Polycythemia (Small Group Session 23)

Question 1

What are some possible causes for relative polycythemia?

Answer 1

Relative Polycythemia causes:

• Dehydration
• Diuretics
• Smoking
• Obesity, hypertension
• Gaisbock’s Polycythemia (middle-aged, obese, male, smoker)
• Testosterone replacements
• EPO doping

Relative polycythemia is due to plasma volume contraction. It is not a true rise in hemoglobin.

Question 2

How is a RBC mass study performed? What information does it provide?

Answer 2

Red cell mass and plasma volume studies

• Used to distinguish true polycythemia from relative polycythemia
• Only needed if hematocrit minimally increased
• Not necessary when Hct >0.60 (men), >0.55 (women)

Process

• RBC are labeled with 51CR
• A known amount of radioactive cells is injected
• After allowing time for mixing, the radioactivity of the RBCs in a sample of the blood is determined
• Since you know the starting volume and concentration of isotope, the final diluted concentration can be used to calculate total body red cell mass
• Albumin labeled with 125I is used to measure plasma volume by the same principle

Question 3

A 62 yr old retired farmer is referred to you with daily headaches. The headaches started 2 months ago. He also has the occasional dizzy spell.

PHx: Unremarkable. He smokes 1/2 pack of cigarettes per day and drinks 2 alcoholic beverages/day.

PE: BP 120/80 HR 80 and regular, normal temp. Head and neck exam is remarkable for plethora. Chest clear to both bases w/ no abnormal sounds. Cardiac exam is unremarkable. Abdomen is soft, non-tender, with dullness over Traube’s space. No masses were felt.

Investigations: Hb 190 g/L (140-180), MCV 78 fL (76-98), Hematocrit 55% (0.40-0.54), platelets 440 x 10⁹/L, WBC 9.0 x 10⁹/L with a normal differential.

What further investigations should be ordered to make a diagnosis?

Answer 3

R/O Relative Polycythemia

• Red cell mass and plasma volume studies

Secondary Polycythemia

• Oxy-hemoglobin dissociation curve (P50 determination)
• Abdominal U/S
• Urinalysis for microscopic blood
• CXR
• ECG

Primary Polycythemia

• JAK-2
• EPO levels (low in primary polycythemia, high in secondary polycythemia, and normal in relative polycythemia)
• Bone marrow biopsy (looking for hypercellular bone marrow (all three cell lines, low or absent iron stores = low MCV)

Question 4

A 62 yr old retired farmer is referred to you with daily headaches. The headaches started 2 months ago. He also has the occasional dizzy spell.

PHx: Unremarkable. He smokes 1/2 pack of cigarettes per day and drinks 2 alcoholic beverages/day.

PE: BP 120/80 HR 80 and regular, normal temp. Head and neck exam is remarkable for plethora. Chest clear to both bases w/ no abnormal sounds. Cardiac exam is unremarkable. Abdomen is soft, non-tender, with dullness over Traube’s space. No masses were felt.

Investigations: Hb 190 g/L (140-180), MCV 78 fL (76-98), Hematocrit 55% (0.40-0.54), platelets 440 x 109/L, WBC 9.0 x 109/L with a normal differential.

The patient quits smoking for 1 month and returns to the clinic with a hemoglobin of 195 g/L. What do you now suspect is the reason for the increase in hemoglobin? What testing do you order?

Answer 4

This could be a result of primary polycythemia - polycythemia vera. Testing to confirm this diagnosis includes EPO level (PV EPO = low), JAK-2 (PV = JAK-2 +), Bone marrow biopsy (looking for hypercellular bone marrow).

Question 5

A 62 yr old retired farmer is referred to you with daily headaches. The headaches started 2 months ago. He also has the occasional dizzy spell.

PHx: Unremarkable. He smokes 1/2 pack of cigarettes per day and drinks 2 alcoholic beverages/day.

PE: BP 120/80 HR 80 and regular, normal temp. Head and neck exam is remarkable for plethora. Chest clear to both bases w/ no abnormal sounds. Cardiac exam is unremarkable. Abdomen is soft, non-tender, with dullness over Traube’s space. No masses were felt.

Investigations: Hb 190 g/L (140-180), MCV 78 fL (76-98), Hematocrit 55% (0.40-0.54), platelets 440 x 109/L, WBC 9.0 x 109/L with a normal differential.

The patient quits smoking for 1 month and returns to the clinic with a hemoglobin of 195 g/L.

Why are the platelets elevated?

Answer 5

This patient likely has a clonal stem cell disorder (PV) that affects myeloid cell lines. This causes hyperproliferation in the bone marrow (JAK-2 receptor is always on, don’t need EPO). Iron deficiency can also cause an increase in platelets.

JAK-2 is a “gain of function” mutation and it is acquired

• Normal EPO receptor is inactive - JH1 is inhibited by JH2
• With EPO binding, conformational changes release JH1 from inhibition
• With the JAK2 mutation, JH2 does not inhibit JH1 so the receptor is active w/o EPO binding

Question 6

What are the clinical features of polycythemia vera?

Answer 6

PV clinical features are secondary to high red cell mass and hyperviscosity

• Bleeding complications: epistaxis, gingival bleeding, ecchymoses, and GI bleeding
  
  • Due to platelet abnormalities
• Thrombotic complications: DVT, PE, thrombophlebitis, increased incidence of stroke, MI
  
  • Due to increased blood viscosity, increased platelet number and/or activity
• Erythromelalgia (burning pain in hands and feet and erythema of the skin)
  
  • Associated with platelets >400 x 10⁹/L
  • Pathognomonic microvascular thrombotic complications in PV and ET
• Pruritus, especially after warm bath or shower
  
  • Due to cutaneous and mast cell degranulation and histamine release
• Epigastric distress, PUD
  
  • Due to increased histamine from tissue basophils, alterations in gastric mucosal blood flow due to increased blood viscosity
• Gout (hyperuricemia)
  
  • Due to increased cell turnover
• Characteristic physical findings
  
  • Plethora of face and plams
  • Splenomegaly, hepatomegaly

Question 7

What treatment modalities are available for PV?

Answer 7

Phlebotomy to keep hct <0.45

• May require frequent phlebotomies initially
• Eventually patients become iron deficient - limits RBC production; do NOT replace iron

Low dose ASA

• Show to reduce thrombotic events but slight increase in bleeding
• Used if no contraindications

Hydroxyurea

• Oral chemotherapy
• Recommended for all high risk pts
• Reduces risk of thrombosis
  
  • Lowers platelets/RBC
  • Decreased phlebotomy needs
• Alternates include interferon, busulfan, anegralide

Question 8

Explain the risk assessment of PV patients and how that directs their treatment as per the table provided.

Answer 8

Question 9

What are the findings in bone marrow in pts with PV?

Answer 9

• Bone marrow in PV is hypercellular, hyperplastic
• There are ++RBCs and megakaryocytes
• PV is extremely proliferative