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his third article in our series
‘CBE – what next?’ outlines
disease processes that affect
white blood cells; it is an overview
of the causes of both increased and
decreased white cell counts designed
to guide initial investigations.
The white cell count (WCC)
measures two components; the total
number of white blood cells and the
differential count, which measures the
percentage of each cell type present i.e.
neutrophils, lymphocytes, monocytes,
eosinophils and basophils.
The number of white cells in the
bloodstream changes rapidly in
response to a variety of stimuli such
as shock, acute stress, infection, drugs,
acute and chronic inflammation, and
changes in hormone levels.
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The normal WCC range in a healthy
adult Caucasian male is 4 – 11 x 109/L.
Females of reproductive age generally
have higher counts than men that tend
to fluctuate with menstruation, and
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the reference ranges for children are
notably higher (Table 1).
It is normal for sub Saharan Africans
to have a lower WCC; the ranges
are 2.8 – 7.4 x109/L (WCC) and
1.0 – 4.0 x 109/L (neutrophils).
Interestingly in normal subjects, and
for all groups, the WCC is generally
higher towards the end of the day.
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Leucocytosis (an increase in total
WCC) most often results from an
increase in neutrophils but other cell
types may be responsible, hence it is
important to check the differential
count when interpreting leucocytosis.
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Common physiological causes of
neutrophilia include pregnancy and
exercise.
Pregnancy is associated with a marked
rise in the neutrophil count (5.9 – 16.9
x 109/L in the third trimester) with a
‘left shift’. Increased ‘toxic granulation’
of the neutrophils resembling infection
also occurs. Vigorous exercise normally
results in a doubling of the neutrophil
count for a short time.
Patients taking corticosteroids often
have a persistent increase in neutrophils
reflecting a number of changes to
neutrophil kinetics, including decreased
movement into tissues.
Neutrophilia is also associated with any
pathological condition that stimulates
increased marrow output of neutrophils.
Common causes are acute and chronic
bacterial infections, gout, pseudogout,
tissue damage including burns and
myocardial infarction, haemorrhage,
hypoxia, seizures and pain. Early
viral infection may also give a raised
neutrophil count.
The presence of precursor myeloid
cells or blasts should prompt
consultation with a haematologist.
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The normal lymphocyte counts of
infants and children are considerably
higher than those of adults and so
it is important to use age-adjusted
reference ranges (Table 1).
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Young children can often have
dramatically elevated lymphocyte
counts in response to viral infections,
Bordetella pertussis (whooping cough)
and other intracellular pathogens.
then lymphocyte surface marker
studies are recommended (10mL
EDTA required). The presence of a
clonal population of B cells suggests
a lymphoproliferative disorder.
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In acute viral infections, especially
EBV (Epstein-Barr virus or glandular
fever), the cells may show striking
reactive changes, and hence will be
referred to as ‘reactive lymphocytes’
on the blood film report. The IMVS
will perform a Paul-Bunnell test when
reactive lymphocytes are present
in an appropriate clinical context.
Some adult smokers show a persistent
mild rise in lymphocytes that usually
does not require further investigation.
A persistently elevated lymphocyte
count may uncommonly reflect an
underlying lymphoproliferative
disorder. If the changes on a blood
film accompanying lymphocytosis
show lymphocytes of unusual
appearance, for example atypical
lymphocytes or malignant cells,
)-63.EWSLETTER3PRING
For assistance in interpreting the
results of the marker studies please
contact the IMVS duty haematologist,
or refer the patient to a haematologist.
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Mild monocytosis can be seen in
chronic infections such as diabetic
ulcers, osteomyelitis and tuberculosis
or as a bacterial infection is resolving.
Monocytosis in an elderly patient,
especially if there is a history of
recurrent infection or cytopenia, may
suggest underlying myelodysplastic
syndrome. Blood film assessment is
used to exclude dysplastic features.
A persistent increase in the monocyte
count could be missed if the total white
cell count remains normal, which
underscores the need to review the
differential count.
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Eosinophil counts are higher in
neonates and tend to decline in the
elderly. The most common cause
of an elevated eosinophil count
in Australians is allergic disease
(particularly asthma, hay fever and
eczema). However, parasitic infection
should be considered in at risk
populations including remote area
Aborigines, migrants and refugees.
In hospitalised patients, eosinophilia
can be a useful sign of drug allergy.
In uncomplicated asthma, the
eosinophil count rarely exceeds
2 x 109/L. Higher counts, especially
if associated with severe eczema
and decreased pulmonary function,
suggest allergic aspergillosis or
Churg-Strauss syndrome.
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Basophilia is rare, and whilst basophils
are involved in allergic responses,
chronic myeloid leukaemia (CML)
should be considered. Increased
production may also be associated
with bone marrow disorders or
viral infection.
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Leucopenia (a decrease in total WCC)
most often results from a decrease in
neutrophils. The life-span of a typical
human neutrophil is short, about 3 – 6
hours, hence the WCC is often the
first warning sign that a patient may
be developing bone marrow failure,
however viral infection, systemic
autoimmune disease and disease
of the liver or spleen may also lead
to a decreased count. An examination
of the blood film for characteristic
morphological changes, can rapidly
provide vital diagnostic information.
Detection of unexpected neutropenia
must be confirmed immediately on
a blood film as other abnormal cells
may be present that give a clue to
the aetiology. When the cause is not
apparent from history and blood film
examination, a bone marrow biopsy
is usually necessary.
If there is any evidence of infection
such as fever greater than 38°C or
hypotension, hospitalisation and
treatment with broad spectrum
intravenous antibiotics is required.
Clinically significant decreases in
other cell lineages are rare and do
not tend to influence the total WCC.
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The most common causes of
neutropenia include:
• early viral infection
• adverse drug reactions
• severe bacterial infection and
• bone marrow failure
– due to replacement of
marrow by tumour cells
or stem cell reduction
as in aplastic anaemia.
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The WCC and differential portion
of a CBE, particularly in combination
with a blood film report, can provide
useful insights into advancing your
differential diagnosis.
In the next issue, our final article in
the series ‘CBE what next?’ examines
platelets. ▲
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Viral pathogens detected by all
IMVS laboratories for the period
1st January to 29th October 2006
and 2007.
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These respiratory pathogens are
most easily diagnosed by collecting
a deep nasal swab, nasopharyngeal
aspirate, throat swab or sputum.
To order viral swab collection kits
please telephone the IMVS Call
Centre on 8222 3000 and ask
for Consumer Products.
Rapid viral detection results
are available within 24 hours
of specimen receipt.
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