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\title{An extensive arterial thrombosis with lower limb ischemia in a COVID-19
patient: a case report.}



\author[1]{Johary Andriamamonjisoa}%
\author[1]{Etienne RAKOTOMIJORO}%
\author[1]{Volatiana Andriananja}%
\author[1]{Mihaja Raberahona}%
\author[2]{Radonirina Lazasoa Andrianasolo}%
\author[3]{Rivonirina Andry Rakotoarivelo}%
\author[4]{MAMY RANDRIA}%
\affil[1]{University of Antananarivo Faculty of Medicine}%
\affil[2]{Endocrinology Department, Joseph Raseta Befelatanana University Hospital Center, Antananarivo, Madagascar}%
\affil[3]{University of fianarantsos, Faculty of medecine, Departement of Infectious Diseases}%
\affil[4]{Centre Hospitalier Universitaire Befelatanana Antananarivo}%


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  \date{May 30, 2024}


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\textbf{An extensive arterial thrombosis with lower limb ischemia in a
COVID-19 patient: a case report.}

Johary Andriamamonjisoa Andriamizanaka\textsuperscript{1}, Etienne
Rakotomijoro\textsuperscript{2}, Volatiana
Andriananja\textsuperscript{3}, Mihaja Raberahona\textsuperscript{4},
Radonirina Lazasoa Andrianasolo\textsuperscript{5}, Rivonirina Andry
Rakotoarivelo\textsuperscript{6}, Jean de Dieu Randria
Mamy\textsuperscript{7}

\textbf{ABSTRACT:}

\textbf{Background:} The COVID-19 pandemic is responsible for huge
morbidity and mortality throughout the world. Several serious
complications of this disease have been reported. It can cause
hypercoagulability, which may lead to venous and arterial thromboembolic
diseases. This hypercoagulability state is also associated with high
morbidity and mortality. Arterial thrombosis in COVID-19 is poorly
described compared to venous thrombosis and pulmonary embolism. We
report a case of an extensive arterial thrombosis leading to a limb
ischemia with extremely high D-dimer in a COVID-19 patient.

\textbf{Case presentation:} A 69-year-old man was hospitalized for
febrile dyspnea. He is a hypertensive and diabetic patient. On
admission, pulse oxygen saturation was 72\% on room air. He had cyanosis
of the left foot up to the mid-thigh. The left pedal, posterior tibial,
popliteal and femoral pulses were abolished. Chest CT scan was in favour
of COVID-19. He has a high D-dimer level of 257 344 ng/ml. Arterial
Echo-Doppler found an extensive intraluminal thrombus along the arterial
axes of the left lower limb, completely obstructing them, starting from
the primitive iliac artery just after its bifurcation with the aorta and
extending distally (external iliac; common femoral; superficial femoral;
popliteal; anterior tibial; posterior tibial; fibular and pedal). The
patient was diagnosed with COVID-19 critical form, associated with
ischemia of the left lower limb secondary to an extensive arterial
thrombosis. He was receiving anticoagulation, and underwent surgical
amputation of the ischemic limb. The patient survived the event;
however, he was on long-term oxygen therapy at home.

\textbf{Conclusions:} Arterial thrombosis may occur during COVID-19 and
may be responsible for peripheral or central ischemia aggravating
morbidity and mortality. The occurrence of these events is related to
the D-dimer value. Anticoagulation is an important part of the
management of COVID-19, especially in severe forms in order to limit the
occurrence of these thromboembolic diseases.

\textbf{Key words:} COVID-19, D-dimer, ischemia, arterial thrombosis,
case report

\textbf{Background:}

COVID-19 is a leading cause of morbidity and mortality worldwide. Apart
from the respiratory complications which are responsible for most of the
deaths, several serious complications have been reported including
compressive emphysema or acute pancreatitis. COVID-19 can also induce a
hypercoagulable state, at the origin of venous and arterial
thromboembolic events. This hypercoagulability is associated with high
morbidity and mortality {[}1,2{]}. The literature mainly describes
venous thromboembolic events and pulmonary embolisms {[}3,4{]}. Arterial
thrombosis during COVID-19 is poorly described compared to venous
thrombosis. According to literature, it can occur with a prevalence of
0.13\% in a hospitalized patient who tested positive for COVID-19 and
0.19\% in patients who tested negative {[}5{]}. We report a case of an
extensive arterial thrombosis with extremely high D-dimer level that
resulted in a lower limb ischemia in a COVID-19 patient.

\textbf{Case presentation:}

A 69-year-old man was hospitalized with febrile dyspnea at the military
hospital of Antananarivo. He reported a close contact with a confirmed
case of COVID-19 5 days before the onset of symptoms. His history
included hypertension treated with Losartan 100mg per day, type 2
diabetes treated with Metformin 1500mg/day, alcoholism and smoking
cessation for 10 years (9.5 pack-years). He has no known history of
peripheral artery disease. For 13 days prior to his admission, he
presented with a dry cough, shortness of breath at rest without
orthopnea, fever, asthenia and anorexia. Two days before
hospitalization, he felt a spontaneous severe pain with swelling of the
left lower limb. Physical examination revealed a body mass index of
28.7~kg/m2, a pulsed oxygen saturation of 72\% on room air, a
respiratory rate of 23 per minute, a high temperature of 38.9\selectlanguage{ngerman}°C, a heart
rate of~117~beats per minute, a blood pressure of 135/80 mmHg and
bilateral clinical signs of pneumonia. He presented a cyanosis of the
left foot up to the mid-thigh (Figure 1), a hypoesthesia of the left
lower limb and the skin was cool. The left pedal, posterior tibial,
popliteal and femoral pulses were abolished.

The nasopharyngeal swab for SARS-CoV-2 reverse transcriptase-polymerase
chain reaction (rt-PCR) performed on admission was negative. The
complete blood count showed a haemoglobin level of 13.3 g/dl (13.5-17.5
g/dl) a white blood cells count of 11.81~G/L (5-10~G/L) and a platelet
count of 81~G/L (150-400 G/L). The C-reactive protein was 82.6 mg/L
(\textless{}6 mg/l). The creatinine was 187 \selectlanguage{greek}µ\selectlanguage{english}mol/L (65.4-119.3 \selectlanguage{greek}µ\selectlanguage{english}mol/L).
The blood sodium level was 141 mmol/L (135-145 mmol/l) and the blood
potassium level was 4.9 mmol/L (3.6-5.2 mmol/l). The glycated
haemoglobin was 7.5\% (\textless{}6\%). The D-dimer was 514 times the
upper normal limit (220-500 ng/mL). The troponin was normal. The
electrocardiogram showed a regular tachycardia with a heart rate of 103
bpm. Chest CT scan was in favour of COVID-19 showing ground glass images
with 50-75\% involvement, without pulmonary embolism (Figure 2). The
arterial doppler ultrasound showed an extensive intraluminal thrombus
along the arterial axes of the left lower limb, completely obstructing
them, starting from the common iliac artery just after its bifurcation
with the aorta and extending distally (external iliac, common femoral,
superficial femoral, popliteal, anterior tibial, posterior tibial,
fibular and pedal), without any detectable collateral circulation
(Figure 3 a, b, c). The patient was diagnosed with a severe COVID-19
associated with acute ischemia of the whole left lower limb secondary to
an extensive arterial thrombosis. He was receiving oxygen therapy with a
high concentration oxygen mask at 15 L/min, corticosteroid therapy with
intravenous dexamethasone (12 mg/day), subcutaneous therapeutic
anticoagulation with enoxaparin at a curative dose (8000UI x2/day), oral
antibiotic therapy with levofloxacin (1g/day) and insulin therapy
(rapid-acting insulin 14UI x3/day and long-acting insulin 20 UI/day).
The patient was transferred to the surgical ward due to aggravation of
the ischemia with skin necrosis of extremities and underwent an
amputation of the ischemic left lower limb. The post-operative follow-up
was simple. The patient was discharged after 28 days of hospitalization
and was under long-term oxygen therapy at home. At one month follow-up,
he remained well and there was no recurrence of other ischemia.

\textbf{Discussion and conclusion:}

We report here a case of a hypertensive and diabetic patient presenting
a severe form of COVID 19 associated with an ischemia of the left lower
limb with an extremely high d-dimer level.

High D-dimer value is associated with severe infection and high risk of
thromboembolic events during COVID-19 {[}6{]}. Arterial occlusion can be
life threatening or can lead to significant disabilities. Our patient
had a history of hypertension, previous smoking and type 2 diabetes.
According to the literature, these comorbidities are significantly
associated with the occurrence of arterial thrombosis during COVD-19
{[}5{]}. He was diagnosed with a severe form of COVID-19 and presented
at the same time an ischemia of the left lower limb secondary to an
extensive thrombosis of several arteries in the left lower limb. Our
patient had a D-dimer up to 514 times the upper normal level. The
d-dimer level correlates with the severity of the disease and is a
reliable prognostic marker of in-hospital mortality in those admitted
with COVID-19 {[}6--8{]}. The risk of death is therefore high for our
patient. In COVID-19, arterial thrombosis mainly involves the heart, the
brain, the kidney and the bowels. There were only few reported cases of
arterial thrombosis involving limbs including the left arm, the left
leg, the right arm and the right leg {[}5{]}. However, our case involved
the entire left lower limb (thigh, leg, foot).

Gold DD. et al. reported a series of cases of arterial thrombosis. The
first case had a thrombosis of the two renal arteries, the superior
mesenteric artery and the celiac trunk. The second case had a thrombosis
of the aorta, the celiac trunk, hepatic and the splenic arteries. The
third case had a cerebral, pulmonary, splenic and renal thrombosis. The
fourth case had a thrombosis of the lung, the spleen and the kidney. The
last case was a peripheral thrombosis with an occlusion of the radial
and ulnar arteries {[}9{]}. All five patients had arterial occlusions
that were life-threatening or disabling, and four of the five patients
did not survive. Despite the severity of the COVID-19 and the arterial
occlusion, our case had survived. However, the delay in the management
led to a total obstruction of the artery causing ischemia which resulted
in amputation. The outcome was unexpected given the severity of COVID-19
and the extensive arterial occlusions in a country like Madagascar with
limited technical platform and resources.

One limitation associated with this case report is that we have not been
able to perform any serology test for covid 19 to strengthen the
diagnosis made by chest CT scan, due to unavailability of this test.

We report a case of an extensive peripheral arterial thrombus with an
extremely high D-dimer during COVID-19. Arterial thrombosis can occur
during COVID-19, causing peripheral or central ischemia with increased
morbidity and mortality. The occurrence of these events is related to
the D-dimer value {[}10{]}. Thus, this report underlines the potential
role of anticoagulation in COVID-19 especially in severe forms and
furthermore in patient with cardiovascular comorbidities, or in the case
of a high D-dimer value in order to limit the occurrence of
thromboembolic diseases.

\textbf{List of abbreviations:}

- COVID-19: coronavirus disease 2019

- SARS-CoV-2: severe acute respiratory syndrome-coronavirus-2

- ECG: electrocardiograph

\textbf{Acknowledgements:} We thank the team of the Infectious Diseases
Department for the care of the patient. We also thank the patient for
accepting the publication of his case.

\textbf{Authors' contributions:}

AAJ, RE, AV: Patient management, data collection and manuscript drafting

RM, ARL, RRA, RMJD: Manuscript revision

All authors approved the final manuscript.

\textbf{Funding:} none.

\textbf{Availability of data and material:} the photo, the anonymised CT
and Doppler ultrasound sections are available from the corresponding
author.

\textbf{Declarations}

\textbf{Ethical approval and consent to participate:} not applicable.

\textbf{Consent for publication} : The patient was informed about the
case report, why the case was peculiar and the authors' interest in
publishing his case. The patient willingly gave informed consent to
allow the authors to use the CT scan and arterial Doppler images for
this case report. The patient's anonymity is well respected.

\textbf{Competing interests:} none.

\textbf{Authors' information} :

(1)Faculty of Medicine Antananarivo, Joseph Raseta Befelatanana
University Hospital Antananarivo, Antananarivo 101, department of
Infectious Diseases, Madagascar. (2)Faculty of Medicine Antananarivo,
Joseph Raseta Befelatanana University Hospital Antananarivo,
Antananarivo 101, department of Infectious Diseases, Madagascar.
(3)Faculty of Medicine Antananarivo, Joseph Raseta Befelatanana
University Hospital Antananarivo, Antananarivo 101, department of
Infectious Diseases, Madagascar. (4)Faculty of Medicine Antananarivo,
Joseph Raseta Befelatanana University Hospital Antananarivo,
Antananarivo 101, department of Infectious Diseases, Madagascar.
(5)Faculty of Medicine Antananarivo, Joseph Raseta Befelatanana
University Hospital Antananarivo, Antananarivo 101, department of
Infectious Diseases, Madagascar. (6)Faculty of Medicine, University of
Fianarantsoa, University Hospital Tambohobe Fianarantsoa, Fianarantsoa
301, Madagascar. (7)Faculty of Medicine Antananarivo, Joseph Raseta
Befelatanana University Hospital Antananarivo, Antananarivo 101,
department of Infectious Diseases, Madagascar.

\textbf{Legend of figures:}

\textbf{Figure 1:} Photo of the patient's lower limbs showing the
cyanosis from the left foot to the middle of the left thigh

\textbf{Figure 2:} Chest CT scan without injection of contrast medium,
axial section showing multiple extensive ground-glass areas occupying
50-75\% of the lung parenchyma, peripherally and centrally distributed,
bilaterally subpleural, associated with fine intralobular reticulations
giving a crazy paving appearance and areas of condensation especially in
the posterior basal segments of the lower lobe bilaterally.

\textbf{Figure 3 a:} Arterial Doppler ultrasound of the arterial axes of
the left lower limb showing an extensive intraluminal thrombus along the
arterial axes of the left lower limb, totally obstructive, starting from
the primitive iliac artery just after its bifurcation with the aorta and
extending distally (external iliac; common femoral; superficial femoral;
popliteal; anterior tibial; posterior tibial; fibular and pedal)

\textbf{Figure 3 b, c:} Arterial Doppler ultrasound, other view of the
left lower limb arterial thrombosis

\emph{ }

\textbf{References} :

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2. Connors JM, Levy JH. Thromboinflammation and the hypercoagulability
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3. Helms J, Severac F, Merdji H, Schenck M, Clere-Jehl R, Baldacini M,
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6. Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z, et al. D-dimer as a
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8. Ganesan R, Mahajan V, Singla K, Konar S, Samra T, Sundaram SK, et al.
Mortality Prediction of COVID-19 Patients at Intensive Care Unit
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9. Gold D, Kurd R, Einav S. Don't forget arterial thrombosis in patients
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10. Garg K, Barfield ME, Pezold ML, Sadek M, Cayne NS, Lugo J, et al.
Arterial thromboembolism associated with COVID-19 and elevated D-dimer
levels. J Vasc Surg Cases Innov Tech. 2020 Jun 17;6(3):348--51.\selectlanguage{english}
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