High platelet turnover and reactivity in renal transplant recipients patients

Cesari, Francesca; Marcucci, Rossella; Gori, Anna Maria; Caporale, Roberto; Fanelli, Alessandra; Paniccia, Rita; Zanazzi, M.; Bertoni, E.; Larti, A.; Salvadori, Maurizio; Gensini, Gian Franco; Abbate, Rosanna

doi:10.1160/th10-02-0124

Cited by 14 publications

(1 citation statement)

References 39 publications

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“…In the healthy population, the mean percentages of IPF and reticulated PLTs are 3.4% and 1.4–2.2%, respectively [ 48 ]. The IPF can be moderately expanded in coronary artery disease [ 49 ], renal transplant recipients [ 50 ] or thrombocytopenic neonates [ 51 ], or can dramatically rise to 20% or more in PLT consuming diseases such as disseminated intravascular coagulation or autoimmune thrombocytopenia [ 52 ]. Higher IPFs have been reported, but could be artifactual, due to interference from apoptotic blood cell fragments [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Decay of mRNA and Ribosomal RNA during Platelet Aging and Its Correlation with Translation Activity

et al. 2016

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Previous investigations have indicated that RNAs are mostly present in the minor population of the youngest platelets, whereas translation in platelets could be biologically important. To attempt to solve this paradox, we studied changes in the RNA content of reticulated platelets, i.e., young cells brightly stained by thiazole orange (TObright), a fluorescent probe for RNAs. We provoked in mice strong thrombocytopenia followed by dramatic thrombocytosis characterized by a short period with a vast majority of reticulated platelets. During thrombocytosis, the TObright platelet count rapidly reached a maximum, after which TOdim platelets accumulated, suggesting that most of the former were converted into the latter within 12 h. Experiments on platelets, freshly isolated or incubated ex vivo at 37°C, indicated that their “RNA content”, here corresponding to the amounts of extracted RNA, and the percentage of TObright platelets were positively correlated. The “RNA Content” normalized to the number of platelets could be 20 to 40 fold higher when 80–90% of the cells were reticulated (20–40 fg/platelet), than when only 5–10% of control cells were TObright (less than 1fg/platelet). TObright platelets, incubated ex vivo at 37°C or transfused into mice, became TOdim within 24 h. Ex vivo at 37°C, platelets lost about half of their ribosomal and beta actin RNAs within 6 hours, and more than 98% of them after 24 hours. Accordingly, fluorescence in situ hybridization techniques confirmed the presence of beta actin mRNAs in most reticulated-enriched platelets, but detected them in only a minor subset of control platelets. In vitro, constitutive translation decreased considerably within less than 6 hours, questioning how protein synthesis in platelets, especially in non-reticulated ones, could have a biological function in vivo. Nevertheless, constitutive transient translation in young platelets under pathological conditions characterized by a dramatic increase in circulating reticulated platelets could deserve to be investigated.

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Section: Discussionmentioning

confidence: 99%

Time-Dependent Decay of mRNA and Ribosomal RNA during Platelet Aging and Its Correlation with Translation Activity

et al. 2016

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Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness

Ibrahim

Nadipalli

DeLao

et al. 2011

J Thromb Thrombolysis

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The mechanisms for the variability in antiplatelet effects of clopidogrel are not elucidated entirely. Immature (reticulated) platelets may modulate the antiplatelet effects of clopidogrel but must be measured using flow cytometry. Whether new automated detection techniques yield similar results is not known. The objectives of the study to evaluate the role of immature platelets assessed by an automated method in response to the antiplatelet effects of clopidogrel. Twenty-nine healthy volunteers had platelet studies performed before and 1 week after 75 mg daily dosing of clopidogrel. Immature platelet fraction (IPF) was determined using an automated particle counter. Subjects were stratified into tertiles based on the IPF. Platelet studies included light transmission aggregometry (LTA), and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) determined by platelet reactivity index (PRI). Baseline platelet aggregation responses to 2, 5 and 20 μM ADP, were similar in all three tertiles, however they were greater in the upper than in the lower tertile of immature platelets after clopidogrel in response to 5 μM ADP (54% vs. 23%, P = 0.02), with concordant trends for the other two concentrations. PRI was also greater in the upper tertile after clopidogrel (71.2% vs. 57.8%, P = 0.04). The frequency of clopidogrel hyporesponsiveness (aggregation >50% in response to 5 μM of ADP) was also higher in the upper tertile when compared to lower tertile, (60%) versus (10%) respectively (P = 0.02). [corrected]. Immature platelets measured using an automated method, are associated with impaired response to antiplatelet effects of clopidogrel.

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Stress-Induced Hyperviscosity in the Pathophysiology of Takotsubo Cardiomyopathy

Cecchi

Parodi

Giglioli

et al. 2013

The American Journal of Cardiology

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High platelet turnover and reactivity in renal transplant recipients patients

Cited by 14 publications

References 39 publications

Time-Dependent Decay of mRNA and Ribosomal RNA during Platelet Aging and Its Correlation with Translation Activity

Time-Dependent Decay of mRNA and Ribosomal RNA during Platelet Aging and Its Correlation with Translation Activity

Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness

Stress-Induced Hyperviscosity in the Pathophysiology of Takotsubo Cardiomyopathy

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