(2023) 17:223
Demir et al. Journal of Medical Case Reports
https://doi.org/10.1186/s13256-023-03936-8

Journal of
Medical Case Reports

Open Access

CASE REPORT

Ischemic stroke in the setting
of supratherapeutic International Normalized
Ratio following coronavirus disease 2019
infection: a case report
Gokhan Demir1*, Rama Hommos2, Sally Sami Al‑Sirhan2, Hashem Abu Serhan3, Muhannad Haddadin1,
Umar Bin Rashid1 and Yamane Chawa1

Abstract
Background SARS-CoV-19 infection is associated with an increased risk of thrombotic events. We present a case of
acute middle cerebral artery ischemic stroke in a patient with SARS-CoV-19 infection despite being on warfarin with
supratherapeutic INR (International Normalized Ratio).
Case presentation A 68-year-old Caucasian female with multiple comorbidities was admitted to the hospital with
symptoms of upper respiratory tract infection. A rapid antigen test confirmed the diagnosis of COVID-19 pneumo‑
nia, and intravenous remdesivir was initiated. On the fifth day of admission, the patient experienced sudden onset
confusion, slurred speech, left-sided hemiplegia, right-sided eye deviation, and left-sided facial droop. Imaging studies
revealed an occlusion of the distal anterior M2 segment of the right middle cerebral artery, and an MRI of the brain
confirmed an acute right MCA infarction. Notably, the patient was receiving warfarin therapy with a supratherapeutic
INR of 3.2.
Conclusions This case report highlights the potential for thromboembolic events, including stroke, in patients
with COVID-19 infection, even when receiving therapeutic anticoagulation therapy. Healthcare providers should be
vigilant for signs of thrombosis in COVID-19 patients, particularly those with pre-existing risk factors. Further research
is necessary to understand the pathophysiology and optimal management of thrombotic complications in COVID-19
patients.
Keywords Stroke, SARS-CoV-19, Ischemia, Infarction, INR, Middle cerebral artery

*Correspondence:
Gokhan Demir
gdemir@hamad.qa
1
Department of Internal Medicine, Hamad General Hospital, Doha, Qatar
2
College of Medicine, Qatar University, Doha, Qatar
3
Department of Ophthalmology, Hamad General Hospital, Doha, Qatar

Background
Thus far, acute ischemic stroke (AIS) has been reported
to complicate 1%–5% of coronavirus disease 2019
(COVID-19) infections [1]. Severe COVID-19 infection is associated with a high risk of thrombosis, since
patients exhibit all three components of Virchow’s triad,
and in those who experience a profound systemic inflammatory response to COVID-19 infection, there may be an
increased risk of prothrombotic events [2, 3].

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Demir et al. Journal of Medical Case Reports

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There have been reports of an increased tendency to
develop coagulopathy in SARS-CoV-2-infected patients
[4], and there is evidence that the degree of coagulopathy is correlated with the severity of respiratory sickness
[5]. The main thrombotic event is recognized as venous
thromboembolism, but stroke is also identified, although
this conclusion is debatable [6] due to a lack of high-quality evidence. The process of increased risk of ischemic
stroke in COVID-19 patients is not well-established,
although different studies have proposed several mechanisms, including cytokine storm [7].
Thromboembolism prophylaxis has been used since
the beginning of the COVID-19 pandemic, but it has
become rapidly clear that a routine prophylactic dose—
usually of low molecular weight heparin (LMWH)—was
often insufficient to prevent venous thrombosis in these
patients [1]. The high incidence of thrombotic events,
even with prophylactic dose anticoagulation, has led physicians to use intermediate or even therapeutic doses of
anticoagulants [3].
This case report presents a unique and challenging scenario of a patient who was hospitalized with COVID-19
and later developed an acute ischemic stroke. The presented case adds to the growing body of literature on
COVID-19-associated stroke and underscores the need
for a multidisciplinary approach to the management of
COVID-19 patients. By sharing this case report, we aim
to contribute to the medical knowledge and improve the
care of COVID-19 patients, particularly those at risk of
developing neurological complications.

Case presentation
A 68-year-old Caucasian female with a known case of
atrial fibrillation (­CHA2DS2-VASc 4), diabetes mellitus type 2, hypercholesterolemia, hypertension, diffuse
large B cell lymphoma treated with chemotherapy in
2017(since then patient was on remission), heart failure
with a reduced ejection fraction of 39% presented to a
tertiary hospital in September 2022, complaining of dry
cough for 5 days duration, accompanied by subjective
fever, nausea, and dysuria.
Her vital signs were stable upon presentation (blood
pressure 114/63 mmHg, breath rate 18/minute, heart rate
73/minute, axillary temperature 36.9 °C). On lung auscultation, the presence of basal crackles was appreciated.
Lower limb edema was noted. Neurological exam was
grossly unremarkable, she was alert and oriented, power
exam was 5/5 for all extremities, Cranial nerves II-XII
were intact and speech was normal. The patient reported
receiving all three doses of the COVID-19 vaccine
(Pfizer-BioNTech), the last dose being in October 2021.
The patient’s current pharmacological regimen consists
of several medications, namely rosuvastatin (10 mg tablet

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once daily), warfarin (1.5 mg tablet once daily), bisoprolol (7.5 mg tablet once daily), perindopril (5 mg tablet
once daily), furosemide (80 mg tablet twice daily), insulin aspart (18 units before breakfast and 10 units before
lunch), insulin glargine (24 units once at bedtime), metformin (500 mg tablet twice daily), sitagliptin (100 mg
tablet once daily), and ferrous sulfate (190 mg tablet once
daily). She had no previous history of surgery and did not
smoke or take alcohol or illicit drugs. She reported a history of four pregnancies resulting in the birth of two male
and two female offspring without any record of fetal loss.
Currently unemployed, she resides with her husband,
who provides assistance with daily tasks. Her familial
medical history was unremarkable for any cerebrovascular or cardiovascular disorders among first-degree
relatives. However, both parents were diagnosed with
diabetes.
Laboratory investigations revealed the following:
hemoglobin 9.4 gm/dL, white blood cells (WBC) 12 × 103
uL, sodium 123 mmol/L, potassium 3.8 mmol/L, magnesium 0.71 mmol/L, C reactive protein (CRP) 239 mg/L,
procalcitonin 6.41 ng/mL, creatinine 95 umol/L,
international normalized ratio (INR) 3.2, and glucose
12.1 mmol/L. Blood cultures were negative for aerobic
and anaerobic organisms. Urinalysis results were positive
for WBC 3,672 uL and red blood cells (RBC) 28 uL, and
the urine culture was found to be positive for multidrugresistant Escherichia coli (E. coli) sensitive to meropenem. The COVID-19 rapid antigen test was positive, and
the chest X-ray showed bilateral lung congestive changes
seen with patchy infiltrate in the right lower lung zone.
(Fig. 1).
Based on the investigations done, a diagnosis of
COVID-19 with a multidrug-resistant E. coli urinary

Fig. 1 Anteroposterior (AP) chest X-ray on the day of admission

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(2023) 17:223

tract infection was made. The patient was diagnosed with
hypervolemic hyponatremia. To manage this condition, a
fluid restriction of 1 L per day was implemented, in conjunction with oral administration of 600 mg of sodium
chloride tablets three times daily. As per the established protocol for COVID-19 management in patients
with multiple comorbidities at our hospital, remdesivir
(200 mg IV daily) was initiated for a duration of 5 days.
Additionally, meropenem (1000 mg IV three times a day)
was administered to address the patient’s symptomatic
urinary tract infection. This decision was made in light of
a previous positive culture for extended-spectrum betalactamase (ESBL)-producing E. coli in the patient’s urine.
She started to improve clinically and, in terms of laboratory results, planned to be discharged after five days
after admission.
On fifth day of admission, the patient developed a sudden onset of confusion and slurred speech. On initial
assessment, there was clear dense left-sided hemiplegia
with right-sided eyes deviation and a left facial droop.
Vitally, the patient maintained saturation in room air
with a heart rate of 100 beats per minute, blood pressure
of 150/96 mmHg, respiratory rate of 20, and temperature
of 36.7 °C. On neurological assessment, she was alert, but
disoriented and dysarthric. Cranial nerve examination
was significant for left gaze palsy, and testing for power
was significant for strength 0/5 on the left side and 4 + /5
on the right side extremities. At that time, the Glasgow

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Coma Scale (GCS) was 15/15, and the National Institutes
of Health Stroke Scale (NIHSS) score was 16. Based on
the sudden onset of neurological deficits such as sudden
left extremity weakness, left facial palsy and dysarthria,
the stroke protocol was activated. The INR was 4.9.
A head CT and perfusion study were performed on
after 2 h of initial presentation, which revealed a focal
area of matched perfusion defect seen in the right frontoparietal cortical and subcortical region, denoting
core infarct with surrounding penumbra and occlusion
of the distal anterior M2 segment of the right middle
cerebral artery (MCA).
A diagnosis of acute ischemic stroke was made, but
the patient was not a candidate for thrombolysis or
thrombectomy due to an INR of 4.9. One day after the
initial CT scan, an additional head MRI and MRA was
done which showed right frontal area of 4 × 2.3 cm of
diffusion restriction with no hemorrhagic changes
(Fig. 2).
Due to swallowing difficulty post-stroke, a nasogastric tube (NGT) was inserted. Interestingly, the patient’s
INR increased, reaching a peak of 5.4, despite holding
warfarin since admission. However, 6 days later, the
patient’s INR went down to 2.2, and she was transferred
for rehabilitation.
At follow-up at the rehabilitation institute after one
month, the patient still had hemiplegia, and her motor
power was tested at 1/5 in the left upper limb and 3/5 in
the left lower limb, showing minor improvement. The

Fig. 2 A In Diffusion-weighted magnetic resonance of brain imaging showing right frontoparietal diffusion restriction suggesting acute infarction.
B Magnetic resonance angiography (MRA) of brain demonstrates a paucity of vessels on the right side when compared to the left side and the
middle cerebral artery superior trunk occlusion (blue arrow)

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INR had stabilized in the range of 1.9 to 2.1 during this
month. During the six-month follow-up appointment
at the Stroke clinic, the patient continued to exhibit
residual left-sided weakness, primarily impacting her
arm. However, the patient reported no new, recurrent,
or worsening neurological symptoms.

Discussion
We present the case of a 68-year-old woman with confirmed COVID-19, who subsequently suffered from an
ischemic cerebral stroke despite receiving anticoagulant
therapy.
The association between thromboembolic events
and COVID-19 is well known [8, 9]. The incidence of
ischemic stroke was ≈10 times higher during the first
14 days after COVID-19 diagnosis as compared with
the control intervals [8]. Not only COVID-19 infection
itself but also the severity of COVID-19 might lead to
increased acute stroke incidence. According to a recent
meta-analysis, the total incidence of ischemic strokes was
1.76% among all COVID-19 patients. Based on the severity of the disease, the total stroke rate of patients with
severe COVID-19 was 3.37% (95% CI: 1.74–5.44), and
that of patients with non-severe COVID-19 was 0.61%
[10].
The exact mechanism by which COVID-19 increases
the risk of acute stroke remains unknown. Certain studies have proposed the idea that an inflammatory cytokine
storm might contribute to a hypercoagulable state and
endothelial damage [7]. Moreover, patients with COVID19 who were admitted to the ICU had higher levels of
granulocyte–macrophage colony-stimulating factor,
interferon gamma-induced protein 10, monocyte chemoattractant protein-1, macrophage inflammatory protein
1a, and TNF-α, suggesting the presence of this excessive
inflammatory process in critically ill patients [9].
Concurrently, other factors that may have contributed
to our patient developing stroke could be chronic atrial
fibrillation, diabetes and hypertension. The patient had
controlled blood pressure readings before and after the
stroke event. Even though the electrocardiography (EKG)
rhythm was atrial fibrillation rhythm, the transthoracic echocardiogram showed no intracardiac masses or
thrombi. At the time of the stroke event, our patient had
an INR of 4.9, which would have made an ischemic stroke
quite unlikely to happen.
In addition, our patient had hypercholesterolemia,
which was controlled by statin use. Hence, previous literature has shown that hypercholesterolemia and hypertension are both independent factors for ischemic stroke
[11]. It has been suggested that they have a potential synergistic effect on the risk of ischemic stroke [12]. Both
hypercholesterolemia and hypertension contribute to the

Page 4 of 5

thickening of carotid artery intima-media, thereby reducing the blood supply to the brain and leading to ischemic
stroke [13, 14]. However, the patient was primarily taking rosuvastatin 10 mg; statins control blood lipids, and
play a significant role in primary and secondary stroke
prevention [15, 16]. Referring to this patient’s INR-controlled lipid panels, it is unlikely to have been the main
cause of her ischemic stroke. Studies have shown that
individuals with carotid artery stenosis have a higher risk
of stroke, particularly ischemic stroke, proportional of
the degree of stenosis [17]. However, the CT angiogram
in this patient did not reveal any significant stenosis or
atherosclerosis in the aortic arch, origin, or cavernous
segments of the internal carotid arteries.
Despite anticoagulation, our patient suffered a right
MCA infarct. Several questions emerged with this case
report that may require further research. First, arterial
thromboembolism is rare when compared with venous
thromboembolism, specifically as a COVID-19-related
sequela [18]. A limited number of cases of arterial thrombotic infarcts due to COVID-19 have been reported in
the literature [2, 19–22]. Second, the source of thrombosis in our patient was not confirmed with follow-up studies; thus, we cannot ascertain whether thrombosis was a
localized event, an extracranial embolic event, or a combination of both [2, 20]. Finally, our patient was therapeutically anticoagulated with a high INR, yet still had an
arterial thrombotic infarct.
This rare presentation presents the question of whether
COVID-19 is associated with ischemic stroke despite the
supratherapeutic dose of anticoagulants. If yes, then is
there a possibility of a future increase in the anticoagulant dose required for similar encounters? Nevertheless,
the use of anticoagulation therapy has become a common
prophylactic management in COVID-19 due to its ability
to trigger a coagulopathy cascade. In our institution, we
administer only 40 mg/day of prophylactic enoxaparin to
our COVID-19 patients in the inpatient setting as a routine practice (Additional file 1).

Learning points
1. SARS-CoV-19 infection is associated with an
increased risk of thrombotic events.
2. Ischemic stroke may occur in patients with SARSCoV-19 infection despite therapeutic INR.
3. Caution should be exercised when manipulating
doses of anticoagulation therapy in patients with
SARS-CoV-19 infection.

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(2023) 17:223

Conclusion
We present a case of middle cerebral artery ischemic
stroke in a patient with SARS-CoV-19 infection despite
being on warfarin with supratherapeutic INR. In light of
this case, it is important for clinicians to be cognizant of
the potential for thromboembolic events in COVID-19
patients, such as stroke, even in patients who are receiving therapeutic anticoagulation therapy.
Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s13256-​023-​03936-8.
Additional file 1. 2013 CARE Checklist is provided as supplementary
document.
Acknowledgements
I would like to extend my thanks to Prof. Yahya Paksoy, MD, Department of
Neuroradiology, Hamad General Hospital for providing the MRI images.
Author contributions
GD, RH, SSA, HAS, MH, UBR, and YC contributed to the conception of the work,
the writing and editing of the manuscript, and critical revision. All authors read
and approved the final manuscript.
Funding
Open Access funding provided by the Qatar National Library. This research
was funded by the Qatar National Library (QNL).

Page 5 of 5

4.
5.
6.
7.
8.

9.
10.
11.
12.

13.

14.

Availability of data and materials
Not applicable.
15.

Declarations
Ethics approval and consent to participate
Written informed consent for participation and publication was sought from
the patient as per hospital protocol. Ethical approval was also obtained from
the institutional review board.

16.

17.

Consent for publication
Written informed consent was obtained from the patient for the publication
of this case report and any accompanying images. A copy of the written con‑
sent form is available for review by the Editor-in-Chief of this journal.

18.

Competing interests
The authors declare that they do not have any competing interests.

19.

Received: 13 December 2022 Accepted: 17 April 2023

20.
21.

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