Soodabeh Safai-Kutti

An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: a study of patients with polycythaemia vera and apparent polycythaemia.

The 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 >18·5 g/dl in males and >16·5 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 >18·5 g/dl indicate the presence of AE. Conversely, 14% of male AP patients would be misdiagnosed as having AE. A Hb > 16·5 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 ≥0·60 an AE was always present, and this was true for both male and female subjects.

Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Göteborg, Sweden, during 1983-99.

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.

The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera

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).

The presence of a significant association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia

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).

In Vitro Labelling of Platelets: an Experimental Study on Healthy Asplenic Subjects using Two Different Incubation Media

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‐citratedextrose (RCD) solution (Abrahamsen, 1968), was employed as incubation medium.

No increased frequency of trisomies 8 and 9 by fluorescence in situ hybridization in untreated patients with essential thrombocythemia

Essential thrombocythemia (ET) is one of the diseases included among the myeloproliferative disorders in which trisomies for chromosomes 8 and 9 commonly occur. In ET, only a few patients are known to show clonal abnormalities. With fluorescence in situ hybridization (FISH), interphase cells can be evaluated and clones can be detected even though not revealed by conventional cytogenetic methods. By using FISH for enumeration of chromosomes 8 and 9 in bone marrow cells, we studied 22 patients with ET; 20 of them were investigated at the time of diagnosis when they were still untreated with myelosuppressive agents. Only two patients had trisomy 8; one of them was also found to have +8 with conventional cytogenetics. None of the patients had trisomy 9; two patients had borderline values in comparison to a control group. Thus, in ET, no increased frequency of patients with trisomy for 8 or 9 at the time of diagnosis could be detected with FISH.

Zinc and Anorexia Nervosa

Excerpt To the editor: We read with interest the excellent review of zinc by Russell and coworkers (1). Because some circumstantial evidence indicates that zinc deficiency may be involved in the pa...

Red cell mass, spleen size and plasma erythropoietin in polycythaemia vera and apparent polycythaemia.

Most frequently, an elevated packed cell volume (PCV) value arouses the suspicion of a polycythaemic state. The aim of the present work was to assess a few readily available variables which could help the clinician to differentiate between polycythaemia vera (PV) and apparent polycythaemia (AP). During a 5-year period, 31 consecutive newly diagnosed patients with PV were identified, and during a 4-year period 38 consecutive subjects were considered to be afflicted with AP. In each subject: (i) the red cell mass (RCM) and plasma volume were measured, (ii) the spleen size was assessed using γ-camera imaging, and (iii) the plasma erythropoietin (EPO) concentration was determined. The diagnosis of PV was based upon recently proposed criteria. By definition, all PV patients had absolute erythrocytosis, i.e. the RCM was greater than 25% above the mean normal predicted value for the individual. There was no statistical difference between the plasma volumes for PV and AP patients. However, the mean measured/predicted plasma volume for subjects with AP was significantly lower than the mean for PV. The means for spleen scan areas (posterior and left lateral projections) for AP patients were identical to the mean reference values for our laboratory. As compared to AP, in PV the spleen scan areas were significantly increased, and the lateral spleen scan area was significantly larger than the posterior area. It was also shown that, in contrast to AP, both spleen scan areas were significantly larger in male than in female PV patients. All PV patients had plasma EPO concentrations below the lower reference limit, and in 68% of the patients undetectable EPO concentrations were present. Most AP patients (84%) had EPO values within the reference range; 8% had slightly subnormal, but not undetectable, plasma EPO levels.

The red cell mass, plasma erythropoietin and spleen size in apparent polycythaemia

Abstract: It has been shown previously that measurement of the spleen size and plasma erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work‐up of patients with polycythaemia vera. The aim of the present work was to evaluate their value in the assessment of apparent polycythaemia (AP). Therefore, over a 24‐month period we routinely performed bone marrow biopsies, measurement of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma camera scintigraphy and determination of the plasma EPO concentration in consecutive patients referred to us because of elevated values for packed cell volume (>0.48 in females and >0.51 in males). After having excluded patients with clonal and secondary polycythaemias we were left with 38 patients (27 males and 11 females) with AP. In all of them the measured RCM was within normal range, i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were characterized by moderate increase in RCM and a concomitant moderate decrease in PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in males and by 12% in females; conversely, as compared to the predicted values the average measured value for PV was reduced by 17% in males and by 8% in females. The average RCM for males was 29 ± 3 ml/kg; the corresponding figure for females was 23 ± 4 ml/kg. It was shown that 86% of the subjects had plasma EPO concentrations within the control range; the remaining had values slightly above or below the control range. The mean posterior spleen scan area was 57 ± 16 cm2 and mean left lateral area 57 ± 17 cm2; the reference value for spleen scan area (for both projections) is 57 ± 12 cm2. Of the patients 35/38 (92%) had a spleen scan area within the mean + 2SD for controls and 38 subjects (100%) had values within the mean + 3SD. It is concluded that measurement of plasma EPO and a careful assessment of the spleen size should always be considered in the evaluation of patients with elevated values for venous packed cell volume.

The incidence and survival of acute de novo leukaemias in Estonia and in a well‐defined region of western Sweden during 1982–1996: a survey of patients aged ≥65 years

Objectives.  To compare the incidence and survival of acute de novo leukaemias with particular reference to political/socio‐economic and environmental factors in two neighbouring countries over the three 5‐year periods (1982–1996).