Polycythemia Vera - Episode 1

Impressions of a 75-Year-Old Man With PV

Ruben A. Mesa, MD, FACP:This is a classic presentation of polycythemia vera [PV]. A 75-year-old gentleman presents to his primary physician with marked pruritus with bathing. The physician examines the patient, finds him to have a lot of rubor, or kind of a red-in-face presentation. But the rest of the exam is pretty unremarkable. He does not find any enlargements of the spleen and takes a thorough history. There’s been no prior blood clot or bleeding. But the blood tests demonstrate marked erythrocytosis, very high hemoglobin, hematocrit, and erythropoietin levels, which is the lower limits of normal, which is consistent with a potential myeloproliferative neoplasm. Subsequently, the physician orders the test forJAK2V617F, which confirms the diagnosis of polycythemia vera.

The physician, trying to meet the diagnostic criteria of the World Health Organization [WHO], recommends a bone marrow aspirate and biopsy to the patient. The patient declines. Yet one can say by prior WHO criteria, as well as accepted clinical practice, the patient has polycythemia vera.

Patients can present with polycythemia vera in a range of ways. They may present because of symptoms—in particular, pruritus being 1 of the most common; or they might present with headaches, fatigue, or night sweats. They might present because they actually had a thrombotic event. It’s not uncommon that this is diagnosed in the hospital when a patient had an unexpected heart attack, stroke, deep vein thrombosis, or pulmonary embolism. There are certain blood clots in unusual spots that are more common with polycythemia vera. Splenic vein thromboses or sagittal vein thromboses in the skull—any of these atypical areas are, in particular, very suspicious for polycythemia vera.

Finally, there are individuals who present because they are having a routine complete blood count for some other reason. Maybe they are screening for a health insurance physical or a pre-employment physical and are found to have marked erythrocytosis or leukocytosis or thrombocytosis. So that work-up typically begins with, first, a clinical suspicion and evaluation of the peripheral blood counts, as well as the analysis of the serum erythropoietin level, which typically is either normal or low because there is this feedback loop, an inappropriate suppression of the erythropoietin level, and then finally a confirmation in the majority of individuals of an MPN [myeloproliferative neoplasms]—driver mutation. That is primarily theJAK2V617F, which is found in about 90% to 95% of patients, with aJAK2exon 12 mutation being present in a small minority. Most laboratories now will perform a reflexJAK2exon 12 mutation analysis if they suspect PV—if theJAK2V617FF, the more common mutation, is not present.

In the real world, patients might present in a whole range of ways. They may present initially with a high white count or a high platelet count, and because of pre-existing iron deficiency they may not be fully manifesting their erythrocytosis. This is not uncommon in women of menstrual age, who may have a chronic or severe iron deficiency as part of the equation.

Individuals who go on clinical trials typically will meet very specific eligibility criteria, have the classic distribution of marked erythrocytosis, and depending upon the study, may have other prerequisite features such as splenomegaly or leukocytosis above a certain threshold.

Transcript edited for clarity.

Case: 75-Year-Old Man Diagnosed With Polycythemia Vera

January 2018

  • A 75-year old man presents to PCP for routine evaluation; feels well but complains of pruritus exacerbated by hot showers
  • PE: Unremarkable
  • PMH: No prior history of thrombosis, hypertension managed with statin
  • Lab values:
    • HGB: 18.9 g/dL
    • Hct: .56 L/L
    • RBC: 68 x 1012/L
    • WBC: 10.6 x 109/L
    • Serum EPO: 4.1 mU/mL
  • Bone Marrow biopsy declined
  • Cytogenetics: JAK-V617Fmutation