Idiopathic Thrombocytopenic Purpura

Arvinder Bir
1
, Wiam Bshara
2
, Marina George
1
,Marwan G Fakih
1
Departments of
1
Medicine and
2
Pathology, Roswell Park Cancer Institute. Buffalo NY, USA
ABSTRACT
Context
Pancreatic
adenocarcinoma
presenting as idiopathic thrombocytopenic
purpura has not been previously reported in
the literature.
Case report A newly diagnosed patient with
metastatic pancreatic adenocarcinoma
developed thrombocytopenic purpura prior to
initiation of chemotherapy. Generalized
petechiae were present and peripheral smear
revealed giant platelets. Drug induced and
other thrombotic platelet consuming disorders
were ruled out. Her platelets returned to
normal after being treated with steroids.
Conclusions ITP can be associated with
metastatic pancreatic adenocarcinoma and can
respond well to steroid treatment.
INTRODUCTION
Cancer of the pancreas is the fourth leading
cause of cancer-related death in the United
States, and is second only to colorectal cancer
as a cause of digestive cancer-related death.
Approximately 33,730 new cases are
anticipated in 2006, with 32,300 expected
deaths [1]. Tumors of the pancreatic body or
tail usually present with pain and weight loss,
while those in the head of the gland typically
present with steatorrhea, weight loss, and
jaundice. The recent onset of atypical diabetes
mellitus, a history of recent but unexplained
thrombophlebitis [2], or previous attacks of
pancreatitis are sometimes noted. Pancreatic
cancer manifesting with idiopathic
thrombocytopenic purpura (ITP) has not been
previously reported. We are presenting the
case of a patient who developed ITP before
the initiation of the chemotherapy.
CASE REPORT
A 63-year-old Caucasian female presented
with abdominal pain and fatigue. She was
noted to be anemic with hemoglobin of 9.1
g/dL (reference range: 12.5-15.5 g/dL) and a
platelet count of 312 x10
9
/L (reference range:
150-450 x10
9
/L). Her upper and lower
gastrointestinal endoscopies were normal.
Computed tomography (CT) scan showed
multiple low density masses in liver and
spleen with largest in the liver measuring 5.7
cm. Biopsy of the largest liver metastasis
revealed adenocarcinoma but the primary
could not be confirmed. CA 19-9 was 24,737
U/mL (reference range: 0-35 U/mL), CA 125
was 864 U/mL (reference range: 0-30.2
U/mL) and CEA was 205.4 ng/mL (reference
range: 0-2.5 ng/mL). A Doppler of the left
lower extremity, performed in an outside
institute, was done to investigate lower
extremity edema and redness and revealed
superficial phlebitis.
The patient presented to our institute for a
second opinion. Her platelet count on the day
of her first visit was 299 x10
9
/L, hemoglobin

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 6 - November 2006. [ISSN 1590-8577]
648
of 9.1 g/dL and white blood cells of 12.9
x10
9
/L (reference range: 4-11 x10
9
/L). The
chemistry was unremarkable except for
alkaline phosphatase of 426 U/L (reference
range: 38-126 U/L), alanine aminotransferase
(ALT) of 90 U/L (reference range: 11-66
U/L) and aspartate aminotransferase (AST) of
85 U/L (reference range: 15-46 U/L). Her
medications included lansoprazole 15 mg per
os daily, ferrous gluconate 325 mg per os
daily, oxycodone 20 mg per os twice daily,
alprazolam 0.25 mg per os every 6 h as
needed, multivitamin per os daily, bisacodyl
suppository as needed. A repeat CT scan
(Figure 1) was performed which showed a
1.2x2.0 cm lesion in the tail of the pancreas
suspicious of a primary and confirmed
extensive metastatic disease to the liver. A
large infarct in the lower third of the spleen
and thrombosis of the bilateral gonadal vein
were also noted.
An ultrasound guided core biopsy of the liver
lesion was repeated one week after her
baseline visit; this showed atypical angulated
glands with desmoplasia consistent with
metastatic,
moderately
differentiated
adenocarcinoma
from
primary
pancreaticobiliary origin (Figure 2).
On the day of liver biopsy she was noted to
have bruises and multiple petechiae and on
further questioning she voiced that she had
been having black colored stools. The
complete blood count checked after the
procedure showed the platelet count of 2
x10
9
/L and hemoglobin of 7.6 g/dL.
There was no history of any new medications.
Disseminated intravascular coagulation
profile was normal: prothrombin time 14.8
sec (reference range: 11.7-15.0 sec); partial
thromboplastin time 24 sec (reference range:
23-35 sec); INR =1.3, D-dimer greater than 4
µg/fibrinogen equivalent units (reference
range: 0-0.5 µg/fibrinogen equivalent units),
fibrinogen 385 mg/dL (reference range: 200-
420 mg/dL).
Peripheral smear was consistent with ITP
with presence of megaplatelets and lack of
schistocytes (Figure 3). A diagnosis of ITP
was made based on clinical grounds. She was
started on prednisone at 1 mg/kg (80 mg)
daily. Her platelet count rose to 8.0, 47, and
Figure 1. Pancreatic tail mass (black arrow) with
metastatic liver lesions.
Figure 2. Core needle biopsy of the liver lesion shows
atypical angulated glands with desmoplasia consistent
with metastatic, moderately differentiated adeno-
carcinoma from primary pancreaticobiliary-origin
(H&E x400).
Figure 3. Peripheral smear showing megaplatelet
(arrow).

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 6 - November 2006. [ISSN 1590-8577]
649
155 x10
9
/L on the 3
rd
, 7
th
, and 11
th
days of
prednisone, respectively.
The initial presence of megaplatelets coupled
with the complete resolution of thrombo-
cytopenia with high dose prednisone
treatment was considered pathognomonic of
ITP in this case. Thus, no anti-platelet
antibodies or bone marrow biopsy were
performed.
Chemotherapy was initiated with gemcitabine
1000 mg/m
2
on day 1 and 8 on every 21 day
cycle and capecitabine 650 mg/m
2
per os
twice daily for 2 weeks out of 3 week cycle.
One week later, she developed a deep vein
thrombosis of the left lower extremity and
was started on enoxaparin at 1.5 mg/kg/day
subcutaneously. Her platelets remained more
than 100 x10
9
/L during chemotherapy, which
allowed a complete wean off prednisone.
Unfortunately, her disease progressed after 2
cycles of chemotherapy and supportive
measures were initiated. One week after the
chemotherapy was stopped, she developed
confusion and hemiparesis. A magnetic
resonance imaging (MRI) of the brain
revealed a right frontal infarct. She died
shortly after.
DISCUSSION
To our knowledge, this is the first reported
case of metastatic pancreatic cancer
presenting as ITP. The diagnosis of
paraneoplastic pancreatic cancer-associated
ITP was made in the absence of disseminated
intravascular coagulation and with the lack of
any new drug interventions (drug induced
ITP). This autoimmune process was
supported by the presence of megaplatelets
and by its response to steroids prior to
initiation of treatment. An extensive review of
the literature revealed one prior case of ITP in
the setting of a pancreatic adenoma but none
were reported in association with metastatic
pancreatic cancer [3]. The underlying
mechanism of ITP in our patient is not known
but it could be immune mediated as described
in other solid tumor malignancies.
The diagnosis of ITP is usually one of
exclusion of underlying systemic disorders
that result in increased peripheral destruction
or decreased production of platelets. ITP is an
autoimmune disorder characterized by auto
reactive antibodies against platelets resulting
in splenic sequestration and thrombo-
cytopenia. Immune mediated thrombocyto-
penia can also occur in the settings of
lymphoproliferative disorders, especially
chronic lymphocytic leukemia. The
association between ITP and lymphoma, in
particular Hodgkin disease, has also been
frequently reported [4, 5, 6]. There have been
approx 20 cases of ITP reported in association
with various solid tumors, including lung,
breast, and ovarian cancers [7, 8, 9]. Kim and
Boggs [10] reported malignancy in 10 of 52
consecutive patients admitted for ITP; six of
the ten cases had solid tumors.
Studies have shown that circulating immune
complexes are involved in the regulation of a
variety of immune phenomena. Horvath et al.
[11] reported the presence of circulating
immune complex in 16 of 26 (62%) patients
with breast cancer. Circulating immune
complexes have been shown to interact with
platelets. The presence of platelet-activating
immune complexes may lead to in vivo
aggregation and thrombocytopenia.
Thrombocytopenia in pancreatic cancer is
usually
attributed
to
disseminated
intravascular coagulation, leading to
discontinuation of chemotherapy and/or
anticoagulation therapy. This case highlights
the possibility of paraneoplastic ITP in
association with advanced pancreatic cancer.
The management of this entity includes high
dose steroid therapy and prompt initiation of
chemotherapy.
CONCLUSION
Pancreatic cancer can present with
paraneoplastic manifestation of an ITP. Its
relationship to survival is unknown due to the
rare presentation.
Received September 5
th
, 2006 - Accepted
September 20
th
, 2006

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JOP. J Pancreas (Online) 2006; 7(6):647-650.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 6 - November 2006. [ISSN 1590-8577]
650
Keywords
Purpura, Thrombocytopenic,
Idiopathic; Steroids
Abbreviations
ITP:
idiopathic
thrombocytopenic purpura
Correspondence
Marwan G Fakih
Department of Medicine. GI Service
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo, NY, 14263
USA
Phone +1-716.845.8189/3362
Fax: +1-716.845.3305
E-mail: marwan.fakih@roswellpark.org
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