Diagnosis of Intermediate-Risk Polycythemia Vera

Ruben A. Mesa, MD:This is a 39-year-old gentleman with polycythemia vera. Specifically, he presented with significant erythrocytosis without leukocytosis or thrombocytosis. He had a bone marrow aspirate and biopsy done, which showed morphologic features consistent with polycythemia vera, as well as the presence of theJAK2mutation. He had a normal karyotype. He did not have a significant increase in fibrosis; he just had 1+ fibrosis. So, he met the WHO 2016 criteria for a diagnosis of polycythemia vera. Now, in managing a patient like this, we have to first assess their risk. And the risk factors for polycythemia vera that we consider are an age greater than 60 and prior thrombotic events or hemorrhagic events, which this individual has not had. However, this individual does have significant cardiovascular risk factors—some hypertension, some diabetes—and those are additional factors. So, in my practice, I would consider this individual as having an intermediate-risk polycythemia vera.

The goals for managing a patient like this are several-fold. They are really aimed at trying to prevent thrombosis or bleeding, and they include, certainly, trying to manage his cardiovascular risk factors. So, individuals are managed on a basis of phlebotomy to control the hematocrit. Ideally, in 2017, we know our targets would be a hematocrit of less than 45%, as well as the use of low-dose aspirin: 81 mg in the United States but 100 mg or less, given the different formulations, around the world. We’ll be monitoring the patient to be sure that we’re keeping up with their phlebotomy—it needs to keep the hematocrit under 45%—as well as making certain they’re not having vascular events, they’re not developing splenomegaly, and they’re not developing symptoms or other difficult disease features.

This patient began on phlebotomies and, after 3 months, is having difficulties with phlebotomy, having a variety of side effects: fatigue, dizziness, and other problematic issues. So, the individual has begun on hydroxyurea as a cytoreductive therapy. The need for phlebotomies continues, and the dose of hydroxyurea is increased further from 1000 mg to 1500 mg a day.

Transcript edited for clarity.

January 2015

• A 39-year-old male presents with headache and weight loss
• He is a 2-pack a day smoker
• PMH includes type 2 diabetes, moderately controlled on medication; newly-diagnosed hypertension
• Physical exam: BP, 176/94, otherwise unremarkable
• Laboratory values:
  • Hb; 233 g/L
  • Hct; 68.9%;
  • Mean corpusc. vol.; 81 fL
  • Leukocytes; 4.4 × 10⁹/L
  • Platelets; 145 × 10⁹/L
• Bone marrow biopsy;
  • MF-3 fibrosis and megakaryocytic hyperplasia with atypia
  • Normal karyotype
  • JAK2-positive
• Patient was started on phlebotomy as needed and aspirin

April 2015

• Patient had 3 phlebotomies in the last 3 months.
• He reported increasing dizziness, headaches and nausea
• He was continued on phlebotomy as needed; aspirin was continued
• Patient was started on Hydroxyurea 1000 mg daily

July 2015

• Patient comes back 3 months later, he has had 2 phlebotomies
• Hydroxyurea is increased to 1500 mg

October 2015

• Patient returns 3 months later with pruritus, still requiring phlebotomy
• He is started on hydroxyurea 2000 mg daily

January 2016

• The patient has had 2 phlebotomies since his last visit; he reports abdominal fullness
• He also has restless legs and is complaining that food tastes funny
• Spleen is palpable 7 cm below costal margin