Letter to the Editors - Exploring platelet indices as disease biomarkers: prospective use and methodological challenges.

Platelet indices have generated tremendous interests as versatile disease markers. Recently, Balkarli et al1, Yilmaz and Yilmaz2, Almis et al3 and Tekin et al4 have investigated platelet indices in relation to Behcet’s disease, retinal vein occlusion, hepatitis A and infants with meconiumstained amniotic fluid, respectively; whereas Tulgar et al5 have examined the effects of smoking on platelet indices. While the prospective use of these indices is attractive, there are certain methodological issues that are frequently overlooked by some researchers, which may limit the validity of their findings. We wish to draw attention to these important issues. For instance, platelet indices are influenced by the type of anticoagulant used (EDTA or citrate)6,7, and platelets undergo time-dependent morphological changes, which may cause temporal alterations in the platelet indices6-8. This is especially pertinent while using EDTA tubes. Thus, measurements should be preferably performed within 2 hours from venipuncture8. But, several reports have not clearly mentioned about the anticoagulants used1,3,5, or the time delay since sample collection1,5. Another concern is the confounding bias. Platelet indices are influenced by covariates like age, sex, serum lipids, smoking, and alcohol9,10, and also by co-morbidities like hypertension, diabetes mellitus, fatty liver disease, obesity and coronary artery disease. Many of these relevant confounders were not accounted for in some of the reports1,3. Further, Balkarli et al1 suggested neutrophil/lymphocyte ratio (NLR) as a diagnostic marker for active Behcet’s disease. Given the fact that NLR is an indicator of undergoing inflammation in several conditions, it would have been better had they substantiated their results with receiver operating characteristic (ROC) curve analysis. To conclude, platelet indices hold the promise to be valuable disease biomarkers. However, the associated pre-analytical variables, confounders and methodological challenges need to be duly addressed for realizing this potential.