skip to main content
usmle step 2 ck

Polycythemia Vera & Myeloproliferative Neoplasms

Clonal myeloid disorders including polycythemia vera, essential thrombocythemia, and myelofibrosis, often driven by JAK2/CALR/MPL mutations and complicated by thrombosis

Review date
reviewed 2026-05-04
Reading time
9 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Hematology & Oncologyless-commonlong-term-condition
On this page
Condition details
Hematology & Oncology
less-common
9 min read
reviewed 2026-05-04
practice step 2 ck questions →

About This Page

This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

  • Polycythemia vera is clonal erythrocytosis usually caused by JAK2 mutation and low erythropoietin
  • Classic symptoms include aquagenic pruritus, erythromelalgia, headache, visual symptoms, and thrombosis
  • PV treatment target is hematocrit <45% with phlebotomy plus low-dose aspirin unless contraindicated
  • High-risk PV or ET usually means age >60 or prior thrombosis; cytoreduction with hydroxyurea is common
  • Myelofibrosis presents with splenomegaly, constitutional symptoms, teardrop cells, and dry tap marrow

Overview

Myeloproliferative neoplasms are clonal disorders with overproduction of mature myeloid cells. Philadelphia chromosome-negative MPNs include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2 V617F is common in PV and many ET/myelofibrosis cases; CALR and MPL mutations also occur.

Epidemiology

MPNs are uncommon and usually present in middle-aged to older adults. PV and ET have long survival but significant thrombotic risk. Secondary erythrocytosis is much more common than PV and is driven by hypoxia, smoking, sleep apnea, testosterone, or EPO-producing tumors.

Clinical Features

Symptoms
Headache, dizziness, visual disturbance, tinnitus
Aquagenic pruritus after hot shower in PV
Erythromelalgia: burning red painful hands or feet
Thrombosis: stroke, MI, Budd-Chiari syndrome, DVT/PE
Myelofibrosis: weight loss, night sweats, early satiety from splenomegaly
Signs
Plethora, hypertension, splenomegaly
Hepatosplenomegaly in myelofibrosis
Digital ischemia or neurologic deficits from thrombosis
Bleeding can occur with extreme thrombocytosis due to acquired vWD

Investigations

First-line
CBC with differentialPV: elevated hemoglobin/hematocrit often with leukocytosis/thrombocytosis. ET: isolated thrombocytosis
Erythropoietin levelLow EPO supports PV; high EPO suggests secondary erythrocytosis
JAK2 V617F testingPositive in most PV and many ET/myelofibrosis cases
Second-line
CALR and MPL mutation testingUsed when JAK2 negative and ET/myelofibrosis suspected
Peripheral smearTeardrop cells and leukoerythroblastosis suggest myelofibrosis
Oxygen saturation, carboxyhemoglobin, sleep apnea evaluationEvaluate secondary erythrocytosis when EPO is high or JAK2 negative
Specialist
Bone marrow biopsyRequired for many MPN diagnoses and fibrosis assessment; dry tap suggests myelofibrosis
vWF testingExtreme thrombocytosis with bleeding suggests acquired von Willebrand syndrome

Management

NCCN Guidelines for Myeloproliferative Neoplasms
1
Polycythemia vera
  • Phlebotomy to maintain hematocrit <45%
  • Low-dose aspirin unless contraindicated
  • Hydroxyurea for high-risk patients, frequent phlebotomy need, symptomatic splenomegaly, or uncontrolled counts
2
Essential thrombocythemia
  • Risk stratify by age, thrombosis history, JAK2 status, and cardiovascular risk
  • Low-dose aspirin for many patients, especially microvascular symptoms
  • Hydroxyurea for high-risk ET; interferon often preferred in pregnancy or younger selected patients
3
Myelofibrosis
  • JAK inhibitors such as ruxolitinib or fedratinib for symptomatic splenomegaly/constitutional symptoms
  • Transfusion and anemia-directed support
  • Allogeneic stem cell transplant for selected higher-risk patients

Complications

  • Thrombosis: Arterial and venous events, including Budd-Chiari syndrome
  • Bleeding: Especially acquired vWD with extreme thrombocytosis
  • Progression: PV/ET can evolve to myelofibrosis or AML
  • Splenic infarction or massive splenomegaly: Particularly myelofibrosis
USMLE Step 2 CK Exam Tips
  • 1PV: high hematocrit + low EPO + JAK2 mutation
  • 2Secondary erythrocytosis: high EPO from hypoxia or EPO-producing tumor
  • 3Aquagenic pruritus and erythromelalgia are classic PV clues
  • 4PV treatment goal: hematocrit <45%
  • 5Teardrop cells + massive splenomegaly + dry tap = myelofibrosis
  • 6CML is Philadelphia chromosome-positive; PV/ET/myelofibrosis are usually Philadelphia-negative
  • 7Extreme thrombocytosis can cause acquired vWD and bleeding

Put your reading into practice

Topic-specific question practice is not linked for this article yet.

Choose USMLE Step 2 CK questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.

Choose USMLE Step 2 CK practice

After your session, return to this section to revisit the reading and choose your next review.

Verified Sources & References

NCCN Clinical Practice Guidelines in Oncology
Your learning path

Save your place and choose what comes next

sign in to save your learning

Hematology & Oncology · Article 21 of 24