Myth exploded

CASE REPORT

Stroke due to typical thrombotic thrombocytopenic
purpura treated successfully with intravenous
thrombolysis and therapeutic plasma exchange
Matteo Boattini,1 Gaetano Procaccianti2
1

Department of Internal
Medicine, Santa Marta’s
Hospital, Lisbon, Portugal
2
Stroke Unit, Ospedale
Maggiore, IRCCS, Bologna,
Italy
Correspondence to
Dr Matteo Boattini,
matteoboattini@gmail.com

SUMMARY
We report a case of a 39-year-old man with expressive
aphasia due to occlusion of the temporal stem of the
left middle cerebral artery. Laboratory tests showed
microangiopathic haemolytic anaemia and
thrombocytopenia. A thrombotic thrombocytopenic
purpura (TTP) was diagnosed, and thrombolytic therapy
(TT) with alteplase followed by therapeutic plasma
exchange (TPE) were performed with complete resolution
of symptoms. The gold standard TTP treatment is TPE,
and its delay can be lethal. The use of TT in TTP is
controversial and has potential risks. This case shows a
successful TT in a patient with typical TTP presenting as
a stroke due to a large cerebral artery occlusion.

BACKGROUND
Thrombotic thrombocytopenic purpura (TTP) is an
uncommon and severe disease with an incidence of
3.7 cases/million /year in adults.1 Ischaemic stroke
has been reported as a consequence of TTP.2–4
However, strokes due to a large cerebral artery
occlusion (LCAO) are rare in patients with TTP.2
Standard TTP treatment is therapeutic plasma
exchange (TPE). The prognosis is generally good
when TTP is diagnosed early. Thrombolytic
therapy (TT) is of proven benefit for selected
patients with acute cerebral ischaemia,5 and its use
has been reported only in atypical TTP with
normal platelet count.2 4 We report a case of a
patient with typical TTP (tTTP) and a stroke due
to LCAO whose neurological deficits recovered
after combined TT and TPE.
Can TT have contributed to TPE in saving brain
parenchyma and vessels in this case of tTTP presenting with a stroke due to LCAO?

INVESTIGATIONS
Brain CT did not show any sign of ischaemia or
haemorrhage. CT angiography showed normal carotids and vertebral arteries but revealed occlusion of
the temporal stem of the left middle cerebral artery
(TSLMCA; figure 1A, white arrow). Haemoglobin
was 7.4 g/dl (normal values, 14–16), white blood
cells WBC count 11 830/mm3 (4 200–9000), platelet count 27 000/mm3 (130 000–450 000), D-dimer
394 mg/l (<280), international normalised ratio
(INR) 1.16, total bilirubin 1.35 mg/dl (0.1–1.0),
indirect bilirubin 1.16 mg/dl (<0.80), aspartate aminotransferase (AST) 47 U/l (<38), lactate dehydrogenase (LDH) 2058 U/l (<480), C reactive protein
(CRP) 1.21 mg/dl (<0.50), erythrocyte sedimentation rate 2 mm/h (<20), glycosylated haemoglobin
HbA1c 4.9% (<6.1). Renal function, electrolytes,
urinalysis, lipid profile, serum iron, ferritin, transferrin and homocysteine were normal. Reticulocyte
count was elevated. Peripheral blood smear showed
schistocytes; Coombs test was negative. Serum
tests for antinuclear, anti-DNA, anti-Sm, anti-RNP,
anticardiolipin antibody titres and lupus anticoagulants were negative. HIV, hepatitis B virus
(HBV) and hepatitis C virus (HCV) serology were
negative as well.

DIFFERENTIAL DIAGNOSIS
There was no history of bloody diarrhoea or recent
infection. He was not on any drug.
A diagnosis of tTTP was made, based on microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, fever and stroke. In a young patient with
no atherosclerotic risk factors who presents with
stroke and thrombocytopenia, differential diagnosis
includes vasculitis, antiphospholipid syndrome,
infections, toxic drugs and thrombophilia.2

TREATMENT
CASE PRESENTATION

To cite: Boattini M,
Procaccianti G. BMJ Case
Reports Published online:
[please include Day Month
Year] doi:10.1136/bcr-2012008426

A previously healthy 39-year-old man was referred
to our Stroke Unit for headache, sudden speaking
difficulty and right limbs paresthesias started in the
preceding 90 min. He did not smoke, drink alcohol
or use any drug. His family history was negative
for premature strokes or thrombotic disorders. On
examination, he presented with expressive aphasia;
National Institute of Health Stroke Score (NIHSS)
was 4. Blood pressure was 130/70mm Hg pulse rate
88 bpm, respiratory rate 16/min and temperature
38.3°C. The air oxygen saturation was 98%.

Boattini M, et al. BMJ Case Reports 2013. doi:10.1136/bcr-2012-008426

Informed consent was obtained, and intravenous
TT with alteplase was performed 100 min after the
onset of symptoms. The paresthesias of the right
limbs resolved, and TPE was performed after 6 h.
The patient’s conditions improved over the next
24 h (NIHSS=0) and CT angiography on day 7
showed complete recanalisation of the TSLMCA
(figure 1B, white arrow) and no sign of ischaemia
or haemorrhage.

OUTCOME AND FOLLOW-UP
No TT complication was observed. MAHA gradually improved and platelet count normalised.
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Myth exploded
Figure 1 Three-dimensional CT
angiography showed occlusion of the
temporal stem of the left middle
cerebral artery (TSLMCA; A, white
arrow), and on day 7, it showed
complete recanalisation of the TSLMCA
(B, white arrow).

He was discharged on day 15 in good clinical condition and
never relapsed.

DISCUSSION
TTP, first described by Moschowitz in 1925, is an acute syndrome with multiorgan abnormalities. Although they have different epidemiologies, aetiology, response to therapy and
prognosis, TTP and haemolytic uraemic syndrome (HUS) are
commonly associated and referred to as TTP-HUS. The diagnostic pentad of TTP-HUS includes MAHA, thrombocytopenia,
neurological symptoms, renal failure and fever.
Predominant neurological symptoms and signs (such as headache, confusion, seizures, focal abnormalities, transient ischaemic attack, stroke and coma) are suggestive of TTP, whereas
severe renal failure is more suggestive of HUS.
TTP is associated with a deficit in the activity of ADAMTS13,
a von Willebrand factor cleaving protease, which produces platelet clumping and subsequent microvascular thrombosis with
fibrin deposition, red blood cell fragmentation (schistocytes),
release of inflammatory cytokines, high levels of plasminogenactivator inhibitor type 1 and other prothrombotic mediators.
TTP can be idiopathic, acquired or due to congenital
ADAMTS13 deficiency. ADAMTS13 deficiency (<10%) and the
presence of ADAMTS13 inhibitor distinguish idiopathic and
acquired TTP from the congenital form.6
Secondary TTP is due to infections, autoimmune disease, vasculitis, pregnancy, bone marrow transplantation, cardiovascular
surgery, drugs (quinine, immunosuppressive or cancer therapy,
antiplatelet agents such as ticlopidine and clopidogrel), antiphospholipid syndrome or unusual thrombophilia.2
Clinical findings can be non-specific; laboratory findings distinguish tTTP, with MAHA and thrombocytopenia, from atypical TTP (aTTP), which has no specific alteration, and this is
why the diagnosis is challenging.
Testing ADAMTS13 deficiency is not recommended for confirming the diagnosis because it can be present in other conditions such as sepsis with disseminated intravascular coagulation
or ischaemic organ failure.7 However, ADAMTS13 deficiency
can anticipate the long-term relapse risk, because patients with
severe ADAMTS13 deficiency relapse more frequently.8
Standard TTP treatment is TPE; the use of TT in acute
ischaemic TTP stroke is controversial and can lead to negative
consequences.9
2

To our knowledge, only two cases of aTTP with ischaemic stroke due to LCAO treated with TT have been
reported.2 4 Idowu et al described the case of a
48-year-old Afro-American woman with a history of recurrent ischaemic strokes and aTTP. She presented with an
acute M2 right middle cerebral artery (MCA) occlusion and
underwent intra-arterial TT and thrombectomy. Her neurological symptoms did not improve, and new right MCA
ischaemic areas with haemorrhagic change were detected on
brain MRI.
Sevy et al described a case of a 30-year-old woman with an
acute myeloblastic leukaemia M1 right MCA occlusion who
underwent intravenous TT. Her focal deficits partially recovered; however, her clinical conditions worsened due to an M2
right MCA residual thrombus, which was treated by unfractioned heparin.
In both these cases, TTP was initially misdiagnosed and TPE
was delayed.
Early TT is a proven success in acute ischaemic stroke in
order to restore cerebral blood flow and reduce ischaemic
damage of tissue and vessels. In the case reported by Sevy et al,
TT seemed to re-establish cerebral blood flow, which however
worsened lately due to a new thrombotic phenomenon. In the
case we report, TT promptly restored cerebral blood flow and
early TPE prevented arterial reocclusion. However, it is unclear
to disentangle the efficacy of TT on clinical improvement,
because its effect overlapped with TPE.
Haemorrhagic complications of TT in TTP patients should be
always considered.
Thrombocytopenia in TTP is due to platelet clumping
and microvascular thrombosis with fibrin deposition, which
is the target of TT. For this reason, thrombocytopenia
could be probably considered as a relative contraindication
of TT in TPP stroke. Only the patient described by
Idowu et al presented a haemorrhagic complication, which
was probably due to the preexistence of small foci of
petechial haemorrhage.
In conclusion, in the presence of an acute ischaemic stroke
due to LCAO, especially in young adults, it is important to consider TTP diagnosis and, when consistent, to plan emergency
TPE, which is the gold standard treatment. Further data are
needed to understand the real therapeutic value and safety of
TT in TTP stroke due to LCAO.
Boattini M, et al. BMJ Case Reports 2013. doi:10.1136/bcr-2012-008426

Myth exploded
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Learning points
3

▸ Thrombotic thrombocytopenic purpura (TTP) is characterised
by the pentad of microangiopathic haemolytic anaemia,
thrombocytopenia, neurological symptoms, renal
insufficiency and fever.
▸ Thrombotic thrombocytopenic purpura should be always
considered in young adults with ischaemic stroke.
▸ Gold standard treatment for TTP is therapeutic plasma
exchange.
▸ Further data are needed to understand the role of
thrombolytic therapy in stroke due to large cerebral artery
occlusion LCAO in patients with TTP.

4

5

6

7

Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

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REFERENCES

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Furlan M, Robles R, Galbusera M, et al. von Willebrand factor–cleaving protease in
thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J
Med 1998;339:1578–84.
Ono T, Mimuro J, Madoiwa S, et al. Severe secondary deficiency of von Willebrand
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2006;107:528–34.
Hovinga JA Kremer, Vesely SK, Terrel DR, et al. Survival and relapse in patients with
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Boattini M, et al. BMJ Case Reports 2013. doi:10.1136/bcr-2012-008426

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