Reticulated platelets and immature platelet fraction: Clinical applications and method limitations

So-called "reticulated" or "immature platelets," which are newly released into the circulation, are more reactive than mature platelets, contain more RNA, and can be counted using flow cytometry after staining with thiazole orange or using some fully automated hematology analyzers, albeit with numerical disagreement. This review provides an overview of the state of the art of available technology for measuring immature or reticulated platelets (RP) with preanalytical (time stability, biological variation), analytical (methods, imprecision), and postanalytical (reference range) limitations. We also analyzed the clinical conditions in which immature/RP can be considered a diagnostic or prognostic tool (ie, differential diagnosis of thrombocytopenia, recovery after bone marrow or stem cell transplantation, risk assessment in cardiovascular diseases, response to antiplatelet drugs). They might also be of clinical utility in other settings but with lower evidence. The lack of a specific reference method and universal control material, as well as dependency of results on the measurement technique used, calls for different reference intervals and compromises comparison between clinical studies carried out using different analytical methods. To obviate lack of agreement between methods, more specific RNA dyes are necessary and the impact of the platelet size on the fluorescence signal defined. In the harmonization age, also in nomenclature field, a new definition instead of "reticulated" or "immature" platelets would be useful, and "young platelets" might be a more appropriate definition taking into account both the age and the functionality of this platelet fraction.