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Currently, age- and sex-independent reference limits (RLs) are frequently used to interpret platelet counts in seniors. We aimed to define and validate reference intervals (RIs) for platelet counts within the framework of the prospective SENIORLAB study. Subjectively healthy Swiss individuals aged 60 years and older were prospectively included and followed for morbidity and mortality. Participants who had circumstances known to affect platelet counts were excluded. The obtained RIs were validated with indirect statistical methods. Frequencies of abnormal platelet counts in a population-based setting, including 41.5% of the entire age-specific population of the Principality of Liechtenstein, were compared by using age- and sex-independent RIs and the RLs obtained in the present study. For males (n = 542), 95% RIs for platelet counts were defined as follows: 150–300 × 109/L (60–69 years); 130–300 × 109/L (70–79 years); and 120–300 × 109/L (80 years and above). For females (n = 661), the consolidated age-independent 95% RI was 165–355 × 109/L. These RI values were validated by indirect RI determination of 51,687 (30,392 female/21,295 male) patients of the same age. Age- and sex-independent RIs exhibited imbalanced frequencies of abnormal platelet counts between the two sexes, which were corrected by introducing age- and sex-specific RLs. In conclusion, females have higher platelet counts than males. Whereas the upper RL for males remains constant, the lower RL decreases with age. We propose to abandon the practice of employing sex- and age-independent RL for platelet counts in the elderly. [ABSTRACT FROM AUTHOR]