Abstract

Abstract Introduction The complete blood count (CBC) is the most commonly ordered blood test with a large range of reference values that do not consider time of day for interpretation. Clinicians are largely unfamiliar with the influence of time of day on CBC values. Our objective was to systematically review this topic to report on peak and trough timing of CBC values. Methods A systematic search of PubMed, Ovid, Scopus, CINAHL, Cochrane, Embase, and Web of Science was performed for studies evaluating any part of the CBC over 24 hours. The studies were screened for eligibility based on predetermined criteria including: measurement of a part of the CBC with at least 3 time points in 24 hours. In total, 164 full-text articles were screened and 32 were included in the final analysis. The aggregated data was analyzed with the Cosinor package of R statistical environment and Stata SE to create cosinor graphs and Forest plots for each component of the CBC, respectively. Results Of the 32 articles, a metalysis was performed on the following CBC subsets: leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Lymphocytes exhibited a statistically significant diurnal rhythm (p=0.014, n=10 articles) with a peak of 2280.10 cells/uL at 23:17 (CI: 1731.80, 2828.40) and trough of 1661.49 cells/uL at 08:53 (CI: 1242.64, 2080.33). Erythrocytes, hemoglobin, and hematocrit peaked in the morning; while platelets, neutrophils, monocytes, and basophils peaked in the late afternoon and early evening; and lymphocytes and eosinophils peaked late at night. High heterogeneity in the results across studies was noted, likely attributable to the difference in circadian factors controlled. Limitations include the small sample size for each component of the CBC, the limited samples included in the meta analysis, and the significant heterogeneity affecting the results. Conclusion There are significant time of day changes in CBC values that might be important to consider as we move towards precision medicine. Given the limited number of studies with small sample sizes, future work should evaluate large data sources to inform time-dependent interpretation of the CBC. Support (if any)

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