Real-World Polycythemia Care Often Fails to Control Hematocrit

Most patients with polycythemia vera treated under the current standard of care are not keeping their hematocrit (HCT) at the level needed to reduce the risk of dangerous blood clots, according to a new retrospective claims analysis published in the Journal of Blood Medicine.¹ Of patients with available lab data (11% of the full cohort), 85.3% had at least 1 HCT reading at or above 45%—the threshold guidelines identify as the trigger point for thromboembolic risk—despite ongoing treatment with phlebotomy and cytoreductive drugs.

What Did the Claims Data Reveal?

Using the Merative MarketScan Commercial and Medicare databases, the researchers identified 11,311 adults with polycythemia vera who received treatment between 2011 and 2022, following them for a median of 2.8 years. Just over half (51.8%) met criteria for high thromboembolic risk, based on age 60 or older or a prior clot history; 48.2% were classified as low-risk cases (younger age and no thrombosis history). For this analysis, patients were divided by these 2 risk statuses. Their mean overall age was 59 years, and 73.1% were male patients.

At 12 months post index treatments, phlebotomy alone was the dominant treatment strategy, used by 75% of the cohort, while only 12.2% received hydroxyurea alone, 10.9% utilized phlebotomy and hydroxyurea, and 1.9% received ruxolitinib or interferons. Nearly half of patients on phlebotomy required frequent procedures—3 or more sessions in 6 months or 5 or more in a year—and 41.7% of hydroxyurea users were on high-dose regimens. Within the first year, 50.9% of all patients had experienced either this kind of burdensome treatment, an incident thromboembolic event, or both.

How Often Did Patients Experience Clots and Other Complications?

Over the full follow-up period, 15.3% of patients had an incident thromboembolic event, 9.6% developed iron deficiency anemia, 4.4% progressed to a more severe blood cancer such as myelofibrosis, and 83.2% reported at least 1 polycythemia vera–related symptom, most commonly difficulty sleeping, depression or anxiety, and fatigue. High-risk patients fared worse across nearly every measure, with a thromboembolic event rate of 21.3% compared with 9.0% among low-risk patients.

These figures track closely with a separate claims-based analysis published in 2023, which found a 16.1% overall thromboembolic event rate and similarly poor hematologic control; more than half of patients started on phlebotomy alone had HCT levels above 50%.² Together with prospective data from the REVEAL registry, investigators have flagged that nearly half of actively treated US patients showed elevated HCT at enrollment and that symptoms such as fatigue often persisted even when blood counts appeared controlled.^2,3 The new findings reinforce these patterns at a larger scale and over a longer observation window.

Why Is Hematocrit Control So Difficult to Achieve?

Among the subset of patients with at least 2 HCT measurements (n = 1268), only 14.7% consistently stayed below the 45% threshold.¹ Control was worst among patients managed with phlebotomy alone, among whom just 9.4% stayed consistently controlled vs 50.0% of those on high-dose hydroxyurea and 45.8% of those on ruxolitinib or interferons. The authors suggest this could reflect phlebotomy’s role as a reactive rather than sustained control measure.

“[Phlebotomy] is often used as a reactive measure for [hematocrit] ≥ 45%, which may lead to continuous HCT fluctuations rather than sustained control,”¹ they wrote. “In addition, it is unknown how long patients have HCT above 45% before a blood draw reveals the elevated HCT.”

The stakes of this gap are well established elsewhere: an analysis of Veterans Health Administration data found that patients with HCT at or above 45% face a significantly higher risk of thromboembolic events than those who stay below it.⁵ Notably, patients on phlebotomy alone in the current study had largely normal white blood cell (81.5%) and platelet (86.4%) counts despite uncontrolled HCT, pointing to an erythrocytosis-predominant phenotype that phlebotomy cannot fully address without adding myelosuppressive therapy, the authors explained.¹

What Does an Incident Clot Cost the Health System?

For the 1159 patients who experienced a thromboembolic event and had at least a year of follow-up afterward, mean all-cause health care costs in the subsequent 12 months reached $71,195, with 29.2% tied directly to the initial event and the remaining attributable to other all-cause health care claims. Costs were highest when the initial thromboembolic event required hospitalization, averaging $97,264, vs $51,000 to $67,000 for events managed in the emergency department or other outpatient settings.

These figures underscore how the economic burden of inadequate hematocrit control can compound over time, particularly if patients go on to experience recurrent events, the authors explained. They argue that current standard-of-care options—phlebotomy and traditional cytoreductive agents—are not consistently achieving the disease control that guidelines call for, leaving a meaningful share of patients exposed to preventable, costly complications.

They point to nonmyelosuppressive approaches such as hepcidin mimetics, which limit iron available for red blood cell production, including the investigational agent rusfertide, as a potential way to control erythrocytosis without the blood-count tradeoffs seen with hydroxyurea or ruxolitinib. For payers and health systems, the persistence of uncontrolled hematocrit despite active treatment suggests that closing this gap may depend less on adherence to existing drug classes and more on adopting newer mechanisms and more consistent lab monitoring protocols.

References

1. Gerds AT, Fan Q, Jerry M, Cerretani A, Tran AT, Hernandez L. Disease burden, inadequate hematocrit control, and thromboembolic events in patients with polycythemia vera despite current standard of care treatment: a retrospective claims study. J Blood Med. 2026;17:1-19. doi:10.2147/JBM.S626464
2. Verstovsek S, Pemmaraju N, Reaven NL, et al. Real-world treatments and thrombotic events in polycythemia vera patients in the USA. Ann Hematol. 2023;102(3):571-581. doi:10.1007/s00277-023-05089-6
3. Grunwald MR, Burke JM, Kuter DJ, et al. Symptom burden and blood counts in patients with polycythemia vera in the United States: an analysis from the REVEAL study. Clin Lymphoma Myeloma Leuk. 2019;19(9):579-584.e1. doi:10.1016/j.clml.2019.06.001
4. Kuykendall AT, Fine JT, Kremyanskaya M. Contemporary challenges in polycythemia vera management from the perspective of patients and physicians. Clin Lymphoma Myeloma Leuk. 2024;24(8):512-522. doi:10.1016/j.clml.2024.04.003
5. Parasuraman S, Yu J, Paranagama D, et al. Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data. Ann Hematol. 2019;98(11):2533-2539. doi:10.1007/s00277-019-03793-w