CO‐Rebreathing in Essential Thrombocythemia and Polycythemia Vera. A Revival of an Old Methodology to Improve Diagnosis and Phlebotomy Decisions
4 affiliations
- 1Department of Hematology Zealand University Hospital Roskilde Denmark
- 2Detalo Health Aps Hørsholm Denmark
- 3Department of Anesthesia and Intensive Care Zealand University Hospital Roskilde Denmark
- 4Center for Physical Activity Research, Rigshospitalet Copenhagen Denmark
Abstract
The diagnostic landscape for the Philadelphia‐negative myeloproliferative neoplasms (MPNs), particularly in distinguishing Essential Thrombocythemia (ET) from Polycythemia Vera (PV), is compromised. The gold standard for diagnosing PV—measurement of red cell mass (RCM) by radioisotope dilution—has been largely abandoned, leading to widespread misclassification. Thus, an estimated 30%–50% (varying by diagnostic center and testing practice) of JAK2V617F‐positive ET patients may, in fact, have “hidden” PV, depriving them of the cornerstone PV therapy: phlebotomy. This diagnostic inaccuracy exposes a sizable patient population to an unfortunate high risk of life‐threatening thrombotic events. Concurrently, the management of established PV is suboptimal, often relying solely on hematocrit, a flawed parameter especially in iron‐deficient or hydroxyurea‐treated patients. This perspective calls for the revival and clinical implementation of the Carbon Monoxide (CO)‐rebreathing technique as a promising, rapid, and nonradioactive alternative for RCM assessment. Herein, we review the history of this methodology and discuss its potential to improve MPN care by ensuring precise diagnosis, guiding rational phlebotomy, and ultimately reducing thrombotic morbidity and mortality, while also candidly addressing the current evidentiary and practical limitations that must be resolved before clinical adoption, while also offering potential health‐economic benefits.
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BibTeX
@article{hasselbalch2026corebreathing,
title = {{CO‐Rebreathing in Essential Thrombocythemia and Polycythemia Vera. A Revival of an Old Methodology to Improve Diagnosis and Phlebotomy Decisions}},
author = {Hans C. Hasselbalch and Morten Kranker Larsen and Lea Løffler and Camilla Andersen and Isabella Davidsen and Mette Grymer Jensen and Jonas Bechlund and Lasse Kjær and Vibe Skov and Henning Bay Nielsen and Carsten Lundby},
journal = {Cancer Medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72317},
url = {https://doi.org/10.1002/cam4.72317},
note = {CC BY},
}
RIS
TY - JOUR
TI - CO‐Rebreathing in Essential Thrombocythemia and Polycythemia Vera. A Revival of an Old Methodology to Improve Diagnosis and Phlebotomy Decisions
AU - Hans C. Hasselbalch
AU - Morten Kranker Larsen
AU - Lea Løffler
AU - Camilla Andersen
AU - Isabella Davidsen
AU - Mette Grymer Jensen
AU - Jonas Bechlund
AU - Lasse Kjær
AU - Vibe Skov
AU - Henning Bay Nielsen
AU - Carsten Lundby
PY - 2026
DA - 2026/10/24
JO - Cancer Medicine
DO - 10.1002/cam4.72317
UR - https://doi.org/10.1002/cam4.72317
AB - The diagnostic landscape for the Philadelphia‐negative myeloproliferative neoplasms (MPNs), particularly in distinguishing Essential Thrombocythemia (ET) from Polycythemia Vera (PV), is compromised. The gold standard for diagnosing PV—measurement of red cell mass (RCM) by radioisotope dilution—has been largely abandoned, leading to widespread misclassification. Thus, an estimated 30%–50% (varying by diagnostic center and testing practice) of JAK2V617F‐positive ET patients may, in fact, have “hidden” PV, depriving them of the cornerstone PV therapy: phlebotomy. This diagnostic inaccuracy exposes a sizable patient population to an unfortunate high risk of life‐threatening thrombotic events. Concurrently, the management of established PV is suboptimal, often relying solely on hematocrit, a flawed parameter especially in iron‐deficient or hydroxyurea‐treated patients. This perspective calls for the revival and clinical implementation of the Carbon Monoxide (CO)‐rebreathing technique as a promising, rapid, and nonradioactive alternative for RCM assessment. Herein, we review the history of this methodology and discuss its potential to improve MPN care by ensuring precise diagnosis, guiding rational phlebotomy, and ultimately reducing thrombotic morbidity and mortality, while also candidly addressing the current evidentiary and practical limitations that must be resolved before clinical adoption, while also offering potential health‐economic benefits.
SN - 2045-7634
ER -