ISSN 1677-7301 (Online)

THERAPEUTIC CHALLENGE

Acute arterial ischemia in COVID-19

Isquemia arterial aguda em pacientes com COVID-19
Silvia Maqueda Ara1 , Marta Ballesteros Pomar1, Nuria Sanz Pastor1, Cristina Nogal Arias2,
Marcos Del Barrio Fernández1

Abstract
Since the coronavirus pandemic set in in Spain in March 2020, a noteworthy increase in the incidence of acute limb
ischemia (ALI) has been observed. It has been recently discovered that SARS-CoV 2 may lead to ALI secondary to
arterial thrombosis. Elevation of D-dimer (DD) in patients with coronavirus infection (COVID-19) indicates that
a hypercoagulable state causes acute arterial thrombosis. A remarkably high DD elevation has been reported to be
a poor prognosis factor in COVID-19. The ways in which SARS-CoV 2 results in arterial thrombosis may be multiple.
On the other hand, surgical revascularization for ALI is associated with poor outcomes in COVID-19 patients, probably
in relation to hypercoagulability. Here, we describe two ALI cases in patients who required urgent surgical treatment
for limb salvage and were positive for the novel coronavirus infection (COVID 19).
Keywords: COVID-19; ischemia; thrombosis.

Resumo
Desde que a pandemia pelo novo coronavírus se estabeleceu na Espanha, em março de 2020, um aumento notável da
incidência de isquemia aguda de membros foi observado. Recentemente, descobriu-se que o coronavírus 2 causador
da síndrome respiratória aguda grave (SARS-CoV-2) pode ocasionar isquemia aguda de membros secundária à
trombose arterial. A elevação do D-dímero em pacientes acometidos pela doença do novo coronavírus (COVID-19)
indica o estado de hipercoagulabilidade como causa da trombose arterial aguda. Vale destacar que a alta elevação do
D-dímero foi relatada como um fator de prognóstico reservado na COVID-19. Há diversas maneiras pelas quais o SARS-
CoV-2 pode resultar em trombose arterial. Em pacientes com COVID-19, a revascularização cirúrgica para isquemia
aguda de membros está associada a desfechos desfavoráveis, provavelmente relacionados a hipercoagulabilidade.
Descrevemos dois casos de isquemia aguda de membros de pacientes que necessitaram de tratamento cirúrgico de
urgência para salvamento de membro e que haviam testado positivo para COVID-19.
Palavras-chave: COVID-19; isquemia; trombose.

How to cite: Maqueda Ara S, Ballesteros Pomar M, Sanz Pastor N, Nogal Arias C, Del Barrio Fernández M. Acute arterial
ischemia in COVID-19. J Vasc Bras. 2021;20:e20210022. https://doi.org/10.1590/1677-5449.210022

1
Complejo Asistencial Universitario de León – CAULE, León, España.
2
Universidad de Madrid, Madrid, España.
Financial support: None.
Conflicts of interest: No conflicts of interest declared concerning the publication of this article.
Submitted: January 28, 2021. Accepted: March 13, 2021.
The study was carried out at Complejo Asistencial Universitario de León (CAULE), León, España.

Copyright© 2021 The authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Maqueda Ara et al. J Vasc Bras. 2021;20:e20210022. https://doi.org/10.1590/1677-5449.210022 1/4

 Arterial ischemia in COVID-19

INTRODUCTION 28,800) and elevated fibrinogen levels (642 mg/dL).

D-dimer (DD) was markedly increased (72,016 ng/ml).
Since the coronavirus pandemic set in in Spain in
Other results included Creatinine: 2.38mg/DL;
March 2020, a significant increase in the incidence
aspartate aminotransferase (AST): 231U/L and alanine
of acute limb ischemia (ALI) has been observed.
aminotransferase (ALT): 149U/L; creatinine kinase (CK):
Here, we describe two ALI cases in patients with
coronavirus infection (COVID-19). 11,427 IU/L; lactate dehydrogenase (LDH):669 IU/L;
and C-reactive protein (CRP): 98.2 mg/l.
PATIENT 1 Computed tomography (CT) of the chest showed
ground-glass opacity and pulmonary infiltration.
The patient’s angio-CT scan demonstrated mural
Clinical situation
aortic thrombus at the infrarenal abdominal aorta as
A 70-year-old woman presented to the emergency well as thrombotic occlusion of the right iliac artery
department with right lower limb pain and coldness and infrapopliteal vessels (Figures 1 and 2).
for 3 days. The pain developed suddenly without A COVID-19 nucleic acid detection test was
associated trauma and became worse over time. No negative.
history of cough, fatigue or dyspnea was elicited;
however, she had presented fever 9 days previously. What was done
She had a medical history of diabetes mellitus and The patient was taken to the operating room
hyperlipidemia. and underwent a femoral thrombectomy. By means
The patient was afebrile and in no respiratory of a Fogarty embolectomy catheter (Le Maitre®;
distress; pulse oximetry of 94% on 4L of oxygen. The Burlington, MA, USA), an extensive thrombus was
right leg looked pale from the level of the knee. There
was loss of touch sensation in the foot and she had
difficulty moving the leg. All right lower extremity
pulses were absent. There were no arterial Doppler
signals. Pulses in the left leg were normal.
Laboratory results are summarized in Table 1.
They included leukocytosis (white blood cell count of

Table 1. Laboratory findings of COVID patients.

LABORATORY FINDINGS Patient 1 Patient 2
White-cell count (per mm3) 28800 9200
Neutrophils (%) 81% 88% Figure 1. Preoperative computed tomography angiography
(angio CT) with volume rendering 3D reconstruction: thrombotic
Lymphocytes (%) 9% 8.7%
occlusion of the right common and external iliac arteries with
Monocytes (%) 7% 3.2% patent right femoral bifurcation. Of note, healthy and patent
Platelet count (per mm3) 382000 221000 left Ilio-femoral axis (a). Iliac intraluminal thrombus protruding
Hemoglobin (g/liter) 12.3 14.5 into aorta (arrow) (b) (patient #1).
Prothrombin time (PT) (sec) 15.2 21
Activated partial-thromboplastin 28.2 29.8
time (APTT) (sec)
Aspartate aminotransferase (AST) 231 54
(U/liter)
Alanine aminotransferase (ALT) 149 25
(U/liter)
Creatinine (mg/dL) 2.38 0.74
Creatine kinase (U/liter) 11427 329
Lactate dehydrogenase (U/liter) 669 869
Fibrinogen (mg/dL) 642 767
D-dimer (ng/mL) 72016 245196*
High-sensitivity C-reactive protein 98.2 393 Figure 2. Angio CT with volume rendering 3D reconstruction
(CRP) (mg/dL) showing infrafilling of a patent right superficial femoral artery (a).
Total occlusion of the right popliteal artery (arrow) with absence
Serum ferritin (ng/mL) 623 674
of tibial vessels (posterior view). In the left lower extremity, all
IL-6 (pg/mL) - 29.4 infrapopliteal vessels are patent (b), (patient #1).

Maqueda Ara et al. J Vasc Bras. 2021;20:e20210022. https://doi.org/10.1590/1677-5449.210022 2/4

 Arterial ischemia in COVID-19

retrieved from the iliac artery and femoropopliteal but unfortunately the patient died 12 hours later.
segment. The patient received systemic anticoagulation Serologic testing detected IgG-IgM antibodies to
with subcutaneous enoxaparin sodium at 80 mg once SARS-CoV-2.
a day. She recovered femoral and popliteal pulses
but no distal pulses and several hours later mottled
cyanosis appeared at the level of the foot (Figure 3).
Given the irreversible ischemia signs in the foot,
a major amputation was carried out 48 hours later.
Serological testing revealed IgG-IgM antibodies
to SARS-CoV-2.

PATIENT 2

Clinical situation
The patient was a 65-year-old man, with diabetes
mellitus, hyperuricemia, chronic obstructive pulmonary
disease, and atrial fibrillation on oral anticoagulant
(edoxaban 60 mg once a day). He described a 2-day Figure 3. Picture showing patient’s foot several hours after
history of right lower limb pain and coldness. revascularization surgery. Digital cyanosis and fixed staining in
His physical examination revealed a pale and cool foot indicate failed revascularization (a, b) (patient #1).
right leg, with dependent distal rubor. He presented
femoral pulse with audible arterial Doppler signals
at popliteal and distal level. He did not show any
impairment of sensitivity or motility.
Duplex scan examination showed occlusion of
the right superficial femoral and popliteal arteries.
The patient denied any history of cough, fever,
palpitation, or shortness of breath, but chest X-ray
revealed peripheral ground-glass lung opacities and
multifocal air-space disease (Figure 4a).
Laboratory results on admission are summarized
in Table 1. The blood counts showed 9,200 white
blood cells (88% neutrophils and 8.7% lymphocytes).
DD was extremely high (24.5196 ng/ml); CRP:
393 mg/L, CK: 329 IU/L, and LDH: 869 IU/L, all
elevated.
The physical examination revealed irregular heart
rate (102 beats/min), blood pressure of 133/81 mmHg,
temperature of 35.9 °C, and oxygen saturation of 91%.
The COVID-19 nucleic acid detection test was
negative. The following day, the patient’s state became
aggravated despite active treatment. His right foot
was cold and pale with cyanosis and paresthesia
(Figure 4b). The patient noted difficulties in wiggling
the toes. His right femoral pulse was faintly palpable
and no distal Doppler signals were detected.

What was done

The patient was taken to the operating room to Figure 4. (a) Chest X-ray revealing bilateral peripheral ground-
glass lung opacities (typical feature of COVID-19 pneumonia)
perform an urgent thrombectomy. Subcutaneous as well as multifocal air-space disease; (b) Preoperative picture
enoxaparin sodium, 1 mg/kg every 12 hours was showing patient’s ischemic foot which required immediate
started. The clinical condition of the leg improved, revascularization (patient #2).

Maqueda Ara et al. J Vasc Bras. 2021;20:e20210022. https://doi.org/10.1590/1677-5449.210022 3/4

 Arterial ischemia in COVID-19

DISCUSSION 2. Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to

predict in-hospital mortality in patients with Covid-19. J Thromb
COVID-19 caused by SARS-CoV-2 has led to a Haemost. 2020;18(6):1324-9. http://dx.doi.org/10.1111/jth.14859.
pandemic, infecting over 3 million humans globally and PMid:32306492.
causing over 240,000 deaths by early May of 2020.1 3. Arachchillage DR, Laffan M. Abnormal coagulation parameters are
In addition to respiratory disease, SARS-CoV 2 associated with poor prognosis in patients with novel coronavirus
infection may lead to thrombotic events. It has been pneumonia. J Thromb Haemost. 2020;18(5):1233-4. http://dx.doi.
reported that COVID-19 is associated with activation org/10.1111/jth.14820. PMid:32291954.
of the coagulation cascade, marked by increased DD 4. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are
levels.1-3 associated with poor prognosis in patients with novel coronavirus
Recent guidance on management of coagulopathy in pneumonia. J Thromb Haemost. 2020;18(4):844-7. http://dx.doi.
COVID-19 from the International Society of Thrombosis org/10.1111/jth.14768. PMid:32073213.
and Haemostasis (ISTH) arbitrarily defined markedly 5. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on
raised DD on admission as a threefold to fourfold recognition and management of coagulopathy in COVID-19. J
increase.1 We found high DD values in both patients Thromb Haemost. 2020;18(5):1023-6. http://dx.doi.org/10.1111/
(higher than reported by others).4-6 This information jth.14810. PMid:32338827.
could be useful, especially in patients with a negative 6. Wong JP, Viswanathan S, Wang M, Sun LQ, Clark GC, D’Elia RV.
COVID 19 nucleic acid detection requiring urgent Current and future developments in the treatment of virus-induced
surgery for ALI. hypercytokinemia. Future Med Chem. 2017;9(2):169-78. http://
The ways in which SARS-CoV 2 leads to acute dx.doi.org/10.4155/fmc-2016-0181. PMid:28128003.
arterial thrombosis may be multiple:
First, virus infections are accompanied by an
Correspondence
aggressive pro-inflammatory response and insufficient
Silvia Maqueda Ara
anti-inflammatory response. This might induce Complejo Asistencial Universitario de León, Servicio de Angiología y
dysfunction of endothelial cells, resulting in excess Cirugía Vascular
thrombin generation.1 C/ Altos de Nava s/n. Edificio Princesa Sofía, planta 11
Second, release of pro-inflammatory cytokines, 24010 - León, España
which are key mediators of atherosclerosis, may Tel.: +34 987 23 74 00 ext 163164
directly contribute to plaque rupture through local E-mail: [email protected]
inflammation, induction of procoagulant factors, and
hemodynamic changes. Author information
SMA - Holds a MSc degree in Surgery, Universidad de Zaragoza; PhD,
Third, the hypoxia found in severe COVID-19 can Complejo Asistencial Universitario de León (CAULE).
increase blood viscosity and the hypoxia-inducible MBP - Holds a MSc degree in Surgery, Universidad de Madrid; PhD,
transcription factor-dependent signaling pathway. Complejo Asistencial Universitario de León, (CAULE).
Further studies are needed to understand how this NSP - Holds a MSc degree in Surgery, Universidad de Valladolid; PhD,
new pathology leads to acute arterial thrombosis and Complejo Asistencial Universitario de León, (CAULE).
if there is a way to prevent it. CNA - Holds a MSc degree in Surgery, Universidad de Madrid.
MDBF - Holds a MSc degree in Surgery, Universidad de Oviedo; PhD,
Complejo Asistencial Universitario de León, (CAULE).
ETHICS COMMITTEE
This study was approved by the institutional research Author contributions
ethics committee. Authors declare that the manuscript Conception and design: SMA, MBP, NSP, CNA, MDBF
Analysis and interpretation: SMA, MBP, NSP, CNA, MDBF
is in accordance with the Helsinki Declaration and
Data collection: SMA, MBP
with local ethical guidelines. Patients were informed Writing the article: SMA, MBP
and signed informed consent. Critical revision of the article: SMA, MBP, MDBF
Final approval of the article*: SMA, MBP, NSP, CNA, MDBF
REFERENCES Statistical analysis: SMA, MBP, NSP, CNA, MDBF
Overall responsibility: SMA
1. World Health Organization. Coronavirus disease (COVID-19)
situation dashboard. 2020 [cited 2020 may 5]. https://www.who. *All authors have read and approved of the final version of the article
int/emergencies/diseases/novel-coronavirus-2019 submitted to J Vasc Bras.

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