Managing Uncontrolled Polycythemia Vera - Episode 2

Importance of Hematocrit Control in Polycythemia Vera

Srdan Verstovsek, MD:Once we are sure that the patient has polycythemia vera, the next step is to determine the patient’s risk for thrombosis. We know that patients with polycythemia vera are at increased risk for blood clotting, or thrombosis, in general. We can divide them into 2 groups. This is based on 2 factors. One factor is age over 60, and the other factor is history of blood clotting. If the patient has one or the other, he or she is at high risk for thrombosis.

In our particular case, the patient is newly diagnosed with polycythemia vera, never had a blood clot, and is younger than age 60. Therefore, the patient is at low risk for thrombosis. Patients who are at low risk for thrombosis with polycythemia vera are treated in a simple way. They are given baby aspirin (81 mg) to make the blood flow easier. The other treatment is phlebotomy. The aim of a phlebotomy is to decrease the hematocrit level, and the goal is to decease the hematocrit level to below 45%.

In the history of polycythemia vera, we always looked at the experimental information from dogs or other animal models. How would an increased risk of thrombosis correlate with the increased numbers of red blood cells that secrete around the blood, which is polycythemia vera? A few years ago, there was finally a prospective, randomized study done in Europe. The study randomized patients with polycythemia vera with an aim to maintain the hematocrit level below 45% or not to be so strict and allow the hematocrit level to be between 45% and 50%. This prospective, randomized study was stopped early, after about 3 years of follow-up, because it was quite clear that the group that had tight control of hematocrit—below 45%—had fewer thromboembolic events, or fewer clotting episodes. This led to fewer deaths from the complications of having those clots.

The main cause of death in polycythemia vera is linked to a thromboembolic event. So, if we follow what this prospective, randomized study showed (that tight control of hematocrit below 45% leads to fewer thromboembolic events, eventually decreasing the risk for death), that’s the ultimate goal. We should all be following tight control of hematocrit (45%) as the goal of therapy.

Transcript edited for clarity.


June 2016

  • A 49-year old male presents with headache, fatigue, and pain under his left ribs
  • PMH includes depression and newly diagnosed hypertension
  • Physical exam: BP, 160/90; abdominal exam reveals splenomegaly — spleen palpable 6 cm below costal margin
  • Laboratory values:
    • Hb=20.7 g/L
    • HCT= 59.4%
    • WBC=10.2x109/L
    • Platelets= 325 x109/L
  • Bone marrow biopsy:
    • MF-1 fibrosis and megakaryocytic hyperplasia with atypia
    • JAK2-positive
  • Patient was started on phlebotomy as needed and aspirin 81 mg

October 2016

  • Patient returns 4 months later with continued headache and dizziness
  • He has had 3 phlebotomies in the past 3 months
  • Patient was started on hydroxyurea 1000 mg/day

January 2017

  • Patient returns 3 months later with abdominal fullness, continued fatigue, difficulty concentrating, fever, and leg ulcer
  • Laboratory values:
    • Hb= 22.4 g/L
    • HCT= 65.3%
    • WBC=13.3x109/L
    • Platelets=153x109/L
  • Patient is started on ruxolitinib