Required section · Section 5 of 6
Learner decision: choose a bounded action
Rank the case evidence before choosing an initial pathway. The pathway is targeted MPN evaluation in the local diagnostic workflow, with marrow correlation rather than a disease label released from the CBC. A platelet count alone is not enough to choose ET over PV or PMF.
For suspected PV with negative JAK2 V617F and low or normal EPO, the diagnostic pathway warrants JAK2 exon 12 testing (testing variants in exon 12 of JAK2) and marrow evaluation because exon 12 variants can support PV in a V617F-negative setting. For persistent neutrophilia with a full maturation spectrum, basophilia, and thrombocytosis, BCR::ABL1-positive CML is a differential pattern; see HEME-25 for its confirmation pathway.
CALR and MPL are other MPN driver genes; a driver allele burden is the measured fraction of tested DNA carrying a driver variant. A JAK2, CALR, or MPL result supports clonality but cannot independently distinguish PV, ET, and PMF. Triple-negative MPN means an MPN suspected clinically with no detected JAK2, CALR, or MPL driver variant; it still needs integrated marrow review, exclusion of reactive processes, and consideration of other clonal markers.
Ordering exercise
Order the laboratory reasoning steps for this case.
1. Select molecular pathway
Use validated targeted testing in the local pathway.
2. Review smear and prior CBC
Confirm persistence and exclude clumps or an implausible platelet result.
3. Correlate marrow findings
Apply the named framework with morphology and exclusions.
4. Assess secondary and reactive context
Consider explanations for erythrocytosis and thrombocytosis.
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