<i>JAK2</i> Unmutated Erythrocytosis: 2026 Update on Diagnosis and Management
Bibliographic record
Abstract
DISEASE OVERVIEW: JAK2 unmutated erythrocytosis encompasses a heterogeneous spectrum of hereditary and acquired entities. DIAGNOSIS: The foremost step is excluding polycythemia vera (PV) with JAK2 mutation screening (exons 12-15). Apparent polycythemia such as physiological outliers or relative polycythemia secondary to volume contraction should be considered. A historical overview of hematocrit (Hct) and hemoglobin (Hgb) levels helps distinguish longstanding from acquired erythrocytosis. Serum erythropoietin (Epo) levels are variably informative. HEREDITARY ERYTHROCYTOSIS: Hereditary erythrocytosis should be considered in longstanding erythrocytosis with a positive family history; causes include EPOR mutations (subnormal Epo), high oxygen affinity hemoglobin variants, PIEZO1 mutations, 2,3-bisphosphoglycerate deficiency, methemoglobinemia, and germline oxygen sensing pathway mutations (HIF2A-PHD2-VHL). ACQUIRED ERYTHROCYTOSIS: Acquired erythrocytosis results from central (cardiopulmonary disease) or peripheral (renal artery stenosis) hypoxia, Epo-producing tumors (renal cell carcinoma) or drugs (testosterone, sodium glucose co-transporter-2 inhibitors (SGLT2-i), erythropoiesis stimulating agents). IDIOPATHIC ERYTHROCYTOSIS: Idiopathic erythrocytosis is an ill-defined terminology that presumes the existence of an increased Hgb/Hct level without an identifiable etiology. MANAGEMENT: Cytoreductive therapy should be avoided. Phlebotomy should be considered for symptom control. Cardiovascular risk optimization and low-dose aspirin are advised, while the role of HIF2A inhibitors remains unclear. RECENT ADVANCES: EPO mutations which produce hyperactive, hepatic-like Epo were identified. In cases with negative workup but high clinical suspicion, an expanded next generation sequencing panel for hereditary erythrocytosis is recommended. Among drugs, SGLT2-i-associated erythrocytosis is increasingly recognized. FUTURE DIRECTIONS: Advances in molecular hematology are expected to improve the characterization of "idiopathic erythrocytosis". Results from prospective studies are needed to elucidate the underlying pathology and guide management.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".