Proposal of a Diagnostic Workflow for Peripheral Blood Smear Testing Based on Complete Blood Count Flag Analysis

Leukemia requires early detection, especially in acute forms, but standard tests such as bone marrow biopsy and molecular assays are often costly and unavailable in smaller hospitals. In these settings, complete blood count with peripheral blood smear examination provides a practical alternative. Analyzer-generated flags may suggest abnormal cells, yet false positives are common, and without a standardized protocol, smear review is often overlooked, leading to delayed diagnosis. This study aimed to develop and validate a stepwise peripheral blood smear protocol for small hospitals by analyzing blast-flagged complete blood count cases, correlating findings with diagnoses, and facilitating early leukemia detection and timely referral in resource-limited settings.

This retrospective study was conducted at a small hospital in South Korea. Three datasets were analyzed: 1) 60 patients diagnosed with leukemia (Jan 2020 - Dec 2024), 2) 633 CBC samples flagged with "Blast/Abn Lympho?" or "Left Shift" (Feb 2023 - Jan 2025), and 3) 43,450 CBC samples without any flagging or hematological abnormalities (control group). The flags were automated alerts indicating the presence of immature or abnor-mal white blood cells (WBCs), prompting PBS review. Descriptive statistics summarized demographic and hematological parameters, and group comparisons were performed using chi-squared and independent t-tests, with significance set at p < 0.05.

Of the 633 flagged samples, 20 cases (3.2%) showed blast cells on PBS, 19 of which occurred in samples with elevated WBC counts. Several were confirmed as leukemia and referred early for treatment. Flagged cases showed significantly higher WBCs and lower hemoglobin levels than control cases (p < 0.0001), supporting the clinical relevance of analyzer flagging.

The proposed workflow facilitates the early detection of hematological malignancies using existing CBC flagging. Our study also underscores the pivotal role of clinical laboratory scientists in diagnostic decision-making, especially in resource-limited environments.