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ONLINE EXCLUSIVE
Comparing the Results of Coagulation Tests
on Blood Drawn by Venipuncture and Through
Heparinized Tunneled Venous Access Devices
in Pediatric Patients With Cancer
Pamela S. Hinds, PhD, Alice Quargnenti, BSN, Jami Gattuso, MSN, Deo Kumar Srivastava, PhD,
Xin Tong, MPH, Linda Penn, MT (AMT), Nancy West, RN, Patricia Cathey, RN,
Darlene Hawkins, RN, Judith Wilimas, MD, Matthew Starr, BSN, and David Head, MD
Key Points . . .
Purpose/Objectives: To compare the accuracy of three
coagulation tests (prothrombin time [PT], activated partial
thromboplastin time [aPTT], and fibrinogen [FBG]) per-
Although sequential discard volumes (6 ml, 9 ml, and 12 ml)
formed on blood samples collected through heparinized
from a tunneled venous access device (TVAD) become closer
tunneled venous access devices (TVADs) with those from
in value to the coagulation values from a venipuncture, the
venipuncture.
TVAD values are statistically significantly different at all dis-
Design: Descriptive comparative with patients serving as
card volumes from the coagulation values.
their own controls.
Setting: Pediatric comprehensive care setting for chil-
Reviews by clinical experts comparing TVAD and venipunc-
dren and adolescents experiencing catastrophic dis-
ture coagulation values indicated that, of the three coagulation
eases.
indicators (PT, FBG, aPTT), the aPTT values were more likely
to be evaluated as clinically significantly different from each
Sample: 53 patients who had TVADs, had not received
other than were the values of the other two indicators.
asparaginase during the previous 14 days, and had coagu-
lation studies ordered. Patients ranged in age from 220
--
years (X = 9.2 years, SD = 5). The most common diagnoses
were neuroblastoma and acute myelocytic leukemia.
Pamela S. Hinds, PhD, is director of nursing research in the Division
Methods: Blood was collected through TVADs within sec-
of Patient Care Services, Alice Quargnenti, BSN, is a staff nurse in the
onds of collection of the venipuncture sample. The first 3 ml
Hematology/Oncology Inpatient Unit, Jami Gattuso, MSN, is a nurs-
of blood from a TVAD was discarded; the research nurse
ing research specialist in the Division of Patient Care Services, Deo
then drew three sequential samples of 3 ml each. Labora-
Kumar Srivastava, PhD, is an associate member in the Department
tory personnel were blinded to the source of all four
of Biostatistics, Xin Tong, MPH, is an associate biostatistician in the
samples until all analyses had been completed.
Department of Biostatistics, Linda Penn, MT (AMT), is a technician
Main Research Variables: PT, aPTT, and FBG.
in the Department of Pathology, Nancy West, RN, is a lead clinical re-
Findings: For all patients, results of PT, aPTT, and FBG tests
search associate in the Critical Care Division, Patricia Cathey, RN,
on each of the three blood samples obtained through the
is a clinical nurse coordinator, Darlene Hawkins, RN, is a pediatric
TVAD differed significantly from results of the same tests on
oncology nurse in the Ambulatory Care Unit, Judith Wilimas, MD, is
blood obtained by venipuncture.
a member of the International Outreach Program, and Matthew Starr,
Conclusions: These findings indicate that neither a 6
BSN, is a student in the Professional Oncology Program, all at St.
ml, 9 ml, nor 12 ml discard from a heparinized TVAD is suf-
Jude Children's Research Hospital in Memphis, TN. David Head,
ficient to yield clinically trustworthy PT, aPTT, or FBG val-
MD, is interim chair of pathology and medical director of laboratory
ues.
medicine at Vanderbilt Medical Center in Nashville. This study was
Implications for Nursing: Nurses who have been per-
funded, in part, by a grant from the Association of Pediatric Oncol-
suaded by patients or parents to withdraw blood samples
ogy Nurses, the Cancer Center Support Grant P30 CA-21765 from the
for coagulation indicators from a TVAD rather than from a
National Cancer Institute, and the American Lebanese Syrian Asso-
venipuncture should have access to this research-based in-
ciated Charities. (Submitted April 2001. Accepted for publication Au-
formation that the three indicators, particularly aPTT, differ
gust 23, 2001.) (Mention of specific products and opinions related to
significantly from each other as to make it unreliable and
those products do not indicate or imply endorsement by the Oncology
potentially unsafe to sample blood from a TVAD to assess
Nursing Forum or the Oncology Nursing Society.)
coagulation.
Digital Object Identifier: 10.1188/02.ONF.E26E34
ONF VOL 29, NO 3, 2002
E26
Coagulation Studies From Arterial Routes
ost children and adolescents receiving treatment for
M
cancer require the insertion of one or more tunneled
The literature review revealed seven studies (Gregersen,
venous access devices (TVADs) during the course of
Underhill, Detter, Schmer, & Lax, 1987; Kaplow, 1988;
treatment (Wiener et al., 1992). Manipulating and managing
Konopad, Grace, Johnston, Noseworthy, & Shustack, 1992;
TVADs primarily is the responsibility of nurses and, some-
Merenstein, 1971; Molyneaux, Papciak, & Rorem, 1987;
times, of carefully trained parents. In many, but not all, clinical
R e i n h a r d t , Tonneson, Bracey, & Goodnough, 1987;
settings, heparinized solutions regularly are instilled into
Richiuso, 1998) that concluded that accurate coagulation
TVADs to maintain patency. Because the heparinized solution
studies for certain indicators could be obtained from arterial
might affect results of some coagulation tests, blood samples for
lines if an adequate discard volume was obtained prior to
such tests usually are drawn by venipuncture according to in-
sampling. The consistent factor of each study was the con-
stitutional policy. Venipuncture is a painful and troubling pro-
cept of catheter dead space, defined operationally as "the
cedure for children and adolescents. When a TVAD is in place,
arterial lumen and the stopcock from which the blood
patients and their family members prefer that blood samples be
samples are drawn" (Laxson & Titler, 1994, p. 16). The
collected from that device. At times, the pleas of patients and
studies differed with regard to the procedure used to obtain
their parents have persuaded healthcare providers to ignore
arterial blood samples and the volumes needed to clear the
policy and instead collect blood samples for coagulation tests
dead space (see Table 1).
from a TVAD. Indeed, nurses and physicians have described
An in vitro study conducted in 1971 investigated the ac-
instances when they chose varying amounts of discarded blood
curacy of aPTT and PT values obtained from umbilical ar-
from a TVAD before collecting a coagulation sample. Labora-
tery catheters with a dead space of 0.8 ml. The study used
tory technicians have described processing coagulation samples
heparin concentrations of 1 u/ml and tested discard volumes
with suspicion as to the sample source; they say that unusual
ranging from 04.5 ml. The study found that a volume equal
values are common and second draws often become necessary.
to five times the catheter's dead space, which was 4 ml, was
Coagulation values from TVADs might be aberrant and, if they
needed to obtain accurate aPTT and PT values (Merenstein,
are not recognized as spurious, might lead to inappropriate
1971).
medical decisions. If standard procedures used to manage
Two in vitro studies tested the accuracy of arterial catheters
TVADs could be altered safely to yield accurate coagulation
with a dead space of 0.8 ml, using heparin concentrations of
values, patients could avoid venipuncture. The purpose of this
2 u/ml. The first published study measured aPTT values from
single-site study was to determine whether measured values of
60 paired samples obtained from 24 patients (Molyneaux et
coagulation indicators (activated partial thromboplastin time
al., 1987). Discard volumes tested ranged from 1.64.8 ml,
[aPTT], prothrombin time [PT], and fibrinogen [FBG]) differed
which was six times the catheter's dead space. The second
significantly for samples collected sequentially through a
study, published five years later, measured both aPTT and PT
TVAD from those collected by venipuncture.
values from a sample of critically ill adults (N = 41) who had
venipuncture samples obtained simultaneously and served as
Literature Review
their own control (Konopad et al., 1992). Discard volumes of
3 ml, 5.3 ml, and 7.6 ml were tested. Statistically significant
The first published report of the relationship between coagu-
differences between the arterial and venipuncture samples for
lation abnormality and use of an indwelling catheter appeared
all three discard volumes were found. Despite that, the authors
in the New England Journal of Medicine in 1970 in the form of
argued that the differences, although statistically significant,
were not necessarily clinically significant. The authors con-
a letter to the editor by C.J. Bark, MD, clinical pathologist. The
cluded that a 3 ml discard for obtaining accurate PT values
letter reported that tests on a blood sample obtained through a
from an arterial catheter and a 5.3 ml discard for accurate
heparinized device used for monitoring the central venous pres-
aPTT values was sufficient.
sure of a patient undergoing postoperative dialysis revealed a
In another study, researchers compared simultaneously ob-
prolonged aPTT (Bark, 1970). An initial diagnosis of heparin
tained venous samples with those drawn from the sampling
overdose was made but later was refuted when a subsequent
port of Lab-Site high-pressure tubing. Within the sample
sample obtained by venipuncture revealed a normal aPTT. This
population of 25 critically ill patients who were in an intensive
clinical experience prompted Bark to draw normal citrated
care unit or recently had undergone surgery, the researchers
plasma through the patient's heparinized IV line. The aPTT of
concluded that both aPTT and PT values could be obtained
this plasma sample was abnormally prolonged, yet a sample
accurately from the specified brand of sampling ports (Cicala,
taken after the line was flushed with 50 ml of normal saline
Cannon, Larson, & Fabian, 1988). In a study by Lew, Hutch-
yielded a normal aPTT. Bark called this finding a "type of co-
inson, and Lin (1991), the accuracy of a central venous pres-
agulation nondisease" (p. 1214).
sure (CVP) line also was considered. The authors concluded
In the 25 years that have followed the introduction of the
that the PT values differed significantly for the discard volume
phenomenon of "coagulation nondisease," numerous studies
of dead space plus 5 ml in the CVP samples when compared
have been conducted (primarily on adult patients) to test the
to venipuncture. They found no significant differences in
accuracy of coagulation studies on samples obtained from
aPTT values. The third of the 0.6 ml dead space studies inves-
heparinized catheters. For the purpose of this review, the au-
tigated aPTT and thrombin time (TT) values within a sample
thors selected articles that evaluated coagulation studies on
of adult patients with cardiac disease (N = 30) and reported
samples obtained from arterial and venous routes. Although
that a 5.1 ml discard volume was necessary to obtain accurate
the results cannot be generalized beyond catheter type, patient
aPTT values. Furthermore, the authors concluded that TT
population, or methodology used in each study, the principles
values only could be obtained accurately by venipuncture
of the effects of heparin on blood coagulation were the physi-
(Gregersen et al., 1987).
ologic framework for each reviewed study.
HINDS VOL 29, NO 3, 2002
E27
Table 1. Summary of Published Studies of Coagulation Tests Using Blood Drawn Through Arterial Catheters
Catheter
Heparin
Discard
Recommended
Dependent
Dead Space
Concentration
Volume(s)
Method or
Investigator
Variable
(ml)
(u/ml)
Sample Size
Tested
Discard Volume
0.8
1
5 x DS
0 (in vitro study)
0 ml, 0.9 ml, 1.8
Merenstein,
aPPT
ml, 2.7 ml, 3.6
1971
PT
ml, 4.5 ml
0.6
6
Venipuncture
24 patients
3 ml, 6 ml
Kajs, 1986
aPTT
indicated
0.6
4
5.1 ml for aPPT
30 patients
0.6 ml, 5.1 ml,
Gregersen
aPTT
tests; venipunc-
9.6 ml, 14.1 ml,
et al., 1987
TT
ture indicated
18.6 ml
for TT tests
0.8
2
6 x DS
24 patients
1.6 ml, 3.2 ml,
Molyneaux
aPTT
4.8 ml
et al., 1987
0.65
5 x DS
1, 2, or 4
9 dogs
2 x DS, 4 x DS,
Reinhardt
aPTT
6 x DS, 8 x DS,
et al., 1987
PT
10 x DS, 12 x DS,
TT
14 x DS
1.0
10 x DS
1
50 patients
10 ml
Kaplow, 1988
aPTT
PT
0.1
NR
1
25 patients
NA
Cicala et al.,
aPTT
1988
PT
0.6
1, 2
NR
60 patients
3.1 ml
Lew et al., 1991
aPTT
(2.5 ml + DS)
PT
5.6 ml
(5.0 ml + DS)
12.5 ml
(10.0 ml + DS)
0.8
3 ml for PT tests
2
41 patients
3 ml
Konopad,
aPTT
5.3 ml for aPTT
5.3 ml
et al., 1992
PT
tests
7.6 ml
Venipuncture
2.5
2
35 patients
10 ml
Hancock, 1993
aPTT
indicated
12.5 ml
15.0 ml
14 x DS
0.85
NR
8 ml
16 patients
Richiuso, 1998
aPTT
12 ml
aPTT--activated partial thromboplastin time; DS--dead space; NA--not applicable; NR--not reported; PT--prothrombin time; TT--
thrombin time
A canine study (N = 9) evaluated aPTT, PT, and TT values
experienced percutaneous transluminal coronary angioplasty.
to determine whether heparin concentrations of 1 u/ml, 2 u/ml
The findings of this study disagreed with those of the eight pre-
or 4 u/ml could be cleared from the arterial catheter dead
viously reviewed studies by concluding that venipuncture was
space of 0.65 ml (Reinhardt et al., 1987). Discard volumes
the indicated route for obtaining accurate aPTT values.
tested ranged from 214 times the catheter's dead space. The
Of the 11 studies reviewed, nine involved patients who were
finding of this study supported that accurate aPTT, PT, and
18 years of age or older. Seven of the 11 studies using arterial
TT values could be obtained using a discard volume of five
catheters concluded that the results of coagulation tests per-
times the dead space.
formed on blood samples drawn through these catheters were
Kaplow (1988) compared aPTT and PT venipuncture val-
accurate if adequate discard volumes were obtained before
ues in arterial samples from 50 acutely ill adult patients with
sampling, two concluded that venipuncture was indicated, and
various oncologic or medical diagnoses. The arterial catheter
two made no recommendation. Three studies examined the ac-
dead space was 1.0 ml. The heparin concentration was 1 u/ml.
curacy of aPTT and PT results; a fourth study examined the ac-
No significant differences were found when a 10 ml discard
curacy of aPTT and TT results. Heparin concentrations varied
volume was obtained prior to sampling.
from 16 u/ml. Reported discard volumes ranged from 0.1
The largest arterial catheter dead space studied was 2.5 ml
18.6 ml. The largest dead space of any arterial catheter studied
(Hancock, 1993). The only variable considered in the experi-
was 2.5 ml, and the smallest was 0.1 ml. Of the studies that
ment was aPTT values. The study tested heparin 2 u/ml and
indicated catheter type, site, or specific product name, none
discard volumes ranging from 1015 ml in 35 subjects who had
investigated the same kind of arterial catheter (see Table 1).
ONF VOL 29, NO 3, 2002
E28
ranged from 1100 u/ml, and discard volumes ranged from
Coagulation Studies From Venous Routes
0 25 ml. A dead space volume was reported only in two stud-
The use of a heparinized saline flush to maintain the pa-
ies.
tency of an indwelling central venous catheter also has
In the seven venous catheter studies, sample size ranged
prompted concerns about the accuracy of coagulation tests on
from 1230 patients (see Table 2). Study samples were com-
blood obtained from such catheters. Of seven coagulation
prised of patients with cancer or patients waiting for open-
studies of samples obtained from heparinized central venous
heart surgery (their ages were not specified). Pediatric oncol-
c a t h e t e r s , one study focused solely on aPTT values
ogy and hematology patients were included in only one of
(Almadrones, Godbold, Raaf, & Ennis, 1987), two included
the reviewed studies (Ellis, 1993). Findings and recommen-
PT values and aPTT studies (Ellis, 1993; Pinto, 1994), and
dations from the studies varied considerably. Only Palermo
four included aPTT, PT, activated clotting time (ACT), plate-
et al. (1980) concluded that an appropriate discard volume
let count or FBG, and fibrin/fibrinogen degradation products
(defined as 1.5 ml) made it possible to obtain accurate co-
(FDP) (Barton & Poon, 1986; Mayo, Dimond, Kramer, &
agulation studies from a heparinized central venous catheter.
Horne, 1996; Palermo, Andrews, & Ellison, 1980; van
In contrast, four studies (Almadrones et al., 1987; Barton &
Genderen, Gomes, & Stibbe, 1994). Heparin concentrations
Poon, 1986; Pinto, 1994; van Genderen et al., 1994) con-
Table 2. Summary of Published Studies of Coagulation Tests Using Blood Drawn Through Venous Catheters
Discard
Recommended
Volume(s)
Method or
Dependent
Dead Space
Investigator
Sample Size
Variable
(ml)
Heparin (u/ml)
Tested
Discard Volume
12 patients
1.5 ml, 2.5 ml,
1.5 ml
aPTT
1.5
001
Palermo et al.,
PT
002
3.5 ml, 5.5 ml
1980
ACT
Platelet count
12 patients
0 ml, 10 ml
Venipuncture
aPTT
NR
100
Barton & Poon,
indicated
FBG
1986
FDP
PT
30 patients
10 ml
Venipuncture
aPTT
NR
010
Almadrones et
indicated
al., 1987
14 patients
10 ml
Venipuncture
100
van Genderen
aPTT
NR
indicated
AT-111
et al., 1992
α 2-AP
TAT
FM
F1.2
FbDP
TDP
100
25 patients
5 ml
5 ml + 4 g/ml
NR
Ellis, 1993
aPTT
(or 1 ml) of
PT
protamine
added to aPPT
sample; PT
should be omit-
ted from
coagulopathy
screen.
100
12 patients
6 x DS
Venipuncture
aPTT
0.5
Pinto, 1994
PT
2.0
indicated
aPTT
NR
100
20 patients
5 ml, 10 ml, 15
25 ml from
Mayo et al.,
ml, 20 ml, 25 ml
TVAD in
PT
1995
FBG
nonemergent
situations;
venipuncture
for critical
decisions
α2-AP--alpha-2 antiplasmin; ACT--activated clotting time; aPTT--activated partial thromboplastin time; AT-111--antithrombin 111;
DS--dead space; F1.2--prothrombin activation fragment; FbDP--degradation products of fibron; FBG--fibrinogen; FDP--fibrinogen
degradation products; FM--soluble fibrin; NR--not reported; PT--prothrombin time; TAT--thrombin-antithrombin III complexes; TDP--
total degradation products; TVAD--tunneled venous access device
HINDS VOL 29, NO 3, 2002
E29
cluded that venipuncture was the only appropriate route for
Procedure
obtaining aPTT, FBG, FDP, and PT. The remaining two
Blood samples for coagulation tests first were obtained by
studies came to situation-specific conclusions. One con-
venipuncture. Immediately thereafter, 3 ml of blood was with-
cluded that only venipuncture should be used for critical
drawn from a TVAD and discarded, then three 3 ml samples
clinical decisions but that a 25 ml discard could be sufficient
were drawn sequentially from the TVAD (sample 1, sample
in nonemergent situations. The second study concluded that
2, and sample 3). All four samples (venipuncture sample and
accurate PT values could not be obtained accurately from
three TVAD samples) immediately were placed on ice and
TVADs but that accurate values of aPTT could be obtained
taken to the clinical laboratory for analysis. All study samples
if protamine was added to samples.
from each patient were collected within three minutes. The six
The reviewed studies of arterial and venous catheters had
nurses who shared responsibility for collecting blood speci-
methodologic differences and discrepant findings, and most
mens had completed competency training before initiating the
involved adult patients; thus, a standard of care for collecting
study and repeated the training every four months during the
coagulation samples from TVADs in pediatric patients with
two years of data collection. All samples were collected in
cancer could not be derived from the reviewed studies. There-
accordance with the standard procedures of the institution.
fore, the authors studied a group of pediatric patients to deter-
The research nurse coded all collected samples by using a
mine whether the results of coagulation tests performed on
random-number coding scheme generated by the study bio-
blood sampled sequentially from a TVAD that routinely was
statistician. With that, the laboratory technicians processing
flushed first with heparinized saline differed statistically and
the samples were blinded to the source of each sample. PT and
clinically from the results of tests performed on samples
aPTT values were determined by the COAG-A-Mate X@ (se-
drawn by venipuncture.
rial number 021X1596) during the first year of the study and
then by the MLA1400C (serial number 721CE). FBG values
Methods
w e r e determined by the FibrometerTM (serial number
TOO452). The same reagents and laboratory standards were
Setting
used during the entire study period. Using standard methods,
The study was performed at a comprehensive care center
a single technician processed all samples from the same pa-
for children and adolescents with catastrophic diseases, prima-
tient. After completing the analyses on all four samples, the
rily cancer. The center has 62 inpatient beds and almost 2,000
technician contacted the research nurse, who revealed which
outpatient visits per week. About 200 single- and double-lu-
sample was the venipuncture sample. Only the values from
men TVADs had been placed during each of the five years
the venipuncture sample were used for clinical care purposes.
preceding the study. In the year preceding this study, 6,622
Data Analysis
coagulation tests were ordered, but determining how many
were performed on blood drawn from TVADs or arterial lines
The one-sample Hotelling's T2 test was used to determine
is impossible.
whether the differences in PT, aPTT, and FBG results from the
venipuncture samples and the sequentially collected TVAD
Sample
samples were equal to zero. Because three comparisons were
Patients undergoing coagulation tests in this study were 2
performed, the authors adjusted the p value by using the
20 years of age and had a diagnosis of cancer. Either a single-
Bonferroni method. As a result, a comparison was significant if
or double-lumen TVAD had been inserted previously. To be
the p value was less than 0.017 (0.05 divided by 3). The same
eligible for the study, patients could not have received a dose
statistic was used to determine whether differences existed in the
of asparaginase during the previous 14 days because of the
results of coagulation tests performed on the sequentially drawn
documented influence of this agent on coagulation (Capizzi &
TVAD samples, and the same correction was made for multiple
Holcenberg, 1993; Nowak-Gottl, Werber, Ziemann, Ahlke, &
comparisons. To determine whether significant clinical differ-
Boos, 1996). Consent for study participation was obtained
ences existed between the results of coagulation tests performed
from parents or guardians, as appropriate, and the assent of the
on the venipuncture samples and each of the sequentially drawn
patients was obtained when possible.
TVAD samples, each result was reviewed independently by
Sample Size
three physicians and one nurse practitioner, who indicated
whether any results were different enough from the others to
To determine the sample size needed to achieve the study's
have prompted a change in clinical care. The expert reviewers
objectives, the authors reviewed historical data on coagulation
used the range of seconds to clot formation considered to rep-
tests performed at the study setting during the preceding five
resent normal findings at the study setting: PT = 1015 seconds;
years. During that time, 16,000 coagulation tests had been
aPTT = 2640 seconds; FBG = 150400 seconds.
completed, but many patients had undergone such tests more
than once. To avoid including multiple tests on the same pa-
Results
tient, the authors only used the results of the first coagulation
study for each patient. Therefore, only the results from 1,644
Patients
patient tests were used to determine the sample size. On the
Sixty patients were enrolled in the study. However, the
basis of these findings, the authors determined that a medium-
sequentially drawn samples of one patient were combined
effect size difference of 0.3 for each of the variables (PT,
mistakenly in the laboratory before analysis, the research
aPTT, FBG) would be appropriate. Type I error was con-
nurses were unable to obtain samples through the TVADs of
trolled at the level of 0.05, and the desired power was set at
two patients, the recorded test results for three patients could
90%. When these factors were taken into consideration, the
not be located, and one patient exceeded the age criterion for
required sample size was set at 55 patients.
ONF VOL 29, NO 3, 2002
E30
Table 4. Seconds to Coagulation During Tests on Blood
eligibility. Therefore, the final study sample consisted of 53
Samples Drawn by Venipuncture and Three Samples
patients, most of whom were male and Caucasian (see Table
Sequentially Drawn Through a Tunneled Venous
3). Most had a double-lumen TVAD, and the TVAD dead
Access Device
space ranged from 0.61 ml as reported by the manufacturers
and confirmed by the surgeons who inserted them. The most
--
Coagulation Indicator
n
SD
Median
X
frequently represented diagnoses were neuroblastoma and
acute myelocyticleukemia. The heparin flush concentration
Prothrombin time
used daily to maintain patency was 10 u/ml. The majority of
Venipuncture
53
11.83
1.18
11.6
T V A D s were flushed and clamped at the time of data
TVAD-sample 1
52
12.66
1.60
12.1
collection; only eight had infusions (normal saline hydration
TVAD-sample 2
52
12.19
1.25
11.9
fluids) that were interrupted briefly for this study.
TVAD-sample 3
53
12.09
1.24
11.8
Coagulation Tests
Fibrinogen
Venipuncture
48
311.33
85.23
286.5
All 53 patients underwent venipuncture. PT and aPTT val-
TVAD-sample 1
48
294.06
78.28
271.0
ues were determined for all patients, and FBG values were de-
TVAD-sample 2
47
302.23
81.99
271.0
termined for 48. However, because the laboratory labeled one
TVAD-sample 3
47
301.70
83.05
281.0
PT sample, one FBG sample, and five aPTT samples sequen-
Activated partial
tially drawn from TVADs as "unable to calculate," the number
thromboplastin time
of comparisons varies (see Table 4). Coagulation tests per-
Venipuncture
53
31.59
4.76
31.2
formed on samples drawn through TVADs showed that PT and
TVAD-sample 1
45
54.17
29.67
42.0
aPTT values decreased with each sequential sample; the results
TVAD-sample 2
48
38.49
10.11
36.8
TVAD-sample 3
50
36.00
10.59
33.1
of tests on sample 3 were closest to those of tests performed on
samples obtained by venipuncture. The venipuncture PT values
TVAD--tunneled venous access device
and the sequential TVAD PT values were moderately to
N = 53
strongly correlated; the correlation coefficient increased with
each sequential sample (see Table 5). The venipuncture FBG
values and the sequential TVAD FBG values were strongly
Despite these linear correlations, however, significant differ-
correlated (see Table 6). The venipuncture aPTT values and the
ences existed among the coagulation indicators for each TVAD
TVAD aPTT values were moderately correlated (see Table 7).
sample (see Table 8). To identify the source of the differences,
the authors compared the values of each coagulation indicator
by using an analysis of variance procedure. The findings indi-
Table 3. Demographic Characteristics
cated that all TVAD values differed significantly from the veni-
puncture values (see Table 9). These results were confirmed by
%
Characteristic
n
using a paired t-test statistic. In addition, no differences were
Sex
noted for any of the PT, aPTT, or FBG blood draws between
Male
29
55
single- and double-lumen TVADs (p = 0.160.92). No differ-
Female
24
45
ences were found in any of the blood draws by length of time
Race
since a TVAD had been surgically placed (p = 0.140.93).
Caucasian
37
70
African American
09
17
Clinical Significance
Hispanic
05
9
The panel of four clinicians agreed that 51 of the 53 sets of PT
Other
02
4
values were similar enough that no change in practice would
Diagnosis
have been recommended. Three of the four reviewers found that
Neuroblastoma
18
34
two comparison sets of PT values were so discrepant that either
Acute myeloid leukemia
10
19
Acute lymphoblastic leukemia
05
9
Other malignant neoplasms
03
6
Table 5. Correlations Between Results of Tests
Myelodysplastic syndrome
03
6
Medulloblastoma
02
4
of Prothrombin Time: Venipuncture versus TVAD
Non-Hodgkin's lymphoma
02
4
Osteosarcoma
02
4
Veni-
TVAD
TVAD
TVAD
Chronic myelogenous leukemia
02
4
puncture
Sample 1
Sample 2
Sample 3
Other leukemia
01
2
Germ cell tumors
01
2
Venipuncture
1.000
0.60
0.79
0.85
Wilms tumor
01
2
(n = 52)
(n = 52)
(n = 53)
Choroid plexus carcinoma
01
2
Sample 1
1.000
0.86
0.73
Central nervous system neoplasms
01
2
(n = 51)
(n = 52)
Other
01
2
Sample 2
1.000
0.90
Type of line
(n = 52)
Double lumen
42
79
Single lumen
11
21
TVAD--tunneled venous access device
N = 53
N = 53
Note. All correlations significant at 0.0001
Note. Because of rounding, percentages may not total 100.
HINDS VOL 29, NO 3, 2002
E31
Table 6. Correlations Between Results of Tests of
Table 8. Differences in Results of Coagulation Tests
Fibrinogen Levels: Venipuncture Versus Tunneled
Between Samples Drawn by Venipuncture and Each of
Three Samples Sequentially Drawn Through a Tunneled
Venous Access Device
Venous Access Device
TVAD
TVAD
Veni-
TVAD
Sample 2
Sample 3
puncture
Sample 1
Venipuncture
N
F
p
Venipuncture
1.000
0.96
0.98
0.98
and sample 1
41
17.60
0.0001
(n = 48)
(n = 47)
(n = 47)
and sample 2
44
14.10
0.0001
and sample 3
45
6.81
0.0008
Sample 1
1.000
0.97
0.96
(n = 47)
(n = 47)
N = 53
Sample 2
1.000
0.98
(n = 46)
of PT, aPTT, and FBG tests performed on blood obtained from
TVAD--tunneled venous access device
pediatric patients through heparinized TVADs that have the
N = 53
same or similar dead space, are maintained by similar flushing
Note. All correlations significant at 0.0001
techniques, and where sampling includes the same discard vol-
ume are unreliable for clinical use. Although the discard vol-
ume used in this study was 612 times the dead space, a volume
a second test would have been ordered or a change in care would
equal to or greater than those reported in earlier studies using
have been made for those two patients. One of the discrepancies
venous catheters (Palermo et al., 1980; Pinto, 1994), these vol-
was between the venipuncture values and the values for TVAD
umes still did not prevent statistically and clinically significant
sample 2; the other was between the venipuncture values and the
differences in the results of PT and aPTT tests performed on
values for TVAD sample 3. The clinical experts agreed as to the
blood drawn by venipuncture and through TVADs. Thus, these
similarity among the 48 sets of FBG values and concluded that
study findings indicate that venipuncture is the recommended
no change in care was indicated by those values. Two or more
method of obtaining blood samples for coagulation studies in
of the clinical experts found that 19 of 53 sets of aPTT values
this patient population under these or similar conditions.
were different enough that a second test or a change in care
This conclusion is the same as that reported by four previ-
would have been indicated (see Table 10). Twelve of these dis-
ous studies but different from those reported by Palermo et al.
crepancies were found between the venipuncture values and the
(1980) and Ellis (1993), who concluded that, in a slight ma-
values for TVAD sample 2, and seven were found between the
jority of patients and with certain manipulations, satisfactory
venipuncture values and the values for TVAD sample 3.
coagulation test results could be achieved when blood was
drawn through TVADs or central venous lines. In both of
Discussion
those studies, protamine sulfate was added to the TVAD
samples to neutralize the heparin. Ellis concluded that even
The stimuli for this study were the patients' and family mem-
with that adjustment, venipuncture still was the preferred ap-
bers' objections to the potentially painful procedure of veni-
proach for about 52% of pediatric patients with cancer. He
puncture to obtain coagulation samples and the reluctance of
warned that false-positive test results limited the use of prota-
nurses to attempt venipunctures for ordered coagulation stud-
mine sulfate. Given these qualifying comments, his recom-
ies because of patient and parent protestations. The motivation
mendation to use TVADs for coagulation indicators in routine
of the study team was to demonstrate the need for venipuncture
clinical practice situations might be premature.
to obtain accurate coagulation values or to demonstrate the sci-
Although caution is merited in using TVADs to draw blood
entific basis for not needing to rely only on values obtained by
for coagulation studies, certain trends should be considered in
venipuncture. The findings of this study indicate that the results
the relationship between the results of tests on blood drawn by
venipuncture and through TVADs. The results of PT and aPTT
Table 7. Correlations Between Results of Tests of
tests on sequentially drawn TVAD samples became more simi-
Activated Partial Thromboplastin Time: Venipuncture
lar descriptively to those of such tests on blood drawn by veni-
Versus Tunneled Venous Access Device
puncture. That is, in the current study, the results of tests per-
formed on TVAD sample 3 were more similar to the results of
Veni-
TVAD
TVAD
TVAD
tests on blood drawn by venipuncture than were the results of
puncture
Sample 1
Sample 2
Sample 3
such tests performed on samples 1 and 2. The results of coagu-
lation tests performed on each subsequent TVAD sample tended
Venipuncture
1.000
0.17
0.54
0.50
to become more similar to the results of tests performed on veni-
p = 0.26
p = 0.0001
p = 0.0002
(n = 45)
(n = 48)
(n = 50)
puncture samples. Finally, the size and significance of the dif-
ference between the venipuncture values and the TVAD values
Sample 1
1.000
0.73
0.38
decreased with each subsequent sample. These trends suggested
p = 0.0001
p = 0.01
that as discard volumes increase, the results of coagulation tests
(n = 44)
(n = 44)
on samples drawn through TVADs are more likely to be simi-
Sample 2
1.000
0.77
lar to the results of such tests on samples drawn by venipuncture.
(n = 47)
The four clinicians' assessments of clinical significance did
not concur with the statistical conclusions about FBG values but
TVAD--tunneled venous access device
did concur with the statistical conclusions about aPTT values.
N = 53
ONF VOL 29, NO 3, 2002
E32
Table 9. Differences in Results of Coagulation Tests
Limitations
Performed on Samples Drawn by Venipuncture and
This study had stricter eligibility criteria, a more explicit
Three Samples Sequentially Drawn Through a Tunneled
data collection procedure, and a larger sample size than pre-
Venous Access Device
viously reported studies; nevertheless, certain limitations were
apparent. The majority of participating patients did not have
Coagulation Indicator
n
F
p
infusions at the time of data collection; thus, the influence of
continuous infusions on accuracy of coagulation indicators
Prothrombin time
cannot be determined. The variables of TVAD flush (e.g.,
Venipuncture--
TVAD sample 1
41
20.03
0.0001
heparin concentration, amount of flush, number of times the
TVAD had been flushed in the previous 24 hours) were not
Venipuncture--
studied. The potential usefulness of protamine sulfate also was
TVAD sample 2
44
16.14
0.0002
not considered.
Venipuncture--
Future studies certainly could be designed to include a larger
TVAD sample 3
45
6.98
0.0114
discard volume. However, as the discard volume increases, the
need to reinfuse the discarded blood will become more likely in
Fibrinogen
pediatric participants. Reinfusion adds a step to the blood-col-
Venipuncture--
TVAD sample 1
41
24.32
0.0001
lection process and might increase the likelihood of error or
contamination. Alternatively, adding protamine sulfate or an-
Venipuncture--
other product to neutralize the heparin could be considered.
TVAD sample 2
44
15.25
0.0003
However, because these agents increase the possibility of false-
Venipuncture--
positive readings and inconsistent laboratory findings, they are
TVAD sample 3
45
8.97
0.0045
unlikely to be clinically useful in the near future. In rare clini-
cal situations, a venipuncture might not be preferable and coagu-
Activated partial
lation samples might need to be drawn from a TVAD. If veni-
thromboplastin time
Venipuncture--
puncture were mandated by institutional policy, a medical order
TVAD sample 1
41
25.81
0.0001
would be needed to legitimatize drawing the samples from a
TVAD. The nurse also would need to document the source of
Venipuncture--
the sample (TVAD) and the reasons for the policy exception.
TVAD sample 2
44
30.42
0.0001
The nurse should explain this change in care as an exception to
Venipuncture--
the patient, family members, and staff. Given all of these con-
TVAD sample 3
45
10.32
0.0025
siderations, the authors recommend that venipuncture continue
to be used for collecting blood for coagulation studies and that
TVAD--tunneled venous access device
nurses and other healthcare providers alert patients and parents
N = 53
to the scientific basis for this practice recommendation when
they are considering venous access device placement. In addi-
With regard to the FBG values, the ratings of the four clinicians
tion, future research about the accuracy of coagulation indica-
indicated that they found the venipuncture values similar enough
tors drawn from TVADs should include study of the heparin
to all three of the TVAD values that they would not have recom-
flush (e.g., volume, timing, frequency) and the influence of con-
mended a change in care or ordered a second test. This differ-
tinuous infusions (e.g., type, duration).
ence between statistical and clinical significance estimates is
difficult to explain but might be a result of the relatively large
The authors acknowledge the contributions to this work of Kattie Pring,
range of FBG values that are considered to be within clinically
MSN; Belinda Mandrell, MSN, PNP; Bassem Razzouk, MD; Gregory Hale,
normal limits. With regard to aPTT values, the ratings of the
MD; and Linda Watts-Parker.
four clinicians indicated that more than a third of the TVAD
values were beyond the normal clinical range, an outcome that
Author Contact: Pamela S. Hinds, PhD, can be reached at
probably would have prompted change in care or a retest. These
p a m . h i n d s @ s t j u d e . o r g , with copy to editor at rose_mary@
clinical estimates support the findings of the statistical analysis.
earthlink.net.
Table 10. Descriptive Summary of the Clinical Experts' Ratings of Discrepant Results of Coagulation Tests Performed
on Samples Drawn by Venipuncture and Through a Tunneled Venous Access Device
# of Agreements Recommending Practice Change
# of Patient Sets of
# of Agreements Recommending
n (%)
Values Compared
No Practice Changes
N
n (%)
4 Raters
3 Raters
2 Raters
PT
53
51 (96)
1 (2)
1 (2)
0
FBG
48
48 (100)
aPPT
53
34 (64)
10 (19)
3 (6)
6 (11)
aPTT--activated partial thromboplastin time; FBG--fibrinogen; PT--prothrombin time
N = 53
HINDS VOL 29, NO 3, 2002
E33
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