Document 6428088

6
Platelet abnor
Dr Simon McRae
CBE illustrated report
Analytes
Result
Range ✜
Analytes
Haemoglobin
140 g/L
(115 – 155)
White Cell Count
RBC
4.26 x 1012 / L
(3.80 – 5.20)
Neutrophils
PCV
0.42 L/L
(0.35 – 0.45)
Lymphocytes
Result
59.0 %
34.0 %
Result
Range
5.03 x l 09/L
(4.00 – 11.00)
2.97 x l 09/L
(1.80 – 7.50)
9
(1.00 – 3.50)
9
1.71 x l 0 /L
MCV
90.0 fL
(80.0 – 98.0)
Monocytes
6.0 %
0.30 x l 0 /L
(0.20 – 0.80)
MCH
32.9 pg
(27.0 – 33.0)
Eosinophils
0.8 %
0.04 x l 09/L
(0.02 – 0.50)
MCHC
330 g/L
(315 – 355)
Basophils
RDW
14.0 %
(11.5 – 15.5)
Platelets
*52
(150 – 400)
0.2 %
9
0.01 x l0 /L
(0.00 – 0.10)
✜ Female reference ranges
P
latelet abnormalities are
common and often discovered
as an incidental finding during
‘routine’ investigations; however,
as consequences range from benign
to fatal they create an important
diagnostic challenge.
Thrombocytosis
No
Quantitative defects of platelets, either
too many (thrombocytosis) or too few
(thrombocytopenia), can lead to the
clinical complications of thrombosis
or bleeding respectively. The purpose
of this article is to provide a diagnostic
approach to the underlying cause of
these quantitative platelet disorders.
? Myeloproliferative
Primary
(Haematology
referral)
Reactive ?
? Myelodysplasia
Thrombocytosis
Defined as a platelet count greater
than 400 x 109/L, there are numerous
potential causes of thrombocytosis.
Broadly they can be divided into
primary (marrow disorders) and
secondary (reactive) causes. Before
considering a primary marrow disorder
as the cause of an elevated platelet
count, a secondary or reactive cause
should be excluded.
IMVS Newsletter 68 Summer 2008
Positive
Negative
BCR-ABL
CML
ET
PRV
Myelofibrosis
Bone Marrow
to confirm
Yes
Treat underlying
cause
7
Part lV
next?
malities
REACTIVE CAUSES
Reactive causes are by far the most
common cause of thrombocytosis in
the general population. The clinical
context in which thrombocytosis occurs
may suggest that the increased platelet
count is reactive in nature. Common
scenarios include:
• iron deficiency
• inflammatory disorders
–
e.g. connective tissue
disorders, inflammatory bowel
disease, tissue injury/trauma,
sepsis or infection
• malignancy
• previous splenectomy
• rebound thrombocytosis following
haemorrhage.
As well as causing thrombocytosis
in its own right, iron deficiency may
mask an underlying diagnosis of
polycythaemia rubra vera (PRV)
and hence should be excluded.
Similarly, the possibility of underlying
malignancy needs to be considered.
Investigation to exclude it should be
guided by clinical symptoms and signs.
you n o w ?
did A normal kplatelet
count
is 150 – 400 x 109/L.
With a life span ~ 10 days,
an average 15 x 1010
platelets must be
produced every
day.
† Myelodysplasia is a common
cause of thrombocytopenia
>60 years, and may be associated
with dyplastic features on film.
* Dependent on severity.
While spontaneous bleeding is
uncommon in patients with a
platelet count >30 x 109/L, for
those <100 x 109/L consider
referral.
Thrombocytopenia†
฀
฀
฀
฀ ฀
฀
฀
฀
฀
฀
Abnormal
Platelet
clumps
Platelets
abnormal
Spurious?
Inherited
Red cells
abnormal
Red + white cells
abnormal
Pancytopenia
(see text)
Abnormal
Normal
APTT / INR
D-dimer
DIC?
฀
฀
฀
Microangiopathy?
฀
฀
฀
฀
฀
Thrombocytopenia
Thrombocytosis after an acute insult
such as trauma may persist for up to a
month, and can reach levels as high as
1000 x 109/L and hence the magnitude
of the increase alone cannot be used
to distinguish primary from reactive
causes. Further laboratory investigation
may provide additional supportive
evidence. A concurrent marked acute
phase response (e.g. raised ESR, CRP)
suggests reactive thrombocytosis,
although it does not entirely exclude
a primary process.
With the advent of automated counters,
the finding of thrombocytopenia,
defined as a platelet count of less than
150 x 109/L, has become a common
clinical problem. The implications of the
underlying cause of thrombocytopenia
range in severity from having no clinical
relevance to being potentially fatal.
Patients in whom a secondary cause
for thrombocytosis cannot be identified,
particularly when the platelet count
is persistently above 600 x 109/L,
should be referred to a haematologist
to exclude a primary bone marrow
disorder (see Thrombocytosis Referrals).
Spurious causes of thrombocytopenia
must be excluded to avoid unnecessary
further investigation and management.
Clot formation in the sample is a
common cause of thrombocytopenia;
these samples are discarded and
a repeat sample recommended.
IMVS Newsletter 68 Summer 2008
Immune (ITP)
Normal
Blood film
The IMVS will perform a blood film
examination as an initial investigation
in all patients with thrombocytopenia.
฀
฀
฀
฀
฀
฀
Approximately 0.2% of all individuals
will have platelets that clump when
their blood is exposed to the EDTA
anticoagulant in blood specimen
containers (purple top). The clumping
causes a falsely low platelet count, an
abnormality that will only be detected
by examining a blood film. Where
platelet clumping due to EDTA is
confirmed we recommend collecting
an additional sample in a Na citrate
(blue top) tube for future requests.
ASSOCIATED ABNORMALITIES
IS IT ARTEFACTUAL?
Thrombocytopenia associated
with pancytopenia most commonly
reflects bone marrow failure due to
conditions such as acute leukaemia or
myelodysplasia, marrow infiltration by
secondary processes such as carcinoma,
or less commonly aplastic anaemia.
8
Important treatable causes such as
B12/folate deficiency or hypersplenism
should not be forgotten. In patients
receiving cytotoxic drugs marrow
suppression is also a common cause.
Findings in the peripheral blood
film such as immature cells in
leukaemic conditions, dysplastic
changes in myelodysplasia, or a
leuco-erythroblastic picture in marrow
infiltration may suggest the likely
diagnosis; a bone marrow examination
is normally required for confirmation.
Hypersplenism, often associated with
liver disease, is a relatively common
cause of pancytopenia due to the
sequestration of blood within the
spleen; it should be considered
in the appropriate patient groups.
Immune mediated
Immune thrombocytopenic purpura
is a relatively common cause of
isolated thrombocytopenia in both
adults and children. The underlying
cause is thought to be accelerated
platelet destruction due to autoantibodies. Spontaneous clinically
significant bleeding is rare unless
the platelet count falls to less than
30 x 109/L. The diagnosis of ITP is
one of exclusion. Once spurious and
other causes have been excluded, and
provided the rest of the blood count
and film is normal, a bone marrow
examination is not required to make
the diagnosis in patients under 60;
older than this, due to the increased
risk of myelodysplasia, bone marrow
examination is advisable.
less prominent and renal impairment
more marked in HUS. A diagnosis
of TTP/HUS should be considered
in all patients with unexplained
thrombocytopenia, and is suggested
by prominent red cell fragmentation
on the peripheral film, and features of
haemolysis such as a raised LD. The
coagulation screen is usually normal,
as opposed to patients with DIC.
Conditions associated with TTP/HUS
include malignancy, pregnancy, drugs
(ticlopidine, cyclosporin, gemcitabine),
auto-immune disorders, and infectious
diarrhoea, although it is common
for no cause to be identified. The
degree of thrombocytopenia is often
moderate to severe. If TTP/HUS
is suspected, urgent referral to
a specialist centre is required.
ISOLATED THROMBOCYTOPENIA
Although the above causes of
thrombocytopenia may predominantly
manifest as thrombocytopenia, finding
a low platelet count in isolation is
more likely to be due to a number
of other conditions:
• inherited thrombocytopenia
• immune mediated thrombocytopenia
–
idiopathic thrombocytopenic
purpura (ITP)
–
drug mediated immune
thrombocytopenia
• thrombocytopenia related to
microangiopathic haemolysis
• disseminated intravascular
coagulation (DIC)
• myelodysplasia.
Inherited thrombocytopenia
This most commonly presents in
infancy, however diagnosis may be
delayed until adult years. Pointers
to an inherited cause include family
history, the lack of a previously
documented normal platelet,
and often abnormal peripheral
blood film morphology including
giant platelets (Mediterranean
macrothrombocytopenia, Bernard
Soulier-Syndrome, May Hegglin
syndrome) or abnormal inclusions in
other cells (May-Hegglin syndrome).
This again emphasises the importance
of film examination in the diagnosis.
IMVS Newsletter 68 Summer 2008
HIT should be considered with recent
exposure to heparin
Drug induced causes of immune
thrombocytopenia should be carefully
considered in all patients with
thrombocytopenia. Common candidates
include quinine, sulphonamides,
IIb/IIIa antagonists and heparin.
Specific tests can be performed for
quinine and heparin related antibodies.
The diagnosis of heparin induced
thrombocytopenia (HIT) is important,
due to the high rate of often severe
thrombotic complications in the
absence of alternative anticoagulant
therapy. Specific laboratory testing
for HIT should be considered in all
patients with thrombocytopenia and
recent exposure to heparin (normally
5 – 14 days after first exposure).
MAHA
The spectrum of diseases associated
with microangiopathic haemolytic
anaemia (MAHA), ranging from
thrombotic thrombocytopenia purpura
(TTP) to the haemolytic uraemic
syndrome (HUS), are important causes
of thrombocytopenia to recognise early.
TTP is characterised by the clinical
features of thrombocytopenia,
fragmentary haemolytic anaemia,
neurological features and often renal
impairment. Neurological features are
DIC
Disseminated intravascular coagulation
is a syndrome characterised by
initial widespread activation of
the coagulation system, leading to
secondary consumption of coagulation
factors and platelets and a resulting
coagulopathy. Thrombocytopenia
in the setting of conditions known
to be associated with DIC, such as
sepsis, massive trauma, malignancy
and obstetric disasters should lead
to consideration of this as the cause.
While red cell fragmentation can also
be seen on the peripheral blood film
in patients with DIC, it is normally
less marked than in TTP/HUS, and
the coagulation screen is almost
always abnormal with a prolonged
PT, APTT and significantly elevated
D-dimer levels. Treatment of DIC
is of the primary cause, along with
supportive use of blood products
as clinically indicated.
Further assistance
The IMVS on-call haematologist can
help to guide the diagnostic process
and determine both the need for and
urgency of specialist referral. ▲