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EMERGENCY CASEBOOK

Thrombotic thrombocytopenic purpura mimicking acute
ischemic stroke
E Aksay, S Kiyan, M Ersel, O Hudaverdi
...............................................................................................................................
Emerg Med J 2006;23:e51 (http://www.emjonline.com/cgi/content/full/23/9/e51). doi: 10.1136/emj.2006.036327

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by thrombocytopenia, haemolytic anemia, fluctuating neurological deficits, fever, and
renal impairment. This case report is about a young man who
presented with acute onset right sided paralysis, dysarthria,
and central facial paralysis, suggestive of cerebrovascular
accident, but eventually diagnosed as TTP. In addition, the
clinical presentation of TTP is discussed and some teaching
points for the emergency physicians are emphasised.

T

hrombotic thrombocytopenic purpura (TTP) is a rare
disorder, and its clinical presentation mimics that of a
variety of other diseases. Early diagnosis is important as
TTP is a life threatening illness with mortality exceeding 90%
in the absence of emergent, appropriate treatment.

CASE REPORT
A previously healthy 36 year old man presented to our
emergency department (ED) with right arm weakness,
numbness on the right side of face, and difficulty speaking,
which developed an hour before presentation. He had had a
fever, cough, headache, and bleeding from the gums for 10
days. On examination, the patient’s blood pressure was 160/
100 mm Hg, pulse 94 beats/min, respiratory rate 14 breaths/
min, and temperature 38.0 ËšC. Neurological examination
revealed 2/5 right arm weakness, 4/5 right leg weakness,
dysarthria, and right central facial palsy. There was no nuchal
rigidity or cerebellar abnormalities.
After blood was drawn for laboratory tests, he underwent
cranial computed tomography (CT) within 30 minutes. The
CT scan did not show any intracranial or subarachnoid
haemorrhage, or any signs of ischaemia. After another half
an hour, his neurological findings resolved. A diagosis of
transient ischaemic attack was considered and admission to
the neurology department planned. Results of the laboratory
tests were unexpected: white blood cell count 12 000 6 109,
haemoglobin 74 g/l (7.4 g/dl), haematocrit 0.21 (21.1%), and
platelet count 11 000 6 109. Urea, creatinine, electrolytes,
and liver function were normal. Urinalysis was remarkable
with +3 erythrocytes. Levels of indirect bilirubin and lactate
dehydrogenase were elevated. Intravascular haemolysis was
suspected and a blood smear requested. Three hours after
presentation, the previous neurological symptoms reappeared
for an hour and then resolved again gradually. The blood
smear was remarkable for fragmented erythrocytes (fig 1).
The intravascular haemolysis, thrombocytopenia, haematuria, fluctuant neurological findings, and fever were
consistent with a diagnosis of TTP. The patient was admitted,
and he underwent plasma exchange emergently. He did not
have any neurological symptoms during the course of
treatment. Complete remission was achieved on day 12 after
admission, and he was discharged on day 16.

DISCUSSION
TTP is a life threatening disease, characterised by thrombocytopenia, microangiopathic hemolytic anaemia, fluctuating
neurological signs, renal failure, and fever. The condition is
rare with an annual incidence in adults of 3.7 per million. It
is seen predominantly in women, usually between 30 and 40
years of age.1
The pathogenesis of TTP is attributed to the presence of
unusually large von Willebrand factor (vWF) multimers that
lead to platelet clumping and subsequent microvascular
thrombosis. These vWF multimers are normally cleaved into
smaller protein units by a metalloprotease enzyme, the von
Willebrand factor cleaving protease (ADAMTS-13).
Impairment of ADAMTS-13 activity leads to an excessive
accumulation of vWF, which then may lead to the onset of
TTP. TTP is mostly idiopathic, but may be triggered by clinical
situations such as bacterial or viral infections, pregnancy,
drugs (for example, clopidogrel, ticlopidine, quinine, ciclosporin), and autoimmune disorders (systemic lupus erythematosus, thyroiditis, and antiphospholipid syndrome).2 3
Identification of the first acute TTP episode is challenging
as no specific clinical symptom or biological criterion is
available for the diagnosis. Suspicion of TTP relies on the
association of several clinical symptoms and laboratory
results. The brain is the commonest target for ischaemia,
and abnormal neurological findings present in most cases of
TTP. Patients usually develop headache, confusion, ataxia,
seizures, and mental status and focal abnormalities. Other
frequent symptoms are fever, weakness, arthralgia, myalgia,
jaundice, nausea, vomiting, diarrhoea and abdominal pain.
Skin and mucosal bleeding secondary to the thrombocytopenia is also common.2 3 Patients may have renal abnormalities including oligoanuria, acute renal failure, albuminuria,
and microscopic haematuria.2 Consumption thrombocytopenia is present in most cases, with platelet counts often
below 20 000 6 109. The widespread deposition of fibrin in
the vessels leads to mechanical trauma to the passing red
blood cells, resulting in fragmented red blood cells on the
blood smear. Haemoglobin is usually below 80 g/l (8 g/dl)

Figure 1 Blood smear revealed fragmented erythrocytes suggesting
intravascular haemolysis.

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secondary to haemolytic anaemia. Elevated lactate dehydrogenase and bilirubin levels may represent intravascular
haemolysis.1–3
Currently plasma exchange treatment is indicated for all
adult patients with a clinical diagnosis of TTP. Since the
availability of plasma exchange treatment, mortality has
fallen from 90% to about 10%. As delay in the initiation of
plasma exchange correlates with treatment failure, early
diagnosis and treatment is essential.4
According to the 2005 American Heart Association guideline for cardiopulmonary resuscitation and emergency
cardiovascular care, our patient was a candidate for
thrombolytic therapy for ischaemic stroke within first two
hours of presentation. However, right sided weakness, central
facial palsy, and dysarthria have been reported to be
associated with TTP.3 These neurological manifestations of
TTP can easily be mistaken for acute ischaemic stroke, which
requires early thrombolysis. Administration of thrombolytic
drugs to patients with TTP misdiagnosed as acute ischaemic
stroke may lead to detrimental consequences. Therefore the
laboratory test results of patients presenting with signs and
symptoms of acute ischaemic stroke must be checked
carefully, and TTP should be borne in mind as a differential
diagnosis.

CONCLUSION
Rapid diagnosis and treatment are necessary for decreasing
the risk of fatal outcome in patients with TTP. Emergency
physicians should be familiar with the clinical presentation
and laboratory abnormalities of TTP to be able to make the
diagnosis early on. In patients presenting with fluctuant

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Aksay, Kiyan, Ersel, et al

neurological findings, thrombocytopenia, heamolytic anemia,
and fever, the diagnosis of TTP should be considered.
.....................

Authors’ affiliations

E Aksay, S Kiyan, M Ersel, Department of Emergency Medicine, Ege
University Hospital, Izmir, Turkey
O Hudaverdi, Department of Internal Medicine, Ege University Hospital,
Izmir, Turkey
Competing interests: none declared
Informed consent was obtained for publication of the person’s details in
this report.
Correspondence to: Dr E Aksay, Ege Universitesi Hastanesi, Acil Tıp
Anabilim Dalı, 35100, Bornova, Izmir/TURKEY; ersin.aksay@ege.edu.tr
Accepted for publication 16 April 2006

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thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting
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2003;102:60–8.
3 Peyvandi F, Ferrari S, Lavoretano S, et al. von Willebrand factor cleaving
protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100
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4 Gurkan E, Baslamisli F, Guvenc B, et al. Thrombotic thrombocytopenic
purpura in southern Turkey: a single-center experience of 29 cases. Clin Lab
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