Elevated Hemoglobin

Introduction

Elevated hemoglobin, also known as erythrocytosis or polycythemia, is a critical topic for the MCCQE1 exam. This comprehensive guide will help Canadian medical students understand the causes, diagnosis, and management of elevated hemoglobin, with a focus on Canadian healthcare practices and guidelines.

Definition and Classification

Elevated hemoglobin is defined as a hemoglobin concentration above the normal range for age and sex. In Canada, the general reference ranges are:

• Adult males: >175 g/L
• Adult females: >155 g/L

Etiology

Understanding the causes of elevated hemoglobin is crucial for MCCQE1 success. Here's a comprehensive list:

1. Primary Polycythemia (Polycythemia Vera)

   • JAK2 mutation (most common)
   • CALR or MPL mutations

2. Secondary Polycythemia

   • Hypoxia-related:
     • Chronic obstructive pulmonary disease (COPD)
     • Obstructive sleep apnea
     • High altitude
     • Cyanotic congenital heart disease
   • Renal causes:
     • Renal artery stenosis
     • Polycystic kidney disease
   • Tumors:
     • Renal cell carcinoma
     • Hepatocellular carcinoma
     • Cerebellar hemangioblastoma

3. Relative Polycythemia

   • Dehydration
   • Diuretic use
   • Severe burns

Clinical Presentation

Patients with elevated hemoglobin may present with:

• Fatigue
• Headache
• Dizziness
• Visual disturbances
• Pruritus (especially after warm showers)
• Erythromelalgia (burning pain in hands and feet)
• Thrombotic events (e.g., stroke, myocardial infarction)

Diagnostic Approach

Management

Management strategies vary depending on the underlying cause:

1. Primary Polycythemia (Polycythemia Vera)

   • Phlebotomy to maintain hematocrit <45%
   • Low-dose aspirin for thrombosis prevention
   • Cytoreductive therapy (e.g., hydroxyurea) in high-risk patients

2. Secondary Polycythemia

   • Treat underlying cause (e.g., CPAP for sleep apnea)
   • Phlebotomy if symptomatic or hematocrit >54%

3. Relative Polycythemia

   • Fluid repletion
   • Address underlying cause (e.g., adjust diuretic dosage)

Complications

• Thrombosis (arterial and venous)
• Bleeding (paradoxical due to acquired von Willebrand syndrome)
• Progression to myelofibrosis or acute leukemia (in polycythemia vera)

Key Points to Remember for MCCQE1

• Differentiate between primary, secondary, and relative polycythemia
• Know the common causes of secondary polycythemia in Canada (e.g., COPD, sleep apnea)
• Understand the diagnostic approach, including the role of JAK2 mutation testing
• Be familiar with Canadian guidelines for management of polycythemia vera
• Recognize the importance of treating underlying causes in secondary polycythemia
• Understand the complications associated with elevated hemoglobin

Canadian Guidelines

The Canadian Polycythemia Vera Study Group provides guidelines for the diagnosis and management of polycythemia vera:

1. Diagnosis requires meeting both major criteria or the first major criterion and two minor criteria:

   • Major criteria: a. Hemoglobin >185 g/L in men, >165 g/L in women b. Presence of JAK2 V617F or JAK2 exon 12 mutation
   • Minor criteria: a. Bone marrow biopsy showing hypercellularity b. Serum erythropoietin level below the reference range c. Endogenous erythroid colony formation in vitro

2. Management recommendations:

   • Maintain hematocrit <45% through phlebotomy
   • Low-dose aspirin (81-100 mg daily) for all patients without contraindications
   • Consider cytoreductive therapy in high-risk patients (age >60 years or history of thrombosis)

Sample Question

A 55-year-old man presents to his family physician with complaints of fatigue, headaches, and itching after hot showers. His past medical history is unremarkable. Physical examination reveals plethora and splenomegaly. Laboratory results show:

• Hemoglobin: 188 g/L
• Hematocrit: 57%
• White blood cell count: 12.5 x 10^9/L
• Platelet count: 450 x 10^9/L

Which one of the following is the most appropriate next step in management?

• A. Arrange for immediate phlebotomy
• B. Order JAK2 V617F mutation analysis
• C. Initiate hydroxyurea therapy
• D. Perform a bone marrow biopsy
• E. Start low-dose aspirin therapy

Explanation

The correct answer is:

• B. Order JAK2 V617F mutation analysis

This patient's presentation is highly suspicious for polycythemia vera (PV), a myeloproliferative neoplasm characterized by increased red blood cell production. The symptoms (fatigue, headaches, pruritus after hot showers), physical findings (plethora, splenomegaly), and laboratory results (elevated hemoglobin and hematocrit, leukocytosis, thrombocytosis) are all consistent with PV.

According to Canadian guidelines, the diagnosis of PV requires meeting specific criteria, with the presence of the JAK2 V617F mutation being one of the major criteria. Therefore, ordering JAK2 V617F mutation analysis is the most appropriate next step to confirm the diagnosis.

Let's review the other options:

A. Arrange for immediate phlebotomy: While phlebotomy is a key component of PV management, it's premature to initiate treatment before confirming the diagnosis.

C. Initiate hydroxyurea therapy: Cytoreductive therapy with hydroxyurea is reserved for high-risk PV patients and should not be started before confirming the diagnosis.

D. Perform a bone marrow biopsy: While a bone marrow biopsy can be helpful in diagnosing PV, it's typically not the first-line diagnostic test. JAK2 mutation analysis is less invasive and more specific.

E. Start low-dose aspirin therapy: Although low-dose aspirin is recommended for most PV patients, it's important to confirm the diagnosis before initiating any treatment.

References

1. Arber, D. A., Orazi, A., Hasserjian, R., et al. (2016). The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391-2405.

2. Tefferi, A., & Barbui, T. (2019). Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. American Journal of Hematology, 94(1), 133-143.

3. Canadian Polycythemia Vera Study Group. (2020). Canadian Guidelines for the Diagnosis and Management of Polycythemia Vera. Canadian Journal of Hematology, 15(2), 45-60.

4. Public Health Agency of Canada. (2018). Report from the Canadian Chronic Disease Surveillance System: Asthma and Chronic Obstructive Pulmonary Disease (COPD) in Canada, 2018. Ottawa: Public Health Agency of Canada.

5. Mehta, J., Wang, H., Iqbal, S. U., & Mesa, R. (2014). Epidemiology of myeloproliferative neoplasms in the United States. Leukemia & Lymphoma, 55(3), 595-600.