Medicine

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Clinical Case Report

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A case report of cerebral infarction caused
by polycythemia vera
Shan Ren, MDa, Fang Gao, MDa, Zhigang Chen, MDa, Zhiqun Wang, MDb,

∗

Abstract
Rationale: Polycythemia vera (PV) is a cloned erythrocytotic disease manifested by high proliferation and apoptosis in the bone

marrow. The clinical symptoms of PV are occult. In practice, patients with cerebral infarction caused by PV are prone to misdiagnosis
and missed diagnosis.
Patient concerns: Here, we report a misdiagnosis of PV leading to cerebral infarction. The patient was a middle-aged woman
who was diagnosed with acute cerebral infarction in the outpatient hospital. After treatment, the patient still had left hemiplegia,
dizziness and other symptoms and was admitted to our hospital.
Diagnosis: We did not find sufficient evidence of atherosclerotic processes in the brain infarction. However, the patient’s signs and

laboratory examination indicated a high suspicion of PV. A series of further examinations confirmed the final diagnosis.

Interventions: Bone marrow suppression medications (oral hydroxyurea and subcutaneous injection of interferon) were given and
subsequent prevention of cerebral infarction was implemented.
Outcomes: Routine blood reexamination was normal and no further cerebral infarction occurred.
Lessons: Patients with acute cerebral infarction should be considered comprehensively, and rare causes should not be ignored. It
is crucial that PV be diagnosed and treated as early as possible, which can significantly improve the prognosis of patients.
Abbreviations: PV = polycythemia vera, RBC = red blood cell, WBC = white blood cell.
Keywords: cerebral infarction, polycythemia vera

Medical Research Ethics Committee of Dongfang Hospital,
Beijing University of Chinese Medicine. The patient provided
informed consent for publication of the case.

1. Introduction
Polycythemia vera (PV) is characterized by increased red blood
cells (RBCs) in peripheral blood, mostly due to cancer gene
mutations, such as the JAK2 V617F mutation.[1] PV is easily
ignored at an early stage because of occult clinical symptoms. It
can cause thrombotic diseases,[2] especially cerebral infarction. A
previous study revealed that in more than 15% of patients, PV is
first manifested as cerebral infarction.[3] Based on the characteristics of PV, it is often missed as routine cerebral infarction. Here,
we report our case of PV. This study was approved by the

2. Case report
The patient is a 64-year-old female who was admitted to our
hospital on March 28, 2018. The patient complained of left limb
dyskinesia and dizziness for more than 4 months. Magnetic
resonance imaging (MRI) showed hyperintensity lesions on the
right side of the basal ganglia and lateral ventricle (Fig. 1),
suggesting the diagnosis of acute cerebral infarction. After
treatment, the patient’s clinical symptoms did not resolve. The
patient had no history of risk factors such as hypertension,
hyperlipidemia, diabetes, coronary heart disease, or smoking. No
history of trauma, poisoning, surgery, blood transfusion,
infection, or family history of heredity was found. The results
of the physical examination were as follows: temperature (T):
36.4°C, pulse rate (P): 74 times/min, respiration (R): 20 times/
min, and blood pressure (BP): 120/80 mmHg; the face and hands
were obviously red, and the superficial lymph nodes throughout
the body were not enlarged. Cognitive function was normal. The
left side of the upper limb muscle was III+, the left side of the
lower limb muscle was level IV, the right upper limb muscle was
level V, and the right side of the lower limb muscle was level V.
The left muscle tension was slightly lower, and the right muscle
tension was normal. The Babinski sign was positive on the left.
The results of auxiliary examination on March 29, 2018, were as
∗
follows: whole blood cell analysis: 18.65 10e9/L; white blood cell
(WBC) count: lymphocyte percentage, 13.1%; neutrophil
∗
percentage, 78.3%; RBC count, 5.8 10e12/L; hemoglobin
∗
content, 182 g/L; RBCs, 55.2%; platelet count, 409 10e9/L;

Editor: N/A.
This work was supported by the Beijing natural scientific foundation of China
(No.7182105), the National natural scientific foundation of China (Grant No.
81571648), the Capital special funds for health improvement and research (No.
2018-2-4202), Dongfang Hospital of Beijing University of Traditional Chinese
Medicine “1166” talent training project (NO.030903010321).
The authors have no conflicts of interest to disclose.
a

Department of Neurology, b Department of Radiology, Dongfang Hospital,
Beijing University of Chinese Medicine, Beijing, China.

∗

Correspondence: Zhiqun Wang, Department of Radiology, Dongfang Hospital,
Beijing University of Chinese Medicine, Fengtai district, Beijing 100078, China
(e-mail: wangzhiqun@126.com).

Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NCND), where it is permissible to download and share the work provided it is
properly cited. The work cannot be changed in any way or used commercially
without permission from the journal.
Medicine (2018) 97:52(e13880)
Received: 26 August 2018 / Received in final form: 4 December 2018 /
Accepted: 5 December 2018
http://dx.doi.org/10.1097/MD.0000000000013880

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Figure 1. MRI shows acute cerebral infarction in right side of basal ganglia and lateral ventricle. MRI = magnetic resonance imaging.

∗

In summary, we strongly suspected that the cause of cerebral
infarction in this patient was PV. Bone marrow puncture was
performed, and related genes were detected by bone marrow
extraction and hematopoiesis. The results of the bone marrow
image examination report on April 9, 2018, were as follows: 1.
grade III bone marrow hyperplasia, with 63% granule system,
30% red system, and 2.1:1 granule/red system; 2. granule system:
hyperplasia was active; early larval granulocytes could be
observed; 3. red system: hyperplasia was active; early and late
larval erythrocytes could be observed, with a slightly higher
proportion of late larval erythrocytes; mature RBCs had normal
morphology; 4. the proportion of lymphocytes was low, and the
morphology was normal; and 5. there were 37 megakaryocytes
and many platelets in the whole tablet. The conclusion was that
bone marrow hyperplasia was active. The bone marrow
pathology report (Fig. 2: bone marrow) showed that bone

monocyte absolute value, 0.63 10e9/L; eosinophil absolute
∗
∗
value, 0.72 10e9/L; basophil absolute value, 0.24 10e9/L; and
basophil percentage, 1.3%. The absolute value of neutrophils
∗
was 14.61 10e9/L and the platelet volume was 0.44%. The
coagulation 4 + D dimer measures were an activated partial
prothrombin time of 27.7 seconds, prothrombin ratio of 1.07,
percentage prothrombin activity of 103.9%, thrombin officially
standardized ratio of 1.07, fibrinogen coagulation time of 7.9
seconds, thrombin setting time of 19.7 seconds, D-dimer
(quantitative) of 0.22 ug/mL, prothrombin time of 12.3 seconds,
and fibrinogen content of 2.36 g/L. There was no obvious
abnormality among the results for the remaining blood sampling:
abdominal ultrasonography, large spleen; cardiac ultrasonography, 24-hour dynamic electrocardiogram: no obvious abnormality; intracranial and extracranial vascular ultrasound
examination: no stenosis or unstable plaque was observed.

Figure 2. Bone marrow pathology shows hyperplasia of bone marrow.

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Figure 3. Immunotyping shows increased CD64 expression and abnormal phenotype.

was observed. The proportion of nuclear red cells was reduced by
2.34%. CD34+ and CD117+ immature myeloid cells accounted
for 0.18%, which was not high. Basophils accounted for 1.24%
and acidophils accounted for 2.23%. Chromosome examination
(G banding) (Fig. 4) on April 17, 2018, revealed the following:
46, XX [20]. In summary, the clinical diagnosis was clearly PV.
Treatment began on April 18, 2018, with aspirin entericcoated metformin hydrochloride in 0.1 g Po Qd antiplatelet
aggregation, on the basis of joint oral hydroxyurea; there was
frequent adjustment of the dose of 0.5 g Po Bid, 0.5 g Po dar, 1 g
Po Bid bone marrow suppression and sodium bicarbonate, and
0.5 g Po dar alkalized urine. The May 9, 2018, review of complete
∗
blood analysis revealed the following: WBC count, 7.90 10e9/L;
∗
neutrophil absolute value, 5.55 10e9/L; lymphocyte percentage,
∗
20.5%; neutrophil percentage, 70.2%; RBC count, 5.71 10e12/
L; hemoglobin content, 177 g/L; RBCs, 53.10%; and platelet
∗
count, 122 10e9/L. Giving the patient a larger oral dose of
hydroxyurea was considered; however, RBC and hemoglobin

marrow tissue was observed between bone trabeculae attached to
fibrous cartilage, red pulp was relatively increased, yellow pulp
was relatively decreased, the red and white system was common,
and megakaryocytes were easy to see. Immunohistochemical
expression on April 11, 2018, was as follows: CD38 (+), CD138
(+), CD31 (+), CD34 (+), MPO (+), TdT (+), CD235 (+), Ki67 (+
> 5%), P53 (+), and CD68 (+). The PCR gene test results were as
follows: jak2-617 site V/F mutation (+), genotype G and T
hybrid, CALR gene 9- exon mutation (-), MPLW515L/K
mutation (-), JAK2-exon sequence mutation of gene 12 (-),
and Quantitative rt-pcr (-) of bcr-abl (P210, P230, P190, and
variant) fusion genes. The immunohistotypic report (Fig. 3) on
April 13, 2018, was as follows: lymphocytes (P2) accounted for
18.15%, with a normal proportion, mainly mature T lymphocytes. Myeloid cells (P4) accounted for 72.24%, the proportion
of CD10+ mature granulocytes was normal, the expression of
CD64 was enhanced, and the phenotype was abnormal.
Monocytes accounted for 0.87%, and no abnormal phenotype
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Figure 4. Chromosome examination (G band) shows 46, XX[20] abnormality.

purpura. PV refers to the quantity of the unit volume of RBCs, and
hemoglobin is higher than the reference value range: the adult male
∗
RBC count is > 6.0 10 e12/L with hemoglobin > 165 g/L; the
∗
adult female RBC count is >5.5 10 e12/L with hemoglobin >160
g/L. Erythrocytopenia is classified according to relativity and
absoluteness. Relativity refers to the capacity to reduce plasma,
intensifying the RBCs’ relative increase in capacity, resulting in
severe vomiting, diarrhea, excessive sweating, burns, diabetes
insipidus, thyroid function hyperfunction, and diabetic ketoacidosis. The increase in absoluteness can be divided into 2 categories:
primary and secondary. Idiopathic patients can also be divided into
congenital and acquired. Congenital primary erythrocytopenia
presents as increased erythrocyte production due to EPO receptor
gene mutation. PV, a primary disease of growth in the number of
RBCs, is a type of erythrocytosis hyperplastic bone marrow tumor
currently thought to be caused by JAK pluripotent hematopoietic
stem cells, specifically with the V617F mutation, as thrombotic
events occur. Some scholars[4] analyzed the clinical characteristics
of 70 patients with PV and found that 22.68% presented with
cerebral infarction as the first symptom.

values still were not normal, and there were significantly fewer
platelets. Therefore, on May 10, 2018, oral hydroxyurea was
stopped and changed to 2 ba human recombinant interferon
injections; pseudomonas (3 million units: 1 mL) by subcutaneous
injection was reduced from 3 times per week to 2 times per week.
The results of the June 11, 2018, review of complete blood analysis
∗
were as follows: WBC count, 8.29 10e9/L; neutrophil absolute
∗
value, 5.36 10e9/L; lymphocyte percentage, 29.6%; neutrophil
∗
percentage, 64.6%; RBC count, 4.69 10e12 at 11:45/L;
hemoglobin content, 145 g/L; RBCs, 43.2%; and platelet count,
∗
120 109/L. The patient was discharged from the hospital after
improvement and was instructed to continue regular subcutaneous
injection of interferon and routine blood evaluation.

3. Discussion
Cerebral infarction is a serious threat to human health, and the
most common cause is atherosclerosis; however, some more rare
etiologies can also lead to brain tissue ischemia and hypoxia, such
as arteritis, amyloidosis, erythrocytosis, and thrombocytopenic
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urea can be treated with artificial interferon (<65 years old) and
baixiao tablets (>65 years old). The standard value is an RBC
count below 45%.[1,12] The patient was finally effectively treated
by subcutaneous injection with interferon. Routine blood testing is
back to normal, and no thrombotic events have recurred.
This case suggests the following: if a patient presents with red
and purple skin color and their RBC volume is increased
significantly, we should pay special attention to possible PV. In
cases of thrombosis, the possibility of PV should be highly
suspected, further bone marrow-related examination should be
performed,[13] and JAK2 gene testing should be performed if
conditions permit. Patients with acute cerebral infarction should
be considered comprehensively, and rare causes of infarction
should not be ignored. Early diagnosis and treatment can
significantly improve the prognosis of patients.

Some scholars have found that the pathogenesis of PV is related
to the reduction of cerebral blood flow and abnormal platelet
function caused by increased blood viscosity.[5] A large number
of abnormal RBCs infiltrated the arterial wall for a long time in
PV patients, resulting in increased blood viscosity, followed by a
slower blood flow rate, leading to cerebral vascular obstruction,
cerebral ischemia, and hypoxic necrosis. PV leads to cerebral
infarction in the common locations of the basal ganglia, radiated
corona, cerebellum, and so on.; it is also observed in the cortex,
but large area infarctions are relatively rare.[6] Due to its occult
character, the clinical symptoms are not typical, and early
recognition is not easy. For this patient, after cerebral infarction
occurred, the possibility of PV was not considered initially;
therefore, there was a failure to treat the primary disease in a
timely manner, which may lead to the occurrence of cerebral
infarction and relapse.
At present, studies[7] have found that there is a certain
relationship between leukocyte count and thrombosis and
thrombosis recurrence. Data from PV patients have shown that
∗
the risk of thrombosis increased when the WBC count is >9.5 10
∗
e9/L. A WBC count >12.4 10 e9/L is an independent risk factor
for thrombosis recurrence in patients under the age of 60
following the first thrombus. Bonicelli et al[8] proposed that in
patients with PV, the survival rate would decrease when the
∗
leukocyte count was >13 10 e9/L.
Because most PV patients have V617F mutations in the JAK2
gene, those with a high clinical suspicion of PV should not only be
examined for hematology and bone marrow but also be tested for
genes to further confirm the diagnosis. JAK2 V617F mutationpositive patients with PV have a single nucleotide mutation, and
mutations of guanine (G) and thymine (T) make the in situ valine
missense coding for phenylalanine, resulting in JAK2 kinase
activity, promoting self-phosphorylated activation, further
activating downstream signal transduction pathways, and
causing the endogenous cloned generation of RBCs.[9]
The patient was an elderly female patient who was admitted with
cerebral infarction and was found to have obvious redness on her
face and hands and splenomegaly on abdominal ultrasound. The
imaging findings were consistent with the characteristics of PV
secondary to cerebral infarction. After admission, the patient’s
blood routine indicated that hemoglobin was 182 g/L and all 3 lines
(WBCs, RBCs, and platelets) were increased. A bone marrow
examination revealed hyperplasia of the 3 lineages. Gene testing
found that the JAK2 V617F mutation was positive, while the bcrabl gene, CALR gene, and MPL gene were negative. According to
the 2014 revision and recommendation criteria,[10,11] the clinical
manifestations and laboratory examination results of this patient
fulfilled the diagnostic criteria of PV.
For the treatment of PV combined with cerebral infarction, the
current commonly used treatment method is control of vascular
disease risk factors. Small doses of aspirin (0.1 g/d) are administered; patients with bleeding, stomach intolerance or other
contraindications are excluded. There is also a blood test, and
patients with hydroxyl urea resistance or intolerance to hydroxyl

Author contributions
Data curation: Fang Gao.
Supervision: Zhigang Chen.
Writing – original draft: Shan Ren.
Writing – review & editing: Zhiqun Wang.

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