Laboratory stewardship of qualitative JAK2 V617F testing: a complete blood count-based framework for improving diagnostic yield

We characterized qualitative JAK2 V617F testing performed with and without prespecified hematologic features, compared diagnostic yield between these categories, and evaluated associations between complete blood count (CBC) parameters and qualitative JAK2 V617F positivity.

We retrospectively analyzed 2979 qualitative JAK2 V617F test orders (October 2025 to February 2026) from a large reference laboratory. Orders were categorized by the presence or absence of prespecified hematologic features: erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women), thrombocytosis (≥450 × 109/L), leukocytosis (>11 × 109/L), and basophilia. Diagnostic yield, odds ratios, and testing efficiency were calculated using same-day CBC specimens; differential counts were exploratory. Financial impact was modeled at the 2026 Medicare Clinical Laboratory Fee Schedule rate ($91.66/test).

Overall, 136 of 2979 tests (4.6%) were positive. Testing with at least 1 prespecified feature had higher yield than testing without (6.2% vs 2.1%; odds ratio, 3.07; 95% CI, 1.98-4.77; P < .001). Basophilia (41.1%) and thrombocytosis (24.5%) showed the highest yield. Testing without any prespecified feature required 47.5 tests per positive case. Monocyte and eosinophil counts showed modest associations with positivity. The lower-yield category comprised 39.9% of testing, with a maximum modeled financial impact of $108 900 over 5 months ($261 000 annually).

The likelihood of qualitative JAK2 V617F positivity varies markedly with routine CBC parameters, which can identify a higher-yield testing population. Because clinical indications were not available, testing performed without these features cannot be characterized as inappropriate. Criteria based on CBC findings can identify a higher-yield testing population and may serve as a framework for targeted decision support strategies.