Summary. Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason. the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established. Keywords: red cell mass, plasma volume, normal values, interpretation.Recommended methods for the measurement of red cell mass (RCM) and plasma volume (PV) have been drawn up by the Radionuclide Panel of the International Committee for Standardization in Haematology (1 980b). These methods are now widely followed and provide within-method accuracy in the order of 2-3%.The remaining problem with RCM and PV measurements is the interpretation of the results. Traditionally, results and normal values have been expressed in terms of ml per kg total body weight. Indeed, the widely quoted Polycythaemia

In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.

Nonradiomimetic drugs, hydroxyurea (HU) and pipobroman (Pi), were administred to relatively young subjects with polycythemia vera (PV) in an attempt to decrease the leukemogenic risk observed in patients treated with 32P. Clinical safety, hematological efficacy, risk of carcinoma or leukemia, and frequency of progression to myelofibrosis have not yet been defined in long-term studies, and no comparative studies of HU and Pi have been conducted. Since 1980, 292 patients with PV diagnosed before the age of 65 years were randomized to receive treatment with HU (25 mg/kg/d, followed by low-dose maintenance) or Pi (1.2 mg/kg/d, followed by low-dose maintenance). Patients were followed until death or until May 1997. Drug tolerance was often poor; leg ulcers and buccal aphthous ulcers (with HU) and gastric pain and diarrhea (with Pi) sometimes required treatment change, mainly in the HU arm. Hematological stability, especially in terms of platelet count, was very often insufficient with HU (45% of cases), but the risk of thrombo-embolic event was similar in both arms. Actuarial survival was similar in the two arms and shorter than that of the reference population. The risk of leukemia was approximately 10% at the 13th year, with no significant difference between the two arms. The risk of carcinoma (when excluding the skin cancers) was similar in both groups. There was a high risk of progression to myelofibrosis in the patients treated by HU, which was significantly higher than with Pi.

Summary.The indication for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP) remains a controversial subject. The mortality rate of persistent thrombocytopenia is very low, except in severe cases. Conversely, the risks of splenectomy are significant (in the present series, morbidity: 4 . 1% mortality: 1 . 4%), with a success rate of only 60-75%. It is therefore useful to define a parameter able to predict the efficacy or failure of splenectomy.An analysis of 578 cases of chronic ITP, where the site of platelet destruction has been determined, is presented. 268 of these cases had been splenectomized. When platelet destruction was splenic, 96% of subjects aged 5-30 years and 91% of cases over the age of 30 years obtained a remission. Conversely, when platelet destruction was hepatic or diffuse, failure or incomplete results were observed in 92% of cases. The site of platelet destruction therefore constitutes a parameter which can help the clinician to make the decision to perform splenectomy.Keywords: thrombocytopenic purpura, platelet kinetics, site of platelet sequestration, splenectomy.We have previously reported a correlation between the site of platelet destruction and the efficacy of splenectomy in 222 cases of idiopathic thrombocytopenic purpura (ITP), 103 of whom underwent splenectomy (Najean et al, 1991). Our conclusions concerning children were criticized at that time, more because of the surgical indications (which were considered to be excessive) than for the actual isotope study (Reid, 1992). Only one similar study has since been published, confirming the predictive value of the method in 51 cases (Lamy et al, 1993). In a recent retrospective study (George et al, 1996), which proposed a practice guideline for diagnosis and treatment of ITP, isotopic assessment was only briefly considered as a measurement of platelet life-span for diagnostic purposes, but not for determination of the site of destruction as an aid to therapeutic decisions.At the time of writing, 578 cases of chronic ITP have undergone a kinetic study of autologous platelets labelled with 111 Indium-oxinate, 268 of whom have been splenectomized. PATIENTS AND METHODSAll of the cases studied (103 children aged 5-15 years, 146 adolescents or young adults aged 15-30 years, and 329 cases over the age of 30 years) had clinically documented thrombocytopenic purpura which could be considered to be idiopathic (systemic lupus erythematosus, viral infection, especially by HIV, lymphoma, and, in the elderly, myelodysplasia, were eliminated). Cases of genetic chronic thrombocytopenia due to a production defect were excluded. These cases of ITP were chronic, and had symptoms present for at least 6 months. We did not investigate pregnant women or very young children. The sex ratio in each age-group showed the same female predominance (M=F ¼ 0 : 6).Almost all patients had been previously treated (corticosteroids, immunoglobulins, danazol, and, in rare cases, azathioprine or vincristine). At the time of the isotope study, one half of the c...

Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting <2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.