Coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing 2019–2020 pandemic. Venous thromboembolism (VTE), a frequent cardiovascular and/or respiratory complication among hospitalized patients, is one of the known sequelae of the illness. Hospitalized COVID-19 patients are often elderly, immobile, and show signs of coagulopathy. Therefore, it is reasonable to assume a high incidence of VTE among these patients. Presently, the incidence of VTE is estimated at around 25% of patients hospitalized in the intensive care unit for COVID-19 even under anticoagulant treatment at prophylactic doses. In this review, we discuss present knowledge of the topic, the unique challenges of diagnosis and treatment of VTE, as well as some of the potential mechanisms of increased risk for VTE during the illness. Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease.

1.
Morens
DM
,
Daszak
P
,
Taubenberger
JK
.
Escaping Pandora’s Box - Another Novel Coronavirus
.
N Engl J Med
.
2020
Apr
;
382
(
14
):
1293
5
.
[PubMed]
0028-4793
2.
Hui
DS
,
I Azhar
E
,
Madani
TA
,
Ntoumi
F
,
Kock
R
,
Dar
O
, et al.
The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China
.
Int J Infect Dis
.
2020
Feb
;
91
:
264
6
.
[PubMed]
1201-9712
3.
Home. https://www.who.int. Accessed April 7, 2020.
4.
Yang
J
,
Zheng
Y
,
Gou
X
, et al.
Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis
.
Int J Infect Dis
.
2020
;
0
(
0
):
[PubMed]
1201-9712
5.
Zhou
F
,
Yu
T
,
Du
R
,
Fan
G
,
Liu
Y
,
Liu
Z
, et al.
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
.
Lancet
.
2020
Mar
;
395
(
10229
):
1054
62
.
[PubMed]
0140-6736
6.
Chen
N
,
Zhou
M
,
Dong
X
,
Qu
J
,
Gong
F
,
Han
Y
, et al.
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
.
Lancet
.
2020
Feb
;
395
(
10223
):
507
13
.
[PubMed]
0140-6736
7.
Wu
C
,
Chen
X
,
Cai
Y
,
Xia
J
,
Zhou
X
,
Xu
S
, et al.
Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China
.
JAMA Intern Med
.
2020
Mar
;(
March
):
[PubMed]
2168-6106
8.
Cui
S
,
Chen
S
,
Li
X
,
Liu
S
,
Wang
F
.
Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.
Journal of Thrombosis and Haemostasis. n/a(n/a). doi:
9.
Guan
W
,
Ni
Z
,
Hu
Y
, et al.
Clinical Characteristics of Coronavirus Disease 2019 in China.
New England Journal of Medicine.
2020
;0(0):null. doi:
10.
Tang
N
,
Li
D
,
Wang
X
,
Sun
Z
.
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia
.
J Thromb Haemost
.
2020
Apr
;
18
(
4
):
844
7
.
[PubMed]
1538-7933
11.
2019
ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) | European Heart Journal | Oxford Academic. https://academic.oup.com/eurheartj/article/41/4/543/5556136. Accessed April 7, 2020.
12.
Vikas Aggarwal. Acute Management of Pulmonary Embolism - American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2017/10/23/12/12/acute-management-of-pulmonary-embolism. Accessed April 14, 2020.
13.
Raskob
GE
,
Angchaisuksiri
P
,
Blanco
AN
,
Buller
H
,
Gallus
A
,
Hunt
BJ
, et al.;
ISTH Steering Committee for World Thrombosis Day
.
Thrombosis: a major contributor to global disease burden
.
Arterioscler Thromb Vasc Biol
.
2014
Nov
;
34
(
11
):
2363
71
.
[PubMed]
1079-5642
14.
Klok
FA
,
Kruip
MJ
,
van der Meer
NJ
,
Arbous
MS
,
Gommers
DA
,
Kant
KM
, et al.
Incidence of thrombotic complications in critically ill ICU patients with COVID-19
.
Thromb Res
.
2020
Apr
;(
April
):
S0049-3848(20)30120-1
.
[PubMed]
0049-3848
15.
Dolhnikoff
M
,
Duarte-Neto
AN
,
de Almeida Monteiro
RA
, et al.
Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. Journal of Thrombosis and Haemostasis.
2020
;n/a(n/a). doi:
16.
Yumeng
Yao
,
Zhongshan Hospital, Fudan University, Jiatian Cao, et al
.
D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study.
April
2020
. doi:
17.
Danzi
GB
,
Loffi
M
,
Galeazzi
G
,
Gherbesi
E
.
Acute pulmonary embolism and COVID-19 pneumonia: a random association?
Eur Heart J
.
2020
Mar
;(
March
):
ehaa254
.
[PubMed]
0195-668X
18.
Xie
Y
,
Wang
X
,
Yang
P
,
Zhang
S
.
COVID-19 Complicated by Acute Pulmonary Embolism. Radiology
.
Cardiothoracic Imaging.
2020
;
2
(
2
):
e200067
.
19.
Darzi
AJ
,
Karam
SG
,
Charide
R
,
Etxeandia Ikobaltzeta
I
,
Cushman
M
,
Gould
MK
, et al.
Prognostic factors for VTE and Bleeding in Hospitalized Medical Patients: a systematic review and meta-analysis
.
Blood
.
2020
Feb
;(
February
):
blood.2019003603
.
[PubMed]
0006-4971
20.
Driggin
E
,
Madhavan
MV
,
Bikdeli
B
,
Chuich
T
,
Laracy
J
,
Bondi-Zoccai
G
, et al.
Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic
.
J Am Coll Cardiol
.
2020
Mar
;(
March
):
S0735-1097(20)34637-4
.
[PubMed]
0735-1097
21.
Guo
T
,
Fan
Y
,
Chen
M
,
Wu
X
,
Zhang
L
,
He
T
, et al.
Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)
.
JAMA Cardiol
.
2020
Mar
;(
March
):
[PubMed]
2380-6583
22.
Shi
S
,
Qin
M
,
Shen
B
,
Cai
Y
,
Liu
T
,
Yang
F
, et al.
Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China
.
JAMA Cardiol
.
2020
Mar
;(
March
):
[PubMed]
2380-6583
23.
Johnson
ED
,
Schell
JC
,
Rodgers
GM
.
The D-dimer assay
.
Am J Hematol
.
2019
Jul
;
94
(
7
):
833
9
.
[PubMed]
1096-8652
24.
Yu
B
,
Li
X
,
Chen
J
, et al.
Evaluation of Variation in D-Dimer Levels among COVID-19 and Bacterial Pneumonia: A Retrospective Analysis. In Review;
2020
. doi:
25.
Zuckier
LS
,
Moadel
RM
,
Haramati
LB
,
Freeman
L
.
Diagnostic evaluation of pulmonary embolism during the COVID-19 pandemic
.
J Nucl Med
.
2020
Apr
;(
April
):
jnumed.120.245571
.
[PubMed]
0161-5505
26.
Weg
JG
,
Froehlich
JB
.
Ultrasonography of leg veins in patients suspected of having pulmonary embolism
.
Ann Intern Med
.
1998
Feb
;
128
(
3
):
243
.
[PubMed]
0003-4819
27.
Lim
W
,
Le Gal
G
,
Bates
SM
,
Righini
M
,
Haramati
LB
,
Lang
E
, et al.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism
.
Blood Adv
.
2018
Nov
;
2
(
22
):
3226
56
.
[PubMed]
2473-9529
28.
Liu
Y
,
Gayle
AA
,
Wilder-Smith
A
,
Rocklöv
J
.
The reproductive number of COVID-19 is higher compared to SARS coronavirus
.
J Travel Med
.
2020
Mar
;
27
(
2
):
taaa021
.
[PubMed]
1195-1982
29.
Tritschler
T
,
Kraaijpoel
N
,
Le Gal
G
,
Wells
PS
.
Venous Thromboembolism: Advances in Diagnosis and Treatment
.
JAMA
.
2018
Oct
;
320
(
15
):
1583
94
.
[PubMed]
0098-7484
30.
Kearon
C
,
Akl
EA
,
Ornelas
J
,
Blaivas
A
,
Jimenez
D
,
Bounameaux
H
, et al.
Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report
.
Chest
.
2016
Feb
;
149
(
2
):
315
52
.
[PubMed]
0012-3692
31.
Wang
J
,
Hajizadeh
N
,
Moore
EE
, et al.
Tissue Plasminogen Activator (tPA) Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Case Series. Journal of Thrombosis and Haemostasis. n/a(n/a). doi:
32.
Anticoagulation Guidance Emerging for Severe COVID-19
. https://www.medpagetoday.com/infectiousdisease/covid19/85865. Published April 8,
2020
. Accessed April 9, 2020.
33.
Liverpool COVID-19 Interactions
. https://www.covid19-druginteractions.org/. Accessed April 16, 2020.
34.
Bikdeli
B
,
Madhavan
MV
,
Jimenez
D
,
Chuich
T
,
Dreyfus
I
,
Driggin
E
, et al.
COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up
.
J Am Coll Cardiol
.
2020
Apr
;(
April
):
S0735-1097(20)35008-7
.
[PubMed]
1558-3597
35.
Yin
S
,
Huang
M
,
Li
D
,
Tang
N
.
Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2
.
J Thromb Thrombolysis
.
2020
Apr
;(
April
):
[PubMed]
1573-742X
36.
Tang
N
,
Bai
H
,
Chen
X
,
Gong
J
,
Li
D
,
Sun
Z
.
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease
.
2019
patients with coagulopathy. Journal of Thrombosis and Haemostasis. n/a(n/a). doi:
37.
Gao
Y
,
Li
T
,
Han
M
, et al.
Diagnostic Utility of Clinical Laboratory Data Determinations for Patients with the Severe COVID-19. Journal of Medical Virology. n/a(n/a). doi:
38.
Chen
T
,
Wu
D
,
Chen
H
,
Yan
W
,
Yang
D
,
Chen
G
, et al.
Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study
.
BMJ
.
2020
Mar
;
368
:
m1091
.
[PubMed]
0959-8138
39.
COVID-19 and VTE-Anticoagulation - Hematology.org. https://hematology.org:443/covid-19/covid-19-and-vte-anticoagulation. Accessed April 16, 2020.
40.
Thachil
J
,
Tang
N
,
Gando
S
, et al.
ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis. n/a(n/a). doi:
41.
Phillippe
HM
.
Overview of venous thromboembolism
.
Am J Manag Care
.
2017
Dec
;
23
(
20
Suppl
):
S376
82
.
[PubMed]
1936-2692
42.
Cho
JK
,
Han
JH
,
Park
SW
,
Kim
KS
.
Deep vein thrombosis after spine operation in prone position with subclavian venous catheterization: a case report
.
Korean J Anesthesiol
.
2014
Jul
;
67
(
1
):
61
5
.
[PubMed]
2005-6419
43.
Yokoyama
M
,
Ueda
W
,
Hirakawa
M
,
Yamamoto
H
.
Hemodynamic effect of the prone position during anesthesia
.
Acta Anaesthesiol Scand
.
1991
Nov
;
35
(
8
):
741
4
.
[PubMed]
0001-5172
44.
Guo
J
,
Huang
Z
,
Lin
L
,
Lv
J
.
Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection
.
J Am Heart Assoc
.
2020
Apr
;
9
(
7
):
e016219
.
[PubMed]
2047-9980
45.
Phend
C
. COVID-19: Abnormal Clotting Common in More Severe Disease. https://www.medpagetoday.com/infectiousdisease/covid19/85577. Published March 24,
2020
. Accessed April 9, 2020.
46.
Chen
YG
,
Lin
TY
,
Huang
WY
,
Lin
CL
,
Dai
MS
,
Kao
CH
.
Association between pneumococcal pneumonia and venous thromboembolism in hospitalized patients: A nationwide population-based study
.
Respirology
.
2015
Jul
;
20
(
5
):
799
804
.
[PubMed]
1323-7799
47.
Zhang
Y
,
Xiao
M
,
Zhang
S
, et al.
Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. April
2020
:NEJMc2007575. doi:
48.
Campbell
CM
,
Kahwash
R
.
Will Complement Inhibition be the New Target in Treating COVID-19 Related Systemic Thrombosis?
Circulation
.
2020
Apr
;
0
(
0
):
[PubMed]
1524-4539
49.
Gupta
N
,
Zhao
YY
,
Evans
CE
.
The stimulation of thrombosis by hypoxia
.
Thromb Res
.
2019
Sep
;
181
:
77
83
.
[PubMed]
0049-3848
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