Page 325 - Textbook of Pathology, 6th Edition

of red cell folate. Red cell folate values are decreased in MORPHOLOGIC FEATURES. The most characteristic 309
patients with megaloblastic anaemia as well as in patients pathologic finding in PA is gastric atrophy affecting the
with pernicious anaemia. acid- and pepsin-secreting portion of the stomach and
sparing the antrum (Chapter 20). Gastric epithelium may
Treatment show cellular atypia. About 2-3% cases of PA develop
carcinoma of the stomach. Other pathologic changes are
Most cases of megaloblastic anaemia need therapy with secondary to vitamin B deficiency and include
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appropriate vitamin. This includes: hydroxycobalamin as megaloblastoid alterations in the gastric and intestinal
intramuscular injection 1000 μg for 3 weeks and oral folic epithelium and neurologic abnormalities such as
acid 5 mg tablets daily for 4 months. Severely-anaemic peripheral neuropathy and spinal cord damage.
patients in whom a definite deficiency of either vitamin
cannot be established with certainty are treated with both Clinical Features
vitamins concurrently. Blood transfusion should be avoided
since it may cause circulatory overload. Packed cells may, The disease has insidious onset and progresses slowly. The
however, be infused slowly. clinical manifestations are mainly due to vitamin B 12
Treatment of megaloblastic anaemia is quite gratifying. deficiency. These include: anaemia, glossitis, neurological
The marrow begins to revert back to normal morphology abnormalities (neuropathy, subacute combined degeneration CHAPTER 12
within a few hours of initiating treatment and becomes of the spinal cord, retrobulbar neuritis), gastrointestinal
manifestations (diarrhoea, anorexia, weight loss, dyspepsia),
normoblastic within 48 hours of start of treatment. Reticulo- hepatosplenomegaly, congestive heart failure and
cytosis appears within 4-5 days after therapy is started and haemorrhagic manifestations. Other autoimmune diseases
peaks at day 7. Haemoglobin should rise by 2-3 g/dl each such as autoimmune thyroiditis may be associated.
fortnight. The peripheral neuropathy may show some
improvement but subacute combined degeneration of the Diagnostic Criteria
spinal cord is irreversible.
Since diagnosis of PA requires the patient to receive
lifelong parenteral B therapy, the diagnosis of PA is made
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PERNICIOUS ANAEMIA by combined clinical and laboratory evaluation as per
Pernicious anaemia (PA) was first described by Addison in following diagnostic criteria:
1855 as a chronic disorder of middle-aged and elderly I. Major criteria:
individual of either sex in which intrinsic factor (IF) secretion i) Low serum B level in presence of normal renal function
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ceases owing to atrophy of the gastric mucosa. The condition ii) Megaloblastic anaemia in bone marrow examination,
is, therefore, also termed Addisonian megaloblastic anaemia. which should not be due to folate deficiency
The average age at presentation is 60 years but rarely it can iii) Positive test for IF antibody
be seen in children under 10 years of age (juvenile pernicious II. Minor laboratory criteria:
anaemia). PA is seen most frequently in individuals of i) Macrocytosis in PBF
northern European descent and African Americans and is ii) Anaemia of variable degree
uncommon in South Europeans and Orientals. iii) Hypergastrinaemia
iv) Positive gastric parietal cell antibody
Pathogenesis v) Raised plasma homocysteine level Introduction to Haematopoietic System and Disorders of Erythroid Series
There is evidence to suggest that the atrophy of gastric vi) Gastric pH above 6
mucosa in PA resulting in absence or low level of IF is caused III. Minor clinical criteria:
by an autoimmune reaction against gastric parietal cells. The i) Neurologic features of parasthaesia, numbness or ataxia
evidences in support of immunological abnormalities in ii) Hypothyroidism
pernicious anaemia are as under: iii) Family history of PA or hypothyroidism
1. The incidence of PA is high in patients with other auto- iv) Vitiligo
immune diseases such as Graves’ disease, myxoedema, IV. Reference standard criteria:
thyroiditis, vitiligo, diabetes and idiopathic adrenocortical i) Schilling test showing malabsorption of oral cyano-
insufficiency.
cobalamin corrected by simultaneous administration of
2. Patients with PA have abnormal circulating autoantibodies IF.
such as anti-parietal cell antibody (90% cases) and anti-
intrinsic factor antibody (50% cases). Treatment
3. Relatives of patients with PA have an increased incidence Patients of PA are treated with vitamin B in the following
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of the disease or increased presence of autoantibodies. way:
4. Corticosteroids have been reported to be beneficial in 1. Parenteral vitamin B replacement therapy.
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curing the disease both pathologically and clinically. 2. Symptomatic and supportive therapy such as
5. PA is more common in patients with agammaglobulinaemia physiotherapy for neurologic deficits and occasionally blood
supporting the role of cellular immune system in destruction transfusion.
of parietal cells. 3. Follow-up for early detection of cancer of the stomach.