―Case Reports―

Cerebral Infarction in a Patient with Macrothrombocytopenia with
Leukocyte Inclusions
(MTCP, May-Hegglin Anomaly!
Sebastian Syndrome)
Yutaka Nishiyama1, Junko Akaishi2, Toshiya Katsumata1,
Ken-ichiro Katsura1 and Yasuo Katayama1
1

Department of Neurological, Nephrological and Rheumatological Science, Graduate School of Medicine, Nippon Medical School
2

Department of Biological Regulation and Regenerative Surgery, Graduate School of Medicine, Nippon Medical School

Abstract
We report on a 78-year-old woman patient with macrothrombocytopenia with leukocyte
inclusions (MTCP, May-Hegglin anomaly!
Sebastian syndrome), who had no history of
hemorrhagic symptoms and had a platelet count of 10,000 or less, but had a cerebral infarction.
The patient was found to have idiopathic thrombocytopenic purpura, hypertension, and atrial
fibrillation 16 years ago, yet received no medication. She was found to have had a cerebral
infarction with aphasia as the chief complaint and was admitted to our hospital.
Thrombocytopenia was found in three family members. Blood examinations revealed normal
bleeding time and platelet aggregation ability. The patient was found to have the triad of giant
platelets, thrombocytopenia, and inclusion bodies in leukocytes. Genetic analysis showed a
mutation of the MYH-9 gene in the patientʼs second daughter. Consequently, this patient
received a diagnosis of MTCP. There have only been a few reports of the onset of thrombosis
in patients with MTCP and no reports of the onset of cerebral infarction. Our report is the
first case of MTCP in a patient with cerebral infarction.
(J Nippon Med Sch 2008; 75: 228―232)
Key words: cerebral infarction, macrothrombocytopeia, May-Hegglin anomaly

MTCP includes multiple syndromes, such as MayIntroduction

Hegglin anomaly and Sebastian syndrome. These
two syndromes are differentiated by differences in

Macrothrombocytopenia with leukocyte inclusions

the micromorphologic features of the inclusion

(MTCP) is a rare dominantly inherited thrombocytic

bodies within leukocytes1. Additionally, Fetcher

abnormality that is characterized by the presence of

syndrome,

three signs: giant platelets, thrombocytopenia, and

symptoms, is also present1,2. Recently, Kunishima et

inclusion bodies in leukocytes (Doehle-like bodies).

al. have reported that a mutation of the nonmuscle

which

is

complicated

by

Alport

Correspondence to Yutaka Nishiyama, Department of Internal Medicine (Division of Neurology, Nephrology, and
Rheumatology), Nippon Medical School, 1―1―5 Sendagi Bunkyo-ku, Tokyo 113―8603, Japan
E-mail: yutakanms@yahoo.co.jp
Journal Website (http:!
!
www.nms.ac.jp!
jnms!
)

228

J Nippon Med Sch 2008; 75 (4)

Cerebral Infarction in MTCP

myosin chain A (NMHHCA, MYH-9) gene induces
MTCP3. There have thus far been no reports of
cerebral infarction in patients with MTCP. The
patient we now report on had clinical features of
MTCP, without symptoms or examination findings
indicative of idiopathic thrombocytopenic purpura or
antiphospholipid antibody syndrome. Thus, this case
is, to our knowledge, the first reported case of
cerebral infarction in a patient with MTCP.
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J Nippon Med Sch 2008; 75 (4)

229

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who had a cerebral infarction. At the age of 62, she

caudate nucleus, the right temporal!
parietal lobe,

was found to have idiopathic thrombocytopenic

and the left frontal lobe (Fig. 2b). Although no

purpura, hypertension, and atrial fibrillation. She had

antiphospholipid antibodies or LE cells were found,

no history of any medication or bleeding. In October

the titre of platelet-associated IgG (PAIgG) was

200X, the patient consulted our hospital with a chief

increased.

complaint of aphasia. She was found to have had a

aggregation ability were within their normal ranges.

cerebral

Upon

Levels of fibrinolytic factors, such as protein S,

admission, neurological examination revealed typical

protein C, and antithrombin III, were within their

conduction aphasia and mild right hemiparesis. No

normal ranges (Table 1). Blood smears showed the

notable physiological findings were present. The

presence of giant platelets. The findings of the

patientʼs family history included thrombocytopenia

normal bleeding time and the family history of

in a younger sister and two daughters (Fig. 1).

thrombocytopenia suggested the presence of MTCP.

Hematologic examinations showed thrombocytopenia

To analyze the localization of abnormal NMMHCA

with a thrombocyte count of 10,000 !
µL. Computed

protein

tomography showed an infarct lesion at the left

immunofluorescence staining with an anti-NMMHCA

angular

Transthoracic

antibody was performed with peripheral blood

echocardiography showed no intracardiac thrombus

smear specimens. Although the entire cytoplasm of

or valvular disease. Carotid ultrasonography showed

normal control leukocytes was diffusely stained, the

mild bilateral atherosclerotic changes of the carotid

inclusion bodies in granulocytes appeared as stained

arteries.

with

granules (Fig. 3). The patient could not give consent

concentrated glycerin-fructose (400 mL per day) and

for genetic analyses because of aphasia, but after

edaravone (60 mg per day) was performed. However,

informed consent was obtained from the patientʼs

impaired consciousness and left hemiplegia appeared

second

on the eighth hospital day, and magnetic resonance

performed. A point mutation was detected, and an

of the head revealed new infarct lesions in the right

MYH9 gene abnormality (1,165th arginine was

230

infarction

gyrus

After

and

was

(Fig. 2a).

admission,

admitted.

treatment

The

in

daughter,

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the

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genetic

and

platelet

leukocytes,

analyses

were

J Nippon Med Sch 2008; 75 (4)

Cerebral Infarction in MTCP

abnormal

localization

of

associated

with

formation

the

NMMHCA
of

might

be

neutrophilic

inclusion bodies. The results of immunofluorescence
staining may support the diagnosis of MTCP in our
patient.
Many patients with MTCP have no symptoms or
exhibit a mild bleeding tendency, depending on the
platelet count. Platelet function is normal, the

a

bleeding time is not markedly prolonged, and
markers reflecting platelet function, such as βthromboglobulin and platelet factor-4 are within the
normal ranges5. In our patient, bleeding symptoms
did not appear and platelet dysfunction or prolonged
bleeding time was not observed. The characteristics
of this case closely resemble those in previous
reports.

c

b

This case is unusual because cerebral infarction
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occurred in the setting of thrombocytopenia. As
factors inducing thrombosis in thrombocytopenia,
the

presence

of

thrombotic

thrombocytopenic

purpura or antiphospholipid antibody syndrome has
been identified. It has been reported that cerebral
infarction occurs in 9% to 15% of patients with
antiphospholipid antibody syndrome6,7. For such
patients, an antithrombocytic agent (aspirin) or
anticoagulant

( warfarin

administered

to

prevent

potassium )
thrombosis.

is

usually
However,

because the presence of risk factors of thrombosis,
changed to cysteine at exon 26) was thus proved.

such as the platelet count, bleeding tendency, and

The patient was fed via a tube and was treated with

atrial fibrillation, differs from patient to patient, a

an antihypertensive agent. During hospitalization,

standard

treatment

neither

patients

with

antithrombocytic

drugs

nor

warfarin

to

prevent

thrombocytopenia

thrombosis
has

not

in

been

8

potassium was administered. On March 200X, the

established . There were no findings to suggest

patient was moved to a sanatorium.

thrombotic

thrombocytopenic

purpura

or

antiphospholipid antibody syndrome in the present
Discussion

case.
Although there have been no reports of cerebral

MTCP

is

a

with

infraction in patients with MTCP, McDunn et al.

thrombocytopenia and is associated with NMHHCA

have reported coronary arterial thrombosis in a 62-

gene

the

year-old woman9. Findings in this case were a

localization of NMMHCA in leukocytes, analyses

platelet count of 24,000 !
µL, normal platelet function

using

been

and aggregation ability, and no history of bleeding

performed . In this case, NMMHCA appeared as

symptoms. McDunn et al. have suggested that

stained granules in leukocytes, a staining pattern

patients with MTCP might have a thrombotic

that differs from that in normal leukocytes. This

tendency because of the size of platelets rather than

finding, suggested by Kunishima et al4, indicates that

the platelet count. In a report on a patient with

mutations.

rare

genetic

Recently,

immunofluorescence

to

disease
investigate

staining

have

4

J Nippon Med Sch 2008; 75 (4)

231

Y. Nishiyama, et al

MTCP having acute myocardial infarction, Goto et
al. have concluded that in MTCP, the platelet count
is so low that the size of platelets increases as a
compensatory
Willebrand

mechansim

factor

in

dependent

view

of

platelet

a

von

formation

occurring under the effect of blood flow and that
that is why a bleeding tendency is absent despite
the low platelet count in many patients with
MTCP10. In our patient, although no complications,
such as bleeding symptoms and platelet dysfunction,
were found, with a history of hypertension and the
presence of atrial fibrillation acting as mechanisms of
cerebral

infarction,

a

cardiogenic

embolism

is

possible. However, no cardiac thrombus was found
with

transthoracic

ultrasonography.

No

clear

abnormalities of coagulation were found. Therefore,
we could not confirm the main cause of the cerebral
embolism in this patient with thrombocytopenia.
A standard treatment for thrombosis in MTCP has
not been established. However, because patients can
have cerebral infarction, as in the present case, it is
necessary to find the best medical strategy by
accumulating data from such cases in the future.
References
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of thrombocytopenia with giant platelets and
inclusion bodies in the leukocytes. Blut 1990; 60: 53―
60.

232

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( May-Hegglin
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(Received, March 10, 2008)
(Accepted, April 18, 2008)

J Nippon Med Sch 2008; 75 (4)