S1 File -

Objectives
This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs.
Methods
Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18−80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter’s analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula.
Results
Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries.
Conclusion
RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.