Importance of Hematocrit Control in Polycythemia Vera

Maintaining Hct Level <45% Was Evaluated in a Randomized Clinical Study (Marchioli et al, 2013)1

The CYTO-PV trial was a randomized clinical trial that examined risk for cardiovascular death or major thrombosis associated with specific hematocrit levels in patients with PV.

The study included 365 adult patients with PV being treated with phlebotomy, hydroxyurea (HU), or both.

Patients were randomized into one of two groups with different target hematocrit (Hct) levels.

  • One group received more aggressive treatment for an Hct target less than 45% (low-Hct group), and the other group received less aggressive treatment for an Hct target of 45% to 50% (high-Hct group)
  • The composite primary end point was the time until cardiovascular death or major thrombotic events
  • Therapy options for maintaining Hct levels within the respective treatment groups were phlebotomy, cytoreductive drugs, or both
  • Baseline characteristics were balanced between both groups
  • ≈50% had received an initial diagnosis of PV within 2 years before enrollment
  • 67.1% were at high risk because of age ≥65 or previous thrombosis
Probability of Remaining Event Free Over Time
chart is shown that depicts the probability of remaining event free of disease
In a multivariable, time-dependent analysis, the results indicate the risk of thrombosis was increased in patients with a WBC count >7 × 109/L (ie, HR >1), becoming statistically significant at WBC >11 × 109/L HR=3.90 (95% CI: 1.24-12.3); P=.022
Kaplan-Meier curves adapted with permission from the Massachusetts Medical Society. CI = confidence interval Hct = hematocrit HR = hazard ratio WBC = white blood cell Kaplan-Meier curves for primary composite end point

Role of Phlebotomy in Maintenance of Target Hematocrit <45%

Phlebotomy is one of the first interventions used in patients with PV, in addition to low-dose aspirin. In patients who are considered at high risk (age >60 or with previous history of thrombosis), cytoreductive agents may be utilized in addition to phlebotomy.3 Poor tolerance of phlebotomy or requirement for frequent phlebotomy, among other factors, are also considered indicators for cytoreductive therapy.3

The goal of phlebotomy is to reduce the red blood cell mass by creating a state of iron deficiency.4

The Spanish Registry of Polycythemia Vera is an observational database of >1,300 patients. Hematocrit control was evaluated in a retrospective study of 533 patients with polycythemia vera who were treated with hydroxyurea with or without phlebotomy.5

Sixteen percent (85/533) of patients received ≥3 phlebotomies per year in addition to hydroxyurea to maintain their hematocrit. Patients requiring ≥3 phlebotomies per year were5:

  • Treated with significantly higher doses of the cytoreductive agent compared with patients receiving 0 to 2 phlebotomies
  • Unable to achieve a median hematocrit <45% despite cytoreductive therapy and phlebotomy
Hematocrit During Retrospective Study Period in Patients Receiving HU and Phlebotomy
chart shows the hematocrit on the y axis and the x axis shows the number of months of therapy

1. Marchioli R, Finazzi G, Specchia G, et al; for the CYTO-PV Collaborative Group. N Engl J Med. 2013;368:22-33. 2. Barbui T, Masciulli A, Marfisi MR, et al. Blood. 2015;126(4):560-561. 3. Barbui T, Barosi G, Birgegard G, et al. J Clin Oncol. 2011;29(6):761-770. 4. Spivak JL. Blood. 2002;100(13):4272-4290. 5. Alvarez-Larrán A, Pérez-Encinas M, Ferrer-Marín F, et al. Haematologica. 2017;102(1):103-109.

The potential impact of a target hematocrit level of <45% on major thrombosis or cardiac death.
By: MPN Connect
An animated video highlighting PV pathophysiology and mechanisms of disease.