vet

1. Original Study Journal of Veterinary Emergency and Critical Care 24(4) 2014, pp 381–387
doi: 10.1111/vec.12209
The effect of hetastarch 670/0.75 administered
in vivo as a constant rate infusion on platelet
closure time in the dog
Kim A. Helmbold, DVM, MPH; Matthew S. Mellema, DVM, PhD, DACVECC; Kate Hopper, BVSc,
PhD, DACVECC and Steven E. Epstein, DVM, DACVECC
Abstract
Objective – To evaluate the effects of hetastarch 670/0.75 on canine platelet function and clinical bleeding
following its administration as a constant rate infusion (CRI) at 1 mL/kg/h and 2 mL/kg/h for 24 hours.
Design – In vivo, prospective, open-label, crossover study.
Setting – Research laboratory at a university veterinary facility.
Animals – Eight healthy, adult male research dogs.
Interventions – Each dog received 1 mL/kg/h hetastarch for 24 hours then 2 mL/kg/h with a washout period of
10 weeks between each experiment. Platelet closure time (CT) was measured using a platelet function analyzer
with collagen adenosine diphosphate (ADP) cartridges. CT measurements were performed at baseline and 6,
12, and 24 hours following initiation of hetastarch infusion.
Measurements and Main Results – At 1 mL/kg/h, mean CT was significantly increased at the 12- and 24-hour
time point relative to the baseline value, although mean CT never rose to a value above the reference interval
during the 24-hour infusion. At 2 mL/kg/h, median CT was also significantly increased at the 12- and 24-hour
time point relative to the baseline value. Administration of 2 mL/kg/h did progressively prolong the median
CT value though only exceeded the reference interval at the 24-hour time point. Despite the prolongation of
median CT, there was no clinical evidence of spontaneous bleeding in any dog during the 24-hour infusion at
either CRI rate.
Conclusions – Hetastarch 670/0.75 when used as a 24-hour CRI at 1 and 2 mL/kg/h prolongs CT in healthy
dogs at 6, 12, and 24 hours. Median CT only exceeded the reference interval at 24 hours at 2 mL/kg/h.
(J Vet Emerg Crit Care 2014; 24(4): 381–387) doi: 10.1111/vec.12209
Keywords: colloid, platelet function, coagulation, fluid therapy, hydroxyethyl starch
Introduction
The potential for bleeding consequences following hy-
droxyethyl starch (HES) solution administration has
been the focus of many investigations. Hemostatic ab-
normalities reported include decreases in plasma con-
centrations of von Willebrand factor (vWF:Ag) and
factor VIII coagulant (VIII:C), impaired fibrin polymer-
ization, and decreased platelet aggregation.1–13
Several
From the Veterinary Medical Teaching Hospital (Helmbold), and Depart-
ment of Veterinary Surgical and Radiological Sciences (Mellema, Hopper,
Epstein), School of Veterinary Medicine, University of California at Davis,
Davis, CA 95616.
The authors declare no conflict of interest.
Address correspondence and reprint requests to
Dr. Matthew Mellema, Department of Veterinary Surgical and Radiological
Sciences, School of Veterinary Medicine, University of California at Davis, 1
Garrod Dr, Davis, CA 95616, USA. Email: msmellema@ucdavis.edu
Submitted January 14, 2013; Accepted June 04, 2014.
Abbreviations
HES hydroxyethyl starch
CRI constant rate infusion
CT closure time
PFA-100 platelet function analyzer
vWF von Willebrand factor
veterinary reports of the hemostatic alterations result-
ing from hetastarch administration have used a com-
mercially available platelet function analyzer (PFA-100)
as the primary outcome measure.14,15
The PFA-100 mea-
sures the time it takes for a platelet plug to form and
occlude a conduit [ie, closure time (CT)] in vitro un-
der simulated vascular flow conditions. Closure time is
considered both a sensitive and specific tool (94%–95.7%
and 88%–100%, respectively) for identifying moderate to
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2. K. A. Helmbold et al.
severe platelet dysfunction in people16
as well as in
dogs.17
The utility of this tool for identifying more sub-
tle forms of platelet dysfunction remains uncertain. The
PFA-100, which is the only method using high shear
stress in a capillary tube to stimulate platelet activation,
aggregation, and adhesion, is felt to sufficiently model
in vivo physiologic conditions.16–18
Some aspects of the hemostatic consequences of HES
solutions have been previously studied in veterinary
medicine. Smart et al14
demonstrated in a canine model
that a single 20 mL/kg IV bolus over 1 hour of 6%
HES 670/0.75 increased CT for at least 5 hours fol-
lowing administration.14
Wierenga et al15
investigated
the in vitro effect of two HES preparations on canine
platelet function.15
This study showed that serial dilu-
tion of whole blood with HES 670/0.75 in 0.9% NaCl
solution significantly depressed platelet plug formation
to a greater degree than comparable hemodilution with
0.9% NaCl alone. Recently, a study performed by Chohan
et al19
compared the effects of administration of 6%
HES 670/0.75 versus lactated Ringer’s solution on clini-
cal bleeding and hemostatic variables during orthopedic
surgery.19
The authors concluded that hetastarch admin-
istered as a bolus of 10 mL/kg IV over 20 minutes was
not associated with increased clinical bleeding or sig-
nificant abnormalities in vWF:Ag, FVIII:C, or platelet
aggregation.
HES solutions are administered as constant rate infu-
sion (CRI) for intravascular volume maintenance20
and
long-term colloid osmotic pressure support21,22
typically
at a rate up to 1 mL/kg/h. These rates reflect recogni-
tion of recommended daily maximal doses in the 20–
30 mL/kg/d range, and are largely extrapolated from
human literature.23,24
At clinically relevant doses, 6%
HES 670/0.75 administration alters platelet function fol-
lowing bolus administration.14,19
It is unknown whether
there are important differences in the hemostatic effects
of HES solutions when they are administered as a CRI
rather than as a rapid bolus.
To the authors’ knowledge, there are no published
studies investigating the effects HES solutions have on
platelet function (nor the clinical consequences) after CRI
therapy. The objectives of this study were to (1) evalu-
ate the effect of HES 670/0.75 as a constant rate infu-
sion at 1 mL/kg/h and at 2 mL/kg/h on canine platelet
function and (2) describe any clinical evidence of sponta-
neous bleeding in healthy dogs receiving HES 670/0.75
at these rates for 24 hours. Our experimental hypothe-
sis was that a greater total daily dose of HES 670/0.75
would be required to significantly prolong CT in healthy
dogs when CRI administration is performed compared
to bolus delivery.
Materials and Methods
Eight healthy, 1–2-year-old male Hound cross research
dogs weighing between 20.2 and 27.7 kg were obtained
for this prospective study. Dogs were deemed healthy
based on physical examination and unremarkable find-
ings on blood work consisting of a CBC, coagulation
profile, and biochemistry profile. Seven of 8 dogs had
not received any medications known to alter coagula-
tion tests prior to the start of this study. One dog had
received a nonsteroidal anti-inflammatory medicationa
for the treatment of panosteitis previously, but had not
received this agent for 3 months prior to entry into the
study and was in remission during those months. All
dogs were fed a balanced commercial dog food diet and
had access to free choice water during the study. Animal
handling and procedures were approved by the Univer-
sity of California, Davis, Institutional Animal Care and
Use Committee.
Eight dogs received 1 mL/kg/h CRI infusion of HES
670/0.75 in 0.9% NaClb
for 24 hours during the first
experimental infusion period whereas seven received 2
mL/kg/h during the second. Assignment to the 1 or 2
mL/kg/h protocol was not randomized and each dog
received the lower dose during the first experimental
period and the higher dose during the second. In each of
the infusion studies, the dogs served as their own con-
trol with a washout period of 10 weeks between each
experimental infusion. This arrangement was arrived at
in consultation with the Institutional Animal Care and
Use Committee and designed to minimize potential ad-
verse events due to the infusion. Any dogs exhibiting
signs of spontaneous bleeding during the 1 mL/kg/h
protocol were to be withdrawn from the study and were
not to receive the higher infusion rate.
At the beginning and end of each experiment, each
dog was sedated with 0.1 mg/kg acepromazine maleate
IV for restraint purposes. A 16 Ga, single lumen, 5.5
inch catheterc
was placed in the jugular vein asepti-
cally prior to the start and removed at the conclusion
of each treatment. The catheter was used for both ad-
ministration of hetastarch as well as blood sampling.
Six milliliters of blood was scavenged into 0.5 mL of
heparinized saline and returned following each sample
collection. Hematocrit and total plasma protein measure-
ments were performed at 0 hour and 24 hours. Directly
following catheter placement, 4.8 mL of whole blood was
collected for analysis of the CBC, coagulation profile, and
biochemistry profile. One milliliter was placed into an
EDTA tube,d
2 mL into a sterile glass (serum) tube,e
and
1.8 mL into a tube containing 3.8% trisodium citrate.f
The
citrate-containing tube was placed on ice and all sam-
ples were run immediately by the institution’s central
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3. Hetastarch 670/0.75 constant rate infusion
clinical laboratory. Blood was drawn for the CT mea-
surement before the start of the CRI and 6, 12, and 24
hours after the start of the CRI. Blood was collected
and 1.8 mL separate aliquots were placed directly into
3.8% trisodium citrate tubes. The blood was maintained
at 18.3°C and analyzed immediately within 20 min-
utes of collection. CT was measured in duplicate by
use of a bench top platelet analyzer (PFA–100g
) with
collagen/ADP-coated cartridgesh
according to manufac-
turer instructions. The PFA-100 has been described in
detail elsewhere.25
The CT reference interval of 71–118
seconds for this specific PFA-100 machine used by our in-
stitution’s Comparative Platelet Biology Laboratory was
used.26
The accuracy of the PFA was checked daily us-
ing quality control standards prior to sample analysis.
Testing was repeated on a sample if one replicate was
immeasurable, if there was a flow obstruction, or if the
duplicate sample was outside of the PFA-calculated ac-
ceptable coefficient of variation range (10%). The PFA
machine was relocated from the Comparative Platelet
Biology lab to the area in which the dogs were housed to
allow for immediate sample analysis.
The dogs were monitored continuously by study per-
sonnel during the study period for clinical signs of
hemostatic abnormalities. Petechiae and ecchymosis on
skin and mucous membranes, epistaxis, bleeding from
catheter or venipuncture sites, and pigmenturia were
recorded if noted.
Statistical Analysis
Duplicate samples for CT were averaged for analysis
purposes. Normality testing was performed using the
Shapiro-Wilk test. All data for the 1 mL/kg/h infusion
protocol were normally distributed. However, not all of
the data at each time point from the 2 mL/kg/h infusion
protocol were normally distributed. Thus, the authors
have elected to present all data as both mean (±SD) as
well as median (interquartile range) for both datasets
for simplicity. For the 1 mL/kg/h data, one-way re-
peated measures analysis of variance was performed to
detect CT differences due to duration of the HES infusion
(equivalent to cumulative dose since the infusion rate did
not vary). For both the 1 and 2 mL/kg/h dataset, Fried-
man repeated measures analysis of variance on ranks
was performed to detect CT differences due to duration
of the hetastarch infusion (again equivalent to cumu-
lative dose). Post-hoc Tukey or Dunn’s testing was the
multiple comparison procedure used to isolate the group
or groups that differed from the others when one-way
repeated measures analysis of variance or Friedman re-
peated measures analysis of variance on ranks revealed
significant time effects were present. For simplicity and
consistency, data in both Figures 1 and 2 are uniformly
Figure 1: Median platelet closure time in seconds following het-
astarch administration at 1 mL/kg/h for 0, 6, 12, and 24 hours.
The upper and lower borders of the boxes represent interquar-
tile range while the limits of the whiskers denote the minimum
and maximum values. The horizontal line within the box rep-
resents the median value. The dashed horizontal lines indicate
the upper and lower limits of the reference interval for platelet
closure time at our institution for canine samples. (∗) denotes a
mean value found to be statistically significantly different than
the mean value at baseline and at 6 hour. (#) denotes a mean
value found to be statistically significantly different than the
mean value at baseline, 6 hour and at 12 hour. Significance was
set at P 0.05 for all comparisons.
Figure 2: Median platelet closure time (CT) in seconds following
hetastarch administration at 2 mL/kg/h for 0, 6, 12, and 24 hours.
The upper and lower borders of the boxes represent interquartile
range while the limits of the whiskers denote the minimum and
maximum values. The horizontal line within the box represents
the median value. The dashed horizontal lines indicate the upper
and lower limits of the reference interval for platelet CT at our
institution for canine samples. (∗) denotes a median value found
to be statistically significantly different than the median value
at baseline. (#) denotes a median value found to be statistically
significantly different than the median value at baseline and at
6 hours. Significance was set at P 0.05 for all comparisons.
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4. K. A. Helmbold et al.
Table 1: Effects of hetastarch 670/0.75 on platelet closure time administered as a continuous rate infusion at 1 mL/kg/h in dogs
Mean Standard Median 25% Interquartile 75% Interquartile
Hour (seconds) error (seconds) range range
0 73.125 3.466 72.000 60.5 80.5
6 70.125 2.520 68.000 63.0 75.5
12 84.750 3.146 82.500 75.5 88.0
24 107.125 3.617 106.500 96.0 116.0
Table 2: Effects of hetastarch 670/0.75 on platelet closure time administered as a continuous rate infusion at 2 mL/kg/h in dogs
Mean Standard Median 25% interquartile 75% interquartile
Hour (seconds) error (seconds) range range
0 65.000 7.118 64.000 60.8 71.5
6 68.500 6.430 67.000 64.0 73.0
12 121.929 16.161 96.000 90.0 139.0
24 173.357 20.530 132.500 107.0 246.0
presented based on medians/interquartile range (IQR)
and the nonparametric analysis methods. The findings
obtained when the 1 mL/kg/h data were analyzed via
parametric and nonparametric methods did not differ.
A P-value of 0.05 was considered significant in all in-
stances. All statistical testing was performed with com-
mercial statistical software.i
Results
Demographic data and baseline variables were similar
among dogs. All dogs had normal platelet counts [160
− 285 × 109
/L (160 – 285 × 103
/␮L); (reference interval
150–400 × 109
/L (150 − 400 × 103
/␮L)], a mildly de-
creased hematocrit [0.322–0.395 L/L (32.2–39.5%); (refer-
ence interval 0.40–0.55 L/L (40–55%)], and normal pro-
thrombin time [7.8–9.0 seconds; (reference interval 7.0–
9.3 seconds)] and fibrinogen [4.23–6.20 ␮mol/L (144–
211 mg/dL); reference interval 3.21–9.14 ␮mol/L (109–
311 mg/dL)]. Normal to slightly prolonged activated
partial thromboplastin time (aPTT) [12.3–14.8 seconds;
(reference interval 10.4–12.9 seconds)] was noted. Bio-
chemistry profiles were within normal reference inter-
vals except for mild hypoglobulinemia [11–15 g/L (1.1–
1.5 g/dL); reference interval 17–31 g/L (1.7–3.1 g/dL)] in
all dogs. Reference intervals used were those established
by our institution’s central clinical laboratory. Hemat-
ocrit at the conclusion of each study was the same for
each dog as it was at the beginning.
When administered as a CRI at 1–2 mL/kg/h HES
670/0.75 infusion significantly (P 0.05) increased
platelet CT from baseline to end infusion (24-hour time
point) at both the 1 mL/kg/h and 2 mL/kg/h rates (Ta-
bles 1 and 2 and Figures 1 and 2). For the 1 mL/kg/h
infusion rate, the mean CT value at 12 and 24 hours were
significantly increased compared to baseline. The 6-hour
time point was not significantly different from the base-
line value (Table 1 and Figure 1). Although there was
a significant increase in mean CT value after 12 hours
of administration of the 1 mL/kg/h infusion rate, mean
values did not rise above the upper limit of the normal
reference interval for the PFA-100 at any time point dur-
ing the 24-hour infusion (Figure 1). Following infusion
at the 2 mL/kg/h infusion rate, median CT values at
12 and 24 hour were significantly increased compared
to baseline. The 6-hour time point median value was not
significantly different from the baseline median value al-
though it was significantly lower than the median value
at 24 hours (Table 2 and Figure 2). Administration of 2
mL/kg/h did result in CT values above the reference
interval for 2 dogs at 12 hours and 4 dogs at 24 hours.
However, median CT for the group exceeded the refer-
ence interval only at the 24-hour time point (Figure 2).
Eight dogs completed the 1mL/kg/h study, though
only 7 completed the 2 mL/kg/h study. The IV catheter
on one of the dogs became clotted and due to our insti-
tutions animal care and use protocol we were unable to
replace it, thus forcing this dog to drop out of the sec-
ond study. Despite the increase in platelet closure time
following hetastarch administration, no clinical abnor-
malities suggestive of primary or secondary hemostatic
defects were detected following HES administration at
either CRI dose.
Discussion
To the authors’ knowledge, this is the first study to inves-
tigate the influence of HES 670/0.75 administered solely
as a CRI on platelet function. Clinical data abnormalities
seen in our study such as low globulin concentrations
can be explained as a normal finding in young dogs.
The mild prolongation of aPTT at baseline is considered
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5. Hetastarch 670/0.75 constant rate infusion
clinically insignificant by the authors. The aPTT is more
sensitive to sample collection artifact than is the pro-
thrombin time.27
Only 1 dog had a hematocrit value be-
low 0.35 L/L (35%) during the 1 mL/kg/h study period,
whereas 4 dogs had a hematocrit below 35% at the start
of the 2 mL/kg/h study. No dog was at or below a 30%
hematocrit value at the start or conclusion of either study
period. A slight decrease in hematocrit at baseline and
at 24 hours is unlikely to affect the CT results. A pre-
vious assessment of the utility of the PFA-100 in dogs
demonstrated that the CT was not increased unless the
hematocrit was 30%.28
Decreased hematocrit at base-
line and at 24 hours could be normal for these young
dogs, but more likely is secondary to the dose of ace-
promazine administered. Acepromazine causes a dose-
dependent decline in hematocrit in dogs secondary to
splenic vessel relaxation and sequestration of red blood
cells within the splenic vasculature.29
This effect occurs
within 30 minutes of administration. In our study, each of
the dogs received a 0.1 mg/kg IV dose of acepromazine
with blood collection approximately 30 to 45 minutes
postadministration. Since baseline and 24 hour hemat-
ocrits were unchanged, it is unlikely this affected our CT
results.
Our experimental hypothesis was that a greater total
daily dose of HES 670/0.75 would be required to sig-
nificantly prolong CT in healthy dogs when CRI admin-
istration is performed rather than bolus delivery. This
hypothesis was based on the pharmacokinetic and phar-
macodynamics of the solution. Support for this hypothe-
sis can be found in our principal finding that infusion of
1 mL/kg/h of HES 670/0.75 for 24 hours (24 mL/kg/d)
does not increase mean CT above the reference inter-
val in healthy dogs. The other main finding of this
study is that infusion of 2 mL/kg/h of HES 670/0.75 for
24 hours (48 mL/kg/d) does increase median CT above
the reference interval in healthy dogs. This suggests that
the total daily dose of HES 670/0.75 that may be ad-
ministered as a CRI to an otherwise healthy dog without
significantly perturbing platelet function likely lies in the
24–48 mL/kg/d range.
Reported canine reference intervals for the PFA-100
vary widely. Veterinary reports utilizing the PFA-100 in
healthy dogs (with the ADP/collagen cartridge) have
documented ranges as low as 42–90 seconds30
and as
high as 55–148 seconds.31
The reference interval we listed
in our study is what the authors use as the CT reference
interval at our institution for canine samples. Though
many veterinary reports cite either Callan and Giger17
for the reference range of 52–86 seconds or Morales et
al30
for the range of 42–90 seconds,30
these studies are
based on far fewer healthy canine samples (n = 20 and
29, respectively) than the largest study on this topic from
Mischke and Keidel (n = 136) where the reference range
in healthy dogs reported is 53–98 seconds.28
The second
largest published study of CT values from healthy canine
subjects (n = 58) also reported a much wider reference
interval (55–148 seconds) than that published by Callan
and Giger 17
or Morales et al.30
Our chosen reference in-
terval for this study lies between these extremes and is
what we use in our clinical cases. The authors felt this
was appropriate given the wide disparity among previ-
ously published reference intervals.17,28,30,31
Obviously,
the interpretation of our findings is heavily dependent
on which reference interval one prefers to apply. The
reader is advised to consider the reference interval in
use at their institution for clinical decision making when
interpreting our results.
Plasma clearance of HES depends on both the molec-
ular weight and degree of substitution. A higher molec-
ular weight range and more extensive molar substation
ratio result in slower elimination.32–34
Numerous reports
in both human and veterinary studies demonstrate that
HES 670/0.75 and 200/0.5 infused over short intervals
produce dose-dependent coagulation abnormalities.2,4,35
A 20 mL/kg IV bolus of hetastarch over 1 hour per-
formed by Smart et al14
resulted in mean CT that ex-
ceeded the reference interval. In contrast, when het-
astarch was administered as a CRI at 24 mL/kg over
24 hours in the present study, mean CT did not exceed
the reference range. In a similar fashion, there are differ-
ences within our study when hetastarch is administered
over different time periods. The mean CT is similar at
6 hours for both 1 and 2 mLkg/h CRI. Although infusion
of colloids with higher molecular weights are associated
with prolonged platelet closure times,6,14,15
a slower in-
fusion as a CRI, instead of an initial bolus may limit the
relative abundance of larger HES molecules at any given
time (due to ongoing amylase degradation of the poly-
mer), therefore requiring more time for CT to be affected.
This thought is substantiated with the CT exceeding the
reference interval after administration of 48 mL/kg over
24 hours. Future studies looking at HES as a CRI over a
longer time period are warranted.
The mechanism of HES-mediated hypocoagulability
has not been completely delineated. It has been docu-
mented in vitro that HES alters the FXIIIa mediated–
fibrin polymer crosslink interaction.5
HES has repeat-
edly been shown to decrease vWF concentrations.3,4
The
precise molecular mechanism underlying this decrease
in vWF is unknown, but has been shown to reflect a
more complex mechanism than simple dilution. Factor
VIII, which is stabilized by vWF, can be decreased as
well.4
Despite these findings, the main mechanism of
HES-induced hypocoagulability is thought to lie with
the platelets themselves. HES administration reduces
the availability of GIIb/IIIa platelet receptors, which are
necessary for platelet aggregation.1,6
In the present study,
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6. K. A. Helmbold et al.
an infusion of a colloid with a relatively high average
molecular weight was associated with prolongation of
platelet closure times, albeit with little evidence of ac-
tual increased bleeding risk even after infusion of larger
volumes.
There are several limitations to this study. The first
is the relatively small sample size, particularly in the
2 mL/kg/h study due to the drop out of one dog from
an irreconcilable catheter malfunction. A second limita-
tion was the use of healthy dogs. The majority of clinical
indications for CRI use of HES would not be in a healthy
patient, rather one that had illness that may or may not
affect platelet function. Additionally, there were occa-
sional IV sampling challenges due to catheter malfunc-
tions that may have affected platelets and prematurely
activated them causing lower than expected CT values.
The use of acepromazine may have impacted our find-
ings, though recent reports state that a dose up to 0.1
mg/kg IV does not alter platelet function as assessed by
a modified thromboelastography assay.36
HES 130/0.4 is now available in the United States for
use in veterinary patients. The proposed benefit of this
colloid solution in dogs over HES 670/0.75 as a bolus
is the reduced effects on hemostasis.37
Caution needs to
be exerted when extrapolating results from studies us-
ing HES 670/0.75 to guide usage of other HES products,
as they differ in molecular weights, molar substitution,
and C2/C6 ratio. A report from human literature com-
paring HES 130/0.4 and 670/0.75 concluded that either
colloid solution was equally efficacious at plasma vol-
ume expansion during major orthopedic surgery.38
It is
uncertain if the data from our study can be extrapolated
for the use of HES 130/0.4 as a CRI and further study of
HES 130/0.4 in this context is warranted.
The results of this study have shown that HES
670/0.75 when used as a 24 hour CRI at 1 and 2 mL/kg/h
increases CT in healthy dogs at 6, 12, and 24 hours though
median CT only exceeded the reference interval at 24
hours during the 2 mL/kg/h study. There was no clini-
cal evidence of bleeding despite the prolonged CT. In ap-
propriate clinical situations, it appears from the present
findings that HES 670/0.75 can be administered safely at
up to 2 mL/kg/h in canine patients with normal platelet
function. In patients requiring invasive surgery, patients
with diminished platelet function, or those predisposed
to bleeding at critical sites (eg lung, central nervous sys-
tem), limiting HES 670/0.75 CRI delivery to 24 mL/kg/d
is advised.
Footnotes
a
Carprofen, Pfizer Animal Health, New York, NY.
b
Hetastarch 670/0.75 in 0.9% NaCl (Hespan), Hospira Inc, Lake Forest, IL.
c
Abbocath – T, Hospira Inc.
d
Vacutainer 2 mL. K3 EDTA0.04 mL, 7.5%. Monoject, Convidien, Mansfield,
MA.
e
Serum tube, silicone coated. 3ml. Monoject, Covidien.
f
Vacutainer 1.8ml. Na Citrate 0.109M, 3.2%. BD Franklin Lakes, NJ.
g
Platelet function analyzer-100, Dade Behring Inc, Deerfield, IL.
h
Collagen/adenosine disphosphate cartridge, Dade Behring Inc.
i
Systat Software Inc, San Jose, CA.
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