Understanding Hematocrit Thresholds in Polycythemia Vera Treatment

In early March, The American Journal of Managed Care^® spoke with Andrew Kuykendall, MD, a clinical researcher at Moffitt Cancer Center who focuses on myeloproliferative neoplasms (MPNs), myelodysplastic syndrome/MPN overlap syndromes, and systemic mastocytosis. Kuykendall is an investigator on the phase 3 VERIFY trial (NCT05210790) of the injectable hepcidin mimetic rusfertide (Takeda) to treat polycythemia vera (PV) by enabling patients to achieve and sustain hematocrit control.¹ Hematocrit is the measure of the percentage of red blood cells in the body.²

Treatment guidelines in PV currently recommend maintaining hematocrit below 45%, with a higher threshold for men vs women.² For part 2 of this interview, Kuykendall explains the reasoning behind having different hematocrit thresholds.

In the first part of the interview, Kuykendall discussed how PV manifests and common ways to reduce its negative impact on patient quality of life.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Why does treatment guidance recommend a higher hematocrit threshold for men vs women?

Really, this just comes down to a different kind of body chemistry between men and women. Men typically have higher levels of testosterone; they have less body water, and they tend to have, just at baseline, higher red blood cell masses, just the number of red blood cells they make, and also higher hematocrits. The idea of, if you're looking at hematocrit 45%, that would actually be kind of a little bit higher than normal for a woman and maybe right at normal for men, so [it's] hard to say that we should probably put the same thresholds.

Now, that being said, a lot of that is kind of just extrapolation from our understanding of men and women, and when we look at clinical trials that have kind of solidified that 45% as a threshold that we try to achieve to reduce risk of thrombosis, that was a trial that enrolled men and women. It was the so-called CYTO-PV study [NCT01645124] that kind of randomized patients with polycythemia vera to keep their hematocrits less than 45% or to allow them to kind of be between 45% and 49%. Those patients who we tried to achieve less than 45%, they had a decreased risk of about 4-fold of major cardiovascular thrombotic events.

While the data would suggest that targeting less than 45% was rational for men and women, we do tend to extrapolate to some degree, based on our understanding of the differences, to say maybe we should try a lower threshold with women.

References

1. Large-scale trial testing the intensity of cytoreductive therapy in polycythemia vera (PV) (CYTO-PV). ClinicalTrials.gov. Updated July 20, 2012. Accessed March 19, 2025. https://clinicaltrials.gov/study/NCT01645124

2. Hematocrit. Cleveland Clinic. Accessed March 19, 2025. https://my.clevelandclinic.org/health/diagnostics/17683-hematocrit