Feb 9, 2026
Key takeaways
Overview
Routine bloodwork is often the first clue that red cell measures are higher than expected. Elevated RBC count, Hgb, or Hct can be transient (for example, from dehydration) or reflect a sustained medical condition. Polycythemia vera (PV) is a myeloproliferative neoplasm in which the bone marrow produces too many blood cells—most prominently red blood cells—and this process is typically associated with an acquired JAK2 mutation. [4][5]
When PV is present, clinicians usually see a consistent pattern over time, not a one-off abnormal result. WHO diagnostic frameworks emphasize elevated Hgb/Hct, JAK2 mutation, and characteristic bone marrow morphology, with subnormal EPO as a supportive (minor) criterion. [2]
Test | Typical finding in PV [2] | Why it happens |
Hemoglobin / Hematocrit | Often above diagnostic thresholds (e.g., Hgb >16.5 g/dL men, >16.0 g/dL women; or Hct >49% men, >48% women, depending on criteria used) | Reflects increased red cell mass [6] |
Erythropoietin (EPO) | Often low/subnormal | Physiologic suppression of EPO in the setting of increased red cells [7] |
JAK2 (V617F or exon 12) | Positive in the great majority (> 95%) of PV [4] | A driver mutation that supports the diagnosis of PV [2] |
Bone marrow biopsy | Hypercellular marrow with trilineage growth (panmyelosis) | unregulated neoplastic proliferation produces panmyelosis [8] |
Many conditions can raise red cell measures, but the mechanism is different.
This pattern more often suggests secondary erythrocytosis (the body is responding to a stimulus, commonly low oxygen).
Sometimes the red cells aren’t truly elevated; instead, plasma (the liquid part of blood) volume is reduced, concentrating the blood (relative polycythemia/hemoconcentration).
Lab Pattern | Clinical clues | Follow-up review |
High Hgb/Hct + low EPO (± panmyelosis) | Primary marrow process | Targeted confirmatory testing might be needed (e.g., JAK2 review ± marrow if indicated)[4][11] |
High Hgb/Hct + normal/high EPO + hypoxia risk factors | Oxygen-driven physiology (secondary erythrocytosis) | Oxygenation (pulse oximetry), sleep or lung risk factors, altitude exposure, and medications.[9][12] |
High Hct + normal EPO + reversible plasma-volume loss | Hemoconcentration (relative polycythemia); |
If polycythemia vera is confirmed, a common foundational strategy is phlebotomy and low-dose aspirin (if no contraindications) with tight Hct control, because maintaining Hct <45% has been associated with lower rates of cardiovascular death and major thrombosis in randomized evidence. [13][14] Cytoreductive therapy (e.g., hydroxyurea or interferon-based approaches) may be used based on risk profile, symptoms, and clinician judgment. [5][15]
For non-PV causes, treatment focuses on the driver (e.g., correcting dehydration, addressing sleep apnea, adjusting contributing medications) and monitoring the response. [3][9]
Final thoughts
A high RBC, hemoglobin, or hematocrit result should be interpreted in context. PV is one important cause of persistent elevation, but clinicians typically rely on a pattern that includes JAK2 mutation testing, bone marrow findings, and EPO/oxygenation assessment to distinguish PV from secondary or relative causes. [3][4]
If your results are repeatedly high, follow up with a hematology team to ensure appropriate testing and a clear diagnosis.