Page 78 - Essential Haematology

64 / Chapter 5 Macrocytic anaemias

loss of the vitamin. Th e deficiency takes at least 2 ATPase, and 50% type I or blocking antibody to IF

years to develop (i.e. the time needed for body which inhibits IF binding to B 12 . Thirty - fi ve per

stores to deplete at the rate of 1 – 2 μ g/day) when cent show a second (type II or precipitating) anti-

there is severe malabsorption of B 12 from the diet. body to IF which inhibits its ileal binding site. IF

Nitrous oxide, however, may rapidly inactivate antibodies are virtually specific for pernicious
body B 12 (see p. 71 ). anaemia but occur in the serum of only half of
patients, whereas the more common parietal cell

antibody is less specific and occurs quite commonly
Pernicious a naemia
in older subjects (e.g. 16% of normal women over
This is caused by autoimmune attack on the gastric 60 years).

mucosa leading to atrophy of the stomach. Th e wall
of the stomach becomes thin, with a plasma cell and

lymphoid infiltrate of the lamina propria. Intestinal
Other c auses of v itamin B 12 d efi ciency

metaplasia may occur. There is achlorhydria and
secretion of IF is absent or almost absent. Serum Congenital lack or abnormality of IF usually
gastrin levels are raised. Helicobater pylori infection presents at approximately 2 years of age when stores
may initiate an autoimmune gastritis which presents of B 12 that were derived from the mother in utero

in younger subjects as iron deficiency and in the have been used up. There is also a form of autoim-
elderly as pernicious anaemia. mune pernicious anaemia that presents in child-
More females than males are affected (1.6 : 1), hood. Specific malabsorption of B 12 is brought

with a peak occurrence at 60 years, and there may about by genetic mutation of the IF – B 12 receptor,
be associated autoimmune disease including the cubilin or of amnionless which is involved in
autoimmune polyendocrine syndrome (Table 5.4 ). processing the IF – B 12 complex. It usually presents
The disease is found in all races but is most common in infancy or childhood and is associated with pro-

in northern Europeans and tends to occur in fami- teinuria in 90% of cases.
lies. There is also an increased incidence of carci- Lesser degrees of B 12 defi ciency occur resulting

noma of the stomach (approximately 2 – 3% of all from inadequate intake of B 12 , malabsorption of
cases of pernicious anaemia). food B 12 , especially in the elderly, atrophic gastritis
(possibly triggered by Helicobacter pylori ) without
IF antibodies and other conditions listed in Table
Antibodies
5.3 . Serum homocysteine and methylmalonic acid
Ninety per cent of patients show parietal cell anti- levels may be mildly raised and serum B 12 levels
+
+
body in the serum directed against gastric H /K - subnormal but in these conditions megaloblastic
anaemia or neuropathy rarely occur.
Table 5.4 Pernicious anaemia: associations.

Folate d efi ciency
Female Vitiligo

This is most often a result of a poor dietary intake
Blue eyes Myxoedema
of folate alone or in combination with a condition
Early greying Hashimoto ’ s disease
of increased folate utilization or malabsorption
Northern European Thyrotoxicosis (Table 5.5 ). Excess cell turnover of any sort, includ-
ing pregnancy, is the main cause of an increased
Familial Addison ’ s disease
need for folate, because the folate molecule becomes
Blood group A Hypoparathyroidism degraded when DNA synthesis is increased. Th e
Hypogammaglobulinaemia
mechanism by which anticonvulsants and barbitu-
Carcinoma of the stomach
rates cause the deficiency is still controversial.