A Rational Approach to JAK2 Mutation Testing in Patients with Elevated Hemoglobin: Results from the JAK2 Prediction Cohort (JAKPOT) Study

J Gen Intern Med. 2023 Jun;38(8):1828-1833. doi: 10.1007/s11606-022-07963-x. Epub 2022 Nov 30.

Abstract

Background: Erythrocytosis, most often measured as an increase in hemoglobin and/or hematocrit, is a common reason for referral to internal medicine and hematology clinics and a rational approach is required to effectively identify patients with polycythemia vera while avoiding over-investigation.

Aim: We aimed to develop and validate a simple rule to predict JAK2 mutation positivity based on complete blood count parameters to aid in the diagnostic approach to patients referred for elevated hemoglobin.

Setting: Internal medicine and hematology clinics at an academic tertiary referral center.

Participants: The JAK2 Prediction Cohort (JAKPOT), a large retrospective cohort (n = 901) of patients evaluated by internal medicine and hematology specialists for elevated hemoglobin.

Design: JAK2 mutation analysis was performed in all patients and clinical and laboratory variables were collected. Patients were randomly divided into derivation and validation cohorts. A prediction rule was developed using data from the derivation cohort and tested in the validation cohort.

Key results: The JAKPOT prediction rule included three variables: (i) red blood cell count >6.45×1012/L, (ii) platelets >350×109/L, and (iii) neutrophils >6.2×109/L; absence of all criteria was effective at ruling out JAK2-positivity with sensitivities 94.7% and 100%, and negative predictive values of 98.8% and 100% in the derivation and validation cohorts, respectively, with an overall low false negative rate of 0.4%. The rule was validated for three different methods of JAK2 testing. Applying this rule to our entire cohort would have resulted in over 50% fewer tests.

Conclusion: In patients with elevated hemoglobin, the use of a simple prediction rule helps to accurately identify patients with a low likelihood of having a JAK2 mutation, potentially limiting costly over-investigation in this common referral population.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Hemoglobins / genetics
  • Humans
  • Janus Kinase 2 / genetics
  • Mutation
  • Polycythemia Vera* / diagnosis
  • Polycythemia Vera* / genetics
  • Polycythemia* / genetics
  • Retrospective Studies

Substances

  • Hemoglobins
  • JAK2 protein, human
  • Janus Kinase 2