# External Validation of the JAKPOT Score for Diagnosing JAK2-Positive Erythrocytosis: A Retrospective Cohort Study

## TL;DR

This study validates a new score to identify JAK2-positive erythrocytosis using blood counts and erythropoietin levels, reducing the need for genetic testing.

## Contribution

The EPO-JAKPOT score combines low EPO and JAKPOT criteria to improve diagnostic accuracy for JAK2 mutations in erythrocytosis.

## Key findings

- JAKPOT+ status had 88% sensitivity for detecting JAK2 mutations.
- Combining low EPO with JAKPOT increased sensitivity to 95%.
- Using EPO-JAKPOT could reduce molecular tests by 55% in similar patient groups.

## Abstract

Background/Objectives: Erythrocytosis is a common laboratory abnormality affecting approximately 4% of males and 0.4% of females. The JAKPOT score was recently developed to differentiate primary from secondary erythrocytosis without molecular testing. JAKPOT+ patients meet any of the following criteria: erythrocytes > 6.45 × 1012/L, platelets > 350 × 109/L, or neutrophils > 6.2 × 109/L. We aimed to validate this score and identify predictors of JAK2-positive erythrocytosis in a retrospective cohort. Methods: We identified 213 patients (50 female, mean age 57 years) with undifferentiated erythrocytosis, serum erythropoietin (EPO) and JAK2 molecular testing (V617F or exon 12) at a tertiary care center in Hamilton, Canada, between 2017 and 2022. Charts were manually reviewed for laboratory data, comorbidities, demographics, and medications. We evaluated the diagnostic accuracy of EPO, JAKPOT, and a combination of low EPO and JAKPOT (EPO-JAKPOT) for predicting JAK2 mutant erythrocytosis. Multivariate logistic regression analysis was performed to detect predictors of JAK2 mutant erythrocytosis. Results: Forty patients (19%) had JAK2 mutations. Older age (p < 0.01), higher platelet count (p < 0.01), and lower EPO (p < 0.01) were associated with JAK2 mutant erythrocytosis in a multivariate analysis. JAKPOT+ status had a sensitivity of 0.88 (95% CI, 0.73–0.94). Combining low EPO or JAKPOT+ status into a new score (EPO-JAKPOT) increased sensitivity to 0.95 (95% CI, 0.83–0.98). Restricting JAK2 testing to only EPO-JAKPOT+ patients would have led to 55% fewer molecular tests in our cohort. Conclusions: The EPO-JAKPOT score shows promise in excluding JAK2 mutant erythrocytosis without molecular testing, but further prospective validation is warranted.