similar in the two groups of animals. No significant difference was found in the PGI2 (prostacyclin) antiaggregating activity released from the aortic rings resuspended in buffer. In contrast, the capacity of plasma to stimulate PGI2 activity from "exhausted" aortic rings (prostacyclin-stimulating factor) was significantly reduced in vitamin E-deficient animals. In conclusion, vitamin E deficiency induces an unbalanced plasma regulation of AA metabolism. This results in an excessive production of platelet TxA2 compared with vascular PGI2 generation. On the other hand, vitamin E deficiency does not seem to affect directly the enzymatic pathways of AA metabolism.

Effects of thromboxane synthetase inhibitors on aggregation of rabbit platelets

Thromboxane (TX) synthetase activity was selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) and sodium (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methyl-propenoate (OKY-1581) (OKYs). Their IC 50 for the rabbit platelet enzyme were found to be 11nM and 3nM respectively. Arachidonic acid (AA) or collagen induced platelet aggregation, and generated TXA 2 and prostaglandins (PGs) in rabbit platelets. OKYs inhibited platelet aggregation and TXA 2 generation without affecting PGs generation, while aspirin inhibited platelet aggregation, and TXA 2 and PGs generation. There was a parallel relation between the degree of inhibition of platelet aggregation and TXA 2 generation by OKYs, but the inhibitory effects of aspirin on platelet aggregation was related to that on both TXA 2 and PGs generation. However, OKYs and aspirin did not inhibit ADP-induced platelet aggregation which did not involve the generation of TXA 2 and PGs. These results suggested that TXA 2 generation is related to platelet aggregation induced by AA or collagen, and that the inhibitory effect of OKYs on platelet aggregation is due to the inhibition of TX synthetase.

Aspirin, prostaglandins, and peripheral gangrene

The effect of aspirin on platelet thromboxane and venous prostaglandin production was determined in a group of 15 healthy adults. Ten received a single 300 mg dose of aspirin and one a single 150 mg dose. The remaining four persons received 40 mg aspirin four times daily. Platelet thromboxane production was measured by radioimmunoassay for thromboxane B 2; vein biopsy was performed before and at a predetermined interval after aspirin ingestion; prostacyclin production was assessed by radioimmunoassay for 6-keto prostaglandin F 1α-. One hundred percent inhibition of thromboxane B 2 production and 61 to 100 (mean 83) percent inhibition of 6-keto prostaglandin F 1α were observed in the five persons in whom repeated biopsy was performed within 12 hours of receiving a single dose of aspirin. This compares with 75 to 100 (mean 90) percent thromboxane B 2 inhibition and 63 to 100 (mean 77) percent 6-keto prostaglandin F 1α inhibition in six persons in whom repeated biopsy was performed within 24 to 72 hours after aspirin ingestion. In the four persons receiving 40 mg aspirin four times daily, there was a statistically significant (p < 0.02) reduction in venous 6-keto prostaglandin F 1α production compared with pre-aspirin values. In this smaller group, the mean percentage 6-keto prostaglandin F 1α inhibition was 87 percent, compared with 98 percent inhibition of thromboxane B 2 production. These results indicate that, in healthy adults, there is little difference in the inhibitory effect of aspirin on prostaglandin biosynthesis by platelets and venous tissue. The clinical response to aspirin in a group of patients with essential thrombocythemia complicated by painful toes associated with pregangrene or gangrene and with or without transient cerebral ischemic attacks is described. Fourteen patients had painful toes with evidence of peripheral ischemia. Three of these also had amaurosis fugax. Two further patients complained solely of transient blurring of vision. All patients received a myelosuppressive agent ( 32p or busulphan) and aspirin. Eleven patients were given 300 to 600 mg of aspirin daily; five received 40 mg of aspirin daily. Only one patient failed to respond to aspirin. In 12 patients, there was complete loss of pain and reversal of the pregangrenous changes of the toes. Following aspirin ingestion, there were no recurrences of the transient ischemic attacks. Pain relief occurred more promptly in persons receiving the larger dose of aspirin. These results support the view that certain complications of essential thrombocythemia, notably painful peripheral ischemia and amaurosis fugax, are platelet-derived and can be controlled by the inhibition of platelet prostaglandin biosynthesis. Aspirin has an inhibitory effect on this hemostatic mechanism.

Platelet prostaglandin production in alcoholic liver disease

Impaired platelet aggregation is a common finding in patients with alcoholic liver disease. This may be due to impairment of prostaglandin synthesis and alterations in the proportions of platelet membrane lipids secondary to changes in circulating lipids. Platelet prostaglandin synthesis was measured by the production of malonaldehyde (MDA), and was increased in patients with alcoholic cirrhosis compared with normal controls. Mean MDA production in cirrhotics was 3.37 nmoles MDA/10 9 platelets, and in controls 1.01 nmoles MDA/10 9 platelets (p < 0.01). Platelet prostaglandin synthesis was significantly related to the serum cholesterol triglyceride ratio (r=0.73, p < 0.005). Platelet aggregation was impaired in 12 14 cirrhotics. Five of the cirrhotics had a factor in their plasma which appeared to enhance the aggregation of normal platelets. Impaired platelet aggregation in patients with alcoholic liver disease appears to be due to a defect in intraplatelet metabolism.

Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclooxygenase defect.

A qualitative platelet abnormality and a bleeding tendency are frequently associated with renal failure and uremia. We demonstrated previously that uremic patients display an abnormal platelet aggregation to arachidonic acid and reduced malondialdehyde production in response to thrombin and arachidonic acid. The objectives of this investigation were: (a) to compare platelet prostaglandin (PG) and thromboxane (TX) production in whole blood and in platelet-rich plasma (PRP) of 21 uremic patients and 22 healthy subjects; (b) to evaluate the concentration and activity of platelet PG- and TX-forming enzymes; (c) to assess the functional responsiveness of the platelet TXA(2)/PGH(2) receptor; (d) to explore the hemostatic consequences of partially reduced TXA(2) production.Platelet immunoreactive TXB(2) production during whole blood clotting was significantly reduced, by approximately 60%, in uremic patients as compared to age- and sex-matched controls. Exogenous thrombin (5-30 IU/ml) failed to restore normal TXB(2) production in uremic platelets. Uremic PRP produced comparable or slightly higher amounts of TXB(2) than normal PRP at arachidonate concentrations 0.25-1 mM. However, when exposed to substrate concentrations >2 mM, uremic PRP produced significantly less TXB(2) than normal PRP. To discriminate between reduced arachidonic acid oxygenation and altered endoperoxide metabolism, the time course of immunoreactive TXB(2) and PGE(2) production was measured during whole blood clotting. The synthesis and release of both cyclooxygenase-derived products was slower and significantly reduced, at all time intervals considered. Furthermore, PGI(2) production in whole blood, as reflected by serum immunoreactive 6-keto-PGF(1alpha) concentrations, was significantly reduced in uremic patients as compared with healthy subjects. PGH synthase levels, as determined by an immunoradiometric assay, were not significantly different in platelets from uremic patients as compared to control platelets. A single 40-mg dose of aspirin given to five healthy volunteers reduced their serum TXB(2) to levels found in uremic patients. This was associated with a significant increase of threshold aggregating concentrations of ADP and arachidonic acid and prolongation of bleeding time. Substantially similar threshold concentrations of U46619, a TXA(2) agonist, induced aggregation of normal and uremic platelets. Prostacyclin induced a significant elevation of uremic platelet cyclic AMP, which was suppressed by U46619, further suggesting normal responsiveness of the TXA(2)/PGH(2) receptor. WE CONCLUDE THAT: (a) an abnormality of platelet arachidonic acid metabolism exists in uremia, leading to a reduced TXA(2) production; (b) the characteristics of this abnormality are consistent with a functional cyclooxygenase defect; (c) reduced TXA(2) production may partially explain the previously described abnormality of platelet function in uremia.

Failure of children with asthma to respond to daily aspirin therapy

Adverse reactions to aspirin in asthmatic patients have been widely described in the past. In contrast to this more frequent complication, several authors have published reports suggesting that aspirin and other nonsteroidal anti-inflammatory drugs can improve asthma. We studied the effect of long-term aspirin administration in children with moderately severe asthma. Ten children who showed no immediate effect of aspirin challenge (either adverse or beneficial) were placed in a 9 wk, double-blind crossover study, receiving aspirin (10 gr twice daily) or placebo for 4 wk, then a 1 wk washout period, followed by aspirin or placebo for 4 wk. There was no difference between aspirin and placebo periods in number of wheezing episodes, frequency of additional bronchodilator or prednisone use, or daily spirometric measurements. Serum thromboxane B 2 levels were significantly reduced during aspirin therapy (p < 0.001), indicating that the patients had complied with the aspirin therapy. Thus long-term administration of aspirin to asthmatics who show no immediate beneficial or adverse response to aspirin challenge appeared not to influence the clinical course of asthma. In addition, inhibition of the platelet prostaglandin cyclooxygenase pathway in these patients did not modify the clinical course of their asthma.

Platelet Release Reaction and Prostaglandin Pathway Activation in Angina Patients during Exercise: Effect of Indobufen

Platelet 14C-serotonin release induced by collagen, and platelet malondialdehyde (M.D.A.) generation induced by thrombin were assessed in twenty patients with stable angina, before and after exercise with a bicycle ergometer. The patients received a single oral 200 mg dose of indobufen or placebo according to a crossover design in double-blind conditions. The M.D.A. concentration increased when exercise was carried out after placebo, whereas indobufen markedly inhibited M.D.A. production and 14C-serotonin release. These results suggest that effort may be an important factor in activation of the platelet prostaglandin pathway and that the use of antithrombotic drugs may be appropriate in patients with angina.

Abnormal Platelet and Vascular Prostaglandin Synthesis in an Infant with Hemolytic Uremic Syndrome

The hemolytic-uremic syndrome (HUS) is a disorder characterized by a microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Pathologic examination reveals thrombotic occlusions in the microcirculation, with the kidney being the main target organ involved. Recently, Remuzzi et al1,2 have demonstrated abnormalities in vascular prostacyclin or prostaglandin I2 (PGI2) formation in HUS. We report further characterization of the abnormality in PGI2 synthesis in a patient with HUS. An abnormality in platelet prostaglandin endoperoxide formation was also observed. CASE REPORT A 4-month-old male infant was hospitalized with anemia, thrombocytopenia, and proteinuria. The neonatal period had been complicated by hyperbilirubinemia necessitating an exchange transfusion.

HEPARIN-INDUCED THROMBOCYTOPENIA: ASSOCIATION OF THROMBOTIC COMPLICATIONS WITH HEPARIN-DEPENDENT IgG ANTIBODY THAT INDUCES THROMBOXANE SYNTHESIS AND PLATELET AGGREGATION

Eleven patients in whom thrombocytopenia developed during heparin therapy were studied. Six patients (group 1) had severe thrombocytopenia with delayed onset and five of these patients had thromboembolic complications. A serum factor which induced heparin-dependent thromboxane B 2 synthesis, 14C-serotonin release, and platelet aggregation was found in all patients in group 1. The serum factor was shown to be IgG. These findings suggest that the mechanism of the severe thrombocytopenia secondary to heparin therapy is immunological and the associated thromboembolic complications may be attributed to in-vivo activation of the platelet prostaglandin pathway and platelet aggregation induced by the heparin-dependent antibody. The five patients in group 2 had mild symptomless thrombocytopenia with early onset. In this group, the heparin-dependent antibody was not found and the mechanism of the thrombocytopenia is probably a direct action of heparin on platelets.

Pharmacology of angioplasty and intravascular thrombolysis.

Interventional angiographic techniques are of increasing importance in the management of arteriosclerosis and its complications. Two areas of particular interest are the treatment of focal arterial stenoses by percutaneous transluminal angioplasty and the treatment of arterial thromboemboli with selective infusion of thrombolytic agents. The administration of multiple drugs, in various combinations, is a critical factor in the success of these interventions. To effectively use this new pharmacoangiography, it is important to understand both the pathophysiology of the atherosclerotic or thrombotic process being treated and the actions of the drugs used. Preserving the effect of angioplasty relies on preventing thrombus formation and preventing recurrence of the atherosclerotic obstruction. Heparin during the procedure is clearly useful for the former, and aspirin in small doses and other antiplatelet medications are indicated for the latter. The precise utility of long-term anticoagulation, of low molecular weight dextran, and of various antiplatelet regimens remains to be proven. The theoretical importance of these medications in improving long-term patency rests on the effects they have on platelet and vessel wall prostaglandins, on intimal smooth muscle cell proliferation, and on the thrombogenicity of injured arterial intima. Fibrinolytic therapy, with streptokinase and urokinase, has been used for many years. Selective intraarterial use, however, is a new and promising application. Intracoronary streptokinase infusion during acute myocardial ischemia appears to prevent or limit infarction in certain patients. Peripheral use for acute arterial occlusion, either in native vessels or in grafts, is an area of great promise. Key considerations are thrombus age, size, and location, and the status of the arterial flow proximal and distal to the obstruction.

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

Effect of furosemide on the in vitro prostaglandin biosynthesis in human platelets

Effect of furosemide at various concentrations (0.05 – 4 mM) was examined on the in vitro biosynthesis of prostaglandins in human platelets. At lower furosemide concentrations (0.05 and 0.1 mM) no effect was observed. At 1 and 2 mM concentrations, PGE significantly (P < 0.01) increased. At 3 and 4 mM concentrations PGE 2 increased though not significantly probably because of the small number of samples (n=5). A decrease in PGD formation was noted at 1–4 mM furosemide concentrations, though significantly only at 3 mM conc. At 1 and 2 mM concentrations, TxB 2 and HHT increased whereas at 3 and 4 mM concentrations these metabolites were decreased. These effects were, however, not significant. No effect was observed on endoperoxide generation at 1 and 2 mM conc. Furosemide at 1 and 2 mM concentrations inhibited ADP- and arachidonic acid induced platelet aggregation. An increased platelet formation of PGE in the presence of furosemide may point to the fact that this drug shows its effect mainly, on the formation of PGE which has been found to exert a profound effect on renal blood flow and thus ameliorates some forms of hypertension.

Effects of cadmium on platelet thromboxane and vascular prostacyclin production

The interaction between cadmium and arachidonic acid metabolism in platelets and vascular tissue was evaluated, in ex vivo experiments, by determining the thromboxane levels in serum and the prostacyclin production by the aortic walls in cadmium-treated rabbits. Cadmium given parenterally for 4 days in doses of 0.25, 0.5, and 1 mg/kg/day produced a dose-dependent increase of serum thromboxane B 2 levels. The effect of cadmium on prostacyclin release was biphasic. The metal, in doses of 0.25 and 0.5 mg/kg/day, inhibited prostacyclin production in an inverse ratio with administered doses. At the higher dose (1 mg/kg/day) cadmium caused an increase in prostacyclin formation. The present results suggest that the vascular action of cadmium is due, in part at least, to the involvement of the vascular-wall and platelet prostaglandin systems.

Structure-activity studies of aspirin and related compounds on platelet aggregation, arachidonic acid metabolism in platelets and artery, and arterial prostacyclin activity

A series of benzoic acid derivatives was tested for specificity of action on human platelet function and platelet prostaglandin (PG) synthesis versus prostacyclin (PGI 2) production by rat and rabbit aorta rings. None of the agents tested was more specific for one system than the other. ASA was more potent than 2-propionyloxybenzoic acid (2-PBA) in inhibiting platelet function and platelet PG synthesis although the potencies of these agents were comparable in inhibiting PGI 2 synthesis. 3-Propionyloxybenzoic acid (3-PBA) caused increased activity in both systems while 2-acetylbenzoic acid (ABA) had only minor effects. A cyclical derivative, 3-methylphthalide (3-MP), inhibited both platelet function and PGI 2 synthesis although it did not inhbit cyclo-oxygenase activity, suggesting a novel mechanism of action. Thus only minor changes in the ASA molecule could be effected without significant changes in pharmacological activity. The investigation of novel agents such as 3-MP may lead to a better understanding of arachidonate metabolism in different tissues and possibly to the development of more tissue-specific drugs.

Human platelet activation by an alkylacetyl analogue of phosphatidylcholine

The present study has evaluated the influence of semi-synthetic platelet-aggregating factor, (PAF) i.e., alkylacetylglycerophosphocholine, on human platelet morphology, biochemistry and function in order to determine if PAF serves as the corrective factor restoring sensitivity to refractory platelets after treatment with epinephrine. Threshold concentrations of PAF caused irreversible platelet aggregation which could be blocked by agents elevating endogenous levels or cyclic AMP or inhibited by antagonists of platelet prostaglandin synthesis and secretion. PAF did not stimulate platelets through α-adrenergic receptors or receptors for arachidonate, endoperoxides or thromboxanes. 24 h after aspirin ingestion, platelets could be aggregated irreversibly by high concentrations, but not by threshold amounts of PAF, even though they were still insensitive to arachidonate. Another less potent PAF derivative, alkenylacetylglycerophosphocholine, blocked aggregation of 24-h aspirin platelets by PAF, but did not inhibit restoration of arachidonate sensitivity and irreversible aggregation when the samples were treated first with epinephrine. Our findings indicate that threshold amounts of PAF activate human platelets in a physiologic manner and cause irreversible aggregation which is dependent on prostaglandin synthesis and the release reaction. The results do not support the concept that PAF is the mediator of the mechanism of membrane modulation through which epinephrine induces correction of the refractory state in prostaglandin I 2-treated or dissociated platelets, or cells obtained from individuals following aspirin ingestion. Thus, the mechanism of platelet membrane modulation is capable of securing irreversible aggregation of secretion, prostaglandin synthesis or PAF formation.

Metabolic studies with probucol in hypercholesterolaemia

Probucol (1 g/day) was administered for 6 months to 16 hypercholesterolaemic patients previously stabilized on diet alone. Total plasma cholesterol fell by 16%, LDL cholesterol by 14% and HDL cholesterol by 41%. The ratio of total cholesterol to HDL cholesterol increased by 40%. Total plasma triglycerides showed a slight upward trend. The extent of the fall in HDL cholesterol was directly proportional to the pre-treatment HDL cholesterol concentration. In 2 patients studied, treatment with Probucol produced a sustained increase in the excretion of endogenous faecal steroids, due to increased faecal bile acids. In 3 patients studied, Probucol increased the degree of cholesterol saturation in gall bladder bile. The Lithogenic Index approximated to pathological levels in 1 patient whose bile was previously relatively saturated with cholesterol. Probucol also appeared to cause a modest reduction in the degree of platelet activation in vivo, with reduced platelet prostaglandin synthesis and reduced release of platelet peptides.

A role for prostaglandins and thromboxanes in the exposure of platelet fibrinogen receptors.

Exposure of fibrinogen receptors by a variety of agonists is a prerequisite for platelet aggregation. Because the synthesis of prostaglandins and thromboxane A2 also occurs during platelet aggregation we wondered whether these agents participate in the exposure of platelet fibrinogen receptors. Therefore, we measured the binding of human 125I-fibrinogen to gel-filtered normal human platelets after prostaglandin and thromboxane synthesis had been inhibited by aspirin or indomethacin. The fibrinogen binding assay was performed at 37 degrees C but without stirring to prevent the formation of platelet aggregates. Platelet secretion, measured with [14C]serotonin, did not occur during the procedure. Aspirin or indomethacin inhibited fibrinogen binding stimulated by 10 microM epinephrine by 53%, and inhibited fibrinogen binding stimulated by 1-2 microM ADP by 37.1%. However, ADP at concentrations greater than 2 microM returned fibrinogen binding toward control values. Scatchard analysis demonstrated that aspirin decreased the number but not the affinity of the exposed fibrinogen receptors. To determine whether prostaglandins are capable of directly exposing fibrinogen receptors, prostaglandin H2 was used to stimulate platelets in the fibrinogen binding assay. Prostaglandin H2 exposed approximately 54,000 fibrinogen receptors/platelet and corrected the deficit in receptor exposure induced by aspirin. These studies demonstrate that platelet prostaglandins or thromboxane A2 can play a direct role in the exposure of platelet fibrinogen receptors. In addition, they suggest that the synthesis of prostaglandins and thromboxane A2 by stimulated platelets may be all that is required for optimal secondary platelet aggregation.

Low dose aspirin, platelet function and prostaglandin synthesis: Influence of epinephrine and alpha adrenergic blockade

The present investigation has evaluated the effects of low doses of oral aspirin on platelet prostaglandin synthesis and function. Whole (80 mg) or half (40 mg) tablets of baby aspirin given to adults had no effect on the response of their platelets to thrombin, ADP and epinephrine, but selectively inhibited aggregation induced by threshold concentrations of arachidonate 16–20 hours after ingestion. Larger amounts of arachidonate overcame the inhibition imposed by low dose aspirin, but not by adult aspirin tablets (600 mg). Epinephrine, in concentrations too low to cause aggregation, restored the sensitivity of aspirin-treated platelets to arachidonate. Studies with a-adrenergic agonists, antagonists and calcium channel blockers demonstrated that the corrective effect of epinephrine was mediated by an a-adrenergic receptor influence on calcium modulation of the platelet membrane.

Glutathione peroxidase, selenium, and prostaglandin synthesis in platelets.

Glutathione peroxidase (GSH-Px) contains 4 selenium atoms/molecule; its activity is increased by selenium dietary intake. The enzyme destroys H2O2 and organic hydroperoxides, contributing to the integrity of biological membranes. GSH-Px activity increased (+100%) in washed platelets of rats administered selenium (0.3 ppm given as sodium selenite) for 60 days from 10.44 +/- 1.10 U/g protein (control rats fed a standard diet) to 20.50 +/- 1.21 U/g protein (mean +/- SE; P less than 0.001). GSH-Px in washed erythrocytes was also stimulated (+70%) after 80 days of selenium dietary intake from 11.60 +/0 0.82 U/g Hb to 19.74 +/- 0.94 U/g Hb (P less than 0.001). Malondialdehyde (MDA), the typical breakdown product of peroxidized lipid and a suitable indicator of platelet prostaglandin production, increased from 0.343 +/- 0.035 nM/3 X 10(8) platelets (control) to 0.478 +/- 0.052 nM/3 X 10(8) platelets after 30 days of selenium treatment (P less than 0.05) and to 0.527 +/- 0.051 nM/3 X 10(8) platelets after 80 days (P less than 0.01). MDA was measured by the thiobarbituric acid method after stimulation with 25 X 10(-4) M arachidonic acid. It is concluded that platelets are very rich in GSH-Px, i.e., activity is greatly increased by oral administration of selenium and that the synthesis of prostaglandins is stimulated too.

Rat Platelet Prostaglandin, Cyclic AMP and Lipid Response to Variations in Dietary Fat

Diets supplying 20 or 40% of the calories as fat with linoleate to saturated fatty acid ratios of 0.4, 0.8 and 5.5 were fed to male weanling rats for 8 and 11 weeks. Recalcification clotting time was not affected by dietary treatment. Concentration of cAMP in the platelets was significantly elevated at the highest level of dietary linoleate. Cyclic AMP was negatively correlated with concentration of dihomo-γ-linolenic acid in platelet phospholipids and positively correlated with prostaglandin E1, suggesting that dihomo-γ-linolenic acid is rapidly converted to prostaglandin E1 causing a rise of cAMP due to stimulation of adenylate cyclase. Dietary treatment did not markedly change the composition of the platelet phospholipid fatty acids and, therefore, resulted in no change in synthesis of the proaggregatory prostaglandin by platelets during clotting. Although the fatty acid composition of the platelet phospholipids remained constant, dietary treatment did affect the total amount of phospholipid fatty acid present in the platelet. Serum concentrations of cholesterol were significantly higher in rats fed the 20% fat diet than in rats fed the 40% fat diet. Platelet cholesterol followed the same trend as serum cholesterol indicating that the cholesterol content of platelets appears to reflect the lipid environment of the plasma.platelet prostaglandin fat cholesterol phospholipid