Tests to establish the cause of secondary polycythemia

Dr Chris Hillis is an assistant professor in the Division of Oncology at McMaster University and hematologist at the Juravinski Hospital and Cancer Centre.

What tests are useful in establishing the cause of secondary polycythemia?

Chris Hillis, MD, MSc: When you are approached with secondary polycythemia—I assume the JAK2 V617F testing has been done and is negative—typically the pathway that we will follow in clinic is guided by the erythropoietin (EPO) level. If the EPO level is low or subnormal but the JAK2 mutation is not present, then we will perform a bone marrow biopsy in those patients because in the rare instance you will still pick up a myeloproliferative neoplasm.

In other patients, who have a high normal or high EPO level, you are most certainly into the territory of secondary polycythemia and the most common causes of that would be respiratory, such as obstructive sleep apnea or smoking. One of your best diagnostic tests in that area is the history and determining if the patient has obstructive sleep apnea, learning from their partner if they snore or have apneic periods, and determining if they smoke. You will find that out from the patient. Then we will pursue pulmonary function testing, sleep studies, and of course an echocardiogram for hypoxic heart disease.

Then, once you have exhausted pulmonary and cardiac causes, you can start to look to the other genetic causes of erythrocytosis, including inherited things that cause erythrocytosis or high hemoglobin affinity for oxygen.