Case Report

Thrombocytopenia and hemorrhagic pleural effusion as

an initial presentation of polycythemia vera
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Amrish Saxena, Sheetal Bodkhe, Deepankar Mishra, Vineeta Singh

Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India

Address for correspondence: Dr. Amrish Saxena, Department of Medicine, MLK‑5, MGIMS Campus, Sevagram, Wardha, Maharashtra, India.
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E‑mail: dramrishsaxena@rediffmail.com

ABSTRACT
Polycythemia vera (PV) is a chronic myeloproliferative disorder in which there is an alteration in the pluripotent progenitor cell leading to
excessive clonal proliferation of erythroid, myeloid and megakaryocytic progenitor cells. The natural history of PV can be divided into several
stages, beginning with asymptomatic, isolated erythrocytosis, progressing to more generalized myeloid proliferation, splenomegaly, and
thrombosis, followed by myelofibrosis, leukoerythroblastosis, cytopenia, and myeloid metaplasia and sometimes, acute leukemia. Isolated
erythrocytosis, leukocytosis, or thrombocytosis or in combination are usually present at the onset of disease. We present the case of a
65‑year‑old man, who developed thrombocytopenia and hemorrhagic pleural effusion as an initial presentation of PV that is extremely rare.
Key words: Complications, hepatosplenomegaly, pleural effusion, polycythemia vera, thrombocytopenia

INTRODUCTION particularly in patients with PV and essential

Polycythemia vera (PV) is a clonal hematopoetic stem
cell disorder with trilineage myeloid involvement.[1] It
is characterized by growth factor‑independent erythroid
proliferation producing an elevated red cell mass. The
incidence of PV is 2/100,000 persons. Thrombotic
events (coronary events, cerebrovascular accidents, deep
vein thrombosis, pulmonary embolism, mesenteric,
hepatic, portal, or splenic vein thrombosis) are a major
complication of PV.[2,3] A cerebrovascular event precedes
the diagnosis in 35% of patients with PV.[1] Both
bleeding and thrombosis can occur in PV.[4]
Over the last two decades, hemostatic abnormalities
in myeloproliferative neoplasms have been the
subject of extensive investigation aimed at elucidating
their pathogenesis and clinical manifestations,
toward providing effective and safe treatment
options. Significant progress has been made in
the understanding of clinical epidemiology and
pathogenesis of thrombohemorrhagic manifestations,
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thrombocythemia (ET).[3]
Hemorrhagic diathesis is more rare than thrombotic
events in PV and ET and mostly affects patients with
a very high platelet count. In these patients, an altered
degradation and function of von Willebrand factor or
qualitative platelet defects can cause mucocutaneous
hemorrhages, which may lead to major gastrointestinal
bleedings.[4] The bleeding tendency can be effectively
treated by cytoreduction.[1,4]
CASE REPORT
A 65‑year‑old man was admitted with a history of
generalized weakness, easy fatigability, weight loss and
pruritus for 2 months. He denied any history of fever,
cough, breathlessness, headache, visual disturbances,
vertigo, tinnitus, hypertension, cerebrovascular stroke,
or myocardial infarction. He had a 30 pack‑year smoking
history and 2 years history of diabetes mellitus. On
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DOI: How to cite this article: Saxena A, Bodkhe S, Mishra D, Singh V.

Thrombocytopenia and hemorrhagic pleural effusion as an initial
10.4103/1658-5127.160210
presentation of polycythemia vera. J Appl Hematol 2015;6:85-7.

© 2015 Journal of Applied Hematology | Published by Wolters Kluwer - Medknow 85

 Saxena, et al.: Thrombocytopenia in PV
physical examination, he was conscious, oriented, afebrile,
anicteric with stable vitals. His tongue was smooth, shiny
and red [Figure 1]. Multiple erythematous excoriated
papules with scratch marks were present all over the
body especially over the trunk [Figure 2]. Petechiae,
ecchymosis, mucosal bleeding and lymphadenopathy
were absent. His respiratory system examination revealed
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decreased breath sounds, decreased vocal resonance
and dullness on percussion in the left infrascapular and
infra‑axillary region. His spleen was palpated 7 cm and
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the liver 5 cm below the costal margin.
His hemogram revealed a hemoglobin (Hb) of 18.8 g/dL, a
hematocrit of 64.4%, erythrocyte count of 8,050,000/mm3,
total leukocyte count of 13,200/mm3, and platelet count
of 21,000/mm3. His renal, liver and thyroid profile were
all normal. His serum erythropoietin level was low at
1.3 mIU/mL (normal 4.3–29 mIU/mL). The result of
Janus Kinase 2 (JAK2V617F) mutation test was positive.
Bone marrow biopsy showed hypercellularity with
prominent erythroid, granulocytic, and megakaryocytic
Figure 1: Smooth and shiny red tongue
Figure 3: Chest radiograph revealed blunting of left costophrenic angle
Journal of Applied Hematology
proliferation. His coagulation profile was normal. His
serological tests were negative for antinuclear antibodies,
antiphospholipid antibodies, hepatitis B virus, hepatitis
C virus and human immunodeficiency virus (HIV).
His chest radiograph revealed blunting of left costophrenic
angle suggestive of left‑sided pleural effusion (PE)
[Figure 3]. A left thoracocentesis revealed hemorrhagic
pleural fluid that did not clot and did not clear on
sequential samples. The pleural fluid was exudative by
Light’s criteria with cytology showing 2100 cells/mm3 with
predominantly mononuclear cells and a few mesothelial
cells and lymphocytes and plenty of RBCs. His pleural
fluid adenosine deaminase was 16 U/L (normal < 40
U/L). Pleural fluid cultures were negative for bacteria,
fungi, and mycobacterium tuberculosis. Pleural fluid
block cytology was negative for malignant cells on two
consecutive occasions. A computerized tomographic scan
of his chest revealed left‑sided pleural effusion [Figure 4].
Further, ultrasonography of abdomen revealed
hepatosplenomegaly with no free fluid or no evidence of
splenic vein or portal vein thrombosis or splenic infarction
and no evidence of a malignant condition.
The diagnosis of PV with thrombocytopenia and left‑sided
pleural effusion was made. Periodic phlebotomies were
done until the hematocrit was decreased to 45%.
Figure 2: Multiple erythematous excoriated papules with scratch
marks present over the trunk
Figure 4: Computed tomography revealed left-sided pleural effusion
86 Vol. 6 • Issue 2 • April-June 2015
 Saxena, et al.: Thrombocytopenia in PV
Myelosuppressive therapy (hydroxyurea 500 mg once
a day) was added. Low‑dose aspirin could not be added
in view of persistent thrombocytopenia that fluctuated
between 16,000 and 44,000/mm3 during the 3 months
follow‑up period.
DISCUSSION
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Revised WHO 2008 criteria for the diagnosis of
PV includes two major criteria and three minor
criteria.[5] The two major criteria include an increased
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Hb level (>18.5 g/dL in men or >16.5 g/dL in woman)
or other evidence of increased red cell volume and
presence of JAK2V617F mutation. The three minor
criteria include BM trilineage myeloproliferation,
subnormal serum EPO level, endogenous erythroid
colony formation (EEC) in vitro. The diagnosis of PV
requires the presence of both major criteria and one
minor criterion, or the presence of the first major
criteria together with two minor criteria. In our
case, two major criteria that is, Hb level >18.5 g/dL,
presence of JAK2 mutation and two minor criteria that
is, BM trilineage hypercellularity and low serum EPO
level are fulfilled.
The cause of thrombocytopenia in our patient could
be either increased sequestration of platelets as a result
of hypersplenism, platelet consumption within the
hemorrhagic pleural effusion or increased clearance
of platelets as a result of immune thrombocytopenic
purpura (ITP). Hypersplenism results in
sequestration (pooling) of platelets in an enlarged
spleen because of slow passage of platelets through
splenic vasculature resulting in thrombocytopenia.[6]
Three cases of ITP coexisting with PV were reported by
Niscola et al., which responded well to oral steroids and
indirectly supported the immunological origin of the
low platelet count in these patients.[7] In our patient,
platelet count did not improve after oral steroid trial,
which did not support the diagnosis of ITP. Platelet
associated IgG and/or IgM antibodies could not be done
in our patient due to financial constraints.
Pleural fluid examination in our patient was
unremarkable for any evidence of malignancy or
infection. The etiology of hemorrhagic pleural
effusion was unclear even after extensive evaluation
for malignancy, infection, autoimmune disease,
or pulmonar y or splenic thrombosis/infarction.
The etiologies of PE in patients with chronic
myeloproliferative diseases reported in the literature
are infiltration of the pleura at the stage of leukemic
transformation, extramedullary hematopoiesis, lung
infections or reactive with the presence of mononuclear
cells, mesothelial cells, and T lymphocytes.[8] In our
Vol. 6 • Issue 2 • April-June 2015
patient, the possibility of pleural reaction secondary
to intrapleural bleeding was considered after excluding
other causes, which might occur as a result of platelet
dysfunction. Left‑sided pleural effusion secondary
to splenic vein thrombosis has been reported in the
literature by Warren and Gibbons.[9] But we did not
find such evidence in abdominal imaging.
Erythrocytosis, leukocytosis or thrombocytosis or in
combination are usually present at the onset of PV.
Thrombocytopenia at the onset of PV with hypercellular
bone marrow is extremely rare. Cytopenias are noticed in
the spent phase (postpolycythemic myeloid metaplasia),
an advanced stage of PV characterized by normalization
of the red cell mass, increased splenomegaly because of
extramedullary hematopoiesis, and collagen fibrosis of
the bone marrow (myelofibrosis).[1,10]
CONCLUSION
Clinicians or hematologists involved in the care of PV
patients should be aware of the unusual occurrence of
thrombocytopenia and hemorrhagic pleural effusion as
initial presentation of PV.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
There are no conflicts of interest.
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