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Editorials
of an elevated Hb, despite an increased Cr-51 RCM.5-7 However, despite the convincing data published in 2005 by Johansson et al.,5 these concerns were not translated into the revised 2007 WHO diagnostic recommendations. These recommendations, therefore, remained unchanged9 and were addressed and met by alternative diagnostic approaches in ET, PV and PMF patients.2 In their 2013 study,3 Silver et al. for the first time prospec-
Figure 1. Association between the hemoglobin (Hb)-concentration, hematocrit, red blood cell (RBC) count and mean corpuscular volume (MCV) values in a 76- year old woman with polycythemia vera. The Figure illustrates that: (i) the RBC count is a a more accurate indicator of erythrocytosis than the Hb-concentration and the hematocrit; (ii) that this dissociation is consequent to iron deficiency as evidenced by a lowered MCV; and (iii) the hyperviscosity state due to the raised RBC count is reflected in a low erythrocyte sedimentation rate (SR) (< 1 or 2 mm/h) (normal range: 2-20 mm/h). The need for phlebotomies in this patient was monitored by the elevated RBC count and the lowered SR, and tightly associated with the emergence of headache, which immediately resolved after phlebotomy.
tively evaluated the accuracy of the 2007 WHO criteria for diagnosing PV, especially in “early-stage” patients. This and other studies support the latest updated WHO criteria (2016) for diagnosing MPN,1,9 which included these novel data with regard to the inaccuracy of the Hb- concentration, and even the hematocrit (HCT), in the dif- ferential diagnosis between ET and PV patients by lower- ing the Hb/HCT thresholds (> 16.5 g/dL/0.49 in men and > 16 g/dL/0.48 in women).1 Thus, the 2013 Silver study in a prospective setting and with a median 5-year follow up time convincingly demonstrated that the surrogate mark- ers Hb and HCT are inadequate in the assessment of an increased RCM for early PV cases, since 64.3%, 28.5%, and 28.5% of their patients would not have been diag- nosed as PV using Hb, HCT, and either Hb or HCT val- ues, respectively.3 Importantly, of the 28 patients with an increased RCM in their study, 18 did not meet the WHO 2007 criteria for an increased Hb value. For the four women, the median Hb count was 15.2 g/dL (range: 14.4- 16.4 g/dL) and for the 14 men 17.2 g/dL (range: 15.6-18.1 g/dL), respectively. Similarly, eight patients (1 woman and 7 men) did not meet the WHO criteria for an increased HCT value, being 44.3% for the woman, and for the seven men the median HCT was 48.5% (range: 45.7-49.4 %).3 Silver et al. also highlighted the value of bone marrow (BM) morphology3 as emphasized in the WHO classification. Accordingly, this study supported previous reports by Johansson et al.,5 Cassinat et al.,6 and Alvarez-Larran et al.7 which all revived ancient knowl- edge, written by the Polycythemia Vera Study Group (PVSG), and underscoring the inaccuracy of the Hb and the HCT values for diagnosing PV and the need for RCM measurement instead.10 This has since fostered intense debate in several reviews and perspective papers express- ing conflicting opinions. On the one hand, some authors believe that only RCM measurements can reliably distin- guish PV from other MPN,2-4,11 while others would disre- gard RCM measurements,12-15 arguing that Hb/HCT thresholds should be used as surrogate markers for RCM measurements. This lively debate has recently been fur- ther fueled by a comprehensive and scholarly review on MPN, emphasizing the urgent need for RCM investiga- tions to distinguish PV from other MPN,16 adding that BM morphology has no place in the distinction of PV from other MPN subtypes.16 Others have highlighted the importance of BM morphology in PV and its usefulness in distinguishing between ET and PV.3,17-21 A very recent study has established a clear-cut distinction between ET and PV, and, therefore, also the reproducibility of BM morphology in so-called masked polycythemia vera (mPV) and its differentiation from ET.21 The disease entity mPV will be further addressed below.
Do the revised and lowered thresholds for Hb/HCT levels unmask undiagnosed PV patients in the general population when “potential PV patients” are being referred?
In 2014, the issue as to which of the three red cell parameters, Hb, HCT or RCM, to use as the diagnostic hallmark of PV was thoroughly reviewed by Barbui et al. They also critically addressed the validity and applicabil- ity of the three major diagnostic classification systems for
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haematologica | 2019; 104(11)