The rise and fall of red cell mass measurement in polycythemia vera

The total blood volume (BV) consists of the part occupied by red blood cells (RBC), which is referred to as red cell mass (RCM), and that occupied by plasma (ie, plasma volume). Quantitative laboratory measurements that are pertinent to RBC, including RBC count, hematocrit (Hct), and hemoglobin (Hgb) are expressed in reference to a given volume of whole blood and are therefore influenced by plasma volume. Consequently, a "direct" RCM measurement has been promoted as a more accurate indicator of the body's red cell content. In accordance with this view, an international group of investigators, then identified as the Polycythemia Vera Study Group (PVSG), recommended that RCM be measured and only if elevated should a patient be considered for participation in a series of clinical trials in PV that were conducted more than 30 years ago. By default, the 'study eligibility' criteria used in these studies became 'diagnostic' criteria without any systematic evaluation for diagnostic accuracy. Furthermore, over the years, it has become evident that RCM measurement is a cumbersome and costly test that is also suboptimal in its diagnostic accuracy. As a result, the specific procedure has been abandoned by the majority of hematologists in certain countries and instead physicians are increasingly using bone marrow histology, serum erythropoietin level, and other disease-characteristic biologic markers as diagnostic tools.