S. M. Lewis

Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology

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.

Myeloid progenitor cells in the circulation of patients with myelofibrosis and other myeloproliferative disorders

Summary. We have measured the numbers of myeloid progenitor cells in the circulation of patients with myelofibrosis (MF) and other myeloproliferative disorders. In general, progenitor cell numbers were increased in the circulation of patients with MF compared with controls. The mean increases were 9‐fold for the multilineage progenitor cells (CFU‐GEMM), 13‐fold for the erythroid progenitor cells (BFU‐E), 37‐fold for the granulocyte‐macrophage progenitor cells (CFU‐GM) and 167‐fold for the megakaryocyte progenitors (CFU‐MK). Splenectomized patients generally had reduced numbers of circulating progenitor cells. In the CFU‐MK assay, mature megakaryocytes cultured from patients with MF regularly showed large vacuoles in the nucleus and cytoplasm, unlike control cells. The increased colony formation in patients with MK, involving especially CFU‐MK colonies, is consistent with the hypothesis that MF is a primary myeloproliferative disorder in which a megakaryocyte‐derived factor predisposes to the formation of marrow fibrosis.

The Pattern of Erythrocyte Destruction in Haemolytic Anaemia, as Studied with Radioactive Chromium

THE introduction of isotope techques and the availability of a suitable isotope label have greatly facilitated the study of the life-span and the sites of destruction of erythrocytes in haemolytic anaemia. Radioactive chromium (51Cr) has several advantages which make it especially suitable for this purpose : the patient’s erythrocytes can be labelled and re-introduced into his own circulation, and so studied in their natural environment; chromium liberated by erythrocyte destruction is not uthzed to relabel other erythrocytes, and the specific activity of the radloactive chromium is sufficiently high for the labelling to be attained with a small and apparently non-toxic amount of chromium. Furthermore, in addition to determining the intensity of haemolysis by measuring the rate of elimination of erythrocytes from the circulation, it is possible to learn somethmg of the nature of the haemolytic process by studying the pattern of elimination. The effect of treatment on the survival of a patient’s erythrocytes can also be studied and the sites of their destruction determined by counting in vim, with special reference to the role of the spleen and liver. Jandl, Greenberg, Yonemoto and Castle (1956), Hughes Jones and Szur (1957) and others have shown that the in vivo counting techque can be of value, too, in predicting the response to splenectomy. In the present paper we describe the results of survival and in vivo counting studies, using 51Cr,.[carried out on patients suffering from hereditary spherocytosis, hereditary elliptocytosis, hereditary non-spherocytic haemolytic anaemia, sickle-cell disease, paroxysmal nocturnal haemoglobinuria and auto-immune acquired haemolytic anaemia.

Anaemia in myelofibrosis: its value in prognosis

Summary. Forty‐four patients with myelofibrosis were investigated in our hospital in the period 1971–81. Their clinical, laboratory and radioisotope parameters were analysed. The direct correlation between plasma volume and splenic red cell pool has highlighted the role of the spleen in the dilutional anaemia seen in myelofibrosis. 52Fe quantitation enabled us to show that the bone marrow contributes relatively more to effective erythropoiesis than the extramedullary sites. The prognostic value of changes in plasma volume and bone marrow 52Fe activity has been demonstrated. We have shown that the Hb: reticulocyte relationship at diagnosis can be used to recognize probable stages of the disease and provides a useful prognostic determinant.

The Influence of Anaemia, Polycythaemia and Splenomegaly on the Relationship between Venous Haematocrit and Red-Cell Volume

A FAIRLY close relationship has been observed between venous haematocrit (packed cell volume, PCV) and the red-cell volume in normal and in anaemic subjects. However, this is not invariable, and the relationship may be upset by a number of factors. These include a disproportionate increase in plasma volume, as has been demonstrated in cirrhosis (Bateman, Slhorr and Elgvin, 1949), nephritis (Eisenberg, 1959) and pregnancy (Verel, Bury and Hope, 1956). Under these circumstances the PCV cannot be regarded as a reliable index of red-cell mass. Anaemia, polycythaemia and splenomegaly are also thought to influence the relationship of PCV and red-cell volume. The present study was undertaken in order to evaluate the effect of these factors on this relationship.

Use of lllIndium‐labelled Platelets to Measure Spleen Function

The distribution of 111In‐labelled platelets following intravenous bolus injection has been studied using a gamma camera and computer system. Liver uptake, which accounted for about 10% of the dose, was completed between 6 and 10 min after injection. Blood pool and splenic 111In, which accounted for the remainder of the dose, reached constant levels simultaneously about 20 min after injection. The kinetics of splenic uptake are consistent with a two compartmental model in which circulating and splenic platelets are in dynamic equilibrium with each other. From analysis of the kinetics, splenic blood flow and the mean transit time of platelets through the spleen have been calculated in normal subjects and in patients with haematological disorders. Blood flow, which was about 200 ml per min in normals, tended to increase with increasing spleen size. Transit time was not dependent on spleen size; it was about 10 min in all but one of the subjects.

Elution Correction in 51Cr Red Cell Survival Studies

Summary. Red cell survival has been studied in 13 normal adults using simultaneous labelling with DF32P and 51Cr; elution correction factors have been determined for the51 Cr labelling in which ACD NIH formula A has been used as an anticoagulant with ICSH recommended method. The mean rate of 51Cr elution was 1.0% per day and there was no demonstrable early loss of either51 Cr or DF32P. The mean value for mean cell lifespan was found to be 111.2 days with an SD of 20.3 days.

Radionuclide Distribution folowing Injection of 111Indium‐labelled Platelets

Platelets labelled with 111In displayed similar survival curves after incubation with 111In‐oxine in plasma, plasma‐saline and dextrose saline media. The use of autologous red cells to cushion platelets during high‐speed centrifugation facilitated platelet resuspension without greatly affecting the duration of the labelling procedure. Quantitative scanning after reinjection of labelled platelets in haematologically normal subjects showed that, initially, splenic indium amounted to about 35% of the injected dose and hepatic indium about 12%; these levels rose only slightly over the subsequent duration of the platelet life span. Subtraction of the signal from indium in platelets thought to be normally pooled within the spleen from the total indium signal gave splenic indium uptake curves which reflected splenic platelet destruction. Initially, the sum of indium levels in spleen, liver and blood equalled 100% of the dose. Thereafter, the sum fell progressively at a rate thought to be approximately equal to the rate of bone marrow uptake.

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction

Summary. The kinetics of platelets labelled with 111In have been studied in a series of 175 subjects including 18 normal volunteers, and 12 patients with idiopathic thrombocytopenic purpura (ITP), but excluding patients in whom there was scintigraphic evidence of intravascular platelet consumption. From analysis of the kinetics, the following parameters were calculated: splenic blood flow (SBF), intrasplenic platelet transit time (t), splenic platelet pool capacity (expressed as a percentage of the total circulating platelet population), the fraction of the dose of labelled platelets ultimately destroyed in the spleen and the mean platelet life span (MPLS).

Studies of splenic function in the myeloproliferative disorders and generalized malignant lymphomas.

The relative importance of splenic red‐cell pooling, sequestration and cell destruction in the causation of anaemia has been studied in 29 patients—16 with generalized lymphoproliferative disease, 12 with myeloproliferative disease and one with idiopathic autoimmune haemolytic anaemia.