Polycythemia vera (PV) is a clonal myeloproliferative neoplasm characterized by uncontrolled erythrocyte production leading to elevated red blood cell mass, often accompanied by increased white blood cells and platelets. The JAK2 V617F mutation is present in approximately 95% of PV cases, with JAK2 exon 12 mutations accounting for most remaining cases. This mutation causes constitutive activation of JAK-STAT signaling, driving erythropoietin-independent erythroid proliferation. PV carries increased risk of thrombosis, the major cause of morbidity and mortality, and can progress to myelofibrosis or acute leukemia. JAK inhibitor ruxolitinib provides targeted therapy for inadequately controlled PV.
Ask a research question about Polycythemia Vera. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Polycythemia Vera
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-01T12:00:00Z'
description: >-
Polycythemia vera (PV) is a clonal myeloproliferative neoplasm characterized by
uncontrolled erythrocyte production leading to elevated red blood cell mass,
often accompanied by increased white blood cells and platelets. The JAK2 V617F
mutation is present in approximately 95% of PV cases, with JAK2 exon 12 mutations
accounting for most remaining cases. This mutation causes constitutive activation
of JAK-STAT signaling, driving erythropoietin-independent erythroid proliferation.
PV carries increased risk of thrombosis, the major cause of morbidity and mortality,
and can progress to myelofibrosis or acute leukemia. JAK inhibitor ruxolitinib
provides targeted therapy for inadequately controlled PV.
categories:
- Hematologic Malignancy
- Myeloproliferative Neoplasm
parents:
- myeloproliferative neoplasm
pathophysiology:
- name: JAK2 V617F Constitutive Activation
description: >-
The JAK2 V617F mutation in the pseudokinase domain eliminates auto-inhibition,
causing constitutive JAK2 tyrosine kinase activity. This renders erythroid
progenitors hypersensitive to or independent of erythropoietin, driving
uncontrolled red blood cell production.
cell_types:
- preferred_term: erythroid progenitor cell
term:
id: CL:0000038
label: erythroid progenitor cell
molecular_functions:
- preferred_term: protein tyrosine kinase activity
modifier: INCREASED
term:
id: GO:0004713
label: protein tyrosine kinase activity
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
downstream:
- target: STAT5 Hyperactivation
description: JAK2 constitutively phosphorylates and activates STAT5
- target: Erythropoietin-Independent Erythropoiesis
description: Mutant progenitors proliferate without EPO stimulation
- name: STAT5 Hyperactivation
description: >-
Constitutive JAK2 activation leads to sustained STAT5 phosphorylation and
transcriptional activation of genes promoting erythroid proliferation and
survival, including BCL-XL and cyclin D1.
biological_processes:
- preferred_term: JAK-STAT signaling pathway
modifier: INCREASED
term:
id: GO:0007259
label: cell surface receptor signaling pathway via JAK-STAT
- name: Erythropoietin-Independent Erythropoiesis
description: >-
JAK2 V617F-mutant erythroid progenitors can proliferate and differentiate
in the absence of erythropoietin, forming endogenous erythroid colonies (EEC)
in culture. This erythropoietin independence is a diagnostic hallmark of PV.
biological_processes:
- preferred_term: erythrocyte differentiation
modifier: INCREASED
term:
id: GO:0030218
label: erythrocyte differentiation
- name: Hyperviscosity and Thrombosis Risk
description: >-
Elevated red blood cell mass increases blood viscosity and promotes
thrombosis. The prothrombotic state is multifactorial, including abnormal
red cell interactions, platelet activation, and endothelial dysfunction.
evidence:
- reference: PMID:41580684
reference_title: "Polycythemia vera and stiff-person syndrome: a case report."
supports: PARTIAL
snippet: "Polycythemia vera (PV) is a myeloproliferative neoplasm, characterized by trilineage hypercellularity, which increases the risk of thrombosis."
explanation: This abstract states that PV is an MPN with increased thrombosis risk, supporting the thrombotic mechanism described.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis"
explanation: Nat Rev Dis Primers review confirms thrombosis is a major clinical hazard in PV.
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0004420 | Arterial thrombosis | Occasional (29-5%)"
explanation: Orphanet documents arterial thrombosis as a recognized complication of PV.
biological_processes:
- preferred_term: blood coagulation
modifier: ABNORMAL
term:
id: GO:0007596
label: blood coagulation
histopathology:
- name: Erythrocytosis
finding_term:
preferred_term: Erythrocytosis
term:
id: NCIT:C113711
label: Erythrocytosis
frequency: VERY_FREQUENT
description: Polycythemia vera is typically characterized by erythrocytosis.
evidence:
- reference: PMID:40246933
reference_title: "Polycythaemia vera."
supports: SUPPORT
snippet: "PV is typically characterized by erythrocytosis and often"
explanation: Abstract states that PV is typically characterized by erythrocytosis.
phenotypes:
- category: Hematologic
name: Polycythemia
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Elevated hemoglobin and hematocrit reflecting increased red blood cell mass.
WHO diagnostic criterion is hemoglobin >16.5 g/dL in men or >16 g/dL in women.
phenotype_term:
preferred_term: Polycythemia
term:
id: HP:0001901
label: Polycythemia
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0001901 | Polycythemia | Very frequent (99-80%)"
explanation: Orphanet classifies polycythemia as very frequent in PV.
- reference: PMID:40246933
supports: SUPPORT
snippet: "PV is typically characterized by erythrocytosis and often leukocytosis and thrombocytosis"
explanation: Nat Rev Dis Primers review confirms erythrocytosis is the defining feature of PV.
- category: Hematologic
name: Thrombocytosis
frequency: OCCASIONAL
description: >-
Elevated platelet count occurs in a subset of patients, contributing
to thrombotic and sometimes bleeding complications.
phenotype_term:
preferred_term: Thrombocytosis
term:
id: HP:0001894
label: Thrombocytosis
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0001894 | Thrombocytosis | Occasional (29-5%)"
explanation: Orphanet classifies thrombocytosis as occasional in PV.
- reference: PMID:40246933
supports: SUPPORT
snippet: "PV is typically characterized by erythrocytosis and often leukocytosis and thrombocytosis"
explanation: Review notes thrombocytosis often accompanies PV.
- category: Hematologic
name: Leukocytosis
frequency: OCCASIONAL
description: >-
Elevated white blood cell count reflects pan-myeloid proliferation driven
by JAK2 activation.
phenotype_term:
preferred_term: Leukocytosis
term:
id: HP:0001974
label: Increased total leukocyte count
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0001974 | Leukocytosis | Occasional (29-5%)"
explanation: Orphanet classifies leukocytosis as occasional in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by erythrocytosis, thrombocytosis, leukocytosis, and splenomegaly."
explanation: REVEAL study confirms leukocytosis is a characteristic feature of PV.
- category: Constitutional
name: Aquagenic Pruritus
frequency: OCCASIONAL
description: >-
Intense itching triggered by contact with water is highly characteristic
of PV. Mechanism involves basophil and mast cell activation.
phenotype_term:
preferred_term: Pruritus
term:
id: HP:0000989
label: Pruritus
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000989 | Pruritus | Occasional (29-5%)"
explanation: Orphanet classifies pruritus as occasional in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "The 5 most common patient-reported symptoms were fatigue, early satiety, inactivity, pruritus, and problems with concentration"
explanation: REVEAL study identifies pruritus as one of the top 5 reported PV symptoms.
- category: Neurological
name: Headache
frequency: VERY_FREQUENT
description: >-
Headaches are common due to hyperviscosity and may improve with phlebotomy.
Severe headache may herald thrombotic complication.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002315 | Headache | Very frequent (99-80%)"
explanation: Orphanet classifies headache as very frequent in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Approximately 50% of patients present with PV-related symptoms, including fatigue, headache, visual disturbances, and pruritus, at the time of diagnosis."
explanation: REVEAL study confirms headache is among the most common presenting symptoms.
- category: Abdominal
name: Splenomegaly
frequency: VERY_FREQUENT
description: >-
Spleen enlargement from extramedullary hematopoiesis and sequestration.
Massive splenomegaly suggests disease progression toward myelofibrosis.
phenotype_term:
preferred_term: Splenomegaly
term:
id: HP:0001744
label: Splenomegaly
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0001744 | Splenomegaly | Very frequent (99-80%)"
explanation: Orphanet classifies splenomegaly as very frequent in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by erythrocytosis, thrombocytosis, leukocytosis, and splenomegaly."
explanation: REVEAL study lists splenomegaly as a defining characteristic of PV.
- category: Constitutional
name: Fatigue
frequency: FREQUENT
description: >-
Fatigue is one of the most common and impactful symptoms, significantly
affecting quality of life even in well-controlled disease.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
explanation: Orphanet classifies fatigue as frequent in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Fatigue was the most frequently reported symptom, with approximately 80% of patients in each blood count control group experiencing at least mild severity."
explanation: REVEAL study confirms fatigue is the most common PV symptom at ~80% prevalence.
- category: Neurological
name: Vertigo
frequency: VERY_FREQUENT
description: >-
Dizziness and vertigo result from hyperviscosity affecting cerebral
microcirculation.
phenotype_term:
preferred_term: Vertigo
term:
id: HP:0002321
label: Vertigo
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002321 | Vertigo | Very frequent (99-80%)"
explanation: Orphanet classifies vertigo as very frequent in PV.
- category: Neurological
name: Tinnitus
frequency: VERY_FREQUENT
description: >-
Tinnitus is attributed to hyperviscosity-related changes in cochlear blood flow.
phenotype_term:
preferred_term: Tinnitus
term:
id: HP:0000360
label: Tinnitus
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000360 | Tinnitus | Very frequent (99-80%)"
explanation: Orphanet classifies tinnitus as very frequent in PV.
- category: Neurological
name: Paresthesia
frequency: FREQUENT
description: >-
Numbness or tingling, especially in extremities, from microvascular
hyperviscosity affecting peripheral nerves.
phenotype_term:
preferred_term: Paresthesia
term:
id: HP:0003401
label: Paresthesia
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0003401 | Paresthesia | Frequent (79-30%)"
explanation: Orphanet classifies paresthesia as frequent in PV.
- category: Neurological
name: Visual Disturbances
frequency: FREQUENT
description: >-
Visual symptoms including blurring, scotomata, and diplopia may occur due
to retinal vascular hyperviscosity or thrombosis.
phenotype_term:
preferred_term: Abnormality of vision
term:
id: HP:0000504
label: Abnormality of vision
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000504 | Abnormality of vision | Frequent (79-30%)"
explanation: Orphanet classifies visual abnormalities as frequent in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Approximately 50% of patients present with PV-related symptoms, including fatigue, headache, visual disturbances, and pruritus, at the time of diagnosis."
explanation: REVEAL study confirms visual disturbances are common presenting symptoms.
- category: Cardiovascular
name: Hypertension
frequency: VERY_FREQUENT
description: >-
Systemic hypertension resulting from increased blood viscosity and
expanded blood volume.
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000822 | Hypertension | Very frequent (99-80%)"
explanation: Orphanet classifies hypertension as very frequent in PV.
- category: Vascular
name: Venous Thrombosis
frequency: OCCASIONAL
description: >-
Deep vein thrombosis and other venous thrombotic events are major
complications, especially in atypical sites such as splanchnic veins.
phenotype_term:
preferred_term: Venous thrombosis
term:
id: HP:0004936
label: Venous thrombosis
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0004936 | Venous thrombosis | Occasional (29-5%)"
explanation: Orphanet classifies venous thrombosis as occasional in PV.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis"
explanation: Review confirms thrombosis (including venous) as a major clinical hazard of PV.
- category: Vascular
name: Arterial Thrombosis
frequency: OCCASIONAL
description: >-
Arterial thrombotic events including stroke, myocardial infarction, and
peripheral arterial occlusion are major causes of morbidity in PV.
phenotype_term:
preferred_term: Arterial thrombosis
term:
id: HP:0004420
label: Arterial thrombosis
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0004420 | Arterial thrombosis | Occasional (29-5%)"
explanation: Orphanet classifies arterial thrombosis as occasional in PV.
- category: Vascular
name: Erythromelalgia
frequency: OCCASIONAL
description: >-
Burning pain and erythema of the extremities (especially feet) caused by
microvascular platelet aggregation. Responds dramatically to aspirin.
phenotype_term:
preferred_term: Erythromelalgia
term:
id: HP:0032147
label: Erythromelalgia
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0032147 | Erythromelalgia | Occasional (29-5%)"
explanation: Orphanet classifies erythromelalgia as occasional in PV.
- category: Bleeding
name: Epistaxis
frequency: VERY_FREQUENT
description: >-
Nosebleeds are common due to acquired von Willebrand disease in
patients with very high platelet counts and mucosal vascular engorgement.
phenotype_term:
preferred_term: Epistaxis
term:
id: HP:0000421
label: Epistaxis
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000421 | Epistaxis | Very frequent (99-80%)"
explanation: Orphanet classifies epistaxis as very frequent in PV.
- category: Bleeding
name: Bruising Susceptibility
frequency: VERY_FREQUENT
description: >-
Easy bruising reflects platelet dysfunction and acquired bleeding
diathesis, particularly when platelet counts are markedly elevated.
phenotype_term:
preferred_term: Bruising susceptibility
term:
id: HP:0000978
label: Bruising susceptibility
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000978 | Bruising susceptibility | Very frequent (99-80%)"
explanation: Orphanet classifies bruising susceptibility as very frequent in PV.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis"
explanation: Review confirms haemorrhage is a major clinical hazard of PV.
- category: Constitutional
name: Weight Loss
frequency: VERY_FREQUENT
description: >-
Unintentional weight loss reflects hypermetabolic state from
myeloproliferation and elevated inflammatory cytokines.
phenotype_term:
preferred_term: Weight loss
term:
id: HP:0001824
label: Weight loss
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0001824 | Weight loss | Very frequent (99-80%)"
explanation: Orphanet classifies weight loss as very frequent in PV.
- category: Constitutional
name: Early Satiety
frequency: OCCASIONAL
description: >-
Feeling of fullness after small meals, typically from splenomegaly
compressing the stomach.
phenotype_term:
preferred_term: Early satiety
term:
id: HP:0033842
label: Early satiety
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0033842 | Early satiety | Occasional (29-5%)"
explanation: Orphanet classifies early satiety as occasional in PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "The 5 most common patient-reported symptoms were fatigue, early satiety, inactivity, pruritus, and problems with concentration"
explanation: REVEAL study identifies early satiety as the second most common patient-reported symptom.
- category: Abdominal
name: Hepatomegaly
frequency: VERY_FREQUENT
description: >-
Liver enlargement from extramedullary hematopoiesis and increased
hepatic blood flow.
phenotype_term:
preferred_term: Hepatomegaly
term:
id: HP:0002240
label: Hepatomegaly
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002240 | Hepatomegaly | Very frequent (99-80%)"
explanation: Orphanet classifies hepatomegaly as very frequent in PV.
- category: Abdominal
name: Abdominal Pain
frequency: VERY_FREQUENT
description: >-
Abdominal discomfort from splenomegaly, hepatomegaly, or splanchnic
vascular congestion.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002027 | Abdominal pain | Very frequent (99-80%)"
explanation: Orphanet classifies abdominal pain as very frequent in PV.
- category: Musculoskeletal
name: Arthralgia
frequency: FREQUENT
description: >-
Joint pain, particularly gout from hyperuricemia secondary to increased
cell turnover.
phenotype_term:
preferred_term: Arthralgia
term:
id: HP:0002829
label: Arthralgia
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002829 | Arthralgia | Frequent (79-30%)"
explanation: Orphanet classifies arthralgia as frequent in PV.
- category: Bleeding
name: Gingival Bleeding
frequency: VERY_FREQUENT
description: >-
Gum bleeding reflects mucosal vascular engorgement and platelet
dysfunction in the setting of markedly elevated hematocrit.
phenotype_term:
preferred_term: Gingival bleeding
term:
id: HP:0000225
label: Gingival bleeding
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0000225 | Gingival bleeding | Very frequent (99-80%)"
explanation: Orphanet classifies gingival bleeding as very frequent in PV.
- category: Vascular
name: Budd-Chiari Syndrome
frequency: OCCASIONAL
description: >-
Hepatic vein thrombosis is a characteristic atypical-site thrombosis
in PV. May be the presenting feature, especially in younger patients.
phenotype_term:
preferred_term: Budd-Chiari syndrome
term:
id: HP:0002639
label: Budd-Chiari syndrome
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "HP:0002639 | Budd-Chiari syndrome | Occasional (29-5%)"
explanation: Orphanet classifies Budd-Chiari syndrome as occasional in PV.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis"
explanation: Review highlights thrombosis in atypical sites as a clinical feature; Budd-Chiari is the prototypical atypical-site thrombosis in PV.
- category: Progression
name: Myelofibrosis
frequency: OCCASIONAL
description: >-
Post-PV myelofibrosis develops in approximately 10% of patients at 10 years.
Characterized by progressive bone marrow fibrosis, worsening splenomegaly,
and cytopenias.
phenotype_term:
preferred_term: Myelofibrosis
term:
id: HP:0011974
label: Myelofibrosis
evidence:
- reference: ORPHA:729
supports: PARTIAL
snippet: "HP:0011974 | Myelofibrosis | Very frequent (99-80%)"
explanation: Orphanet classifies myelofibrosis as very frequent (likely reflecting lifetime cumulative risk); clinical data shows ~10% at 10 years, hence OCCASIONAL frequency used.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis"
explanation: Review confirms transformation to myelofibrosis as a key clinical feature affecting life expectancy.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Ten years after diagnosis, the risks of transformation to post-PV myelofibrosis (MF) and acute myeloid leukemia (AML) are 10% and 5% to 21%, respectively."
explanation: REVEAL study quantifies 10% risk of post-PV MF at 10 years.
- category: Progression
name: Acute Leukemia
frequency: OCCASIONAL
description: >-
Blast-phase transformation (acute myeloid leukemia) occurs in 5-21% of
patients at 10 years. Risk increased by prior cytoreductive therapy and
adverse mutations (ASXL1, TP53).
phenotype_term:
preferred_term: Acute leukemia
term:
id: HP:0002488
label: Acute leukemia
evidence:
- reference: ORPHA:729
supports: PARTIAL
snippet: "HP:0002488 | Acute leukemia | Very frequent (99-80%)"
explanation: Orphanet classifies acute leukemia as very frequent (likely reflecting lifetime cumulative risk); clinical data shows 5-21% at 10 years, hence OCCASIONAL frequency used.
- reference: PMID:40246933
supports: SUPPORT
snippet: "Clinical features include reduced life expectancy due to hazards of thrombosis (often in atypical sites), haemorrhage and transformation to myelofibrosis and less frequently to a form of acute myeloid leukaemia called blast phase."
explanation: Review confirms blast-phase AML transformation as a clinical feature of PV.
- reference: PMID:31303457
supports: SUPPORT
snippet: "Ten years after diagnosis, the risks of transformation to post-PV myelofibrosis (MF) and acute myeloid leukemia (AML) are 10% and 5% to 21%, respectively."
explanation: REVEAL study quantifies 5-21% risk of AML at 10 years.
biochemical:
- name: Serum Erythropoietin
notes: >-
Erythropoietin (EPO) level is characteristically low or low-normal in PV
due to negative feedback from elevated red cell mass. Low EPO helps distinguish
PV from secondary erythrocytosis.
- name: JAK2 V617F Mutation
notes: >-
JAK2 V617F mutation testing is a major diagnostic criterion for PV. Present
in approximately 95% of cases. Variant allele frequency may correlate with
disease burden.
genetic:
- name: JAK2
association: Somatic Activating Mutations
notes: >-
JAK2 V617F occurs in approximately 95% of PV patients. JAK2 exon 12 mutations
account for most remaining cases, typically presenting with isolated erythrocytosis.
Mutation is acquired in hematopoietic stem cells.
evidence:
- reference: ORPHA:729
supports: SUPPORT
snippet: "JAK2 | Janus kinase 2 | hgnc:6192 | Disease-causing somatic mutation(s) in"
explanation: Orphanet confirms JAK2 as the causative gene via somatic mutations.
- reference: PMID:40246933
supports: SUPPORT
snippet: "the JAK2V617F mutation in exon 14 of JAK2 was described, and is known to be present in more than 95% of patients with PV"
explanation: Review confirms JAK2 V617F is present in >95% of PV patients.
- name: TET2
association: Somatic Co-mutation
notes: >-
TET2 mutations are the most common co-occurring mutation in PV, present in
approximately 18% of patients. TET2 mutations may precede or follow JAK2
acquisition and influence clonal architecture.
- name: ASXL1
association: Somatic Co-mutation
notes: >-
ASXL1 mutations occur in approximately 15% of PV patients and are associated
with adverse prognosis, increased risk of myelofibrotic transformation, and
reduced event-free survival.
treatments:
- name: Therapeutic Phlebotomy
description: >-
Therapeutic phlebotomy to maintain hematocrit below 45% is the cornerstone
of treatment for all PV patients. Reduces thrombotic risk by lowering
blood viscosity.
treatment_term:
preferred_term: phlebotomy
term:
id: NCIT:C28221
label: Phlebotomy
- name: Low-Dose Aspirin
description: >-
Low-dose aspirin (81-100 mg daily) is recommended for all PV patients
without contraindications to reduce thrombotic risk. Reduces arterial
and possibly venous thrombosis.
treatment_term:
preferred_term: aspirin therapy
term:
id: MAXO:0000903
label: aspirin therapy
therapeutic_agent:
- preferred_term: acetylsalicylic acid
term:
id: CHEBI:15365
label: acetylsalicylic acid
- name: Hydroxyurea
description: >-
First-line cytoreductive therapy for high-risk PV patients (age >60 years
or prior thrombosis). Reduces all three cell lines and decreases thrombotic
events.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000646
label: cancer chemotherapy
therapeutic_agent:
- preferred_term: hydroxyurea
term:
id: CHEBI:44423
label: hydroxyurea
- name: Ruxolitinib
description: >-
JAK1/JAK2 inhibitor approved for PV inadequately controlled by hydroxyurea.
Provides excellent control of hematocrit, reduces spleen size, and markedly
improves symptom burden including pruritus and fatigue.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: ruxolitinib
term:
id: CHEBI:66919
label: ruxolitinib
- name: Interferon-alpha
description: >-
Alternative to hydroxyurea, particularly for younger patients and during
pregnancy. May induce molecular remissions with reduction in JAK2 V617F
allele burden.
treatment_term:
preferred_term: immunotherapy
term:
id: NCIT:C15262
label: Immunotherapy
disease_term:
preferred_term: polycythemia vera
term:
id: MONDO:0009891
label: acquired polycythemia vera
classifications:
icdo_morphology:
classification_value: Leukemia
harrisons_chapter:
- classification_value: cancer
- classification_value: hematologic malignancy
references:
- reference: DOI:10.1002/ajh.27002
title: 'Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: 'Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management'
supporting_text: Disease OverviewPolycythemia vera (PV) is a JAK2‐mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, constitutional symptoms, microcirculatory disturbances, and increased risk of thrombosis and progression into myelofibrosis (post‐PV MF) or acute myeloid leukemia (AML).DiagnosisA working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women; morphologic confirmation by bone marrow examination is advised but not mandated.CytogeneticsAbnormal karyotype is seen in 15%–20% of patients with the most frequent sole abnormalities being +9 (5%), loss of chromosome Y (4%), +8 (3%), and 20q− (3%).MutationsOver 50% of patients harbor DNA sequence variants/mutations other than JAK2, with the most frequent being TET2 (18%) and ASXL1 (15%).
evidence:
- reference: DOI:10.1002/ajh.27002
reference_title: 'Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Disease OverviewPolycythemia vera (PV) is a JAK2‐mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, constitutional symptoms, microcirculatory disturbances, and increased risk of thrombosis and progression into myelofibrosis (post‐PV MF) or acute myeloid leukemia (AML).DiagnosisA working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women; morphologic confirmation by bone marrow examination is advised but not mandated.CytogeneticsAbnormal karyotype is seen in 15%–20% of patients with the most frequent sole abnormalities being +9 (5%), loss of chromosome Y (4%), +8 (3%), and 20q− (3%).MutationsOver 50% of patients harbor DNA sequence variants/mutations other than JAK2, with the most frequent being TET2 (18%) and ASXL1 (15%).
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.1007/s00277-022-05080-7
title: 'Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis.
supporting_text: Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis.
evidence:
- reference: DOI:10.1007/s00277-022-05080-7
reference_title: 'Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.1007/s00277-023-05089-6
title: Real-world treatments and thrombotic events in polycythemia vera patients in the USA
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death.
supporting_text: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death.
evidence:
- reference: DOI:10.1007/s00277-023-05089-6
reference_title: Real-world treatments and thrombotic events in polycythemia vera patients in the USA
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.1056/evidoa2200335
title: Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera
supporting_text: Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera
- reference: DOI:10.1056/nejmoa2308809
title: Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera
supporting_text: Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera
- reference: DOI:10.1080/17474086.2023.2198698
title: 'Polycythemia vera: aspects of its current diagnosis and initial treatment'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: 'Polycythemia vera: aspects of its current diagnosis and initial treatment'
supporting_text: 'Polycythemia vera: aspects of its current diagnosis and initial treatment'
- reference: DOI:10.1097/moh.0000000000000747
title: 'Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: of review Development of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders.
supporting_text: of review Development of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders.
evidence:
- reference: DOI:10.1097/moh.0000000000000747
reference_title: 'Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: of review Development of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.1186/s40164-023-00415-0
title: 'A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2–4 weeks.
supporting_text: Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2–4 weeks.
evidence:
- reference: DOI:10.1186/s40164-023-00415-0
reference_title: 'A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2–4 weeks.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.1200/jco.22.01935
title: Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation.
supporting_text: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation.
evidence:
- reference: DOI:10.1200/jco.22.01935
reference_title: Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.17863/cam.95022
title: Iron homeostasis governs erythroid phenotype in polycythemia vera.
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Iron homeostasis governs erythroid phenotype in polycythemia vera
supporting_text: Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events.
evidence:
- reference: DOI:10.17863/cam.95022
reference_title: Iron homeostasis governs erythroid phenotype in polycythemia vera.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.3324/haematol.2025.300028
title: 'Preserving thrombosis and life years in polycythemia vera: start by reading the biology of the disease'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: The Swedish nationwide study by Leontyeva et al.
supporting_text: The Swedish nationwide study by Leontyeva et al.
evidence:
- reference: DOI:10.3324/haematol.2025.300028
reference_title: 'Preserving thrombosis and life years in polycythemia vera: start by reading the biology of the disease'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The Swedish nationwide study by Leontyeva et al.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.3390/cancers15143706
title: 'Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study'
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain.
supporting_text: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain.
evidence:
- reference: DOI:10.3390/cancers15143706
reference_title: 'Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.3390/jcm13164952
title: Impact of Phlebotomy on Quality of Life in Low-Risk Polycythemia Vera
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia.
supporting_text: Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia.
evidence:
- reference: DOI:10.3390/jcm13164952
reference_title: Impact of Phlebotomy on Quality of Life in Low-Risk Polycythemia Vera
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia.
explanation: Deep research cited this publication as relevant literature for Polycythemia Vera.
- reference: DOI:10.5603/ahp.102458
title: Recommendations of Polish Adult Leukemia Group concerning diagnostics and treatment of polycythemia vera
found_in:
- Polycythemia_Vera-deep-research-falcon.md
findings:
- statement: Recommendations of Polish Adult Leukemia Group concerning diagnostics and treatment of polycythemia vera
supporting_text: Recommendations of Polish Adult Leukemia Group concerning diagnostics and treatment of polycythemia vera
The evidence set supports “polycythemia vera” and “PV” as the primary naming; additional synonyms (e.g., “polycythaemia vera”) are not explicitly enumerated in the extracted texts.
This report is derived primarily from: - Aggregated guideline/review sources (e.g., American Journal of Hematology 2024 update; national recommendations) (tefferi2023polycythemiavera2024 pages 2-2, goratybor2024recommendationsofpolish pages 2-3). - Randomized trials (e.g., MAJIC-PV; Low-PV; REVIVE) (harrison2023ruxolitinibversusbest pages 1-2, barbui2023ropeginterferonversusstandard pages 1-2, kremyanskaya2024rusfertideahepcidin pages 1-2). - Real-world evidence / claims and EHR analyses (US claims; PV-NET; PV-AIM) (verstovsek2023realworldtreatmentsand pages 1-2, palandri2023predictorsofresponse pages 2-3).
Somatic clonal hematopoiesis driven by activating JAK2 mutations is central: JAK2V617F is present in ~97% of cases; ~3% have other JAK2 mutations including exon 12 (tefferi2023polycythemiavera2024 pages 2-2). Constitutive JAK/STAT activation is repeatedly emphasized as core biology underlying PV manifestations and complications (harrison2023ruxolitinibversusbest pages 1-2).
A 2023 genetic association study explicitly links iron regulation genetics (HFE) to PV diagnosis: - UK Biobank GWAS: 440 PV cases vs 403,351 controls; SNPs in HFE (known hemochromatosis variants) were “highly associated with PV diagnosis,” and FinnGen independently confirmed over-representation of homozygous HFE mutations in PV (bennett2023ironhomeostasisgoverns pages 1-7).
PV phenotype appears to interact strongly with systemic iron biology: - Venesection-induced iron restriction is common, and hepcidin biology modifies disease severity in JAK2V617F PV mouse models (hepcidin upregulation alleviates; hepcidin loss worsens), implying that genetic/physiologic regulation of iron handling can modify PV expression (bennett2023ironhomeostasisgoverns pages 1-7).
From a large 2023 disease update, at/before presentation PV is associated with (examples below): - Palpable splenomegaly: ~36% (tefferi2023polycythemiavera2024 pages 2-2) - Prior thrombosis: ~25% (arterial 15–16%; venous 8–13%) (tefferi2023polycythemiavera2024 pages 2-2) - Major hemorrhage: ~4% (tefferi2023polycythemiavera2024 pages 2-2) - Symptoms/microvascular disturbances: headache, visual disturbances, erythromelalgia, pruritus, splenomegaly discomfort; presentations vary from asymptomatic to thrombotic/bleeding events (tefferi2023polycythemiavera2024 pages 2-2)
A separate expert review notes splenomegaly in a minority in a specific cohort (≈27% any; 6% >5 cm in one series), illustrating variability by cohort/definition (silver2023polycythemiaveraaspects pages 1-3).
A 2024 review focused on low-risk PV reports substantial QoL impact: - ~80% report disease-related QoL impact; fatigue and sleep problems up to 79%; symptoms can include pruritus, pica, cognitive issues, falls, and poor exercise tolerance (visweshwar2024impactofphlebotomy pages 8-10). - Phlebotomy itself negatively affects QoL for many low-risk patients; ~25% reported negative QoL impact and up to 8% discontinued phlebotomy in one cited analysis (visweshwar2024impactofphlebotomy pages 8-10).
(Ontology mappings are suggested based on reported clinical features; the specific HPO IDs are not present in the evidence set and are therefore proposed as likely matches.) - Thrombosis (e.g., venous thrombosis; arterial thrombosis) - Pruritus - Splenomegaly - Headache - Erythromelalgia / microvascular disturbances - Leukocytosis, thrombocytosis, erythrocytosis / elevated hematocrit - Fatigue
Both a 2023 update and 2024 recommendations summarize frequent co-mutations: - Common: TET2 ~18%, ASXL1 ~15%, LNK ~3% (tefferi2023polycythemiavera2024 pages 7-8, goratybor2024recommendationsofpolish pages 2-3). - Adverse mutation sets (examples include SRSF2, IDH2, RUNX1, U2AF1) occur in a minority and are used in prognostic modeling (goratybor2024recommendationsofpolish pages 2-3, tefferi2023polycythemiavera2024 pages 7-8).
Robust, specific environmental exposures (toxins/radiation) were not captured in the retrieved evidence. Cardiovascular comorbidity burden is consistently emphasized as clinically relevant to outcomes and management (verstovsek2023realworldtreatmentsand pages 1-2, silver2023polycythemiaveraaspects pages 1-3).
(Suggested based on described mechanisms; GO IDs not present in evidence set.) - JAK-STAT cascade - Cytokine-mediated signaling pathway - Regulation of iron ion homeostasis / hepcidin-mediated signaling - Blood coagulation / thrombus formation - Inflammatory response - Neutrophil activation and degranulation; NET formation
(Suggested based on described mechanisms; CL IDs not present in evidence set.) - Hematopoietic stem and progenitor cells - Erythroid progenitors - Megakaryocytes/platelets - Neutrophils - Endothelial cells
Suggested UBERON (curated): bone marrow, spleen, blood, vascular endothelium.
PV is primarily a sporadic somatic clonal disorder (JAK2-driven), although germline susceptibility loci (e.g., HFE variants influencing iron regulation) may modify risk (tefferi2023polycythemiavera2024 pages 2-2, bennett2023ironhomeostasisgoverns pages 1-7).
A 2024 recommendation summarizing WHO 2022 states erythrocytosis thresholds: - Hb >16.5 g/dL (men), >16.0 g/dL (women) or Hct >49% (men), >48% (women) (goratybor2024recommendationsofpolish pages 2-3). - Bone marrow trephine showing panmyelosis is a WHO major criterion (goratybor2024recommendationsofpolish pages 2-3). - ICC allows omission of bone marrow in selected cases with very high Hb/Hct plus JAK2 mutation and low EPO (goratybor2024recommendationsofpolish pages 2-3).
Prevent thrombosis and manage symptom burden by maintaining hematocrit <45% and controlling blood counts and cardiovascular risk factors (verstovsek2023realworldtreatmentsand pages 1-2, barbui2023ropeginterferonversusstandard pages 1-2).
(MAXO IDs not present in evidence set; suggested as likely actions) - Therapeutic phlebotomy - Antiplatelet therapy (aspirin) - Cytoreductive therapy (hydroxyurea; interferon) - Janus kinase inhibitor therapy (ruxolitinib) - Hepcidin mimetic therapy / iron restriction therapy (rusfertide)
Primary prevention is not established (somatic clonal disorder), but secondary/tertiary prevention is central: - Maintain hematocrit <45% and manage cardiovascular risk factors to prevent thrombosis (verstovsek2023realworldtreatmentsand pages 1-2, goratybor2024recommendationsofpolish pages 2-3).
No naturally occurring PV analogue in non-human species was captured in the current evidence set.
The following table consolidates key identifiers, statistics, and major trial outcomes used throughout this report.
| Domain | Key facts/data | Source (PMID if present; otherwise DOI/journal) | Publication date | URL |
|---|---|---|---|---|
| Disease overview / classification | Polycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, microcirculatory symptoms, thrombosis risk, and progression to post-PV myelofibrosis or AML (tefferi2023polycythemiavera2024 pages 2-2, silver2023polycythemiaveraaspects pages 1-3) | DOI: 10.1002/ajh.27002; Am J Hematol / DOI: 10.1080/17474086.2023.2198698; Expert Rev Hematol | 2023-06 / 2023-04 | https://doi.org/10.1002/ajh.27002 ; https://doi.org/10.1080/17474086.2023.2198698 |
| Epidemiology | Sweden population-based age-standardized incidence: 1.48 per 100,000 person-years for PV (2000–2014) (tefferi2023polycythemiavera2024 pages 2-2) | DOI: 10.1002/ajh.27002; Am J Hematol | 2023-06 | https://doi.org/10.1002/ajh.27002 |
| Epidemiology | US prevalence estimate: 45–57 per 100,000 (verstovsek2023realworldtreatmentsand pages 1-2) | DOI: 10.1007/s00277-023-05089-6; Ann Hematol | 2023-01 | https://doi.org/10.1007/s00277-023-05089-6 |
| Molecular drivers | JAK2 V617F ~97% of PV; other JAK2 mutations including exon 12 ~3% (tefferi2023polycythemiavera2024 pages 2-2) | DOI: 10.1002/ajh.27002; Am J Hematol | 2023-06 | https://doi.org/10.1002/ajh.27002 |
| Additional molecular lesions | Most frequent additional mutations: TET2 18%, ASXL1 15%, LNK 3%; adverse mutations (e.g., SRSF2, IDH2, RUNX1, U2AF1) occur in a minority and inform prognosis (goratybor2024recommendationsofpolish pages 2-3, tefferi2023polycythemiavera2024 pages 7-8) | DOI: 10.5603/ahp.102458; Acta Haematol Pol / DOI: 10.1002/ajh.27002; Am J Hematol | 2024-12 / 2023-06 | https://doi.org/10.5603/ahp.102458 ; https://doi.org/10.1002/ajh.27002 |
| Diagnostic thresholds (WHO 2022) | Major erythrocytosis threshold: Hb >16.5 g/dL (men), >16.0 g/dL (women) or Hct >49% (men), >48% (women); bone marrow trephine with panmyelosis is a major criterion; low serum EPO is the minor criterion (goratybor2024recommendationsofpolish pages 2-3) | DOI: 10.5603/ahp.102458; Acta Haematol Pol | 2024-12 | https://doi.org/10.5603/ahp.102458 |
| Diagnostic nuance (ICC) | Bone marrow may be omitted in selected ICC cases with markedly elevated values: men Hb >18.5 g/dL or Hct >55.5%; women Hb >16.5 g/dL or Hct >49.5%, plus JAK2 mutation and low EPO (goratybor2024recommendationsofpolish pages 2-3) | DOI: 10.5603/ahp.102458; Acta Haematol Pol | 2024-12 | https://doi.org/10.5603/ahp.102458 |
| Risk stratification | Conventional thrombosis risk groups: low risk = age <60 years and no prior thrombosis; high risk = age ≥60 years and/or prior thrombosis (verstovsek2023realworldtreatmentsand pages 1-2) | DOI: 10.1007/s00277-023-05089-6; Ann Hematol | 2023-01 | https://doi.org/10.1007/s00277-023-05089-6 |
| Common complications at presentation | About 25% have prior thrombosis; 36% have palpable splenomegaly; major hemorrhage about 4% (tefferi2023polycythemiavera2024 pages 2-2) | DOI: 10.1002/ajh.27002; Am J Hematol | 2023-06 | https://doi.org/10.1002/ajh.27002 |
| Hematocrit target / vascular risk | Maintaining Hct <45% is standard; Hct ≥45% significantly increases vascular event/death risk (HR 3.91) (goratybor2024recommendationsofpolish pages 2-3, verstovsek2023realworldtreatmentsand pages 1-2) | DOI: 10.5603/ahp.102458; Acta Haematol Pol / DOI: 10.1007/s00277-023-05089-6; Ann Hematol | 2024-12 / 2023-01 | https://doi.org/10.5603/ahp.102458 ; https://doi.org/10.1007/s00277-023-05089-6 |
| Prognosis / MIPSS-PV | MIPSS-PV median overall survival: low risk 24 years, intermediate risk 13.1 years, high risk 3.2 years; variables include age, leukocytosis, thrombosis history/abnormal karyotype, and SRSF2 depending on model version summarized (goratybor2024recommendationsofpolish pages 2-3, tefferi2023polycythemiavera2024 pages 7-8) | DOI: 10.5603/ahp.102458; Acta Haematol Pol / DOI: 10.1002/ajh.27002; Am J Hematol | 2024-12 / 2023-06 | https://doi.org/10.5603/ahp.102458 ; https://doi.org/10.1002/ajh.27002 |
| Real-world outcomes (US claims) | Among 28,306 treated PV patients (Hct subgroup 4,246), most initiated phlebotomy alone; Hct control was suboptimal, with 54% of high-risk and 64% of low-risk patients on phlebotomy monotherapy sometimes/always >50% Hct; 16% had ≥1 thrombotic event after treatment initiation (20% high-risk, 8% low-risk) (verstovsek2023realworldtreatmentsand pages 1-2) | DOI: 10.1007/s00277-023-05089-6; Ann Hematol | 2023-01 | https://doi.org/10.1007/s00277-023-05089-6 |
| Low-risk ropeginterferon trial (Low-PV) | Randomized phase 2 Low-PV trial: primary endpoint met in 81% with ropeginterferon alfa-2b vs 51% standard therapy; at 24 months, maintained response 83% vs 59% (P=0.02); fewer moderate/severe symptoms (33% vs 67%) and less palpable splenomegaly (14% vs 37%); 7 ropeg patients discontinued for adverse events (barbui2023ropeginterferonversusstandard pages 1-2) | DOI: 10.1056/EVIDoa2200335; NEJM Evidence | 2023-05 | https://doi.org/10.1056/EVIDoa2200335 |
| Ropeginterferon phase 2 (rapid dosing) | Chinese phase 2 ropeginterferon alfa-2b 250–350–500 µg regimen in HU-resistant/intolerant PV: complete hematologic response 61.2% at week 24; JAK2 V617F allele burden declined by 17.8% ± 18.0% by week 24; 14.3% had reversible grade 3 drug-related AEs; no grade 4/5 AEs; no discontinuations due to AEs (kremyanskaya2024rusfertideahepcidin pages 1-2) | DOI: 10.1186/s40164-023-00415-0; Exp Hematol Oncol | 2023-06 | https://doi.org/10.1186/s40164-023-00415-0 |
| REVIVE rusfertide trial | REVIVE (NCT04057040): estimated phlebotomies/year fell from 8.7 ± 2.9 pre-rusfertide to 0.6 ± 1.0 during part 1; mean maximum Hct 44.5% ± 2.2 vs 50.0% ± 5.8 pre-treatment; randomized withdrawal response 60% rusfertide vs 17% placebo (P=0.002); grade 3 AEs 13%, no grade 4/5 events; grade 1–2 injection-site reactions common (kremyanskaya2024rusfertideahepcidin pages 1-2) | DOI: 10.1056/NEJMoa2308809; N Engl J Med | 2024-02 | https://doi.org/10.1056/NEJMoa2308809 |
| Rusfertide development context | Review summary of phase 2 studies: 84% achieved phlebotomy independence by 28 weeks in REVIVE/PACIFIC-related reporting; phase 3 underway (NCT05210790) (handa2023hepcidinmimeticsin pages 4-6, handa2023hepcidinmimeticsin pages 13-15) | DOI: 10.1097/MOH.0000000000000747; Curr Opin Hematol | 2023-12 | https://doi.org/10.1097/MOH.0000000000000747 |
| Hydroxyurea real-world response (PV-NET) | In 563 HU-treated PV patients: 29.5% complete response (166/563), 264 partial response, 133 non-response; among PR/NR patients, 71.3% (283/397) continued HU and 114 switched to ruxolitinib; predictors of CR included no splenomegaly, no pruritus, and HU dose ≥1 g/day (palandri2023predictorsofresponse pages 2-3) | DOI: 10.3390/cancers15143706; Cancers | 2023-07 | https://doi.org/10.3390/cancers15143706 |
| Ruxolitinib clinical activity (RuxoBEAT) | RuxoBEAT futility analysis (NCT02577926) in 28 untreated PV patients: median Hct 46% → 41% at 6 months; median phlebotomies/year 4.0 → 0; pruritus score 2 → 1; night sweats 1.5 → 0 trend; JAK2V617F allele burden significantly decreased; 109 AEs in 24/28 patients, all grade 1–3; no permanent discontinuation due to AEs (koschmieder2023efficacyandsafety pages 1-2) | DOI: 10.1007/s00277-022-05080-7; Ann Hematol | 2023-12 | https://doi.org/10.1007/s00277-022-05080-7 |
| Ruxolitinib benchmark after HU failure | In RESPONSE/RESPONSE-2/MAJIC-PV summaries: hematocrit/spleen control 60%/40% with ruxolitinib vs 20%/0.9% with BAT; RESPONSE-2 hematocrit superiority 62% vs 19%; MAJIC-PV CR 43% vs 26% with BAT (tefferi2023polycythemiavera2024 pages 13-13) | DOI: 10.1002/ajh.27002; Am J Hematol | 2023-06 | https://doi.org/10.1002/ajh.27002 |
Table: This table compiles high-yield quantitative findings and identifiers for polycythemia vera across epidemiology, molecular features, diagnosis, prognosis, and treatment studies. It is useful as a compact evidence map for rapid reference and knowledge-base curation.
References
(tefferi2023polycythemiavera2024 pages 2-2): Ayalew Tefferi and Tiziano Barbui. Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 98:1465-1487, Jun 2023. URL: https://doi.org/10.1002/ajh.27002, doi:10.1002/ajh.27002. This article has 254 citations and is from a domain leading peer-reviewed journal.
(silver2023polycythemiaveraaspects pages 1-3): Richard T Silver and Ghaith Abu-Zeinah. Polycythemia vera: aspects of its current diagnosis and initial treatment. Expert Review of Hematology, 16:253-266, Apr 2023. URL: https://doi.org/10.1080/17474086.2023.2198698, doi:10.1080/17474086.2023.2198698. This article has 8 citations and is from a peer-reviewed journal.
(goratybor2024recommendationsofpolish pages 2-3): Joanna Góra-Tybor, Tomasz Sacha, Maria Bieniaszewska, Marta Sobas, Krzysztof Lewandowski, Patryk Sobieralski, Olga Chyrko, and Aleksandra Gołos. Recommendations of polish adult leukemia group concerning diagnostics and treatment of polycythemia vera. Acta Haematologica Polonica, 55:289-305, Dec 2024. URL: https://doi.org/10.5603/ahp.102458, doi:10.5603/ahp.102458. This article has 5 citations.
(harrison2023ruxolitinibversusbest pages 1-2): Claire N. Harrison, Jyoti Nangalia, Rebecca Boucher, Aimee Jackson, Christina Yap, Jennifer O'Sullivan, Sonia Fox, Isaak Ailts, Amylou C. Dueck, Holly L. Geyer, Ruben A. Mesa, William G. Dunn, Eugene Nadezhdin, Natalia Curto-Garcia, Anna Green, Bridget Wilkins, Jason Coppell, John Laurie, Mamta Garg, Joanne Ewing, Steven Knapper, Josephine Crowe, Frederick Chen, Ioannis Koutsavlis, Anna Godfrey, Siamak Arami, Mark Drummond, Jennifer Byrne, Fiona Clark, Carolyn Mead-Harvey, Elizabeth Joanna Baxter, Mary Frances McMullin, and Adam J. Mead. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. Journal of Clinical Oncology, 41:3534-3544, Jul 2023. URL: https://doi.org/10.1200/jco.22.01935, doi:10.1200/jco.22.01935. This article has 162 citations and is from a highest quality peer-reviewed journal.
(barbui2023ropeginterferonversusstandard pages 1-2): Tiziano Barbui, Alessandro Maria Vannucchi, Valerio De Stefano, Alessandra Carobbio, Arianna Ghirardi, Greta Carioli, Arianna Masciulli, Elena Rossi, Fabio Ciceri, Massimiliano Bonifacio, Alessandra Iurlo, Francesca Palandri, Giulia Benevolo, Fabrizio Pane, Alessandra Ricco, Giuseppe Carli, Marianna Caramella, Davide Rapezzi, Caterina Musolino, Sergio Siragusa, Elisa Rumi, Andrea Patriarca, Nicola Cascavilla, Barbara Mora, Emma Cacciola, Carmela Mannarelli, Giuseppe Gaetano Loscocco, Paola Guglielmelli, Francesca Gesullo, Silvia Betti, Francesca Lunghi, Luigi Scaffidi, Cristina Bucelli, Nicola Vianelli, Marta Bellini, Maria Chiara Finazzi, Gianni Tognoni, and Alessandro Rambaldi. Ropeginterferon versus standard therapy for low-risk patients with polycythemia vera. NEJM Evidence, May 2023. URL: https://doi.org/10.1056/evidoa2200335, doi:10.1056/evidoa2200335. This article has 62 citations and is from a peer-reviewed journal.
(kremyanskaya2024rusfertideahepcidin pages 1-2): Marina Kremyanskaya, Andrew T. Kuykendall, Naveen Pemmaraju, Ellen K. Ritchie, Jason Gotlib, Aaron Gerds, Jeanne Palmer, Kristen Pettit, Uttam K. Nath, Abdulraheem Yacoub, Arturo Molina, Samuel R. Saks, Nishit B. Modi, Frank H. Valone, Sarita Khanna, Suneel Gupta, Srdan Verstovsek, Yelena Z. Ginzburg, and Ronald Hoffman. Rusfertide, a hepcidin mimetic, for control of erythrocytosis in polycythemia vera. The New England journal of medicine, 390 8:723-735, Feb 2024. URL: https://doi.org/10.1056/nejmoa2308809, doi:10.1056/nejmoa2308809. This article has 56 citations and is from a highest quality peer-reviewed journal.
(verstovsek2023realworldtreatmentsand pages 1-2): Srdan Verstovsek, Naveen Pemmaraju, Nancy L. Reaven, Susan E. Funk, Tracy Woody, Frank Valone, and Suneel Gupta. Real-world treatments and thrombotic events in polycythemia vera patients in the usa. Annals of Hematology, 102:571-581, Jan 2023. URL: https://doi.org/10.1007/s00277-023-05089-6, doi:10.1007/s00277-023-05089-6. This article has 28 citations and is from a peer-reviewed journal.
(palandri2023predictorsofresponse pages 2-3): Francesca Palandri, Elena Rossi, Giuseppe Auteri, Massimo Breccia, Simona Paglia, Giulia Benevolo, Elena M. Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Nicola Polverelli, Sara Ceglie, Camilla Mazzoni, Rikard Mullai, Alessia Ripamonti, Bruno Garibaldi, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Giuseppe A. Palumbo, Alessandro Andriani, Michele Cavo, Roberto Latagliata, and Valerio De Stefano. Predictors of response to hydroxyurea and switch to ruxolitinib in hu-resistant polycythaemia vera patients: a real-world pv-net study. Cancers, 15:3706, Jul 2023. URL: https://doi.org/10.3390/cancers15143706, doi:10.3390/cancers15143706. This article has 13 citations.
(bennett2023ironhomeostasisgoverns pages 1-7): Cavan Bennett, Victoria E Jackson, Anne Pettikiriarachchi, Thomas Hayman, Ute Schaeper, Gemma Moir-Meyer, Katherine Fielding, Ricardo Ataide, Danielle Clucas, Andrew Baldi, Alexandra L Garnham, Connie SN Li-Wai-Suen, Stephen J Loughran, E Joanna Baxter, Anthony R Green, Warren S Alexander, Melanie Bahlo, Kate Burbury, Ashley P Ng, and Sant-Rayn Pasricha. Iron homeostasis governs erythroid phenotype in polycythemia vera. JournalArticle, Mar 2023. URL: https://doi.org/10.17863/cam.95022, doi:10.17863/cam.95022. This article has 17 citations.
(visweshwar2024impactofphlebotomy pages 8-10): Nathan Visweshwar, Bradley Fletcher, Michael Jaglal, Damian A. Laber, Ankita Patel, Jennifer Eatrides, Geetha Rajasekharan Rathnakumar, Keshav Visweswaran Iyer, Irmel Ayala, and Arumugam Manoharan. Impact of phlebotomy on quality of life in low-risk polycythemia vera. Journal of Clinical Medicine, 13:4952, Aug 2024. URL: https://doi.org/10.3390/jcm13164952, doi:10.3390/jcm13164952. This article has 5 citations.
(tefferi2023polycythemiavera2024 pages 7-8): Ayalew Tefferi and Tiziano Barbui. Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 98:1465-1487, Jun 2023. URL: https://doi.org/10.1002/ajh.27002, doi:10.1002/ajh.27002. This article has 254 citations and is from a domain leading peer-reviewed journal.
(barbui2026preservingthrombosisand pages 13-15): Tiziano Barbui, Arianna Ghirardi, Annalisa Condorelli, and Marta Sobas. Preserving thrombosis and life years in polycythemia vera: start by reading the biology of the disease. Haematologica, Feb 2026. URL: https://doi.org/10.3324/haematol.2025.300028, doi:10.3324/haematol.2025.300028. This article has 0 citations.
(koschmieder2023efficacyandsafety pages 1-2): Steffen Koschmieder, Susanne Isfort, Dominik Wolf, Florian H. Heidel, Andreas Hochhaus, Philippe Schafhausen, Martin Griesshammer, Denise Wolleschak, Uwe Platzbecker, Konstanze Döhner, Philipp J. Jost, Stefani Parmentier, Markus Schaich, Nikolas von Bubnoff, Frank Stegelmann, Angela Maurer, Martina Crysandt, Deniz Gezer, Maike Kortmann, Jeremy Franklin, Julia Frank, Martin Hellmich, and Tim H. Brümmendorf. Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the ruxobeat clinical trial of the gsg-mpn study group. Annals of Hematology, 102:349-358, Dec 2023. URL: https://doi.org/10.1007/s00277-022-05080-7, doi:10.1007/s00277-022-05080-7. This article has 11 citations and is from a peer-reviewed journal.
(handa2023hepcidinmimeticsin pages 4-6): Shivani Handa, Yelena Ginzburg, Ronald Hoffman, and Marina Kremyanskaya. Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis. Current Opinion in Hematology, 30:45-52, Dec 2023. URL: https://doi.org/10.1097/moh.0000000000000747, doi:10.1097/moh.0000000000000747. This article has 29 citations and is from a peer-reviewed journal.
(handa2023hepcidinmimeticsin pages 13-15): Shivani Handa, Yelena Ginzburg, Ronald Hoffman, and Marina Kremyanskaya. Hepcidin mimetics in polycythemia vera: resolving the irony of iron deficiency and erythrocytosis. Current Opinion in Hematology, 30:45-52, Dec 2023. URL: https://doi.org/10.1097/moh.0000000000000747, doi:10.1097/moh.0000000000000747. This article has 29 citations and is from a peer-reviewed journal.
(tefferi2023polycythemiavera2024 pages 13-13): Ayalew Tefferi and Tiziano Barbui. Polycythemia vera: 2024 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 98:1465-1487, Jun 2023. URL: https://doi.org/10.1002/ajh.27002, doi:10.1002/ajh.27002. This article has 254 citations and is from a domain leading peer-reviewed journal.