A 45-year-old Caucasian female is referred to General Internal Medicine clinic for assessment of microcytosis that was identified during a work-up for life insurance assessment. She has no other past medical history.
- What is your differential for this patient’s erythrocytosis?
- What is the explanation for her microcytosis?
- What investigations would you order?
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Diagnosis: Polycythemia Vera (PV)
CBC findings suggestive of diagnosis:
(1) Reticulocytosis in the presence of normal/high hemoglobin is inappropriate
Q1: What is your differential for this patient’s erythrocytosis?
Primary erthrocytosis (e.g. PV) and secondary causes (see Box)
Q2: What is the explanation for her microcytosis?
Iron deficiency from increased red cell production
Q3:What investigations would you order?
EPO level
Secondary Erythrocytosis
• Lung disease (smoking, hypoxic lung disease)
• Obstructive sleep apnea
• Drugs (testosterone, erythropoietin-agonist)
• Renal cell carcinoma
• Carbon monoxide poisoning
• High altitude
CBC Pearls
• Reticulocytosis with normal/high hemoglobin is abnormal
• EPO is a useful marker to differentiate primary and secondary erythrocytosis
Erythrocytosis is the finding of elevated hemoglobin/hematocrit on CBC. Every diagnosis of erythrocytosis must prompt investigation for the cause. These are divided into primary (i.e. PV) and secondary. PV is myeloproliferative neoplasm resulting in autonomous overproduction of red blood cells. It is caused by mutations that activate growth signalling pathways in cells. The most common mutation (> 95%) in PV patients involves the JAK2 gene. Secondary erythrocytosis is usually driven by erythropoietin (EPO) overproduction, whether it be appropriate (e.g. OSA) or inappropriate (e.g. renal cell carcinoma). Secondary causes should always be excluded in a PV workup (see Box for select differential). EPO is a useful biomarker to differentiate primary from secondary PV – it should be suppressed in primary PV, and normal/elevated in secondary erythrocytosis.
In this situation, the patient also has a microcytosis present (see Case 1). Although there is no anemia, it would be beneficial to send iron studies as this patient had iron deficiency secondary to increase use in red cell production. However, iron supplementation is contraindicated in PV to prevent increased hemoglobin RBC production.