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

Abstract

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 t e c h q u e 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. METHODS Erythrocyte SurvivalThe patient's own erythrocytes were labelled with 51Cr by the method of Mollison and Veall (1955). In a few instances the erythrocytes of an apparently compatible donor were labelled and introduced into the patient's circulation.The erythrocytes from I 5 to 2 0 nil. of blood .collected into sterile acid-citratc-dextrose (ACD) anticoagulant were labelled with approximately IOO uc of NaZ5lCrO4 having a specific activity of 10 PC per ug. After washing with saline, the labelled cells were suspended in s a h e and reinjected. Blood samples were obtained after 10 and 15 minutes, and thereafter at intervals of 1-4 days. The radioactivity of the blood was measured in a well-type scintillation counter with a thallium-activated sodium iodide crystal of 5 cm. diameter. A counting rate of 105 counts per min. per uc was obtained, so that with the dose of 51Cr administcred a count double the background was still present when the blood contained only 3 per cent of its original radioactivity. The measurements of the blood samples obtained 10-1 5 minutes after the injection of the labelled cells were used as a standard for comparison with all subsequent measurements.The measurements were corrected for radioactive decay by reference to a semipermanent agar standard. Correction for elution of chromium from the erythrocytes wa...

Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody.

“…Recent studies using glycine-2-14C as a label have shown directly that the population sensitive to complement is destroyed within 20 days whereas the insensitive population survives more nearly normally (26). This is in accord with evidence from the 51Cr studies in PNH if the biphasic curve is, in fact, due to the presence of two populations (24).…”

“…It has been suggested that some of the cells in PNH blood might be normal from the fact that there is a residuum of cells that resists lysis in the acidified serum test even if the cells are exposed to successive samples of acidified serum (22). Also, complex red cell survival curves have been repeatedly noted with PNH cells both with Ashby differential agglutination and radioisotope techniques (23,24). However, it was not known whether this variability in the rate of destruction in vivo and the insensitivity of some of the cells to acidified serum lysis in zitro was a reflection of a single population of cells with a wide distribution in the severity of the abnormality or of two populations of cells.…”

Chronic hemolytic anemia due to cold agglutinins

“…The autologous red cells of cases 2 and 3 also failed to accumulate predominantly in either the liver or the spleen, which is in keeping with the observation of Lewis, Szur, and Dacie (15). Only in the fourth patient, B. C., was there unequivocal evidence of splenic accumulation of autologous cells.…”

Biometrically Revealed Splenic Differences between Thalassemia, Hereditary Spherocytosis and Elliptocytosis

“…Measurements of survival of elliptocytes in normals and splenectomized subjects with elliptocytosis (12), re search on elliptocytes tagged with radioactive iron (8) and chro mium (43), and measurements of elliptocyte destruction in cir culating blood (8) all indicate that the spleen has a special role in elliptocyte sequestration and hemolysis very probably similar to that for spherocytes.…”