**3. Diagnostic weakness and missing points**

Even with decades passed, measurement of this parameter is still not standardized, as it can easily be obtained with electronic meters. This is a major flaw because many pre-analytical and analytical variables can affect platelet size. The pre-analytical variables include vascular occlusion method, the correctness of the filling of the vial and the mixing of the sample, the type of anticoagulant, the storage temperature and the duration of the analysis. Any inflammatory or malignant process can lead to an increase in these parameters [21].

In practice, these markers, if used alone, may have a low positive predictive value in screening an asymptomatic population. Getting in touch with EDTA, *ethylene diamine tetra acetic acid*, the most common anticoagulant used in laboratory practice, effects the platelet morphology and leads to swelling and an increase in volumes. The differences in the methodology of platelet counting with different automated analytics are most like to be major analytical variable for the measurement [22].

The poor standardization of the number of physiological variables affecting platelet size and the poor standardization of this parameter makes it very unlikely that small differences in this parameter, defined by clinical trials in various clinical conditions, could be used for clinical purposes. In the future, better methodological standardization and more personalized reference intervals may make them as a reliable parameter for differential diagnosis and prognostic identification in daily clinical practice, but there is a need for well-designed clinical trials to confirm this hypothesis [23].
