A 40-year old man presents with a 2 week history of exertional headache and intermittent blurry vision. His medical history is unremarkable apart from some morning headaches and waking up frequently with a cough at night. He is a non-smoker and does not drink any alcohol. On presentation, his blood pressure is 189/105, heart rate 78 bpm and regular, oxygen saturation 95% on room air. The cardiac and respiratory examinations were normal. There was no splenomegaly on examination. Labs revealed a hemoglobin of 191 and a hematocrit of 55%. This lead to a presumptive diagnosis of polycythemia.
What is polycythemia?
Polycythemia is an increase in the concentration of hemoglobin (>50% hematocrit female; >55% hematocrit male) that is either due to a reduction in plasma volume or an increase in the production of red blood cells.
Types of polycythemia
- Primary– This is an erythropoeitin (EPO) independent process where there is an increase production in red blood cells. Polycythemia Rubra Vera (PRV) is a myeloproliferative disorder that results in an increase in production of red blood cells. JAK2, a cytoplasmic tyrosine kinase is activated by EPO in normal circumstances. In 95% of cases of PRV there is a V617F mutation, activating JAK2 without the need for EPO, essentially rendering the “hemoglobin production switch” constantly on.
- Secondary– The secondary causes of polycythemia can simply be categorized as EPO driven processes that are either inappropriate or appropriate physiological responses. I use the acronym HEART for causes of secondary polycythemia.
- H- Hypoxia driven: high altitude, smoking, severe sleep apnea
- E-EPO-secreting tumors: RCC, pheochromocytoma, hepatoma
- A-Adrenal: adrenal adenoma, Cushing’s syndrome
- R- Renal causes: polycystic kidney disease, hydronephrosis
- T-testosterone: anabolic steroids, testosterone supplements
Treatment of polycythemia
- Cytoreduction with hydroxyurea is better than phlebotomy for patients with PRV to target a hematocrit of <45% for males and <42% for females.
- The management of secondary polycythemia centres around treating the underlying cause, however, if patients are symptomatic with symptoms of hyperviscosity temporary measures with phlebotomy can be undertaken. Iron studies should be followed closely to ensure no significant iron deficiency develops with recurrent phlebotomies.
- Patients should also be on ASA 81 mg PO daily to help prevent thrombosis.
BACK TO THE CASE:
Additional investigations included an EPO level, arterial blood gas, abdominal ultrasound and JAK2 mutation testing.
EPO level: 8.6 U/L (normal range: 4.3-29 U/L)
Arterial blood gas on room air: 7.41/42/71/26
JAK2 cytogenetics negative.
The above pointed to a secondary cause for polycythemia with the noted hypoxemia on arterial blood gas, an appropriate physiological response. Further inquiry pointed to a history in keeping with severe sleep apnea as the possible cause for his polycythemia. The treatment centred around recommending a formal sleep study and CPAP contingent on his AHI score* (0-4 normal; 5-14 mild apnea; 15-29 moderate apnea; >30 apnea) and in the interim as needed phlebotomy treatment for hyperviscosity symptoms. He was also started on ASA 81 mg daily.
*AHI is the apnea-hypopnea index. It is the total number of apnea and hypopnea events per hour of sleep and is used as an indicator of sleep apnea severity.
- Stuart BJ, Viera AJ. Polycythemia vera. Am Fam Physician. 2004 May 1. 69(9):2139-44.
- Passamonti F. How to manage polycythemia vera. Leukemia. 2011 Dec 9.