Hematology Oncology · Year 2 · from Hematology Oncology

Case 1: Polycythemia Vera with Thrombosis

Patient Presentation

Demographics: 58-year-old male

Chief Complaint: Headache, facial plethora, and pruritus after showers

History of Present Illness: The patient has had progressive headaches and dizziness for 3 months. He noticed his face appears increasingly red. He reports intense itching after hot showers (aquagenic pruritus). Two weeks ago, he experienced transient vision loss in his right eye lasting 5 minutes. He also mentions burning pain in his fingers and toes.

Past Medical History:

  • Hypertension
  • No prior hematologic disease

Physical Examination:

  • Blood pressure: 162/98 mmHg
  • Heart rate: 78 bpm
  • General: Ruddy, plethoric facies
  • HEENT: Conjunctival injection
  • Cardiac: Regular, no murmurs
  • Abdomen: Splenomegaly (3 cm below costal margin)
  • Extremities: Erythromelalgia (red, warm fingers with burning sensation)

Workup and Results

Laboratory Studies:

  • Hemoglobin: 19.8 g/dL
  • Hematocrit: 59%
  • WBC: 14,200/mcL
  • Platelets: 485,000/mcL
  • Erythropoietin: <1.0 mU/mL (suppressed)

Molecular Testing:

  • JAK2 V617F mutation: Positive

Bone Marrow Biopsy:

  • Hypercellular with trilineage hyperplasia
  • Panmyelosis
  • Clustered, enlarged megakaryocytes

Clinical Image

Facial photograph demonstrating plethoric (ruddy) appearance characteristic of polycythemia vera due to increased red cell mass, along with conjunctival injection.

Diagnosis

Polycythemia Vera with Amaurosis Fugax (High-Risk)

WHO 2016 Diagnostic Criteria Met:

  • Major: Hemoglobin >16.5 g/dL (men)
  • Major: Bone marrow panmyelosis
  • Major: JAK2 V617F mutation
  • Minor: Suppressed erythropoietin

High-risk features: Age >60, history of thrombosis (amaurosis fugax)

Discussion

This case illustrates polycythemia vera:

  • JAK2 V617F Mutation: The lecture states that JAK2 V617F is present in 95% of PV cases. This gain-of-function mutation causes constitutive activation of JAK2 signaling, leading to erythropoietin-independent erythropoiesis.
  • Suppressed EPO: The lecture explains that serum erythropoietin is low/suppressed in PV, distinguishing it from secondary polycythemia where EPO is elevated (hypoxia, EPO-secreting tumors).
  • Aquagenic Pruritus: The lecture describes this characteristic symptom triggered by warm water or showers. It's thought to be related to mast cell degranulation.
  • Thrombosis Risk: The lecture emphasizes that thrombosis is the major cause of morbidity in PV. Both arterial (stroke, MI, amaurosis fugax) and venous (DVT, Budd-Chiari) events occur at increased rates.

Treatment Plan

  1. Phlebotomy:
  • Target hematocrit <45%
  • Continue until iron deficiency develops
  • CURE trial showed benefit of lower hematocrit target
  1. Low-Dose Aspirin:
  • 81-100 mg daily (unless contraindicated)
  • Reduces thrombotic events
  1. Cytoreductive Therapy (High-Risk):
  • Hydroxyurea first-line (500-1000 mg daily)
  • Target: Normalized counts and hematocrit <45%
  1. Management of Specific Symptoms:
  • Erythromelalgia: Aspirin typically effective
  • Pruritus: Antihistamines, SSRIs, ruxolitinib if refractory
  1. Monitoring:
  • CBC every 1-3 months
  • Watch for transformation to myelofibrosis or AML

Teaching Points

  1. JAK2 V617F is present in 95% of PV
  2. Suppressed EPO distinguishes PV from secondary polycythemia
  3. Target hematocrit is <45% (phlebotomy is cornerstone)
  4. High-risk (age >60 OR prior thrombosis) requires cytoreduction
  5. Transformation to myelofibrosis occurs in 15-20% at 15 years

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