Page 77 - Essential Haematology

Chapter 5 Macrocytic anaemias / 63

Table 5.3 Causes of severe vitamin B 12

DNA
defi ciency.
dATP dGTP dCTP dTTP Nutritional
Especially vegans
dTDP Malabsorption
Gastric causes
Pernicious anaemia
Methotrexate
DHF dTMP
polyglutamate Congenital lack or abnormality of intrinsic factor
Total or partial gastrectomy
THF 5, 10-methylene THF dUMP
polyglutamate polyglutamate Intestinal causes
Intestinal stagnant loop syndrome – jejunal
diverticulosis, blind - loop, stricture, etc.
THF Chronic tropical sprue
Methionine Ileal resection and Crohn ’ s disease
B 12
Homocysteine Congenital selective malabsorption with
Methyl THF proteinuria (autosomal recessive megaloblastic
Cell membrane anaemia)
Fish tapeworm
Methyl THF
Plasma
Causes of mild vitamin B 12 defi ciency; other causes of
Small intestine malabsorption of vitamin B 12 (e.g. malabsorption of food
B 12 , in the elderly, atrophic gastritis, severe pancreatitis,
gluten - induced enteropathy, HIV infection or therapy with
metformin): These conditions do not usually lead to
Dietary folates
vitamin B 12 defi ciency suffi cient to cause anaemia or
neuropathy.
Figure 5.5 The biochemical basis of megaloblastic

anaemia caused by vitamin B 12 or folate defi ciency.
Folate is required in one of its coenzyme forms,
5,10 - methylene tetrahydrofolate (THF) polyglutamate,
in the synthesis of thymidine monophosphate from its ase but only very weakly against the human enzyme,
precursor deoxyuridine monophosphate. Vitamin B 12 is is used alone or in combination with a sulphona-
needed to convert methyl THF, which enters the cells mide, as co - trimoxazole. Toxicity caused by
from plasma, to THF, from which polyglutamate forms
of folate are synthesized. Dietary folates are all methotrexate or pyrimethamine is reversed by
converted to methyl THF (a monoglutamate) by the giving the reduced folate, folinic acid (5 - formyl
small intestine. A, adenine; C, cytosine; d, deoxyri- THF).
bose; DHF, dihydrofolate; DP, diphosphate;
G, guanine; MP, monophosphate; T, thymine; Vitamin B 12 d efi ciency

TP, triphosphate; U, uracil.
In Western countries, severe deficiency is usually

caused by (Addisonian) pernicious anaemia (Table
fore inhibit all folate coenzyme reactions, and 5.3 ). Less commonly, it may be caused by veganism
so DNA synthesis (Fig. 5.5 ). Methotrexate is a in which the diet lacks B 12 (usually in Hindu
useful drug, mainly in the treatment of malignant Indians), gastrectomy or small intestinal lesions.

or inflammatory disease (e.g. of the skin) with Mild degrees of B 12 defi ciency have been reported

excessive cell turnover. The weaker antagonist, in the elderly and ascribed to poor diet and malab-
pyrimethamine, is used primarily against malaria. sorption of food B 12 . Th ere is no syndrome of

Trimethoprim, active against bacterial DHF reduct- B 12 deficiency as a result of increased utilization or