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Haemophilia (2015), 1–7
DOI: 10.1111/hae.12665
ORIGINAL ARTICLE
Complications associated with central venous access device
in children with haemophilia: a nationwide multicentre
study in Finland
€ AI
€ N E N , * R . L A S S I L A , † M . A R O L A , ‡ P . L AH
€ T E E N M AK
€ I , § M . M OT
€ T ON
€ EN,¶
K . V E P S AL
€
A . M AK I P E R N A A † k and P . R I I K O N E N *
*Department of Pediatrics Kuopio University Hospital, Kuopio; †Coagulation Disorders Unit, Department of Hematology and
Cancer Center, Helsinki University Central Hospital University of Helsinki, Helsinki; ‡Department of Pediatrics Tampere
University Central Hospital, Tampere; §Department of Pediatrics and Adolescent Medicine Turku University Central Hospital,
Turku; ¶Department of Pediatrics and Adolescence Oulu University Hospital, Oulu; and kChildren’s Hospital Helsinki
University Central Hospital, Helsinki, Finland
Summary. Children with haemophilia require venous
access for regular infusion of coagulation factors. A
central venous access device (CVAD) ensures longterm access but associates with infectious and noninfectious complications with proposed risk factors of
young age at initial CVAD implantation and presence
of an inhibitor. Our aim was to evaluate the incidence
and risk factors for complications associated with
CVAD usage in a retrospective nationwide multicentre
study in five Finnish Paediatric Haemophilia
Treatment Centers. Our study investigated 106
CVADs in 58 patients with 137 971 CVAD days. The
median access survival was 1159 CVAD days, and
most often a malfunction led to CVAD removal after
a long survival (median of 1640 CVAD days). We
detected a very low bloodstream infection rate (0.12/
1000 CVAD days). The presence of neutralizing
inhibitor was a significant risk factor for infection.
Heparin vs. saline flushing did not influence the
CVAD outcome. We detected a lower infection rate
than previously reported, although 90% of the
patients were very young (<2 years) at first insertion
(median age = 1.02 year). Port access was frequent
after initial implantation: six patients (10%) used the
port daily for immune tolerance induction therapy
and 74% at least twice weekly for prophylaxis.
Young age did not increase the risk of infections, as
59% of the CVAD-related infections were recorded in
children over 6 years of age. Our national experience
confirms the safety of prophylactic factor concentrate
administration via ports even in very young children.
Introduction
associated with a number of complications, such as
CVAD-related bloodstream infection (CRBSI), thrombosis or mechanical failure.
According to the literature, infections are the primary complication associated with CVADs and also
the most common reason for their removal [1–3]. The
frequency of CVAD-related infection is partly related
to the maintenance procedures of the device and the
quality of caregiver’s education and training. A malfunction of the CVAD is another common reason for
CVAD removal [2,4].
Young age at initial CVAD implantation and presence of an inhibitor has been proposed as risk factors
for a CVAD infection [2,3,5,6]. The use of heparinized saline solutions to flush and lock CVAD to
reduce catheter occlusion has been recommended. It
has been also been suggested that heparin flushing
Children with severe forms of haemophilia require
regular venous access for infusion of coagulation factors. Repeated peripheral vein punctures are technically problematic in very young children and
subcutaneous contamination is frequent. Thus, surgically inserted central venous access devices (CVADs)
may be required to secure long-term and reliable
venous access. Unfortunately, these devices have been
Correspondence: Pekka Riikonen, Department of Pediatrics,
Kuopio University Hospital, P.O. Box 100, 70029 KYS, Kuopio,
Finland.
Tel.: +358 17 172443; fax: +358 17 172444;
e-mail: [email protected]
Accepted after revision 9 February 2015
© 2015 John Wiley & Sons Ltd
Keywords: central venous access device, children, complications, haemophilia, heparin, infections
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may prevent catheter-related infections. In a prospective, randomized trial conducted in children with cancer, which investigated 203 tunnelled central venous
catheters, there was a higher incidence of catheter
occlusion, and an increased bacteraemia rate with saline flushing when compared with heparin flushing [7].
A systematic review provided a weak evidence that
heparin flushing could reduce the risk of occlusion but
there was no evidence that it could reduce bloodstream infections [8]. After these non-conclusive
results, heparin flushing has not been uniformly used.
The aim of this study was to evaluate the nationwide incidence and risk factors of CVAD-related complications in children with haemophilia in Finland.
Materials and methods
Design and setting
We designed a retrospective multicentre study to evaluate the incidence and risk factors for CVAD complications during the follow-up of 17 years. Our study
was performed in five Finnish Paediatric Haematology-Oncology Centers (Kuopio, Oulu, Turku, Tampere
and Helsinki University Hospitals), which serve also
as haemophilia treatment centres for children and
adolescents. In these centres, CVADs have routinely
been used to facilitate prompt primary prophylactic
clotting factor therapy even in the youngest patients
with haemophilia. It is the standard practice to
implant electively a CVAD into children who are initiating prophylaxis or immune tolerance induction (ITI)
therapy to ensure reliable venous access and to permit
home treatment.
Detailed data on patients and treatment history
were uniformly collected by the principal investigator
(KV) from the medical records of all patients. The registered patient characteristics included date of birth,
type of bleeding disorder, inhibitor development, onset
and reason for prophylaxis, date of CVAD insertion
and removal, indication for CVAD insertion, reason
for CVAD removal and incidence of complications
associated with CVAD usage, age at transition to
peripheral veins and the use of heparinized/non-heparinized saline solution to flush and/or to lock the
CVAD.
Data were collected between June 1996 and September 2013. The Research Ethics committee of Northern
Savo, Finland, provided a favourable opinion for this
study (26//2010), and all patients and/or their parents
provided written informed consent prior to participation.
Patient characteristics and treatment history
All children were eligible with the following criteria:
severe
(FVIII
or
FIX
coagulation
activity
Haemophilia (2015), 1--7
<0.01 IU mL1) or moderate (FVIII:C or FIX:C 0.01–
0.05 IU mL1) haemophilia A or B born between June
1994 and May 2012 and treated in the participating
centres, and who required of CVAD insertion during
the follow-up period. Our national policy is to insert
CVAD very early for primary prophylaxis. A CVAD
was inserted in the majority (87%; 78 of 90; 72 of 74
with severe and 6 of 16 with moderate haemophilia)
of our patients. There were 90 patients of which 66
(73%) provided written informed consent for this
study. Eight of these 66 children did not require a
CVAD. That is the data from a total of 58 patients
with 106 CVADs were analysed.
Children received a tunnelled subcutaneously
implanted CVAD, a ‘port’, to facilitate the administration of factor concentrate. CVADs were inserted
through the subclavian or the internal jugular vein by
an experienced anaesthesiologist in the operating theatre under strict aseptic techniques. Port access was
most often started immediately after implantation. No
antibiotic prophylaxis was used in the catheter lock.
Maintenance procedures such as hand washing and
aseptic techniques were carried out carefully by a specialized trained nursing team or by parents at home.
Parents started the specific aseptic training program
during the first postoperative days. Under supervision,
they learned how to make antiseptic preparation of
the skin, proper port needle placement, delivery of the
concentrate and flushing the CVAD with heparin or
saline. After they were deemed competent to perform
sterile techniques during all procedures, home treatment was initiated.
In case of febrile episodes, parents were advised to
contact the hospital immediately if any fever was
detected. Patients were examined and in the absence
of common symptoms and signs of respiratory infection as a cause of fever, blood samples were drawn
and cultured before initiation of antimicrobial therapy. Most centres obtained paired blood cultures from
a CVAD and a peripheral vein but in some centres
blood cultures were collected only from the CVAD. In
cases where blood cultures were not percutaneously
obtained but culture from CVAD was positive, blood
samples were collected again from the CVAD and cultured. Vancomycin or second or third generation
cephalosporin based empiric antibiotic therapy was
initiated and continued until the CVAD-related bloodstream infection was excluded by culture. When a
bloodstream infection was diagnosed, empiric antimicrobial therapy was later modified based on culture
results and according to the microbiological sensitivity
pattern if needed. In general, the duration of antimicrobial therapy was at least 10 days but a minimum
of 14 days in the case of Staphylococcus aureus.
CVADs were flushed with heparinized saline solution
or non-heparinized saline alone every time the CVAD
was accessed.
© 2015 John Wiley & Sons Ltd
COMPLICATIONS ASSOCIATED WITH CVAD IN CHILDREN
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Complications
Statistical analysis
Complications were defined as any complication
requiring CVAD removal: CVAD malfunction,
mechanical complication, symptomatic deep venous
thrombosis (DVT), CRBSI or a local infection such as
skin or tunnel infection.
A CRBSI was defined according to the guidelines of
the Infectious Diseases Society of America [9]. A
definitive diagnosis required that the same organism
would grow from at least 1 percutaneous blood culture and from a culture of the catheter tip if a port
had been removed for suspected CRBSI, or that two
positive blood cultures were drawn (one from a catheter and the other from a peripheral vein). A presumed
CVAD-related infection was defined with clinical
symptoms of infection (fever, chills, or hypotension)
and with a recognized pathogen cultured from at least
two blood samples (collected from a CVAD on separate occasions) and that the recognized pathogens
were not related to an infection at some other site.
Thus, febrile episodes not fulfilling the definition of
either definitive or presumed CVAD-related infection
were not included in this study. Two infections were
excluded: Staphylococcus aureus-sepsis and multiple
abscesses in a patient with concomitant severe congenital immunodeficiency and Klebsiella pneumonia and
Acinetobacter-bacteraemia in another patient who had
pneumonia and osteomyelitis.
Malfunction was defined as a blockade or an occlusion (difficulty in drawing blood and/or infusing fluids
through the catheter) in the absence of documented
thrombosis. Mechanical complication was defined as a
displacement, that is malpositioning of the catheter
tip, disconnection, split or skin erosion requiring
CVAD removal.
Central venous access device-related thrombosis was
defined as a thrombosis with clinical symptoms or
signs of venous thrombosis diagnosed by venography
or ultrasound.
Early complications were those occurring as a consequence of the catheter insertion procedure. These
include pneumothorax, arrhythmias and major bleeding complications or CRBSI within the first 2 weeks
after CVAD positioning. A major bleeding was
defined according to ISTH recommendations [10].
Data on uncomplicated and elective removals with
improved venous access via peripheral veins due to
ageing were collected. The duration of CVAD placement was calculated from date of positioning until the
date of its removal or until the last follow-up for children, whose CVAD remained in place. Exposure days
(ED) before CVAD removal were estimated according
to the administration frequency of prophylaxis or ITI,
usually thrice weekly for haemophilia A, twice for
haemophilia B and daily for ITI, and treatment days
for major bleeds or surgery.
For each CVAD, the total number of catheter days
was calculated as the total number of days from
CVAD insertion to removal or to the date of last follow-up day. The incidence rate for any complication
per 1000 CVAD days was calculated as 1000 times
the number of complications divided by the total number of CVAD days.
Continuous variables were expressed as median values and ranges. Groups were compared by the log-rank
test. CI at the 95% level and exact p values for incidence rates were calculated. A P-value of <0.05 was
considered statistically significant. All analyses and figures were performed with SPSS software version 21.0;
SPSS Inc. (IBM Corp., Armonk, NY, USA).
© 2015 John Wiley & Sons Ltd
Results
Patients and CVADs
A total of 58 patients with 106 CVADs were included
in this study, which involved a total of 137 971 CVAD
follow-up days. These included 122 053 CVAD days
for patients without inhibitor and 15 918 CVAD days
with inhibitor. Fifty-one patients had severe haemophilia A and two children had severe haemophilia B.
Three patients with moderate haemophilia A and two
patients with moderate haemophilia B were included. Eleven patients (19%) of our cohort had an inhibitor, all of them with severe A haemophilia. Eight of
the 11 inhibitory positive patients were successfully
immune-tolerized and three children had ongoing ITI
therapy.
The main reason for implanting the first CVAD was
the start of prophylaxis (88% of initial insertions).
Additional indications for port insertion were the initiation of ITI therapy and difficult venous access
(10.3% and 1.7% of initial implantations). The median age at first CVAD insertion was 1.02 years
(range = 0.1–9.1 years). The majority (50 of 58;
90%) of patients were very young (≤2 years) at the
time of first insertion. Port access was frequent immediately after initial implantation: six patients (10%)
were using the port daily for ITI, 30 patients (52%)
every second day or three times per week and 13
patients (22%) two times per week for prophylaxis.
Twenty-five children (43%) had one CVAD insertion,
23 children (40%) two CVADs. Ten patients (17%)
had 3–4 CVAD replacements. The median age at transition to peripheral veins was 8.2 years (range = 2.6–
16.2). Detailed data on patients with CVAD are presented in Table 1.
Heparin flushing was carried out with the majority
of the CVADs (90/106; 85%). Sixteen CVADs in 10
patients (two of them had an inhibitor) were flushed
with saline only after using the device.
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Outcome of CVADs
Eighty-nine of the 106 CVADs (84%) had been
removed and 17 CVADs (16%) were still in place at
the end of follow-up period. CVADs remained in
place
for
between
3
and
3778 days
(median = 1159 days). The duration of CVADs in
patients without inhibitor was longer, 1501 median
days than those with inhibitor 782 days (P = 0.002).
Median ED before CVAD removal were 550 for all
patients, and 600 ED for non-inhibitor patients and
365 ED for patients with inhibitor (P = 0.04).
Table 1. Characteristics of patients with CVADs.
Number of patients
Bleeding disorder
Factor VIII deficiency (%)
With inhibitor
Factor IX deficiency (%)
With inhibitor
Haemophilia severity
Severe
Moderate
Indication for first
CVAD insertion (%)
Prophylaxis
ITI
Difficult venous access
Median age at initial
CVAD insertion
(range), years
Age at initial CVAD
insertion, years (%)
<2
2–6
>6
Median age at transition to
peripheral veins
(range), years
Number of CVADS
Number of CVADs
per patient (%)
One
Two
Three
Four
Median duration of CVAD placement (range), days
58
54 (93)
11
4 (7)
0
53
5
51 (88)
6 (10.3)
1 (1.7)
1.02
(0.11–9.14)
52 (90)
2 (3)
4 (7)
8.21
(2.62–16.18)
106
25 (43)
23 (40)
6 (10)
4 (7)
1159/(3–3778)
CVAD, central venous access device; ITI, immune tolerance induction.
Thirty-nine CVADs (37%) were removed electively
after a median of 1175 catheter days because of
improved peripheral venous access. Fifty of all the
106 CVADs (47%) required removal because of some
complication. The most frequent complication was
malfunction (20%, 21 of 106 CVADs). Other reasons
were CVAD-related infections (11%), mechanical
complications (9%), local skin/tunnel infection (5%)
and thrombosis (2%). Port survival according to the
reason for removal is shown in Table 2 and Fig. 1.
Only two early complications occurred: one Staphylococcus aureus septicaemia was encountered within
the first 2 weeks after CVAD positioning and one
major bleed in the area of port entry. The bleed was
recorded in a patient with inhibitor, and it required
CVAD removal 3 days after its insertion. No other
complications such as pneumothorax or arrhythmias
as a consequence of catheter insertion procedure were
recorded. No mortality due to any CVAD-related
complication was detected.
The majority (66%) of the complications requiring
CVAD removal were non-infectious. Malfunction, a
catheter blockade or an occlusion in the absence of
documented thrombosis, was associated with 21 of
106 CVADs (20%) after the long survival, a median
of 1640 CVAD days, with a complication rate (CR)
0.15 per 1000 CVAD days. Ten CVADs (9%) were
removed because of a mechanical complication (CR
0.07) with a shorter survival (445 CVAD days, median). Three of the mechanical complications were skin
erosion over the port, three CVADs had to be
removed after displacement (malpositioning of the
catheter tip) and four after disconnection or splitting
of the catheter.
Two clinically significant CVAD-related thrombosis
were recorded. One non-inhibitor patient had a
thrombosis in the brachiocephalic vein and a patient
with inhibitor suffered a thrombosis in the jugularis
vein during a bleeding episode while treated with bypassing agents without concomitant ITI. The initial
symptom had been a CVAD malfunction.
A total of 17 CRBSIs were detected in 14 CVADs
and in 12 (71%) of these cases required CVAD
Table 2. Outcome of all 106 CVADs.
Removed CVADs
Infectious complications
CVAD-associated bloodstream infection
Local skin/tunnel infection
Non-infectious complications
Malfunction
Mechanical
Thrombosis in situ
Uncomplicated removal (improved
venous access)
Still in use without any complication
Number of CVADs
(non-inhibitor patients), n = 86
Number of CVADs
(inhibitor patients), n = 20
Total number of
CVADs, n = 106
Median duration,
days
74
15
89
1227
9
3
3
2
12
5
937
846
19
8
1
34
2
2
1
5
21
10
2
39
1640
445
831
1175
12
5
17
850
CVAD, central venous access device.
Haemophilia (2015), 1--7
© 2015 John Wiley & Sons Ltd
COMPLICATIONS ASSOCIATED WITH CVAD IN CHILDREN
Local skin or tunnel infections (n = 5) requiring
CVAD removal (n = 2) were very rare. No CVAD
had to be removed because of clinically suspected
CVAD-related infection.
Complication rates for the different risk groups are
summarized in Table 4.
removal. The overall rate of bloodstream infection
was very low, 0.12 infections per 1000 CVAD days.
Five infections developed in three children with inhibitors (three infections during ITI) and 12 infections
occurred in 11 children without inhibitors. The infection rate for children with inhibitors was 0.31 per
1000 CVAD days, and for children without inhibitor
0.1 per 1000 CVAD days, P = 0.004. Three (18%) of
the 17 CVAD-related infections were detected when
the child was under 2 years, 4 (23%) at the age of 2–
6 years and the rest (59%) over 6 years of age. Grampositive organisms were responsible for CVAD-associated bloodstream infections (Table 3).
Thirteen CRBSIs were observed in 90 (14.4%) heparinized ports and four infections in 16 (25%) non-heparinized ports. Bloodstream infection rate per 1000
CVAD days was 0.11 for heparinized and 0.25 for
non-heparinized ports, P = 0.30 (a total follow-up
121 974 and 15 997 days respectively).
Discussion
This relatively large nationwide study of 106 CVADs
in 58 paediatric patients with 137 971 CVAD followup days reports a very low CVAD-related bloodstream
infection rate: 0.12/1000 CVAD days for all and 0.10/
1000 for non-inhibitor patients. Previous reports have
described a wide variety of higher infection rates (0.2–
3.4 infections/1000 CVAD days) [1,2,4–6,11–13]. In a
large meta-analysis with 2704 haemophilia patients
and 2973 CVADs [3], infection was the most common
reason for removal and the incidence of infection was
0.66/1000 catheter days. This might be partly
explained by the high number of external CVADs
(22.6%), the incidence of infection in the fully
implanted CVADs was 31% of that with external
CVADs. One small retrospective single centre study
with 44 CVADs has reported a similar low infection
rate (0.13/1000 CVAD days) as in our study [14], but
they concentrated only on those complications which
required the CVAD removal. Median age at initial
CVAD insertion was higher (22 vs. 12 months) and
there were fewer patients with inhibitors (16% vs.
19%). Our low frequency of complications may reflect
the meticulous and harmonized techniques, centralized
insertion policy, skilled nursing and strong support of
the parents who maintain the devices at home.
The meta-analysis showed that young age at insertion significantly increased the risk for infections:
patients over 6 years were 46% less likely to develop
infection than children aged 2–6 years [3]. In contrast,
in our cohort a young age did not increase the risk of
infections. The majority (59%) of the CVAD-related
infections were recorded when the child was above
6 years of age and only 18% of the infections were
Fig. 1. Port outcome according to the reason for removal. *One with concomitant major bleeding event.
Table 3. Pathogens responsible for CVAD-related bloodstream infections.
Pathogen
Staphylococcus epidermidis
Staphylococcus aureus
Bacillus cereus
Enterococcus faecium
n (%)
5
10
1
1
CVAD removal required
(29)
(59)
(6)
(6)
5
3
8
1
0
CVAD, central venous access device.
Table 4. Complications associated with CVAD and Influence of inhibitor.
Number of CVADs
Total number of CVAD days
Median duration of CVAD placement (range), days
Complication
Malfunction
CVAD-associated
bloodstream infection
Mechanical
Local skin/tunnel infection
Thrombosis
ALL patients, n = 58
Non-inhibitor patients, n = 47
Patients with inhibitor, n = 11
P
106
137 971
1159 (3–3778)
86
122 053
1501 (3–3507)
20
15 918
782 (21–3778)
0.002
Incidence rate (per
1000 CVAD days)/(CI)
Incidence rate (per
1000 CVAD days)/(CI)
Incidence rate (per
1000 CVAD days)/(CI)
0.15/(0.10–0.23)
0.12/(0.08–0.20)
0.16/(0.10–0.24)
0.10/(0.06–0.17)
0.13/(0.03–0.50)
0.31/(0.13–0.75)
0.669
0.004
0.07/(0.04–0.13)
0.03/(0.02–0.09)
0.01/(0.00–0.06)
0.07/(0.03–0.13)
0.02/(0.01–0.08)
0.01/(0.00–0.06)
0.13/(0.03–0.50)
0.13/(0.03–0.50)
0.06/(0.01–0.45)
0.638
0.025
0.062
CVAD, central venous access device; CI, 95% confidence interval per 1000 CVAD days.
© 2015 John Wiley & Sons Ltd
Haemophilia (2015), 1--7
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detected when the child was below 2 years, and 23%
at the age of 2–6 years. When considering the
patients’ very young age at CVAD insertion (90% of
children were under 2 years of age at the first port
implantation), our results with the very low infectious
CR must be considered encouraging.
Inhibitors enhanced the CVAD-related infection
rates by 3-fold. This is consistent with a previous
meta-analysis, which concluded that inhibitors at
insertion significantly increased the infectious risk
[2,3,5,6,15]. The reason for that is mostly due to
more frequent, usually daily device usage during ITI.
We recorded similar infection rates with heparinized
and non-heparinized ports. However, as in our study,
the use of heparin was left to the discretion of the
treating physician and not systemized, the comparison
remains descriptive. The preventive influence of heparin flushing on catheter-related infections still remains
unresolved and prospective evaluation of this practice
should be conducted in the future.
Central venous access device care guidelines have
been as uniform and congruent as possible in our
country. Handling scheme recommendations have
been agreed frequently by our national haemophilia
expert team. However, the retrospective survey with a
long study period for 17 years has its limitations of
data integrity and the ability to detect all changes with
the port handling and teaching techniques to the parents among the different centres along the follow-up
time. Non-infectious complications were the most
common reason for CVAD removal. Incidence of
mechanical complications is similar to previously
reported [2], but the malfunction rate seems to be
higher than that previously reported [4,5,14,15].
When comparing to the findings of a meta-analysis
[3], CVADs remained in situ for twice as long; the
median life span was 1159 days (3.2 years) in our
cohort compared to 578 days (95% CI 456–733 days)
in the meta-analysis. Indwelling duration was even
longer before malfunctions: they were recorded after a
median of 1640 CVAD days. Some malfunctions may
be explained by increasing the age of the patient and
growth, e.g. the catheter tip may be dislodged during
the growth of the child.
References
1 Ljung R. The risk associated with indwelling
catheters in children with haemophilia. Br J
Haematol 2007; 138: 580–6.
2 Titapiwatanakun R, Moir C, Pruthi RK, Stavlo PL, Schmidt KA, Rodriguez V. Central
venous access devices for paediatric patients
with haemophilia: a single-institution experience. Haemophilia 2009; 15: 168–74.
3 Valentino LA, Ewenstein B, Navickis RJ,
Wilkes MM. Central venous access devices
in haemophilia. Haemophilia 2004; 10:
134–46.
Haemophilia (2015), 1--7
In the meta-analysis, the CR for CVAD-related
thrombosis was 0.056 per 1000 CVAD days [3]. This
incidence reported may be an underestimate, because
most CVAD-related thrombi are probably clinically
silent [16]. Two clinically significant thrombotic complications were observed in our cohort. The initial
symptom was CVAD malfunction. We were unable to
assess the prevalence of silent thrombosis because venograms, ultrasound or MRI-angiography were not
routinely performed. A recent study investigating 20
children screened by MRI after the removal of CVAD,
found a high number of silent DVT (25% of patients
had abnormal MRI, consistent with DVT corresponding to CR 0.10/1000 CVAD days) [17].
In conclusion, we report a significantly lower
CVAD-related bloodstream infection rate than previously described, despite the fact that the majority
(90%) of our patients were very young (≤2 years) at
the time of first insertion, and the port access was frequent and long standing (lasting on median
1159 days). Our experience of CVAD emphasizes the
safety of undertaking prophylactic factor concentrate
administration via ports in very young children
enabling home treatment. The meticulous handling of
the insertion and subsequent management with guidance appear to be important and favour a good outcome with these types of ports.
Acknowledgements
This study was supported by a grant from Blood Disease Research Foundation, Finland and Foundation for Pediatric Research, Finland (to KV).
Authorship
KV collected the data, performed the statistical analyses and wrote the
article. RL contributed to writing of the article. PR designed the research
study, analysed the data and wrote the article. All authors read, edited
and approved the final manuscript.
Disclosures
The authors stated that they had no interests which might be perceived as
posing a conflict or bias.
4 Yeoh ZH, Furmedge J, Ekert J, Crameri J,
Curtis N, Barnes C. Central venous access
device-related infections in patients with
haemophilia. J Paediatr Child Health 2013;
49: 242–5.
5 Mancuso ME, Mannucci PM, Sartori A,
Agliardi A, Santagostino E. Feasibility of
prophylaxis and immune tolerance induction regimens in haemophilic children using
fully implantable central venous catheters.
Br J Haematol 2008; 141: 689–95.
6 Van Dijk K, Van Der Bom JG, Bax KN,
Van Der Zee DC, Van Den Berg MH. Use
of implantable venous access devices in
children with severe hemophilia: benefits
and burden. Haematologica 2004; 89: 189–
94.
7 Cesaro S, Tridello G, Cavaliere M et al.
Prospective, randomized trial of two different modalities of flushing central
venous catheters in pediatric patients
with cancer. J Clin Oncol 2009; 27:
2059–65.
8 Mitchell MD, Anderson BJ, Williams K,
Umscheid CA. Heparin flushing and other
interventions to maintain patency of central
venous catheters: a systematic review. J
Adv Nurs 2009; 65: 2007–21.
© 2015 John Wiley & Sons Ltd
COMPLICATIONS ASSOCIATED WITH CVAD IN CHILDREN
9 Mermel LA, Allon M, Bouza E et al. Clinical practice guidelines for the diagnosis and
management of intravascular catheterrelated infection: 2009 update by the Infectious Diseases Society of America. Clin
Infect Dis 2009; 49: 1–45.
10 Schulman S, Angeras U, Bergqvist D et al.
Definition of major bleeding in clinical
investigations of antihemostatic medicinal
products in surgical patients. J Thromb
Haemost 2010; 8: 202–4.
11 Bollard CM, Teague LR, Berry EW, Ockelford PA. The use of central venous
catheters (portacaths) in children with
haemophilia. Haemophilia 2000; 6: 66–
70.
© 2015 John Wiley & Sons Ltd
12 McMahon C, Smith J, Khair K, Liesner
R, Hann IM, Smith OP. Central venous
access devices in children with congenital
coagulation disorders: complications and
long-term outcome. Br J Haematol 2000;
110: 461–8.
13 Tarantino MD, Lail A, Donfield SM et al.
Surveillance of infectious complications
associated with central venous access
devices in children with haemophilia. Haemophilia 2003; 9: 588–92.
14 Upadhyaya M, Richards M, Buckham S,
Squire BR. Long-term results of central
venous access devices in children with haemophilia. Pediatr Surg Int 2009; 25: 503–
6.
7
15 Jeng MR, O’Brien M, Wong W et al.
Monthly recombinant tissue plasminogen
activator administration to implantable
central venous access devices decreases
infections in children with haemophilia.
Haemophilia 2009; 15: 1272–80.
16 Kamphuisen PW, Lee AY. Catheter-related
thrombosis: lifeline or a pain in the neck?
Hematology Am Soc Hematol Educ Program 2012; 2012: 638–44.
17 Ranta S, Kalajoki-Helmio T, Pouttu J,
Makipernaa A. MRI after removal of central venous access device reveals a high
number of asymptomatic thromboses in
children with haemophilia. Haemophilia
2012; 18: 521–6.
Haemophilia (2015), 1--7