Immature Platelets
Authors: Eli I. Lev
Journal: Circulation (2016)

ince the recognition that platelets have an essential role in the pathogenesis of acute coronary syndromes (ACS) and other thrombotic disorders, extensive research has been devoted to understanding platelet physiology and to the development of effective antiplatelet therapy.For several decades, it has been known that the circulating platelet population is heterogeneous in size and age.This population includes young platelets, recently released from the bone marrow by megakaryocytes, which are termed reticulated platelets (RPs).Circulating RPs are identified by staining for messenger ribonucleic acid (mRNA).They are characterized by increased mean volume and a greater number of dense granules than older circulating platelets, and a capacity for ongoing protein synthesis by the residual mRNA.The proportion of RPs in the circulation is increased in situations of enhanced platelet turnover, including ACS.However, it is not clear whether, in ACS, enhanced platelet turnover is the cause or the consequence of the acute atherothrombotic event.The proportion of RPs in the circulation is generally assessed by flow cytometry using thiazole orange staining of mRNA.This method, however, has several limitations.It is relatively expensive and technically demanding, and it lacks standardization of the type and concentration of dye used.For these reasons, a simpler automated method has been developed for quantification of immature platelets.This laboratory method is performed in a fully automated blood analyzer with optical fluorescence capability (eg, Sysmex XE-2100).Platelet mRNA is stained in the autoanalyzer with 2 fluorescent dyes, and cell volume and mRNA content are measured to identify younger platelets.Results are expressed as immature platelet fraction (IPF).Reports have shown good correlation between RP levels (measured by flow cytometry) and IPF.Furthermore, IPF measurement can be incorporated into a complete blood count test with relatively little additional cost.Research of immature platelets has recently focused on 2 main areas: the effect of this platelet population on response to antiplatelet drugs, and the potential association with clinical outcomes in patients with cardiovascular disease.Numerous studies have shown that there is significant interindividual variability in the pharmacodynamic response to aspirin and clopidogrel and, to a much lesser extent, prasugrel and ticagrelor.Furthermore, hyporesponse to these drugs, reflected by high on-treatment platelet reactivity, has been clearly associated with adverse ischemic events.Because RPs are believed to be more prothrombotic and hyperreactive than mature platelets, 1 a higher proportion of RPs could be associated with attenuated response to antiplatelet drugs.In patients with stable coronary artery disease treated with aspirin and clopidogrel, a higher proportion of RPs strongly correlated with reduced response to both drugs, a finding confirmed by subsequent studies in other patient populations. 2We have recently shown that a higher proportion of circulating RPs also correlates strongly with reduced response to prasugrel in patients with acute myocardial infarction. 3This finding has been confirmed by using IPF to quantify immature platelets. 1In contrast with the association between RP levels and Immature Platelets