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SYNOPSIS Folic acid deficiency with the picture of a megaloblastic bone marrow may develop in haemolytic anaemia, and, on the other hand, both vitamin B12 and folic acid deficiency may produce signs of haemolysis. As the correct interpretation of a positive antiglobulin reaction associated with megaloblastic erythropoiesis is particularly important, the effect of deficiency of vitamin B12 and folic acid on the results of the test was investigated in 32 patients with vitamin B12 or folic acid deficiency and a positive antiglobulin reaction was obtained in ten. There was no correlation between the result of the test and the degree of anaemia, and there was no significant difference between the incidence of positive results associated with deficiency of vitamin B12 or folic acid. In determining the significance of a positive result, the time interval before agglutination occurs is sometimes of greater value than the strength of the reaction or the result of the gamma globulin neutralization test.In both the acquired and hereditary types of haemolytic anaemia, the demands of increased red cell production may result in folic acid deficiency and a megaloblastic bone marrow (Chanarin, Dacie, and Mollin, 1959). It is important, therefore, to look for evidence of associated haemolytic disease in patients with megaloblastic erythropoiesis. As deficiency of both vitamin B12 and folic acid reduces the erythrocyte life span, resulting in a low haptoglobin level (Owen, Carew, Cowling, Hoban, and Smith, 1960) and sometimes an increase in unconjugated bilirubin in the serum, the diagnosis of a primary haemolytic disorder may be difficult to determine initially.The result of the direct antiglobulin test is of particular importance in the diagnosis of acquired auto-immune haemolytic anaemia. However, a positive result is not absolutely specific (Dacie and Lewis, 1963), and there has been one detailed report of a patient in whom a positive antiglobulin test was produced by pernicious anaemia (Selwyn and Alexander, 1951). In order to clarify the interpretation of a positive reaction in patients with megaloblastic erythropoiesis, we have investigated the effect of vitamin B12 and folic acid deficiency on the results of the test.

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SYNOPSISThe results of the measurement of vitamin B12 absorption by counting the radioactivity of 5 ml. serum obtained eight to 10 hours after the ingestion of an oral dose of 0 5 ,tg. vitamin B12 labelled with 0-5 ,uc. 57Co are compared with those obtained with the urinary excretion (Schilling) test. Inadequate urine collection and impaired renal function were responsible for low results in the Schilling test in four of the 12 control subjects, and an incomplete urine collection in four patients with pernicious anaemia could have led to doubt about the validity of the low result. It is necessary to measure the absorption of vitamin B12 from the small intestine in order to diagnose the cause of vitamin B12 deficiency with precision. The methods available for measuring the absorption of an oral dose of radioactive vitamin B12 include the estimation of radioactivity in the faeces (Heinle, Welch, Scharf, Meacham, and Prusoff, 1952), the urine (Schilling, 1953), the liver (Glass and Boyd, 1957), and the blood (Booth and Mollin, 1956). Before measuring the hepatic uptake of vitamin B12 the residual radioactivity in the bowel must be cleared by laxatives and an enema, and in the faecal excretion method the preparation of the specimens is unpleasant and it takes an average of seven days to complete the test. Because of these disadvantages the measurement of the excretion of radioactivity in the urine (Schilling test) has been the most widely adopted method. However, the Schilling test also has disadvantages: these are that the test depends upon renal function and a complete 24-hour urine collection, and that the large parenteral dose of non-radioactive vitamin B12 may occasionally obscure the diagnosis.The measurement of radioactivity in a singleReceived for publication 9 May 1966. sample of serum or plasma is clearly the simplest method. However, the amount of radioactivity that appears in the blood after oral doses of 0 5 to 1-0 ,ug. vitamine B12 is small and in the early studies in which vitamin B12 labelled with -"Co, 58Co, or 6OCo was used it was necessary either to obtain large quantities of serum or plasma, to count for long periods in very sensitive scintillation counters, or to use isotopes of high specific activity (Booth and Mollin, 1956;Doscherholmen and Hagen, 1957;Goldberg, Trivedi, and Oliver, 1957). In view of these disadvantages the counting of radioactivity in the blood was not regarded as a satisfactory method for measuring vitamin B12 absorption. However, the lower energy gamma radiation of 57Co is counted with high efficiency by scintillation crystals (Eberle and Gleason, 1960), and when vitamin B12 labelled with 57Co became available, blood counting was again investigated and satisfactory results were obtained using a dose of 0.5 ,uc. and a small volume of serum (Nelp, McAfee, and Wagner, 1963; McCurdy, 1965 Studies were made on 12 volunteer control subjects who were hospital patients with either respiratory infections or a myocardial infarction, and on 17 patients with megaloblastic anaemia.S...