Malondialdehyde (MDA) re-appearance in human platelet density subpopulations after a single intake of aspirin

Boneu, B; Sié, P.; Caranobe, C; Nouvel, C.; Biermé, R

doi:10.1016/0049-3848(80)90033-x

Cited by 36 publications

(16 citation statements)

References 22 publications

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“…This is distinct from evidence provided by methods which measure the capacity of isolated tissues to synthesize eicosanoids ex vivo. The measurement of urinary prostaglandin metabolites has been successfully applied to estimate endogenous prostanoid biosynthesis by several groups of workers (18)(19)(20) The results of the present study are in accord with previous observations that thromboxane generation is highly susceptible to aspirin inhibition (24)(25)(26) (15) and may thus largely reflect extrarenal endogenous prostacyclin bioAspirin, Prostacyclin, Thromboxane A2, and Platelets synthesis (27). Although 6-keto-PGFi, is recovered in urine after systemic administration of prostacyclin (15) it may largely reflect renal prostacyclin synthesis under physiological conditions (26), although this has been disputed (28).…”

Section: Discussionsupporting

confidence: 89%

“…1). When we consider that aspirin has a more prolonged effect on thromboxane B2 or malondialdehyde production by platelets ex vivo (2,(24)(25)(26)) the most obvious interpretation of these data is that extraplatelet sources contribute substantially to Tx-M excretion. Indeed, we noted a second possible example of extraplatelet thromboxane generation contributing to Tx-M excretion.…”

Section: Discussionmentioning

confidence: 99%

“…The organic phase was then back-extracted with pH 8.0 buffer. The organic phase residue obtained after solvent evaporation was dissolved in pH 8 24-h urine collections obtained before and four collections obtained during dosage of two subjects with aspirin 2,600 mg/d were pooled and spiked with 100 ng 2H4 PGI-M per 500 ml urine. The total volume of each pooled sample varied between 4 and 5 liters.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

FitzGerald¹,

Oates²,

Hawiger³

et al. 1983

J. Clin. Invest.

641

268

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A B S T R A C T To assess the pharmacologic effects of aspirin on endogenous prostacyclin and thromboxane biosynthesis, 2,3-dinor-6-keto PGFia (PGI-M) and 2,3-dinor-thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter-and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass spectral identification confirmed continuing prostacyclin biosynthesis during aspirin therapy. Recovery of prostacyclin biosynthesis was incomplete 5 d after drug administration was discontinued. To relate aspirin intake to indices of thromboxane biosynthesis and platelet function, volunteers received 20 mg aspirin daily followed by 2,600 mg aspirin daily, each dose for 7 d in sequential weeks. Increasing aspirin dosage inhibited Tx-M excretion from 70 to 98% of pretreatment control values; platelet TxB2 formation from 4.9 to 0.5% and further inhibited platelet function.An extended study was performed to relate aspirin intake to both thromboxane and prostacyclin genera- tion over a wide range of doses. Aspirin, in the range of 20 to 325 mg/d, resulted in a dose-dependent decline in both Tx-M and PGI-M excretion. At doses of 325-2,600 mg/d Tx-M excretion ranged from 5 to 3% of control values while PGI-M remained at 37-23% of control. 3 d after the last dose of aspirin (2,600 mg/ d) mean Tx-M excretion had returned to 85% of control, whereas mean PGI-M remained at 40% of predosing values. Although the platelet aggregation response (Tmax) to ADP ex vivo was inhibited during administration of the lower doses of aspirin the aggregation response returned to control values during the final two weeks of aspirin administration (1,300 and 2,600 mg aspirin/d) despite continued inhibition of thromboxane biosynthesis.These results suggest that although chronic administration of aspirin results in inhibition of endogenous thromboxane and prostacyclin biosynthesis over a wide dose range, inhibition of thromboxane biosynthesis is more selective at 20 than at 2,600 mg aspirin/d. However, despite this, inhibition of platelet function is not maximal at the lower aspirin dosage. Doses of aspirin in excess of 80 mg/d resulted in substantial inhibition of endogenous prostacyclin biosynthesis. Thus, it is unlikely that any dose of aspirin can maximally inhibit thromboxane generation without also reducing endogenous prostacyclin biosynthesis. These results also indicate that recovery of endogenous prostacyclin biosynthesis is delayed following aspirin administration and that the usual effects of aspirin on platelet function ex vivo may be obscured during chronic aspirin administration in man.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

FitzGerald¹,

Oates²,

Hawiger³

et al. 1983

J. Clin. Invest.

641

268

View full text Add to dashboard Cite

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“…In this context, LD platelets containing few dense bodies could be newly formed platelets. A recent report by Boneu and co-workers, who measured recovery of malonyl dialdehyde (MDA) in human platelet density cohorts following a single dose of aspirin, is consistent with this suggestion [22].…”

Section: Mishory and Danon [21]supporting

confidence: 56%

Evidence that platelet buoyant density, but not size, correlates with platelet age in man

et al. 1981

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Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 = 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 mu3, LD platelets = 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

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“…Some authors take the view that density decreases as platelets circulate [9,10] . Other studies suggest that recently created platelets are less dense and that density increases with age [11][12][13] . Finally, evidence exists indicating that platelet density does not change in vivo [14][15][16] .…”

mentioning

confidence: 99%

Platelet Density Distribution in Essential Thrombocythemia

Milovanovic

Lotfi

Lindahl

et al. 2010

Pathophysiol Haemos Thromb

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Essential thrombocythemia (ET) is characterized by high platelet counts and a slightly increased bleeding risk. Why severe hemorrhage does not occur more frequently is not known. Variations of platelet density (kg/l) depend mainly on cell organelle content in that high-density platelets contain more α and dense granules. This study compares ET patients (n = 2) and healthy volunteers (n = 2) with respect to platelet density subpopulations. A linear Percoll™ gradient containing prostaglandin E₁ was employed to separate platelets according to density. The platelet population was subsequently divided by density into 16 or 17 subpopulations. Determination of platelet counts was carried out. In each density fraction, platelet in vivo activity, i.e. platelet-bound fibrinogen, was measured using a flow cytometer. To further characterize platelet subpopulations, we determined intracellular concentrations of CD40 ligand (CD40L) and P-selectin in all fractions. Patients and controls demonstrated similar density distributions, i.e. 1 density peak. High-density platelets had more surface-bound fibrinogen in conjunction with signs of platelet release reactions, i.e. with few exceptions they contained less CD40L and P-selectin. Peak density platelets showed less surface-bound fibrinogen. These platelets contained less CD40L and P-selectin than nearby denser populations. The light platelets had more surface-bound fibrinogen than peak platelets together with elevated concentrations of CD40L. In ET, the malignant platelet production could exist together with platelets originating from normal megakaryocytes. It is also possible that clonal megakaryocytes produce platelets covering the entire density span. The ‘normal’ density distribution offers a tenable explanation as to why serious bleedings do not occur more frequently.

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Malondialdehyde (MDA) re-appearance in human platelet density subpopulations after a single intake of aspirin

Cited by 36 publications

References 22 publications

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

Evidence that platelet buoyant density, but not size, correlates with platelet age in man

Platelet Density Distribution in Essential Thrombocythemia

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