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Internal MedicineHematologyElevated Hemoglobin

Elevated Hemoglobin (Erythrocytosis)

Introduction to MCCQE1 Objectives

For the MCCQE1, understanding Elevated Hemoglobin (often referred to as Erythrocytosis or Polycythemia) is crucial for the Internal Medicine and Hematology sections. Candidates are expected to demonstrate the CanMEDS Medical Expert role by differentiating between relative, primary, and secondary causes, and by applying appropriate diagnostic algorithms within the Canadian healthcare context.

Elevated hemoglobin is defined as a hemoglobin concentration greater than the upper limit of normal for the patient’s age and sex.

MCCQE1 Definition Thresholds

While local lab reference ranges vary, general thresholds for further investigation in an adult context are:

  • Men: Hemoglobin >165 g/L or Hematocrit >0.49
  • Women: Hemoglobin >160 g/L or Hematocrit >0.48

Terminology and Classification

Understanding the nomenclature is the first step in the diagnostic workup.

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Polycythemia vs. Erythrocytosis: Strictly speaking, Polycythemia refers to an increase in all myeloid cell lines (red blood cells, white blood cells, and platelets), whereas Erythrocytosis refers specifically to increased red blood cell (RBC) mass. However, in clinical practice and on exams, these terms are often used interchangeably to describe elevated hemoglobin.

Classification of Erythrocytosis

The differential diagnosis is best approached by categorizing the condition into Relative (Spurious) or Absolute (True) erythrocytosis.

Definition: Elevated hemoglobin/hematocrit due to a decrease in plasma volume, while the red cell mass remains normal.

Common Causes:

  • Dehydration: Diuretics, vomiting, diarrhea, alcohol intake.
  • Gaisböck Syndrome: Also known as “stress polycythemia,” typically seen in hypertensive, obese, male smokers.

MCCQE1 Tip: Look for signs of volume contraction (tachycardia, hypotension, dry mucous membranes) in the clinical vignette.

Clinical Presentation

Patients may be asymptomatic (incidental finding) or present with symptoms related to hyperviscosity or the underlying cause.

Hyperviscosity Symptoms

When Hematocrit rises (typically >0.55–0.60), blood viscosity increases, leading to:

  • Headache, dizziness, tinnitus, blurred vision.
  • Fatigue, lethargy.
  • Transient Ischemic Attacks (TIAs).

Specific Polycythemia Vera (PV) Features

  • Aquagenic Pruritus: Intense itching after a hot shower (classic MCCQE1 buzzword).
  • Erythromelalgia: Burning pain and erythema in the hands and feet.
  • Splenomegaly: Early satiety, left upper quadrant fullness.
  • Thrombosis: Arterial (stroke, MI) or venous (DVT, PE, Budd-Chiari syndrome).

Diagnostic Approach

The diagnostic workup for elevated hemoglobin is a classic “Branching Logic” problem on the MCCQE1.

Step 1: Confirm the Elevation

Repeat the CBC to rule out lab error or transient dehydration. Ensure hydration status is optimized before repeating.

Step 2: History and Physical Exam

  • History: Smoking status (pack-years), snoring/daytime somnolence (OSA), residence at altitude, history of renal disease, family history.
  • Physical: Oxygen saturation (pulse oximetry), BMI, blood pressure, abdominal exam (splenomegaly, renal masses), skin exam (plethora).

Step 3: Measure Serum Erythropoietin (EPO) level

This is the critical pivot point in the algorithm.

  • Low EPO: Suggests Primary Erythrocytosis (Polycythemia Vera). The marrow is producing RBCs despite no signal.
  • High (or Normal) EPO: Suggests Secondary Erythrocytosis. The marrow is responding to a signal.

Step 4: Targeted Testing based on EPO

  • If EPO is Low:
    • Test for JAK2 V617F mutation.
    • If positive →\rightarrow Polycythemia Vera.
    • If negative →\rightarrow Consider Exon 12 mutation or other MPNs.
  • If EPO is High/Normal:
    • Assess for Hypoxia: Arterial Blood Gas (ABG) includes Carboxyhemoglobin (smokers), Sleep study (OSA).
    • Assess for Tumors: Abdominal Ultrasound or CT (Renal/Liver masses).

Management and Treatment

Management depends entirely on the etiology.

1. Relative Erythrocytosis

  • Rehydration.
  • Modification of risk factors (weight loss, hypertension control, smoking cessation).

2. Secondary Erythrocytosis

  • Treat the underlying cause:
    • Smoking cessation.
    • CPAP for Obstructive Sleep Apnea.
    • Oxygen therapy for chronic hypoxia (if indicated).
    • Surgical resection of EPO-producing tumors.
  • Note: Phlebotomy is generally reserved for patients with symptoms of hyperviscosity in this group, not just to lower the number.

3. Polycythemia Vera (Primary)

The goal is to prevent thrombotic and hemorrhagic complications.

First Line Therapy

  • Phlebotomy: Target Hematocrit <0.45 (for both men and women).
  • Low-dose Aspirin (81 mg): Unless contraindicated, to reduce thrombotic risk.

Cytoreductive Therapy

Indicated for high-risk patients (Age >60 OR history of thrombosis).

  • Hydroxyurea: Most common first-line cytoreductive agent.
  • Interferon-alpha: Option for younger patients or pregnancy.
  • Ruxolitinib: JAK1/2 inhibitor for resistant cases.

Canadian Guidelines & Context

  • Choosing Wisely Canada: While specific “don’t” lists for erythrocytosis are limited, the general principle applies: Do not order JAK2 testing indiscriminately. It should be reserved for patients with sustained absolute erythrocytosis and low/subnormal EPO levels, or strong clinical suspicion of MPN (e.g., splenomegaly, thrombosis).
  • Canadian MPN Group: Recommends strict hematocrit control (<0.45) for PV patients to reduce cardiovascular death and major thrombosis.
  • Epidemiology: In the Canadian context, always consider COPD and OSA as leading causes of secondary erythrocytosis due to population prevalence. In rural/remote areas, consider access to phlebotomy services when planning management.

Key Points to Remember for MCCQE1

  • Mnemonics:
    • 5 P’s of Polycythemia Vera: Plethora (red face), Pruritus (aquagenic), Painful extremities (erythromelalgia), Popped vessels (thrombosis), Palpable spleen.
  • Spurious vs. True: Always rule out dehydration first.
  • The EPO Split: The most useful initial test to differentiate primary from secondary causes is the Serum EPO level.
  • Carboxyhemoglobin: Don’t forget to check this in smokers; smoking causes functional hypoxia leading to secondary erythrocytosis.
  • Target Hct: For PV, the magic number is <0.45.

Sample Question

Clinical Scenario

A 62-year-old male presents to his family physician with complaints of generalized fatigue and frequent headaches over the past 3 months. He also mentions intense itching all over his body after taking hot showers. He has no history of lung disease but has treated hypertension. He is a non-smoker.

Physical Examination:

  • BP: 150/90 mmHg
  • HR: 78 bpm
  • O2 Sat: 98% on room air
  • Abdomen: Palpable spleen tip 4 cm below the left costal margin.
  • Skin: Ruddy complexion (facial plethora).

Laboratory Results:

  • Hemoglobin: 195 g/L (N: 135–175)
  • Hematocrit: 0.58 (N: 0.41–0.50)
  • WBC: 14.5 x 10^9/L (N: 4.5–11.0)
  • Platelets: 550 x 10^9/L (N: 150–400)

Which of the following is the most appropriate next step to confirm the likely diagnosis?

Options

  • A. Bone marrow biopsy
  • B. Arterial blood gas analysis
  • C. Serum erythropoietin (EPO) level
  • D. Testing for JAK2 V617F mutation
  • E. Abdominal CT scan

Explanation

The correct answer is:

  • C. Serum erythropoietin (EPO) level

Detailed Explanation:

This patient presents with classic signs and symptoms of Polycythemia Vera (PV): elevated hemoglobin, pan-myelosis (elevated WBC and platelets), splenomegaly, facial plethora, and the highly specific symptom of aquagenic pruritus.

  1. Serum EPO (Option C): This is the correct initial investigation to differentiate between primary and secondary erythrocytosis. In PV (Primary), EPO levels are typically low or suppressed because the bone marrow is producing RBCs autonomously, signaling the kidneys to stop producing EPO. In secondary causes (like hypoxia or tumors), EPO would be elevated or normal.
  2. JAK2 V617F (Option D): While testing for the JAK2 mutation is the definitive diagnostic test for PV, the diagnostic algorithm typically starts with EPO. If EPO is low, JAK2 testing is then automatically indicated. However, on the MCCQE1, if asked for the next step to differentiate etiology, EPO is often the primary branch point. Note: In some modern clinical pathways, EPO and JAK2 are ordered simultaneously, but conceptually, confirming the EPO status directs the genetic testing.
  3. Bone Marrow Biopsy (Option A): This is a major criterion for diagnosis but is invasive and usually performed after EPO and JAK2 testing have established a high likelihood of an MPN.
  4. Arterial Blood Gas (Option B): This would be appropriate if you suspected hypoxia (Secondary Erythrocytosis), but the patient has normal O2 saturation (98%) and clinical features strongly suggestive of PV.
  5. Abdominal CT (Option E): Used to look for EPO-secreting tumors (RCC/HCC) if EPO were found to be high.

Takeaway: In the workup of erythrocytosis, Serum EPO is the gatekeeper test that distinguishes Primary (Low EPO) from Secondary (High/Normal EPO) causes.

References

  1. Medical Council of Canada. MCCQE Part I Objectives: Hematologic Illness. Available at: mcc.ca 
  2. McMullin MF, et al. A guideline for the diagnosis and management of polycythaemia vera. British Journal of Haematology. 2019.
  3. UpToDate. Diagnostic approach to the patient with polycythemia (erythrocytosis). Accessed 2023.
  4. Canadian MPN Group. Management Guidelines for Myeloproliferative Neoplasms.
  5. Choosing Wisely Canada. Hematology Recommendations. Available at: choosingwiselycanada.org 
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