The direct antiglobulin (Coombs) test in megaloblastic anaemia

Abstract

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.

A Rare Case of Acquired Hemolytic Anemia and Pancytopenia Secondary to Pernicious Anemia

“…In such cases, if anemia does not respond to vitamin B12 supplementation, corticosteroid therapy or therapeutic splenectomy is indicated. Forshaw and Harwood [8] studied the association of a positive antiglobulin reaction with megaloblastic erythropoiesis. Thirty-two patients with megaloblastic anemia were investigated, and the direct antiglobulin test was positive in 10.…”

Pernicious Anæmia Followed by Autoimmune Hæmolytic Anæmia

“…The association of pernicious antemia and a weakly positive antiglobulin test is not considered significant. Recorded cases were not complicated by overt haemolytic anaemia or even compensated hemolysis (Forshau & Harwood 1965, Henneman 1956, Wenner 1959. It seems possible that in these cases gammaglobulins, devoid of antierythrocytic activity, were nonspecifically bound to the red cell membrane.…”

Autoimmune cytopenias in pernicious anemia: A report of four cases and review of the literature

“…First, the transiently positive antibody does not appear to cause hemolysis ; the reticulocyte count is low (16) and increases only after cobalamin replacement. Second, the positive direct Coombs' test usually disappears with cobalamin treatment in those patients (19,20), and there is no role for corticosteroids. The cause of this transient phenomenon is unknown.…”

“…The ineffective erythropoiesis and hemolytic component of cobalamin deficiency can produce increased lactate dehydrogenase activity (lo), indirect hyperbilirubinemia (1 1, 12), a decreased serum haptoglobin level (13), decreased erythrocyte survival (14-16), and occasionally even methemalbuminemia (13) and hemosiderinuria (17). Furthermore, a positive direct Coombs' test is a common finding in untreated pernicious anemia (18)(19)(20). The Coombs' test usually becomes negative after treat-ment with cobalamin, however, and the antibody does not appear to cause hemolysis (19,20).…”

“…Furthermore, a positive direct Coombs' test is a common finding in untreated pernicious anemia (18)(19)(20). The Coombs' test usually becomes negative after treat-ment with cobalamin, however, and the antibody does not appear to cause hemolysis (19,20).…”