SummaryThe diagnosis of polycythaemia vera (PV) has been established upon sets of clinical criteria, which require the presence of absolute erythrocytosis (AE). The most recent clinical criteria for PV, published by the World Health Organization (WHO) in 2001, also required AE, and stated that the measured red cell mass (RCM) could be replaced by a surrogate marker for AE; a haemoglobin (Hb) value of >18AE5 g/dl in males and >16AE5 g/dl in females. The present study evaluated the potential of venous haematocrit (Hct) and Hb values as possible surrogate markers for AE in a series of 77 consecutive patients with PV and 66 patients with apparent polycythaemia (AP), in all of whom the RCM had been previously determined. In only 35% of the male PV patients would Hb values >18AE5 g/dl indicate the presence of AE. Conversely, 14% of male AP patients would be misdiagnosed as having AE. A Hb > 16AE5 g/dl would predict the presence of AE in 63% of the female PV patients, but 35% of female AP cases would be misdiagnosed as having AE. However, when the Hct was ‡0AE60 an AE was always present, and this was true for both male and female subjects.

The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p= 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p< 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival (p =0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival (p =0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis (p =0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors (p =0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content (p =0.0028 and 0.0164, respectively).

Abstract. Johansson P, Kutti J, Andréasson B, SafaiKutti S, Vilén L, Wedel H, Ridell B (Sahlgrenska University Hospital, Göteborg, Sweden). Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Göteborg, Sweden, during 1983-99. J Intern Med 2004 256: 161-165. Objective. In the literature the incidence rates for the chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders (MPD) are known to vary extensively; only a few studies have, however, been concerned with incidence trends over time. Therefore, the aim of the present work was to investigate possible trends as regards incidence rates over time for Ph-MPD. Design. Herein, we carried out a retrospective population-based survey on the incidence of polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (IMF), in the city of Göteborg (Sweden), covering the years 1983-99. Results. The study comprised 416 patients with Ph-MPD. There were 205 patients with PV, 153 patients with ET, 34 with IMF and 24 with unclassified MPD. The annual incidence for PV was 1.97 per 10 5 inhabitants; the corresponding figures for ET and IMF were 1.55 per 10 5 and 0.30 per 10 5 inhabitants, respectively. There was a significant increase in the annual incidence rate for ET (P ¼ 0.008); this increase was significant for male subjects (P ¼ 0.015) but did not reach significance for females (P ¼ 0.118). No such increase over time was recorded as regards PV and IMF. Conclusions. The increasing annual incidence rate for ET is most possibly explained by the more frequent use of automated platelet counts whenever a patient consults a doctor. Thereby, an increasing number of patients with overt thrombocytosis of unknown origin are discovered and will be referred to specialists within the field of haematology for a correct diagnosis.

Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).

Duplicate platelet survival studies, using autologous platelets labelled in vitro with radioactive sodium chromate, were performed on six young healthy asplenic men. In the first experiment plasma, and in the second a Ringer-citrate-dextrose (RCD) solution (Abrahamsen, 1968), was employed as incubation medium. The uptake of chromate by the platelets was about 2.5 times higher in the RCD compared to the plasma experiments. An identical pattern for the immediate behaviour of infused labelled platelets was observed in the duplicate studies, and the recovery of platelet-bound radioactivity remained stable at the 90% level during 2 h post-infusion. In these experiments the means for platelet mean life span (MLS) were identical, 7.2 +/- 0.5 and 7.2 +/- 0.4 days, respectively. These values slightly, but not significantly, exceeded the mean platelet MLS for a control group consisting of 10 young healthy males (6.9 +/- 0.4 days). The means for platelet production rate (P) at the duplicate studies made on the asplenic subjects were 19 +/- 2 X 10(10) and 21 +/- 2 X 10(10) platelets per day, respectively, and did not differ from the mean for P obtained in the control group (22 +/- 2 X 10(10).