Low incidence of symptomatic venous thrombosis associated with peripherally inserted central catheter

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111
Low incidence ofsymptomatic venous thrombosisassociated with
peripherally inserted central catheter
Miguel A. Hinostroza-Sanchez1a*, Jorge Samuel Martinez-Aparicio2, Miguel Franco-Estrada1,
Ana Escobar-Luna1, Miguel A. Carrillo-Martinez1, and Francisco E. Puente-Gallegos1
1Department of Radiology and Imaging, TecSalud Hospitals, Instituto Tecnológico de Estudios Superiores de Monterrey; 2Department of Radiology
and Imaging of The Hospital Zambrano Hellion TecSalud, Instituto Tecnológico de Estudios Superiores de Monterrey. Monterrey, Nuevo Leon, Mexico
ORCID: a0000-0001-8478-0937
FULL RESEARCH ARTICLE
ABSTRACT
Introduction: Central venous catheterization is a common procedure that can be complicated by symptomatic venous
thrombosis. The incidence of this complication in Mexico is unknown. The aim of this study was to determine the incidence
of peripherally inserted central catheter (PICC)-associated symptomatic venous thrombosis (PICC-ASVT).
Material and methods: This retrospective, bicenter cohort study was conducted from April 2018 to December 2019 at Hos-
pital San José and Hospital Zambrano Hellion of the TecSalud System. Patients from all hospital settings who required a
PICC placed under ultrasound guidance were included. Patients with a clinical suspicion of PICC-ASVT underwent
ultrasonography to determine the presence of thrombi. Associated risk factors were analyzed with odds ratios. Ap-value < 0.05
was considered significant. Results: Atotal of 592patients with PICC were included. Twelve PICC-ASVT cases were iden-
tified by Doppler ultrasonography. The incidence was 2.03% (95% CI, 0.89 -3.16). Ten of 12cases occurred in women (OR
4.6, 95% CI, 1 - 21.3). Eight (66.7%) of 12 patients with PICC-ASVT were in the Intensive Care Unit (ICU). In contrast, only
4(33.3%) were in the general ward and Intermediate Care Unit (IMCU) (p < 0.05). Conclusion: The incidence of PICC-ASVT
was low in the Mexican population. Arisk association with female gender and ICU hospitalization was found. This study is
the first in Mexico to report the incidence of PICC-ASVT.
Keywords: Thrombus. PICC line placement. Peripheral venous catheterization. Symptomatic venous thrombosis. Doppler
ultrasound. Interventional radiology.
Corresponding author:
*Miguel A. Hinostroza-Sánchez
E-mail:doc.hinostroza@gmail.com
2696-8444 / © 2022 Federación Mexicana de Radiología e Imagen, A.C. Published by Permanyer. This is an open access article under the
CC BY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Available online: 13-07-2022
J Mex Fed Radiol Imaging. 2022;1(2):111-118
www.JMeXFRI.com
Received for publication: 15-12-2021
Approved for publication: 02-02-2022
DOI: 10.24875/JMEXFRI.M22000015
FEDERACIÓN MEXICANADE RADIOLOGÍA E IMAGEN, A.C
Journal of the Mexican Federation of Radiology and Imaging
Official Journal of the
Journal of the Mexican Federation
of Radiology and Imaging
INTRODUCTION
Central venous catheterization is a high-demand
procedure in hospital settings. Central catheters are
classied as centrally inserted central catheter (CICC)
and peripherally inserted central catheter (PICC).
PICC placement by interventional radiology specia-
lists at TecSalud Hospital System has increased from
185 in 2017 to 397 in 2018 and 483 in 2019.
Ultrasound-guided central venous catheter placement
is recommended. The catheter tip should be placed in
the superior vena cava or the right atrium1. The choice
of the venous access site, central or peripheral,
depends on several factors, such as the indication for
the catheter, the patient’s morphology, and the staff´s
technical training2-12. Advantages of PICC over CICC
are placement is often at the bedside and less risk
of bleeding or pneumothorax; however, supercial
or deep venous thrombosis may be more frequent
withPICC3,4,7,13.

J Mex Fed Radiol iMaging . 2022;1(2):111-118
112
PICC-associated venous thrombosis may be symp-
tomatic or asymptomatic. Most reports in the literature
refer to symptomatic cases due to underdiagnosis of
asymptomatic presentations14. The incidence of PICC-
ASVT varies with a wide range (2.4% to 25.7%)4,6-10,13,15,16.
Several risk factors for symptomatic or asymptomatic
venous thrombosis have been associated with PICC,
such as malignancy,3,6,8,10,17,18 a history of thromboem-
bolism,4,9 catheter diameter and previous surgery3 ,4,8,10.
Central venous catheter-associated venous thrombosis
is important because of its embolic potential, especially
deep venous thrombosis with secondary lung throm-
boembolism in critically ill patients with mechanical
ventilation19 . This condition increases mortality up to
25%4, 20. The incidence of PICC-ASVT in Mexico is
unknown; therefore, the aim of this study was to
determine the incidence of PICC-ASVT in the Mexican
population.
Figure2. Left upper arm deep venous Doppler US in a 62-year-old man with PICC-ASVT. Lower left basilic vein showing the PICC insertion
site (arrow).
US: ultrasound; PICC: peripherally inserted central catheter; PICC-ASVT: PICC-associated symptomatic venous thrombosis.
Figure1. Left upper arm deep venous Doppler US in a 62-year-old man. A: lower left jugular vein showing normal anechoic lumen. B: color
Doppler US shows normal blood flow inside vein lumen.
US: ultrasound.
AB

M.A. Hinostroza-Sánchez et al.: Low incidence of thrombosis in PICC
113
pulsed-wave spectral inspection. An example of normal
ndings in upper extremity venous Doppler examina-
tion is shown in Figure1.
Upper Extremity Venous Thrombosis Doppler US fin-
dings: altered vein compressibility, intraluminal echoge-
nic images and altered vein walls on gray scale;
diminished or absent laminar blood ow on color Doppler
examination and phasic ow loss at pulsed-wave spec-
tral inspection during Valsalva maneuver.
The incidence of PICC-ASVT was calculated by con-
sidering the total number of cases with venous throm-
bosis in relation to the total number of PICCs placed.
Statistical analysis
The mean, standard deviation, median, minimum,
and maximum of the quantitative variables were cal-
culated. Age between men and women was compa-
red using Student’s t-test and the Mann-Whitney U
test. Statistical signicance between categories of
qualitative variables was determined with the chi-
square test and Fisher’s exact test. The odds ratio
was calculated to determine the risk of symptomatic
Table1. Patients and PICC line characteristics
Description Parameter
n592
Age, years, mean ± SD (range) 68 ± 35.1 (10-95)
Sex, n (%), male/female 281 (47.5)/311 (52.5)
Hospital setting, n (%)
Warda
ICU
IMCU
279 (47.1)
243 (41.1)
70 (11.8)
Lumen number, n (%)
3
2
591 (99.8)
1 (0.2)
Catheter gauge, French, mean (range) 5 (4-7)
Catheter duration (days) mean (range) 9 (1-56)
Vessel patency (days) mean (range) 15 (3-27)
PICC: peripherally inserted central catheter; aWard: medical/surgical inpatient,
emergency room, hemodynamic unit, and operating room; ICU: intensive care
unit; IMCU:intermediate care unit.
Table2. Insertion site and catheter tip location in 592 patients with PICC
Catheter insertion site n %
Right basilica 391 66.0
Left basilica 124 20.9
Right humeral 32 5.5
Right cephalic 21 3.7
Left humeral 16 2.7
Left cephalic 61.0
Right Femoral 10.1
Right external jugular vein 10.1
Catheter tip location n %
Superior vena cava 482 81.4
Right Atrium 52 8.9
Right subclavian vein 35 5.9
Left subclavian vein 12 2.2
Right axillary vein 30.5
Right jugular vein 30.5
Left axillary vein 20.3
Right humeral vein 10.1
Left jugular vein 10.1
Left innominate vein 10.1
PICC: peripherally inserted central catheter.
MATERIAL AND METHODS
This retrospective, bicenter cohort study was con-
ducted from April 2018 to December 2019 at Hospital
San José and Hospital Zambrano Hellion of the
TecSalud Hospital System in Monterrey, Nuevo
Leon, Mexico. Adult inpatients of both sexes in who
an interventional radiology specialist placed a PICC
were included. Patients were in the following hospital
settings: ward (medical/surgical inpatient, emer-
gency room, hemodynamic unit, and operating
room), the intermediate care unit (IMCU), and the
adult intensive care unit (ICU). Patients whose cathe-
ters were placed by specialists other than radiolo-
gists and outpatients with a PICC were not included.
The protocol was approved by the Ethics and
Research Institutional Committees, and patients pro-
vided written informed consent.
Definitions
Positive case of PICC-ASVT: patient with clinical sus-
picion determined by referring clinician based on clini-
cal symptoms (pain, edema, increased local
temperature, erythema in the catheter insertion site,
and/or intravenous ow obstruction). The presence of
venous thrombi was conrmed by ultrasound.
Normal Upper Extremity Venous Doppler US fin-
dings: Anechoic lumen and well-dened venous walls
on gray scale imaging; compressibility, laminar blood
ow on color Doppler examination, and phasic ow at

J Mex Fed Radiol iMaging . 2022;1(2):111-118
114
thrombosis associated with PICC comparing two or
more variables with a 95% condence interval; a
p-value < 0.05 was considered signicant. The IBM-
SPSS statistical program (version 20.0. IBM Corp.
Armonk, NY. USA) was used.
RESULTS
A total of 592patients were included with a mean
age of 68 + 35.1(10-95) years (Tab l e 1); 281(47.5%)
participants were men, and 311 were women (52.5%).
Two hundred seventy-nine (47.1%) of 592 patients
with PICC were in the general ward and 243(41.1%)
in the ICU. The number of catheter lumens, caliber,
duration, and vessel patency in days is shown in
Table 1.
The most common PICC insertion site was the right
basilic vein (n = 391, 66.0%) followed by the left basi-
lic vein (n = 124, 20.9%) (Tab l e 2). Only one case of
PICC was in the right femoral vein and one in the
external jugular vein. Figure 2 shows a PICC inser-
tion site in the left basilic vein. The location of the
catheter tip was in the superior vena cava (n = 482,
81.4 %), followed by the right atrium (n =52, 8.8 %);
other locations were infrequent (Ta b l e 2). Doppler
ultrasound was performed in 22patients with clinical
suspicion of PICC-ASVT. Diagnosis was confirmed in
12 patients with an incidence of 2.03% (95% CI,
0.89% to 3.16%).
The characteristics of patients with and without
PICC-ASVT are compared in Table3. Ten of 12cases
were female gender with increased risk of symptomatic
thrombosis (OR 4.6, 95% CI, 1-21.3). Eight (66.7%)
ofthe 12patients with PICC-ASVT were hospitalized
in the ICU, compared with only 4(33.3%) in the inpa-
tient setting and IMCU (p < 0.05). Insertion site, vein
diameter, tip location, and catheter duration were not
signicantly associated with symptomatic venous
thrombosis related to PICC. In 4(33.3%) of 12cases
with PICC-ASVT, an increased risk (OR 5, 95% CI,
1.4-17.7) was observed when the catheter tip was in
the left jugular vein (n=1), right subclavian vein (n =
2), or left subclavian vein (n = 1). Figure3 shows the
presence of a venous thrombus next to the PICC tip
at the conuence of the left jugular and left subclavian
veins. The locations of PICC-ASVT in the 12patients
are described in Ta b l e 4. Deep vein thrombosis was
the most common (n = 7, 58.3%), and the right basilic
vein was the most involved (n = 4, 33.4%). Figure 4
shows a thrombus inside the mid subclavian vein with
partial blood ow.
DISCUSSION
The incidence of PICC-ASVT was low in our study.
Female gender and ICU hospitalization had a risk asso-
ciation. To our knowledge, this study is the rst in
Mexico that reports the incidence of PICC-ASVT.
PICC has been associated with an increased risk of
venous thrombosis3,4,8,14 with a wide incidence (2.4%
to 25.7%) of symptomatic cases. A review of the
literature from 2000 to 2020 showing the incidence of
PICC-ASVT is presented in Table5. Only three authors
reported asymptomatic venous thrombosis10 ,11,15. Liem
et al.3 reported 96 cases of PICC-ASVT with an inci-
dence of 2.6% in a case-control study of 2056 adult
patients from all hospital settings evaluated in 1year.
Figure 3. Left upper arm deep venous Doppler US in a 62-year-old
man with PICC-ASVT. A-B: lower left jugular vein showing intralumi-
nal echogenic material (white arrow), next to the PICC tip inside the
left subclavian vein (blue arrow). C:color Doppler US shows absence
of flow direction. The spectral Doppler US analysis also demonstra-
ted an absence of flow (not shown).
US: Ultrasound; PICC: peripherally inserted central catheter; PICC-ASVT: PICC-
associated symptomatic venous thrombosis.
A
B
C

M.A. Hinostroza-Sánchez et al.: Low incidence of thrombosis in PICC
115
Table4. Sites of PICC-associated symptomatic venous thrombosis
Thrombosis Site Type of thrombosis Total
SVT, n (%) DVT, n (%) n (%)
Right Basilica 4 (33.4) -4 (33.4)
Left Basilica 1 (8.3) -1 (8.3)
Right subclavian -2 (16.7) 2 (16.7)
Right jugular vein -1 (8.3) 1 (8.3)
Left brachial -2 (16.7) 2 (16.7)
Left axillary -1 (8.3) 1 (8.3)
Left subclavian -1 (8.3) 1 (8.3)
Total 5 (41.7%) 7 (58.3) 12 (100)
DVT: deep venous thrombosis; PICC: peripherally inserted central catheter;
SVT:superficial venous thrombosis
Table3. Characteristics of patients with and without PICC-associated symptomatic venous thrombosis
Description Symptomatic venous thrombosis OR (95% CI)
No Yes
n n
Sex
Male
Female
Total
279
301
580
2
10
12
1.0
4.6 (1.0-21.3)
Hospital area
Warda
ICU
IMCU
Total
276
235
69
580
3
8
1
12
1.0
4.9 (0.6-40.1)
2.1 (0.1-34.3)
Insertion site
Rigth basilica
Left basilica
Other embedding sites
Total
384
123
73
580
7
1
4
12
1.0
1.4 (0.05-3.6)
3 (0.8-10.5)
Vein diameter
Low (<3.5 mm)
Medium (3.5 to 4.49 mm)
High (≥4.5 mm)
Totalb
127
255
196
578
2
8
2
12
1.0
1.9 (0.4-9.5)
0.6 (0.1-4.6)
Catheter tip location
Superior vena cava
Right Atrium
Other locations
Total
475
51
54
580
7
1
4
12
1.0
1.3 (0.1-11)
5.0 (1.4-17.7)
PICC duration, days
1 to 4
5 to 9
10 to 14
≥15 days
Totalc
138
178
109
150
575
2
2
2
6
12
1.0
0.7 (0.1-5.5)
1.2 (0.1-9.1)
2.7 (0.5-13.9)
aWard: hospitalization, emergency, operating room, hemodynamics; bInformation no available in two cases; cInformation no available in five cases; CI: confiden-
ce interval; ICU: intensive care unit. IMCU: intermediate care unit; OR: odds ratio; PICC: peripherally inserted central catheter.
In another study of 1728patients from all hospital set-
tings, 57cases of PICC-ASVT resulted in an incidence
of 3.2%4. These results are comparable to our study,
which included 592 patients. PICC-ASVT occurred in
12cases with an incidence of 2.03%. This incidence is
low, which can probably be explained because only
symptomatic patients were included.
Literature reports10,11,13 with a high incidence of PICC-
ASVT (19.4%, 20%, and 25.7%) describe study popu-
lations with small samples of 31, 50, and 70patients
with malignant neoplasms, comorbidities, or critical
conditions in hospital settings of hematology, medicine,
and intensive care, respectively. This incidence is
10-fold higher (19.4%- 25.7%) compared to our study
(2.03%), which included patients from all hospital set-
tings (medical/surgical inpatient, emergency, ICU, and

J Mex Fed Radiol iMaging . 2022;1(2):111-118
116
Table5. Incidence of venous thrombosis and risk factors associated with PICC reported in the literature including the current study
Author,
(country)
Patients
with PICC
(n)
Cases of
thrombosis
(n)
M/F Incidence of
thrombosis
(%)
Symptomatic/
asymptomatic
Risk factors Study design Hospital areas
Grove,8
(USA)
813 32 NR 3.9 Symptomatic Cancer, catheter
diameter
Retrospective
Cohort
All Medical-Surgical
Services
Chemaly,7
(USA)
2063 52 31/19 2.4 Symptomatic NR Case-control All Medical-Surgical
services
Ong,6
(AU)
2882 76 53/23 2.6 Symptomatic Cancer Retrospective
Cohort
All Medical-Surgical
services
Dubois,15
(CA)
214 20 9/11 9.3aSymptomatic/
asymptomatic
Factor II mutation Prospective
Cohort
All Medical-Surgical
services
Periard,10
(CH)
31 6NR 19.4 Asymptomatic Catheter diameter,
malignancy
Clinical trial Department of
Medicine
Lobo,9
(USA)
777 38 NR 4.8 Symptomatic Previous
thromboembolism
Retrospective
cohort
All Medical-Surgical
services
Nash,16
(UK)
376 19 NR 3.7 Symptomatic BCC infection Retrospective
Cohort
Cystic Fibrosis
Clinic
Cortelezzia,13
(IT)
70 18 NR 25.7 Symptomatic Bacteremia Retrospective
Cohort
Department of
Hematology
Evans,4
(USA)
1728 57 NR 3.2 Symptomatic Prior thrombosis,
surgery>1 hour
Cross-sectional All Medical-Surgical
Services
Trerotola,11
(USA)
50 10 NR 20/58 Symptomatic/
asymptomatic
NR Prospective
Cohort
ICUg
Liem,3
(USA)
2056 96 60/36 2.6 Symptomatic Cancer, catheter
diameter
Case-control All Medical-Surgical
services
Nolan,17
(USA)
200 8NR 4Symptomatic NR Retrospective
Cohort
ICU
Current
study, (MX)
592 12 2/10 2.03 Symptomatic Female gender,
ICU hospitalization
Retrospective
Cohort
All Medical-Surgical
Services
aTotal incidence of symptomatic and asymptomatic venous thrombosis.
BCC: Burkholderia cepacia complex; ICU: intensive care unit;. M: male. F: female. NR: not reported. PICC: peripherally inserted central catheter
IMCU) and other reports in the literature3,4 which inclu-
ded patients in all hospital settings (2.4%- 4 %). We
hypothesize that the low incidence of PICC-ASVT in
our study and other reports3,4 may be related to the fact
that patients with less complex pathologies and/or
comorbidities are at lower risk of venous thrombosis.
Several risk factors for PICC-ASVT related to popula-
tion and catheter characteristics have been described
(Table5). We found a higher proportion of cases of PICC-
ASVT in women (n=10, 83.3%) (OR 4.6, 95% CI,
1.0-21.3). This nding has not been previously reported.
Catheter characteristics associated with venous thrombo-
sis include catheter size, number of lumens, and tip loca-
tion3,4,6-11,13,15,16 . We found an association of risk of venous
thrombosis when the catheter tip was in the left jugular
vein, right subclavian vein, or left subclavian vein (OR 5,
95% CI, 1.4 - 17.7). This nding was previously reported
in a systematic review and meta-analysis14. Several risk
factors should be evaluated in the context of the specic
characteristics of the study population. Aliterature review
did not show any risk association of female gender with
PICC-ASVT (Table5). The association of risk with female
gender motivates further research in this area.
The strengths of our study are related to the cohort
design and the fact that the catheter was placed in
all cases by radiologists using a standardized techni-
que and procedure. In addition, PICC-ASVT was con-
rmed with ultrasound in all cases. On the other hand,
our study has some limitations. Clinical diagnoses
and recognized risk factors for PICC-ASVT were not
recorded. Ultrasound was not performed to identify
asymptomatic PICC-associated venous thrombosis.

M.A. Hinostroza-Sánchez et al.: Low incidence of thrombosis in PICC
117
CONCLUSION
In our study, a low incidence of PICC-ASVT was
found. Female gender and ICU hospitalization showed
a risk association. Detection of venous thrombosis asso-
ciated with PICC is variable and related to symptomatic
or asymptomatic presentation and the frequency of
Doppler ultrasound performance15. Prospective studies
are needed to determine the incidence of venous throm-
bosis associated with PICC in asymptomatic and symp-
tomatic patients with follow-up by Doppler ultrasound.
Acknowledgments
The authors thank Professor Ana M. Contreras-
Navarro for her guidance in preparing and writing this
scientic paper.
Funding
Supported with funds from the National Quality
Postgraduate Program of the Consejo Nacional de
Ciencia y Tecnología de México.
Conflicts of interest
The authors declare that they have no conicts of
interest.
Ethical disclosures
Protection of Individuals. This study was conducted
in compliance with the Declaration of Helsinki
(1964)and its subsequent amendments.
Confidentiality of Data. The authors declare that they
followed their center’s protocol for sharing patient data.
Right to privacy and informed consent. The
authors obtained informed consent from the patients in
this study.
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Figure4. Left upper arm deep venous Doppler US in a 62-year-old man with PICC-ASVT. A: mid subclavian vein showing intraluminal echogenic
material compatible with thrombus (arrow). B: color Doppler US examination demonstrates partial blood flow at the edges of the thrombus.
US: ultrasound; PICC: peripherally inserted central catheter; PICC-ASVT: PICC-associated symptomatic venous thrombosis.
AB

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