Dear Editor,

We read with interest the article by Z. Jiang and colleagues entitled “Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults”, which has been recently published by Aging Clinical and Experimental Research [1]. This study adds to the growing literature that uses red blood cell distribution width (RDW) and other complete blood cell (CBC)-derived parameters as biomarkers of chronic systemic inflammation. We would like to add some additional comments for the benefit of the readership of your journal, particularly those interested in the clinical application of the RDW.

First, the RDW may be biased by preanalytical phase variables including (1) time between phlebotomy and analysis (2) transport conditions, and (3) temperature [2]. Moreover, since there is no universally recognized standard for the RDW, differences between RDW results may occur depending on the manufacturer of a given instrument [3]. Unfortunately, these factors are often not reported by authors of clinical studies that use CBC-derived analytes (including the study by Jiang et al.) but would be critical for readers who are considering the use of these parameters, to determine whether the conditions of their laboratories are similar to those reported in the study.

In addition, there is increasing evidence that the RDW increases as a function of patient age, with an ~ 1% increase in the upper limit of the reference age per annum for patients > 60 years old [4, 5]. In addition, females on average have a slightly increased RDW compared to males [4]. For these reasons it may be important for researchers to consider the age and sex-related biologic variation in the RDW in constructing their studies, and for clinicians and laboratorians to consider the use of a separate RDW reference range for patients of advanced age.

We thank Jiang et al. for their publication, which adds to the potentially impactful literature on the clinical use of the RDW. We would suggest that the authors (1) consider a response to this letter that reports the preanalytical and analytical features of their data collection, in the interest of transparency and (2) perform a sex and age-stratified subset analysis to evaluate whether age-related changes in the RDW impact their findings.