The Megaloblastic Anaemias

There are few facets of haematology of more interest to the clinician than the megaloblastic anaemias, ranging as they do from infancy to old age and embracing a number of conditions of widely differing aetiology. In some the pathogenesis of the anaemia is not understood fully, but in all there is a breakdown in the supply. of substances which are essential for the normal maturation of the red blood cells. The concept that megaloblastic change in the bone marrow was the result of a nutritional deficiency was established by the classical work of Minot and Murphy (1926) and Castle (I929). According to Castle, a substance in the food (extrinsic factor) combined with a factor present in normal gastric juice (intrinsic factor) and as a result of the interaction of the two the active haemopoietic principle was formed. The isolation of vitamin B12 from liver (Smith, I948; Rickes et al., 1948) has not altered the fundamental nature of Castle's observations, for recent work has shown that vitamin B12 is probably identical with Castle's extrinsic factor (Berk et al., 1948). Whether it is also identical with the haemopoietic principle is still not certain, for, although, it is active when given parenterally, it may have to be altered in some way by a substance present in the body before it can become haemopoietically. active. The isolation of folic acid (Mitchell et al., I944) and the demonstration that it will restore normal erythropoiesis in all forms of megaloblastic anaemia has shown that a second dietajr factor is necessary for normal blood formation. It is clear that a deficiency of either vitamin B1, or folic acid can lead to the development of a megaloblastic anaemia, but. the exact way in which the two are. related remains unknown. The part played by a deficiency of either of these two vitamins. in the pathogenesis of the megaloblastic anaemias is variable (Fig. i). In true pernicious anaemia and after total gastrectomy lack of intrinsic factor leads to a deficiency of vitamin B12. The fish-tapeworm anaemia probably is also the result of deprivation of this vitamin. All the other megaloblastic anaemias are usually the result of a deficiency of folic acid, but in any one of them there may be an associated deficiency of vitamin B,2.