Abbreviations:
DVT: Deep Vein Thrombosis
WHO: World Health Organization
CT: Computerized Tomography
VITT: Vaccine-Induced Immune Thrombotic Thrombocytopenia
CVT: Cerebral Venous Thrombosis
PTE: Pulmonary Thromboembolism
SVT: Splanchnic Vein Thrombosis
Introduction: Upper limb
deep
vein thrombosis (DVT) is a rare condition, which occurs as a result of
thrombosis in the axillary, subclavian or brachiocephalic veins.
According to previous studies, it occurs spontaneously in 20% of
patients and develops secondary to some risk factors in 80% of
them.1-3 These risk factors are related to Virchow’s
triad; venous flow stasis, venous wall injury, and
hypercoagulability.3 Although upper limb DVT seems to
be benign, it has considerable morbidity and mortality rate and leads to
serious problems such as pulmonary embolism, loss of vascular access,
superior vena cava syndrome, and post-thrombotic syndrome. So, we have
to take it more seriously.1-3
COVID-19 disease is a multisystem infectious disease and affects several
organs and systems including respiratory, cardiovascular,
gastrointestinal, neurologic, coagulation, and immune
system.4 Although certain management and treatment
against COVID-19 have not been released yet, several vaccines are used
around the world to control and prevent this pandemic
disease.5Chinese COVID-19 vaccine named
BBIBP-CorV (Sinopharm vaccine) is an inactivated
whole virus vaccine that was the
fifth authorized vaccine by World Health Organization (WHO) for
emergency use in May 2021 and has a 79% efficacy
rate.6,7 This vaccine requires two doses with an
interval of 21 to 28 days. It is authorized by several countries and
used widely in the Asian population.5-7
It has mild side effects including dizziness, fatigue, headache, nausea,
vomiting, fever, and injection site reactions.6 A
cohort study by Liu et al.8 in 2021 concluded that
inactivated COVID-19 vaccines do not increase the risk of thrombosis. In
this report, we present a 23-year-old man
who came to the emergency
department with the chief complaint of severe pain, generalized
inflammation, and swelling of the right upper limb after getting his
second dose of the Sinopharm vaccine.
Case Presentation: A 23-year-old right-hand-dominant man came
to the emergency department with the chief complaint of severe pain,
generalized inflammation, and swelling of the right upper limb. He
stated that this pain started within 24 hours after receiving his second
dose of the Sinopharm COVID-19 vaccine to the right deltoid muscle about
a month before referring to the hospital. By the time, he noticed
progressive inflammation and swelling in his right arm; and a week
before referring, the pain and swelling started to intensify in a way
that he couldn’t tolerate. So, he self-referred to the emergency
department.
He was an employee, and he did not do manual labor. He didn’t have any
past medical history or any history of COVID-19 disease. He didn’t use
any medication, didn’t mention any specific familial medical history,
and didn’t have a recent history of surgery or trauma. He was a
2-pack-years smoker.
At First, physical examinations were performed in the emergency
department, and the most important finding was the difference in the
size of two limbs by 4 centimeter
in the mid-arm (The right upper
limb was larger). He had generalized swelling, erythema, pitting edema,
and tenderness in his right arm. The pulse of the right radial artery
was weak (+1). He didn’t have any lymphadenopathy on general
examination.
His initial lab tests were normal and there were no significant
findings. Color-doppler ultrasonography of the right upper limb was
requested and the radiologist’s statement was as follows: The distal
half of the axillary vein and the entire length of the subclavian vein
are dilated and incompressible. Echogenic thrombosis is seen within them
(Diagnosis: Right Upper Limb Deep Vein Thrombosis). Computerized
tomography (CT) angiography of the chest was negative for pulmonary
embolism, and there was no evidence of mass and lymphadenopathy.
According to the diagnosis (right upper limb DVT), he was admitted to
the general ward, and treatment was started. Rivaroxaban was prescribed
for 6 days in the hospital, and after 6 days of hospitalization, his
symptoms of right upper limb swelling and pain relatively improved. He
was discharged on Rivaroxaban 15 mg twice a day for 21 days, and then 20
mg daily for 3 months.
During hospitalization, several lab tests were requested to investigate
the cause and etiology of the DVT. The thrombophilia tests were negative
including factor V Leiden, protein C, protein S, and antiphospholipid
antibodies.
He was followed up for 6 months, he was not re-admitted after
discharging and didn’t have any new complaints. Mild swelling and pain
continued for 3 months and then improved. Due to the fact that he was
right-handed, his life and job were affected.
Discussion: COVID-19 disease causes thrombotic complications
such as venous thromboembolism.4 A meta-analysis study
by Tan et al.9 in 2021 was performed on 102 studies
involving 64503 patients. In this study, the frequency rate of
COVID-19-related venous
thromboembolism events was 14.7%
to 17.6%, and the frequency of COVID-19-related arterial thrombotic
events was about 3.9%.9 These events were more common
among critically ill patients who were admitted to the intensive care
unit.10
Previous studies concluded that some of the COVID-19 vaccines increase
the risks of thrombosis and coagulopathy.10 In late
February 2021, a number of thrombotic events named vaccine-induced
immune thrombotic thrombocytopenia (VITT) were reported in relation to
adenoviral vector-based vaccines such as
ChAdOx1-S/nCoV-19 (AstraZeneca
vaccine) and Ad26.COV2.S (Johnson & Johnson/Janssen vaccine). These
events were associated with thrombocytopenia and occurred in various
sites such as cerebral venous thrombosis (CVT), deep vein thrombosis
(DVT), pulmonary thromboembolism (PTE), and splanchnic vein thrombosis
(SVT). A significant mortality rate was reported.10,11
A cohort study by Liu et al.8 in 2021 was designed and
performed to investigate whether inactivated virus COVID-19 vaccines
such as the Sinopharm vaccine induces thrombosis or not. In this study,
406 healthcare workers who had received two doses, 21 days apart, were
included and it was concluded that inactivated whole virus vaccines do
not increase the risk of thrombosis.8
A study by Hameed et al.12 in 2022 discussed four
cases of cerebral venous thrombosis after receiving inactivated COVID-19
vaccines (Sinopharm and Sinovac vaccine) and to our knowledge, there are
two case reports of VITT associated with the Sinopharm
vaccine.13,14
Although upper limb DVT itself is a rare condition and represents about
11% of all DVTs in the general population,2 a study
by Chen et al.3 in 2018 predicted that the prevalence
of this condition will increase. Because of dangerous complications of
Upper limb DVT such as pulmonary embolism, early diagnosis and treatment
are important.3
To our knowledge, there are some case reports of acute upper limb deep
vein thrombosis after getting mRNA Covid-19 vaccines including mRNA-1273
(Moderna vaccine) and BNT162b2 (Pfizer-BioNTech vaccine)
vaccines.15-18 In comparison between our report and
other case reports, the results are relatively similar as follows:
In all cases, there were negative results of thrombophilia workups. In
all cases, there was no evidence of thrombocytopenia, so they were in
contrast to adenoviral vector COVID-19 vaccines such as
ChAdOx1-S/nCoV-19 (AstraZeneca vaccine) and Ad26.COV2.S (Johnson &
Johnson/Janssen vaccine), and
should not be listed in the group of vaccine-induced immune thrombotic
thrombocytopenia (VITT).
In conclusion, according to the imaging findings, laboratory and
thrombophilia tests, and previous studies our case can be introduced as
the first upper limb DVT case after receiving inactivated whole virus
COVID-19 vaccine.
Acknowledgments: The authors are thankful to the patient and
Imam Reza hospital’s general ward staff for their collaboration.