The WHO diagnostic criteria for polycythemia vera—role of red cell mass versus hemoglobin/hematocrit level and morphology
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Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n = 143)/Hct (n = 45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.
KeywordsPolycythemia vera Red cell mass Clinical criteria Bone marrow morphology Masked polycythemia vera WHO classification 2016
This study was conducted under the aegis of CEMPO (Central European Myeloproliferative Organization) which provided the necessary conditions to make it possible.
M.G., L.J., J.T., and H.G. designed the research, contributed patients, participated in data analysis and interpretation, and wrote the paper. I.S. performed the statistical analysis, D.S. the EEC assays, and M.T. the RCM measurements. J.T., L.J., Ch.B.-Sch., and I.S.-K reviewed all bone marrow biopsies. All other authors either contributed patients or participated in reviewing bone marrow morphology.
Compliance with ethical standards
This study was conducted in accordance with the International Conference on Harmonization guidelines for Good Clinical Practice. The clinical study protocol was approved by the Institutional Ethical Committee of the Clinical Center of Serbia, No. 195/11, Date 24.11.2016.
All patients provided written informed consent in accordance with the Declaration of Helsinki prior to study participation.
Conflict of interest
None of the authors have any conflict of interest to disclose with regard to the current manuscript. All of the authors read and approved the final draft.
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