Page 81 - Essential Haematology

Chapter 5 Macrocytic anaemias / 67

ropathy is symmetrical and affects the lower limbs
more than the upper limbs. The patient notices

tingling in the feet, difficulty in walking and may

fall over in the dark. Rarely, optic atrophy or severe
psychiatric symptoms are present. Anaemia may be
severe, mild or even absent, but the blood fi lm and
bone marrow appearances are always abnormal.
The cause of the neuropathy is likely to be

related to the accumulation of S - adenosyl homo-
cysteine and reduced levels of S - adenosyl methio-
nine in nervous tissue resulting in defective
methylation of myelin and other substrates. Th e

Figure 5.11 Megaloblastic anaemia: peripheral blood

evidence that folate deficiency in the adult can cause
fi lm showing oval macrocytes.
a neuropathy is confl icting although there are some
data suggesting it may cause psychiatric changes.
Also that B 12 and/or folate therapy may improve also occur. B 12 defi ciency is associated with reduced

cognitive function and delay Alzheimer s disease in osteoblastic activity. The associations of folate defi -
’
the elderly. ciency with cardiovascular and malignant diseases
are discussed on page 71 .
Neural t ube d efect

Folate or B 12 deficiency in the mother predisposes Laboratory fi ndings
to neural tube defect (NTD) (anencephaly, spina
The anaemia is macrocytic (MCV > 98 fL and often

bifida or encephalocoele) in the fetus (Fig. 5.10 ).
as high as 120 – 140 fL in severe cases) and the mac-

The lower the maternal serum or red cell folate or
rocytes are typically oval in shape (Fig. 5.11 ). Th e
serum B 12 levels (even when these are in the normal
reticulocyte count is low and the total white cell and
range), the higher the incidence of NTDs. Moreover,
platelet counts may be moderately reduced, espe-
supplementation of the diet with folic acid at the
cially in severely anaemic patients. A proportion
time of conception and in early pregnancy reduces
of the neutrophils show hypersegmented nuclei

the incidence of NTD by 75%. The exact mecha-
(with six or more lobes). The bone marrow is

nism is uncertain but is thought to be related to
usually hypercellular and the erythroblasts are
build - up of homocysteine and S - adenosyl homo-
large and show failure of nuclear maturation main-
cysteine in the fetus which may impair methylation

taining an open, fine, lacy primitive chromatin
of various proteins and lipids. A common polymor-
pattern but normal haemoglobinization (Fig. 5.12 ).
phism in the enzyme 5,10 - methylene tetrahydro-
Giant and abnormally shaped metamyelocytes are
folate reductase (5,10 - MTHFR) (677C → T) (see
characteristic.

p. 367 ) results in higher serum homocysteine and

The serum unconjugated bilirubin and lactate

lower serum and red cell folate levels compared
dehydrogenase are raised as a result of marrow cell
with controls. The incidence of the mutation is

breakdown.
higher in the parents and fetus with NTD than in
controls.
Diagnosis of v itamin B 12 or

Other t issue a bnormalities f olate d efi ciency
Sterility is frequent in either sex with severe B 12 It is usual to assay serum B 12 and folate (Table 5.7 ).

or folate deficiency. Macrocytosis, excess apoptosis The serum B 12 is low in megaloblastic anaemia or

and other morphological abnormalities of cervical, neuropathy caused by B 12 defi ciency. The serum and
buccal, bladder and other epithelia occur. red cell folate are both low in megaloblastic anaemia
Widespread reversible melanin pigmentation may caused by folate deficiency. In B 12 defi ciency, the