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PubMed2003

Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction.

BACKGROUND: We observed that the prodrug clopidogrel was less effective in inhibiting platelet aggregation with coadministration of atorvastatin during point-of-care platelet function testing. Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4. METHODS AND RESULTS: Platelet aggregation was measured in 44 patients undergoing coronary artery stent implantation treated with clopidogrel or clopidogrel plus pravastatin or atorvastatin, and in 27 volunteers treated with clopidogrel and either erythromycin or troleandomycin, CYP3A4 inhibitors, or rifampin, a CYP3A4 inducer. Atorvastatin, but not pravastatin, attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner. Percent platelet aggregation was 34+/-23, 58+/-15 (P=0.027), 74+/-10 (P=0.002), and 89+/-7 (P=0.001) in the presence of clopidogrel and 0, 10, 20, and 40 mg of atorvastatin, respectively. Erythromycin attenuated platelet aggregation inhibition (55+/-12 versus 42+/-12% platelet aggregation; P=0.002), as did troleandomycin (78+/-18 versus 45+/-18% platelet aggregation; P<0.0003), whereas rifampin enhanced platelet aggregation inhibition (33+/-18 versus 56+/-20% platelet aggregation, P=0.001). CONCLUSIONS: CYP3A4 activates clopidogrel. Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation. Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel.

Adolescent↗
PubMed1994

Microvascular injury induced by intravascular platelet aggregation. An experimental study.

Microvascular injury due to platelet aggregation was studied in cats for an hour after 1-hour intraaortic infusion of a suspension of collagen fibrils. Haematocrit and numbers of circulating platelets and leukocytes were repeatedly measured in arterial blood and a major cutaneous lymph vessel in the thigh was cannulated for measurement of lymph flow and erythrocyte counts in peripheral lymph. There were seven groups, each of eight cats, viz. normal cats infused with collagen (I) or vehicle (II) and collagen-infused cats which were platelet-depleted--by antiserum (III), or neutrophil-depleted--by anti-serum (IV), or decomplemented--by cobra venom (V), or pretreated with indomethacin--10 mg/kg (VI), or treated with nonimmunized serum (VII). Induced intravascular platelet aggregation reduced the numbers of circulating platelets and leukocytes, and increased haematocrit, lymph flow and numbers of red cells in peripheral lymph. These effects were inhibited by platelet depletion and indomethacin and attenuated by decomplementation and neutrophil depletion. Platelet aggregation was thus shown to induce microvascular injury and increase microvascular permeability, which is partly dependent on complement and neutrophils.

Animals↗
PubMedDate not supplied

Platelet aggregation inhibiting activity of human placental chorioepithelial brush border membrane vesicles.

We investigated the platelet aggregation inhibiting activity of human placental brush border membrane vesicles (BBMV) and obtained the following results. A strong platelet aggregation inhibiting activity existed in placental BBMV. The BBMV inhibited the platelet aggregation induced by ADP, arachidonic acid, collagen and ristocetin in a dose-dependent manner. The protein concentration of BBMV giving 50 per cent inhibition was 52 +/- 6 micrograms/ml for ADP-induced platelet aggregation, 21 +/- 2 micrograms/ml for arachidonic acid-induced platelet aggregation, 19 +/- 2 micrograms/ml for collagen-induced platelet aggregation and 107 +/- 9 micrograms/ml for ristocetin-induced platelet aggregation. There was a high level of ADP degrading activity (ADPase activity) in the placental BBMV. ADP degrading activity of the BBMV: 10.5 +/- 0.5 mumol/mg protein/min was 21 times greater than that of homogenate of the placental villi. The placental BBMV inhibited platelet TXA2 production. In the 40 micrograms/ml protein concentration of placental BBMV, platelet TXA2 production was almost completely inhibited.

Adenosine Diphosphate↗
PubMed1994

Influence of thiofedrine on platelet aggregation, intraplatelet cyclic cAMP and malondialdehyde in rats.

Platelet aggregation and cyclic adenosine monophosphate (cAMP) production were studied by turbidimetry and competitive protein binding assay, respectively, in rats. Thiofedrine (Thi) significantly inhibited adenosine diphosphate (ADP)-induced and thrombin-induced platelet aggregation in vitro, with IC50 values of 0.56 and 0.16 mmol/l, respectively. In vivo, Thi 1.25-5.0 mg/kg i.v. significantly inhibited ADP-induced platelet aggregation at rate of 17.1-40.3%. Thi caused a dose-dependent increase in cAMP levels in rat washed platelets. Malondialdehyde (MDA) levels in rat platelets were measured by colorimetry. Thi had an inhibitory effect on thrombin-induced platelet MDA production. The results suggest that the antiaggregatory action of Thi may be related to metabolism of arachidonic acid (AA) and elevation of cAMP levels.

Adenosine Diphosphate↗
PubMed1984

Platelet aggregation caused by dithiothreitol.

MacIntyre et al. showed that over 1 mM dithiothreitol (DTT) aggregates blood platelets in the presence of fibrinogen; aggregation is not inhibited by prostaglandin E1. We confirmed their data and found that 70 mM 2-mercaptoethanol was also active. DDT-induced aggregation was not associated with platelet shape change or secretion of dense granule contents, was not inhibited by tetracaine or metabolic inhibitors, was prevented at pH 6.5, and prevented, reversed, or arrested by EDTA, depending on when the EDTA was added. DTT did not cause aggregation of thrombasthenic, EDTA-treated, or cold (0 degree C) platelets, which also failed to aggregate with ADP. Platelets stimulated with DTT bound 125I-labeled fibrinogen. Thus DTT appears to "expose" the fibrinogen receptors. SDS gel electrophoresis of platelet fractions prepared by use of Triton X-114 showed that aggregating concentrations of DTT reduced proteins of apparent Mr 69,000 and 52,000 (probably platelet albumin) and, to a variable extent, glycoproteins Ib, IIb and III. Exposure of unlabeled or 125I-labeled platelets to ADP had no discernible effect on the electrophoretic patterns.

Adenosine Diphosphate↗
PubMed1973

Collagen-induced platelet aggregation: involement of an active glycopeptide fragment (alpha1-CB5).

It is widely held that the tertiary structure of collagen is essential for induction of platelet aggregation. However, we have found that the purified alpha1 chain prepared from denatured chick skin collagen aggregates platelets. This activity appears to be confined to a distinct region of the molecule representing less than 4 percent of the length of the alpha1 chain. Of all of the cyanogen bromide peptides of the alpha1 chain tested, only one (alpha1-CB5) was active. This glycopeptide, devoid of any ordered tertiary structure, contains only 36 amino acids and one residue of O-alpha-D-glucopyranosyl-(1 --> 2)-O-beta-D-galactopyranosyloxy-(1 --> 5)-lysine (Glc-Gal-Hyl). Blocking experiments strongly suggest that the Glc-Gal-Hyl is one of the structural determinants involved in collagen-induced platelet aggregation.

Amino Acid Sequence↗
PubMed2003

Effects of barbiturates on human platelet aggregation differ depending on their chemical structures.

The effects of barbiturates on human platelet function are not fully understood. Since we have already revealed the effects and mechanisms of thiopental, thiamylal, and pentobarbital in platelets, the present study attempted to elucidate (i) the effects of other barbiturates on human platelet aggregation, (ii) the underlying mechanisms, and (iii) the structure-function relationship of barbiturates in platelets. Barbiturates, including amobarbital, butalbital, secobarbital, barbital, phenobarbital, metharbital, and primidone, were examined. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and (+)-9,11-epithia-11,12-methano-thromboxane A2 (STA2), a thromboxane A2 analog, was measured using an 8-channel light-transmission aggregometer. The cytosolic free calcium concentration ([Ca2+]i) was measured by fluorometer using fura-2 loaded platelets. Inositol 1,4,5-trisphosphate (IP3) formation induced by STA2 was determined by a commercially available IP3 assay kit. Amobarbital, butalbital, and secobarbital suppressed ADP-, epinephrine- and STA2-induced platelet aggregation and the STA2-induced [Ca2+]i increase, even when Ca2+ influx was blocked by Ni2+. However, they did not affect STA2-induced IP3 formation. Barbital, phenobarbital, metharbital, and primidone (up to 1 mM) had no effect on ADP- and epinephrine-induced platelet aggregation. Thus, we conclude that amobarbital, butalbital, and secobarbital inhibit platelet aggregation by suppressing [Ca2+]i increase without affecting IP3 formation. However, these antiaggregatory effects may not have clinical importance, since the barbiturate concentrations used were higher than clinically relevant ones. The other tested barbiturates had no effects on platelet aggregation. The data indicate that the effects of barbiturates on platelet aggregation differ depending on their chemical structures.

Adult↗
PubMed2006

Arginyl-glycyl-aspartyl (RGD) epitope of human apolipoprotein (a) inhibits platelet aggregation by antagonizing the IIb subunit of the fibrinogen (GPIIb/IIIa) receptor.

An unknown epitope of apolipoprotein (a) antagonizes fibrinogen binding to agonist-stimulated platelet's fibrinogen (GPIIb/IIIa) receptor yielding lipoprotein (a) mediated decreased platelet aggregation. The purpose of this study was to test the hypothesis that human apolipoprotein (a)'s single arginyl-glycyl-aspartyl (RGD) epitope, unique to apolipoprotein (a) in lipoprotein (a) binds to the RGD binding motif on the IIb subunit of the GPIIb/IIIa receptor thus reducing platelet-bound fibrinogen and consequently decreasing agonist-stimulated platelet aggregation. Platelets (N=30 subjects) were prepared from fresh plasma, washed three times in Tyrode's buffer and stimulated using 10 microM ADP or 2 microg/ml collagen. Lipoprotein (a) was isolated from plasma using lectin affinity chromatography followed by ultracentrifugation. The peptide RGDS inhibited (125)I-labelled lipoprotein (a) binding to autologous platelets with IC-50's of 25.1+/-2.2 (mean+/-SEM) and 15.4+/-1.3 microM for collagen- and ADP-stimulation respectively. Further, RGDS reduced platelet binding of (125)I-labelled fibrinogen IC-50's of 35.5+/-3.2 (mean+/-SEM) and 20.7+/-2.2 microM for collagen- and ADP-stimulation respectively. The monoclonal antibody PAC-1, uniquely directed at the RGD binding motif on the IIb subunit on collagen- and ADP-stimulated platelets, inhibited binding of (125)I-labelled lipoprotein (a) with IC-50's of 6.4+/-0.7 and 2.5+/-2.2 microg/10(8) platelets for collagen- and ADP-stimulation respectively. Additionally, PAC-1 reduced platelet bound of (125)I-labelled fibrinogen with IC-50's of 9.0+/-1.4 and 4.1+/-2.2 microg/10(8) platelets for collagen- and ADP-stimulation respectively. In a dose-related fashion, a polyclonal antibody, specific for the RGD epitope on apolipoprotein (a), restored platelet aggregation to control levels, inhibited (125)I-labelled lipoprotein (a) binding, and increased (125)I-labelled fibrinogen by displacing lipoprotein (a) from the GPIIb/IIIa receptor. Thus a never before demonstrated aspect of the mechanism of lipoprotein (a)'s suggested novel role as an endogenous regulator of fibrinogen binding to collagen- and ADP-stimulated platelets has been shown. In conclusion, lipoprotein (a), via apolipoprotein (a)'s RGD epitope, binds to the RGD binding motif on the IIb protein of the GPIIb/IIIa receptor consequently reducing platelet-bound fibrinogen which results in decreased platelet aggregation.

Apoprotein(a)↗
PubMed1999

Specific inhibition of ADP-induced platelet aggregation by clopidogrel in vitro.

1. The thienopyridine clopidogrel is a specific inhibitor of ADP-induced platelet aggregation ex vivo. No direct effects of clopidogrel (< or = 100 microM) on platelet aggregation in vitro have been described so far. 2. Possible in vitro antiaggregatory effects (turbidimetry) of clopidogrel were studied in human platelet-rich plasma and in washed platelets. 3. Incubation of platelet-rich plasma with clopidogrel (< or = 100 microM) for up to 8 h did not result in any inhibition of ADP (6 microM)-induced platelet aggregation. 4. Incubation of washed platelets with clopidogrel resulted in a time- (maximum effects after 30 min) and concentration-dependent (IC50 1.9+/-0.3 microM) inhibition of ADP (6 microM)-induced platelet aggregation. Clopidogrel (30 microM) did not inhibit collagen (2.5 microg ml(-1))-, U46619 (1 microM)- or thrombin (0.1 u ml(-1))-induced platelet aggregation. The inhibition of ADP-induced aggregation by clopidogrel (30 microM) was insurmountable indicating a non-equilibrium antagonism of ADP actions. The R enantiomer SR 25989 C (30 microM) was significantly less active than clopidogrel (30 microM) in inhibiting platelet aggregation (32+/-5% vs 70+/-1% inhibition, P < 0.05, n = 5). 5. In washed platelets, clopidogrel (< or = 30 microM) did not significantly reverse the inhibition of prostaglandin E1 (1 microM)-induced platelet cyclic AMP formation by ADP (6 microM). 6. The antiaggregatory effects of clopidogrel were unchanged when the compound was removed from the platelet suspension. However, platelet inhibition by clopidogrel was completely abolished when albumin (350 mg ml(-1)) was present in the test buffer. 7. It is concluded that clopidogrel specifically inhibits ADP-induced aggregation of washed platelets in vitro without hepatic bioactivation. Inhibition of ADP-induced platelet aggregation by clopidogrel in vitro occurs in the absence of measurable effects on the reversal of PGE1-stimulated cyclic AMP by ADP.

Adenosine Diphosphate↗
PubMed1971

The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3':5'-cyclic monophosphate in platelets.

1. The involvement of intracellular 3':5'-cyclic AMP in the inhibition of platelet aggregation by prostaglandin E(1), isoprenaline and adenosine has been examined by a radiochemical technique. Platelet-rich plasma was incubated with radioactive adenine to incorporate (14)C radioactivity into platelet nucleotides. Pairs of identically treated samples were taken, one for the photometric measurement of platelet aggregation induced by ADP, the other for estimation of the radioactivity of 3':5'-cyclic AMP. 2. Theophylline, papaverine, dipyridamole and 2,6-bis-(diethanolamino)-4-piperidinopyrimido[5,4d]pyrimidine (compound RA233) were found to inhibit 3':5'-cyclic AMP phosphodiesterase from platelets. At concentrations of 3':5'-cyclic AMP greater than 50mum the most active inhibitor was dipyridamole; at 3':5'-cyclic AMP concentrations less than 19mum, papaverine and compound RA233 were more active than dipyridamole. 3. In the presence of compound RA233 (50mum), the effectiveness of prostaglandin E(1) as an inhibitor of platelet aggregation was increased tenfold. Compound RA233 also increased the stimulation by prostaglandin E(1) of the incorporation of radioactivity into 3':5'-cyclic AMP. 4. Compound RA233 (50mum) increased the effectiveness of both adenosine and 2-chloroadenosine as inhibitors of aggregation by 70-100-fold, and in the presence of compound RA233 both adenosine and 2-chloroadenosine stimulated the incorporation of radioactivity into 3':5'-cyclic AMP; the extent of the stimulation was proportional to the logarithm of the nucleoside concentration. 5. Compound RA233 (100-500mum) inhibited platelet aggregation by itself and caused small increases in the radioactivity of 3':5'-cyclic AMP. Partial positive correlations were found between the radioactivity of 3':5'-cyclic AMP in platelets measured at the time of addition of the aggregating agent (ADP) and the extent to which the aggregation was inhibited. 6. The results are interpreted as indicating that adenosine, 2-chloroadenosine, isoprenaline, prostaglandin E(1) and drugs that inhibit platelet 3':5'-cyclic AMP phosphodiesterase all inhibit aggregation by a common mechanism involving intracellular 3':5'-cyclic AMP.

Adenine Nucleotides↗
PubMed1996

Factors that affect the size of platelet aggregates in epinephrine-induced activation: a study using the particle counting method based upon light scattering.

Platelet aggregate size was determined with a newly-developed platelet aggregometer, PA-100 (KOWA), which can quantitatively evaluate the size and number of platelet aggregates by means of the particle counting method based upon light scattering. Epinephrine-induced platelet aggregation consists of two phases, the former characterized by the formation of small-sized aggregates (less than 100 cells), which is followed by the phase of large aggregate formation with concomitant decrease in the number of small aggregates. These findings suggest that small aggregates fuse to form large aggregates. Effects of various inhibitors and antibodies directed against platelet membrane glycoproteins were evaluated on the size of platelet aggregates induced by epinephrine. Cyclooxygenase inhibitors, thromboxane A2 receptor antagonists, and a Na+/H+ exchanger inhibitor (ethylisopropylamiloride) inhibited the formation of large aggregates (more than 100 cells) but not that of small aggregates. Cytochalasin B, which interferes with microfilaments, suppressed large aggregate formation, whereas taxol, which reacts with microtubules, had no effects. Anti-GPIIb/IIIa monoclonal antibody (MoAb) inhibited both the formation of small and large platelet aggregates, while antibodies directed against GPIb, thrombospondin, P-selectin, or PECAM-1 had no effects on platelet aggregate formation. These findings, taken together, suggest that intracellular alkalinization, thromboxane A2 formation and microfilament rearrangement are prerequisites for large platelet aggregate formation. GPIIb/IIIa is involved in the formation of small as well as large aggregates, but a membrane glycoprotein(s) responsible for the transition of small aggregates into large aggregates awaits to be determined.

Arachidonic Acid↗
PubMed1989

[Age differences in platelet aggregation, plasma levels of prostanoid, cyclic nucleotide and lipids in Japanese].

Platelet aggregation induced by adenosine diphosphate (ADP), adrenaline and collagen was studied in various age groups of healthy Japanese. Plasma levels of prostanoid, cyclic nucleotide and lipid (triglyceride and cholesterol) were investigated. Platelet aggregation in females was rather high in all groups compared with males in each age group, although there was no statistical difference. Age dependent increase was not observed. Platelet aggregation response to 1 gamma of adrenaline was either high or low and the levels of collagen-induced platelet aggregation in the low responder group was also significantly lower than those of the high responder group. Positive correlation was obtained between ADP-induced platelet aggregation and serum cholesterol levels. These data suggest platelet aggregation was not influenced by aging but other biochemical or physical conditions of individuals.

Adolescent↗
PubMed1992

[Evaluation of platelet aggregation test by grading curve].

In order to standardize the platelet aggregation test, we used the grading curve (GC) produced by plotting four concentrations (0.5, 1.0, 2.0 and 4.0 microM) of ADP and four concentrations (0.25, 0.5, 1.0 and 2.0 micrograms/ml) of collagen, which are aggregation inducers, along the horizontal axis and plotting their individual rates (%) of aggregation 5 minutes after administration, along the longitudinal axis. The degree of platelet aggregation was classified in 6 stages (Types III, II, I, 0, -I and -II), ranging from marked increase to marked decrease, according to the GC of ADP aggregation in healthy subjects. Type I or 0 ADP aggregation was observed in 78% of the subjects, and Type I collagen aggregation was observed in about 50% of the subjects, whereas patients with cerebral infarction showed distinct increases in Type III and II aggregations of both ADP and collagen. In most patients who were treated with antiplatelet drugs, the aggregation were Type 0, -I or -II. The concentration of inducer, which corresponded to the maximum 50% value of the GC (Max 50) was significantly correlated with the minimum concentration (threshold concentration) in ADP aggregation, at which secondary aggregation was induced even if it was reversible, and with the minimum concentration (threshold concentration) in collagen aggregation, at which the aggregation rate 5 minutes after administration increased to 50% or higher. The GC of platelet aggregation seemed to enable easy determination of the degree of aggregation, and was also considered to be useful for monitoring platelet aggregation during the administration of antiplatelet drugs.

Adult↗
PubMed2001

Platelet aggregability in cardiac syndrome X.

AIMS: To assess platelet aggregability at rest and in response to exercise in patients with cardiac syndrome X (anginal chest pain, ST-segment depression on exercise, angiographically normal coronary arteries). METHODS AND RESULTS: We performed a symptom/sign-limited exercise test in 31 patients with syndrome X, 25 patients with coronary artery disease and 29 healthy subjects. Platelet aggregability was measured in flowing whole blood at baseline, at peak exercise, and after 30 and 120 min, as the time to occlude a collagen/adenosine diphosphate coated ring (aggregation time). Resting aggregation time was shorter in syndrome X patients (83.2+/-12 s), compared to patients with coronary disease (94.0+/-18 s, P<0.01) and to healthy subjects (96.4+/-21 s, P<0.01). With exercise, aggregation time did not change in healthy controls, decreased in patients with coronary disease (-13.8 s at peak; 95% CI, -10.2, -17.3 s;P<0.001), but increased in syndrome X (+17.4 s 30 min after exercise; 95% CI, +10.4, +24.4 s;P<0.0001). The intravenous administration of an adenosine antagonist (theophylline) prevented the exercise-induced prolongation of aggregation time in syndrome X patients (n=11), but had no effect in healthy controls (n=11). CONCLUSION: Platelet aggregability at rest was increased in syndrome X patients, compared to patients with coronary artery disease and healthy subjects. In contrast to patients with coronary disease, however, platelet aggregability was reduced by exercise. This response was prevented by theophylline, strongly suggesting the involvement of adenosine.

Aged↗
PubMed1992

Platelet aggregation in dogs after sedation with acepromazine and atropine and during subsequent general anesthesia and surgery.

Platelet aggregation and adenosine triphosphate (ATP) release were measured by use of the impedance method in blood samples obtained from 25 adult female Beagles before and after sedation with acepromazine (0.13 mg/kg of body weight) and atropine (0.05 mg/kg), and during general anesthesia. General anesthesia was induced by IV administration of thiamylal (average dosage, 2.1 mg/kg; range, 1.2 to 4.2 mg/kg) and was maintained with halothane in oxygen. Samples of jugular venous blood were obtained from each dog, using citrate as anticoagulant. Platelet count was done on each sample. Platelet aggregation and ATP released from the aggregating platelets were measured within 2.5 hours of sample collection, using a whole-blood aggregometer. Adenosine diphosphate (ADP) or collagen was used as aggregating agent. For each aggregating agent, platelet aggregation and ATP release were measured over 6 minutes. After sedation with acepromazine and atropine, significant (P < 0.01) reduction was observed in platelet count (from median values of 341,000 cells/microliters to 283,000 cells/microliters) and in the ability of platelets to aggregate in response to ADP (from 14.0 to 7.0 omega). During the same period, maximal release of ATP in response to collagen also was reduced (from 5.56 mumol to 4.57 mumol; P < 0.01); however, this difference ceased to be significant when ATP release was normalized for platelet count. During general anesthesia and surgery (200 minutes after sedation), platelet count and aggregation responses to ADP and collagen had returned to presedation values. None of the dogs in this study appeared to have hemostasis problems during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acepromazine↗
PubMed1992

Dissociation of inhibitory effects of low-dose ASA on thromboxane production and platelet aggregation in ischemic stroke patients.

Acetylsalicylic acid (ASA) inhibits thromboxane production and hence platelet aggregation. However, individual variations in platelet aggregability and serum thromboxane B2 (TxB2) concentration after a low dose of ASA (40 mg/day) have been reported. To clarify this issue, we studied plasma thromboxane levels and platelet aggregation in 43 ischemic stroke patients. Of the 22 patients who received 100 mg of ASA daily, dissociation between inhibitory effects of ASA on the plasma TxB2 level and threshold concentrations of adenosine diphosphate was found in three cases after one month of drug administration, and in three cases after six, 12 and 18 months of ASA therapy. This dissociation also developed in two patients after one month and six months, respectively, of treatment in the 21 patients who received 300 mg of ASA daily. The dissociation between the inhibitory effects on plasma TxB2 and the circulating platelet aggregate ratio was found in two cases after taking medication for one month, and in four cases after six, 12, 18 and 24 months of therapy in the 100 mg ASA group. In the 300 mg ASA group, dissociation was noted in two cases after one month of medication, and in two cases after six and 12 months of medication. In these patients, although their TxB2 levels were inhibited to almost unmeasurable levels, platelet aggregation was still not inhibited. This ASA inhibitory dissociation phenomenon on platelet function may be due to the low dose of ASA, individual differences in platelet function in response to ASA therapy, or factors other than those involved in the cyclooxygenase system.

Aged↗
PubMed1986

Effect of alternate-day regular and enteric-coated aspirin on platelet aggregation, bleeding time, and thromboxane A2 levels in bleeding-time blood.

The effectiveness of low-dose aspirin for primary prevention of cardiovascular mortality is being assessed among the nearly 22,000 United States physicians currently participating in the Physicians' Health Study. Because of occasional reports of gastric irritation among study participants, two enteric-coated aspirin preparations were tested as possible alternatives to regular compressed aspirin for platelet inhibition. Thirty-three volunteers were assigned randomly to one of four treatment groups: regular aspirin (325 mg), placebo, and two enteric-coated aspirin preparations (325 mg). Pills were administered every other day, duplicating the regimen used in the Physicians' Health Study. Bleeding times, platelet aggregation, and thromboxane A2 levels produced by aggregating platelets in vitro, as well as in collected bleeding-time blood, were determined. Measurements were taken before and after a single dose as well as after seven alternate-day doses. Regular and enteric-coated aspirin preparations were equally efficacious in prolonging the bleeding time, inhibiting platelet aggregation, and suppressing thromboxane A2 production. There was virtually complete suppression of thromboxane A2 production (over 99 percent), by platelets in vitro and in collected bleeding-time blood. The levels were still profoundly reduced (89 percent) 48 hours after the last dose. Enteric-coated aspirin may provide an alternative to regular aspirin in a low-dose regimen designed to inhibit platelet activity.

Adult↗
PubMed2000

Sphingosine-1-phosphate: characterization of its inhibition of platelet aggregation.

In this study, the ability of sphingosine-1-phosphate (S1P) to modulate platelet aggregation induced by other agents in platelet-rich plasma (PRP) was investigated. S1P alone did not stimulate platelet aggregation in PRP. S1P inhibited the platelet aggregation induced by the TRAP peptide (6.75 microM), noradrenaline (NA; 12.5 microM) and the Ca2+ ionophore (5.0-9.5 microM). S1P also increased the response time of platelets to arachidonic acid (AA), but decreased the response time to PMA. S1P displayed a dual effect on sodium fluoride (NaF)-induced platelet aggregation and had no effect on the aggregation induced by ADP or lysophosphatidic acid (LPA). Furthermore, S1P blocked the synergistic interaction of oleyol-lysophosphatidic acid (O-LPA) with the TRAP peptide or noradrenaline, while the synergistic interaction of O-LPA with ADP remained largely unaffected.

Adenosine Diphosphate↗