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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Hematology

The Science of PV: Why Your Body is Overproducing Blood

At a Glance

Polycythemia Vera (PV) is driven by a JAK2 genetic mutation that forces the bone marrow to overproduce blood cells. Doctors diagnose PV using WHO criteria, which evaluate high blood counts, bone marrow crowding (panmyelosis), the presence of the JAK2 mutation, and low EPO hormone levels.

To understand Polycythemia Vera (PV), it helps to look at the “engine” of your blood production. In a healthy body, the production of blood cells is a carefully regulated process. In PV, a genetic glitch causes that process to run out of control [1].

The Broken “On” Switch: The JAK2 Mutation

The driving force behind PV is a mutation in the JAK2 gene. Think of the JAK2 protein as a power switch for making blood cells [2].

  • JAK2 V617F: This is the most common mutation, found in about 95% of people with PV [2][3]. It acts like a broken switch that is stuck in the “on” position, constantly signaling your bone marrow to churn out red blood cells, white blood cells, and platelets, even when the body doesn’t need them [2][1].
  • JAK2 Exon 12: A smaller number of patients (about 3-5%) have a mutation in a different part of the same gene called Exon 12 [4]. These patients often have very high red blood cell counts but may have normal levels of white blood cells and platelets [5].

How Doctors Diagnose PV (2022 WHO Criteria)

Because there are many reasons a person might have a high red blood cell count, doctors use a strict set of rules called the WHO Diagnostic Criteria to confirm a PV diagnosis [6]. To be diagnosed with PV, you generally must meet all three Major Criteria, or the first two Major Criteria plus the Minor Criterion [7][8].

Major Criteria

  1. Elevated Blood Counts: A high level of hemoglobin or hematocrit (the percentage of your blood made of red cells) [7].
    • Men: Hemoglobin >16.5 g/dL or Hematocrit >49%
    • Women: Hemoglobin >16.0 g/dL or Hematocrit >48%
  2. Bone Marrow Hypercellularity: A bone marrow biopsy showing “panmyelosis,” which means the marrow is over-crowded with all three types of blood cells (red, white, and platelets) [9][1].
  3. Presence of a JAK2 Mutation: Testing positive for either the V617F or Exon 12 mutation [7].

Minor Criterion

  1. Low Serum EPO: Your blood test shows a subnormal or “low” level of a hormone called erythropoietin (EPO) [7].

PV vs. Secondary Polycythemia

It is common for the body to make extra red blood cells for “healthy” reasons—this is called secondary polycythemia [10]. It’s important to distinguish this from PV because the treatments are very different.

  • Secondary Polycythemia (The “Helpful” Response): If you smoke, have sleep apnea, or live at a very high altitude, your body may not be getting enough oxygen [11][12]. Your kidneys detect this and pump out more EPO (the “growth” hormone for blood) to tell your marrow to make more red cells to carry oxygen [11]. In these cases, EPO levels will be high [13].
  • Polycythemia Vera (The “Broken” Response): In PV, the bone marrow is making blood cells because of the broken JAK2 switch, not because the body needs them [1]. Your kidneys sense there are already too many red cells and stop making EPO entirely. This is why in PV, EPO levels are very low [14][15].

While secondary polycythemia is a reaction to an outside problem, PV is a primary problem within the bone marrow itself [10]. Unlike secondary causes, PV also increases the risk of blood clots because the cells themselves are often “stickier” due to the JAK2 mutation [16][17].

Common questions in this guide

What is the JAK2 mutation in Polycythemia Vera?
The JAK2 mutation is a genetic change that acts like a broken power switch stuck in the 'on' position. This forces your bone marrow to constantly overproduce red blood cells, white blood cells, and platelets, even when your body does not need them.
What is the difference between Polycythemia Vera and secondary polycythemia?
Polycythemia Vera is a primary bone marrow disorder caused by a genetic mutation. Secondary polycythemia is a natural reaction where your body makes extra blood cells in response to low oxygen levels, which can be triggered by smoking, sleep apnea, or living at high altitudes.
Why are EPO levels low in Polycythemia Vera?
In Polycythemia Vera, the bone marrow produces blood cells uncontrollably due to a genetic mutation. Your kidneys sense that there are already too many red blood cells and stop producing erythropoietin (EPO), the hormone that signals blood production.
What does panmyelosis mean on my bone marrow biopsy?
Panmyelosis means your bone marrow is overcrowded with all three major types of blood cells: red cells, white cells, and platelets. Finding this crowding on a bone marrow biopsy is one of the major criteria doctors use to diagnose Polycythemia Vera.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Can you confirm if I have the JAK2 V617F mutation or the Exon 12 mutation, and how that affects my symptoms?
  2. 2.Was my EPO level suppressed at diagnosis, and how does that help confirm it is PV and not another condition?
  3. 3.What exactly did my bone marrow biopsy show regarding 'panmyelosis'?
  4. 4.If I have sleep apnea or if I smoke, how can we be sure the high red cell count is from PV and not those other factors?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
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    Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management.

    Tefferi A, Barbui T

    American journal of hematology 2023; (98(9)):1465-1487 doi:10.1002/ajh.27002.

    PMID: 37357958
  2. 2

    Hemochromatosis, Erythrocytosis and the JAK2 p.V617F Mutation.

    Langabeer SE

    EJIFCC 2017; (28(1)):92-93.

    PMID: 28439222
  3. 3

    Genetic Background of Polycythemia Vera.

    Regimbeau M, Mary R, Hermetet F, Girodon F

    Genes 2022; (13(4)) doi:10.3390/genes13040637.

    PMID: 35456443
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    Detection of Exon 12 and 14 Mutations in Janus Kinase 2 Gene Including a Novel Mutant in V617F Negative Polycythemia Vera Patients from Pakistan.

    Akram AM, Kausar H, Chaudhary A, et al.

    Journal of Cancer 2018; (9(23)):4341-4345 doi:10.7150/jca.27414.

    PMID: 30519338
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    High frequency of JAK2 exon 12 mutations in Korean patients with polycythaemia vera: novel mutations and clinical significance.

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    Journal of clinical pathology 2016; (69(8)):737-41 doi:10.1136/jclinpath-2016-203649.

    PMID: 27198504
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    The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms.

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    American journal of hematology 2023; (98(1)):166-179 doi:10.1002/ajh.26751.

    PMID: 36200127
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    Update from the latest WHO classification of MPNs: a user's manual.

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    Hematology. American Society of Hematology. Education Program 2016; (2016(1)):534-542 doi:10.1182/asheducation-2016.1.534.

    PMID: 27913526
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    Impact of World Health Organization (WHO) Revised Criteria-2016 on the Diagnosis of Polycythemia Vera.

    Nathany S, Koulmane Laxminarayana SL, Tewari S, et al.

    Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 2020; (36(3)):477-483 doi:10.1007/s12288-019-01202-w.

    PMID: 32647421
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    Clinical features of acquired erythrocytosis: Low levels of serum erythropoietin in a subset of non-neoplastic erythrocytosis patients.

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    Erythrocytosis and CKD: A Review.

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    American journal of kidney diseases : the official journal of the National Kidney Foundation 2024; (84(4)):495-506 doi:10.1053/j.ajkd.2024.02.015.

    PMID: 38621632
  12. 12

    Sodium-glucose co-transporter-2 inhibitor use and JAK2 unmutated erythrocytosis in 100 consecutive cases.

    Gangat N, Abdallah M, Szuber N, et al.

    American journal of hematology 2023; (98(7)):E165-E167 doi:10.1002/ajh.26933.

    PMID: 37073574
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    Obstructive Sleep Apnea Does Not Exclude Polycythemia Vera: A Case Report.

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    PMID: 38213957
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    The frequency of JAK2 V617F mutation and its association with low EPO levels in polycythemia vera patients.

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    PMID: 40337844
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    Revisiting Diagnostic performances of serum erythropoïetin level and JAK2 mutation for polycythemias: analysis of a cohort of 1090 patients with red cell mass measurement.

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    Different Colours of Polycythemia Vera: A Case Series.

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    Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL.

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This page explains the biology and diagnostic criteria of Polycythemia Vera for educational purposes. Always consult your hematologist to interpret your specific lab results, genetic testing, and diagnosis.

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