The controversial role of red blood cell distribution width as a biomarker of acute appendicitis

Dear editor,

M Duyan and N Vural have recently published a cross-sectional study in Tropical Doctor that addresses the performance of the red blood cell distribution width (RDW) to lymphocyte ratio as a predictive biomarker in pediatric patients with suspected acute appendicitis (AA). ¹ I congratulate Duyan and Vural on the publication of their work, which adds to the extensive, albeit controversial, role of RDW in this patient population. The purpose of this letter is to add some additional commentary related to the previous literature on this subject, and to emphasize the impact of preanalytical and analytical phase bias in RDW results.

Overall, the predictive value of the RDW in AA has had varied performance, as summarized in a recently published meta-analysis of 15 previously published studies (5222 patients). ² The subset analysis of the study of Anand et al. showed a high degree of heterogeneity in three pediatric studies of AA vs non-AA controls (I² = 99%). ² Although differences in study design likely contributed to the heterogeneity, potential biases in the data collection among the studies may also be a problem and may have implications for clinicians attempting to use the RDW (and other indices derived from the RDW, such as the RDW to lymphocyte ratio) in their practice.

All complete blood cell count-derived analytes may be subject to preanalytical bias. For the RDW, which is calculated from the red blood cell histogram and is expressed either as its coefficient of variability (RDW-CV) or standard deviation (RDW-SD), the ambient temperature, time between phlebotomy and analysis, anticoagulant type, and storage/ transport conditions (for example, pneumatic tube transport), have been identified as potential sources of bias. ³ It is therefore critical for researchers to control for these variables, and for clinicians to evaluate whether the conditions of their practice environments are sufficiently similar to those reported in a given study. In addition, there is an ongoing problem with standardization of the RDW among the different instrument platforms, ⁴ so reporting of the manufacturer and model of the instrument used in the study would also be important for transparent reporting of data. Given the limited dynamic range (i.e., the range of potential values) of the RDW in the groups reported by Duyan and Vural, 14.09 ± 0.97fL for AA vs 12.7 ± 0.56fL for nonspecific abdominal pain vs 12.04 ± 0.8 for controls, ¹ the overlap between the groups may make the interpretation of individual patient results difficult.

In summary, I thank Duyan and Vural for their work and would welcome a response from them that adds additional technical details, which would improve the transparency of their data.