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its impact on health-related quality of life. Clin Infect Dis 2004;39:342-
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induced by infection with a herpesvirus. Am J Pathol 1979;96:673-706
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of chicken pox. Angiography 1984;35:577-8.
10. Bodensteiner JB,Hille MR,Riggs JE. Clinical features of vascular
thrombosis following varicella. Am J Dis Child 1992;146:100-2.

Immune Thrombocytopenia (ITP) : A Rare

Association of Lymphnode Tuberculosis
Anuj P Surana*, Kishor M Shelgikar**, Sameer Melinkeri***, Arvind Phadke****

Abstract
Although various haematologic abnormalities are known to occur with tuberculosis, association of immune
thrombocytopenia with tuberculosis is uncommon. We report a case of retroperitoneal lymph node
tuberculosis who presented with ITP. A 76 year old female was admitted to our hospital with oral mucosal
bleed and petechial lesions over extremities and abdomen. A diagnosis of immune thrombocytopenia
(ITP) was established. Intravenous Anti-D immunoglobulin and Dexamethasone therapy was started, but
failed to elicit any sustained platelet response. CT abdomen revealed multiple retroperitoneal lymph
nodes with central necrosis. Histopathology (HPE) of these revealed caseating lymphadenitis suggestive
of tuberculosis. After 2 months of anti-tuberculous therapy, the platelet counts returned to normal and
patient was off all therapy for ITP thereby suggesting likely association between tuberculosis and immune
thrombocytopenia.

Introduction

T uberculosis is one of the commonest infectious diseases in India. Various haematologic

abnormalities such as anaemia, leucocytosis, monocytosis, lymphopenia, leucopenia,
thrombocytopenia, thrombocytosis, leukemoid reactions and pancytopenia have been
described in tuberculosis 1 but immune thrombocytopenia (ITP) as the only presenting
feature of tuberculosis is extremely rare with few published reports. 2,3

*
Post Graduate Trainee, Case Report
Consultant Physician and
**

Diabetologist, ***Consultant
Haematologist, ****Professor
and Head of Department,
Department of Medicine,
Maharashtra Medical
Foundation, Joshi Hospital, 778,
Shivaji Nagar,Opposite Kamla
Nehru Park, Pune 411 004.
Received: 15.06.2012;
Revised: 13.08.2012;
Re-revised: 28.09.2012;
Accepted: 09.02.2013
A 76 year old female, known long standing diabetic and hypertensive on regular
treatment, was admitted to our hospital with haemorrhagic bullae in oral cavity and
extensive petechial lesions over lower limbs and abdomen. There was no history of any
haematological disorder or liver disease or significant history of any medication in the
past apart from her usual anti-diabetic and anti-hypertensive medications.
On physical examination, patient was euthermic, pulse 80/min regular, blood pressure
160/90 mmHg. There was no palpable lymphadenopathy or any palpable organomegaly.
The initial total leucocyte count was 6890/cmm with differential count as follows:
neutrophils-57%, lymphocytes 33.5%, monocytes 7.5%, eosinophils 1.9%, basophils

74  © JAPI • january 2014 • VOL. 62

Journal of the association of physicians of india • JANUARY 2014 • VOL. 62 75
Fig. 1 and 2 : CT scan demonstrating enlarged para-aortic, aorto-caval and retrocaval lymph nodes
0.1%. Haemoglobin was 12.1 g/dl; Platelet count on
presentation was 1000 per cubic millimeter. Peripheral
smear examination was unremarkable apart from
paucity of platelets. Liver function tests, renal
function tests and serum electrolyte concentrations
were normal and chest X-ray revealed no abnormality.
Prothrombin time (PT) and activated partial
thromboplastin time (aPTT) were within normal limits
and direct Coombs test was negative. Iron studies
revealed serum ferritin of 120 ng/ml and lipid profile
showed triglycerides of 74 mg/dl.
Subsequently, ultrasonography and CT scan of
the abdomen (Figures 1 and 2) were done which
demonstrated enlarged para-aortic, aorto-caval
and retrocaval lymphnodes - most showing central
necrosis. Largest lymph node measured 2.6 x 1.7
cm. Bone marrow aspiration and biopsy showed
normocellular marrow with adequate megakaryocytes
consistent with peripheral platelet destruction. There
was no evidence of lymphoma or tuberculosis on bone
marrow biopsy.
During the course of her illness, the patient
received 6 units of random donor platelets (RDP’s).
There was only minimal and transient platelet
response to combined modality therapy with anti-rh 0
immunoglobulin and high dose Dexamethasone. The
patient was started on Eltrombopag (Thrombopoietin
receptor agonist) 50 mg OD. Eight days of therapy
effectively raised the platelet count to 9 lakhs / cmm.
Eltrombopag was then withdrawn.
Subsequently an exploratory laparotomy was
performed for biopsy of retroperitoneal lymph
nodes. Histo-pathological examination of these
lymph nodes revealed wide areas of caseation and
scattered granulomas-indicating caseating tubercular
l y m p h a d e n i t i s . A n t i - t u b e r c u l o u s t h e r a p y wa s
instituted with Isoniazid (300 mg) Ofloxacin (400 mg)
Ethambutol (600 mg) and Pyrazinamide (1000 mg) and
patient was discharged.
© JAPI • january 2014 • VOL. 62
Two months following discharge, patient was seen
in good health with a platelet count of 3.4 lakhs / cmm.
She had no side effects related to anti-tuberculous
therapy. She is under regular follow up without any
relapse of thrombocytopenia.
Discussion
ITP is an acquired disorder in which there is
immune mediated destruction of platelets and possibly
inhibition of platelet release from megakaryocytes.
ITP in children usually presents acutely while in
adults it runs a more chronic course, although at times
it can have a very abrupt and stormy presentation.
Common secondary causes of ITP include auto
immune diseases, infections (HIV/hepatitis C) and
drugs (rifampicin). 4
In the present case scenario, following possibilities
were considered in differential diagnosis:
1. Disseminated Intravascular Coagulopathy: DIC
is a complex thrombo haemorrhagic disorder
involving fibrinolysis and consumption of
procoagulants and platelets. Typically, prolonged
coagulation times, thrombocytopenia, high levels
of fibrin split products and microangiopathic
pathology (schistocytes) on peripheral smears are
suggestive findings. In our patient PT and aPTT
were normal, thus ruling out DIC.
2. Thrombotic Thrombocytopenic Purpura (TTP):
Patients with TTP typically report an acute or
subacute onset of symptoms related to neurological
dysfunction, anaemia or thrombocytopenia.
F e ve r o c c u r s i n a p p r o x i m a t e l y 5 0 % o f t h e
patients. Peripheral smears reveal moderate
to severe schistocytosis. Thus, TTP was ruled
out in our patient as there was no evidence of
microangiopathic haemolysis.
3. E va n s S y n d r o m e : E va n s s y n d r o m e i s t h e
co-existence of sequential or simultaneous
direct Coombs – positive AIHA (Autoimmune
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76 Journal of the association of physicians of india • JANUARY 2014 • VOL. 62
haemolytic anaemia) in conjunction with immune
mediated thrombocytopenia, with no known
underlying aetiology. In our patient Evans
syndrome was ruled out as haemoglobin level
was normal and direct Coombs test was negative.
4. Haemophagocytic Syndrome: It represents
a severe hyperinflammatory condition with
cardinal symptoms of prolonged fever, cytopenias,
hepato-splenomegaly and haemophagocytosis. In
addition to pancytopenia, hypofibrinogenaemia
and hypertriglyceridaemia are also present, with
serum ferritin levels paralleling the course of
the disease. Hence in absence of pancytopenia
and any palpable organomegaly and presence
of normal serum ferritin and triglyceride levels
Haemophagocytic syndrome was ruled out.
We t h e r e f o r e d e c i d e d t o i n v e s t i g a t e h e r
further with a CT scan of abdomen. It revealed
retroperitoneal lymphadenopathy with central
necrosis. Histopathological study showed caseation
suggestive of tuberculosis. In absence of any other
convincing cause for severe thrombocytopenia, we
postulate a possible association of tuberculosis with
her clinical presentation; although it may not be
directly causal.
Pa t i e n t s w i t h b o t h p u l m o n a r y a n d e x t r a -
pulmonary tuberculosis may demonstrate
haematological abnormalities such as anaemia,
leucocytosis, monocytosis, lymphopenia,
leucopenia, thrombocytopenia, thrombocytosis,
leukemoid reactions and pancytopenia 1 but severe
thrombocytopenia due to ITP as an association with
tuberculosis is extremely rare. 2,3,5,6
It has been observed that thrombocytopenia in
tuberculosis can occur due to
1. A d e f e c t i n p l a t e l e t p r o d u c t i o n ( m a r r o w
infiltration),
2. Tuberculosis induced haemophagocytic syndrome,
3. Side effect of anti-tuberculous therapy or,
4. Immune-mediated platelet destruction.
Drug-induced thrombocytopenia (i.e. as a side
effect of anti-tuberculous therapy) develops
within 6-7 days in individuals taking drugs for the
first time, and within hours in sensitised patients.
Some patients may not develop thrombocytopenia
for months to years. Further, it has been observed
that the platelet count is usually restored within
a week of cessation of the offending agent.
Corticosteroids have also been used in such
scenarios, with intravenous immune globulin
( I V I g ) o r p l a s m a p h e r e s i s r e s e r ve d f o r l i f e
76  © JAPI • january 2014 • VOL. 62
threatening situations.
Our patient did not show any evidence of
marrow infiltration with tuberculosis, neither
was she exposed to anti-tubercular drugs prior to
development of thrombocytopenia. Thus the only
plausible explanation is immune mediated platelet
destruction associated with tuberculosis. This in itself
is exceedingly rare. 7 Anti-tubercular antibodies cross
reacting with platelets can be a possible hypothesis
for the same.
It is interesting to note that our patient had
a fulminant form of steroid and anti-D resistant
ITP, necessitating a TPO agonist (Eltrombopag)
t o a c h i e ve r e s p o n s e . E l t r o m b o p a g i s a s m a l l
molecule Thrombopoietin receptor agonist for oral
administration. It interacts with the transmembrane
domain of Thrombopoietin receptor (also known as
C-MPI) leading to increased platelet production. 8,9
However, treatment of tuberculosis itself led to
complete remission of ITP suggesting some possible
association.
ITP and tuberculosis are common diseases in India.
A high index of suspicion of tuberculosis may be
warranted in patients presenting with ITP as noted
in our patient, the ITP may be cured with treatment
of tuberculosis.
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