Personalized Interpretation of CBC and the Role of CRP in Early Detection and Monitoring of Blood Infection or Sepsis: A Diagnostic Perspective

ABSTRACT Background and Aims Sepsis remains a leading cause of morbidity and mortality worldwide, particularly in low‐ and middle‐income countries where diagnostic delays are common. The complete blood count (CBC) is widely used as an initial sepsis screening tool due to its availability and affordability. However, reliance on population‐based reference ranges, particularly white blood cell (WBC) counts, often leads to missed or delayed diagnosis, especially in early disease or among immunosuppressed patients. This article examines the diagnostic limitations of conventional CBC interpretation in suspected infection, and propose a personalized, baseline‐informed approach integrating C‐reactive protein (CRP) as an adjunct biomarker for early detection and monitoring. Approach This perspective is based on a narrative synthesis of published literature on sepsis diagnostics, CBC parameters, and inflammatory biomarkers, combined with pathophysiological principles and clinical reasoning relevant to resource‐constrained settings. Evidence from diagnostic studies, systematic reviews, and guideline recommendations was conceptually analyzed to identify limitations of static laboratory thresholds and opportunities for personalized interpretation. Findings Population‐based CBC reference ranges are limited in early sepsis detection due to inter‐individual variation. Personalized interpretation, considering baseline values and serial trends, improves sensitivity in identifying infection. CRP rises earlier and more consistently than WBC, particularly when hematologic responses are blunted. Integrating serial CRP measurements with baseline‐informed CBC trends enhances diagnostic utility, supports timely recognition, and improves monitoring of clinically significant infection. Conclusion Clinicians should shift from interpreting CBC parameters based solely on population reference ranges and instead adopt a baseline‐informed, trend‐based diagnostic approach. In patients with suspected infection, particularly those with normal CBC values or immunosuppression, CRP should be routinely used as an adjunct marker to unmask early or atypical sepsis. In resource‐limited settings, where advanced diagnostics are unavailable, integrated interpretation of personalized CBC trends and serial CRP provides a practical, cost‐effective strategy to improve diagnostic performance.