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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 616-622
Lack of Clinically Significant Contact System Activation During
Platelet Concentrate Filtration by Leukocyte Removal Filters
By
Cheryl F. Scott,
Harvey Brandwein,
John Whitbread, and
Robert W. Colman
From the Temple University School of Medicine, The Sol Sherry
Thrombosis Research Center, Philadelphia, PA; and Scientific and
Laboratory Services, Pall Corp, Port Washington, NY.
 |
ABSTRACT |
When blood (plasma) contacts certain foreign surfaces, factor XII
can activate and trigger a series of reactions leading to cleavage of
kininogens with subsequent release of bradykinin. In this study, we
investigated two different widely used leukocyte removal filters, Pall
PXL8K (A) and Asahi PLS-5A (B), to test whether clinically significant
contact activation occurred during leukodepletion of platelet-rich
plasma (PRP). Kininogens were measured by particle concentration
fluorescence immunoassay (PCFIA), which can detect cleavage of high and
low molecular weight kininogens (HK and LK), the parent molecules of
bradykinin, to determine if contact activation had occurred. A slight,
nonsignificant decrease in HK and LK was observed with filter A after
the first 5 mL was filtered that returned to prefiltration levels by
the end of the filtration. Specific TotK (the combined measurement of
HK and LK heavy chains divided by plasma protein concentration) showed a small, significant decrease with filter A after the first 5 mL of
platelet concentrates was filtered that returned to prefiltration levels by the end of the filtration. There were no significant increases or decreases in the cleaved kininogen index (CKI), an index
of HK proteolytic activation or HK and LK destruction (with release of
bradykinin). These data suggest that small amounts of both HK and LK
initially adsorb to filter A and then desorb, primarily intact. These
data also indicate that no significant contact activation, as measured
by PCFIA, occurs during leukodepletion of platelet concentrates with
either filter A or B.
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INTRODUCTION |
HIGH MOLECULAR WEIGHT kininogen (HK) is
the procofactor for activation of the contact system1 as
well as one of the parent molecules for the vasodilatory peptide,
bradykinin.2 When blood contacts some negatively charged
artificial surfaces, factor XII can become activated3 and,
after a series of enzymatic reactions, HK is cleaved to release
bradykinin, a peptide that can induce hypotension.4 Because
contact activation is a surface-mediated event, the rate of contact
activation is proportional to the surface area contacted.
The cleavage of HK by factor XIIa and plasma kallikrein activates HK
from its procofactor form to the active cofactor, HKa,5 and
concomitantly releases bradykinin.6 In clinical sepsis, the
detection of cleaved HK is the most sensitive indicator of contact
system activation.7
The contact system has been reported to become activated upon exposure
of blood plasma to negatively charged artificial surfaces, with a large
surface area, such as those encountered during cardiopulmonary bypass,8 therapeutic apheresis with hollow-fiber
devices,9 and newer hemodialysis membranes where bradykinin
has also been detected.10,11 Recently, it was hypothesized
that increased contact activation and subsequent accumulation of
bradykinin might occur when platelet concentrates are filtered with
certain negatively-charged leukocyte filtration
devices12-14 and that this could explain the hypotension
that is observed with some patients after transfusion. In this study,
we compared the negatively charged Pall PXL8K leukocyte removal filter
to the positively charged Asahi PLS-5A leukocyte removal filter to
quantify any significant differences in contact activation, as assessed
by the measurement of HK, LK, and TotK during the course of a standard
platelet filtration procedure.
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MATERIALS AND METHODS |
Materials
Pall PXL8K leukocyte filters were obtained from Pall Biomedical
Products Co (East Hills, NY). Filters from the following lots were
used: lots no. 617802, 610405, and 619702 as well as set lots no.
621207 and 621407. Asahi PLS-5A leukocyte filters were obtained from
Baxter Medical Corp (Deerfield Park, IL). Filters from the following
lots were used: lots no. 442H34, A96D19090, A95L05035, and A95L21073.
Carboxylate modified latex (0.8 µm) and Seradyn modified latex (0.8 µm) were generous gifts of Seradyn, Inc (a subsidiary of Mitsubishi
Chemical Corp; Indianapolis, IN). Tween 20, leupeptin, benzamidine,
EDTA, hexadimethrine bromide, sodium azide, soybean trypsin inhibitor,
fluorescein isothiocyanate (FITC)-labeled sheep antimouse IgG (whole
molecule), and sheep antimouse IgG F(ab )2 were all purchased
from Sigma Chemical Co (St Louis, MO). Phe-Phe-Arg-chloromethyl ketone
(PPACK II) and [4-(2-aminoethyl)-benzenesulfonylfluoride, HCl]
(AEBSF) were purchased from Calbiochem (La Jolla, CA). Sheep antihuman
HK and sheep antihuman HK labeled with FITC were purchased from The
Binding Site, Ltd (San Diego, CA).
Preparation of proteinase inhibitor cocktail (PIC).
Benzamidine (100 mmol/L), 400 µg/mL hexadimethrine bromide, 2 mg/mL
soybean trypsin inhibitor (SBTI), 20 mmol/L EDTA, 263 µmol/L
leupeptin, 20 mmol/L AEBSF, and 1 mmol/L PPACK II were dissolved in the
anticoagulant, acid-citrate-dextrose (100 mmol/L trisodium citrate, 67 mmol/L citric acid, and 2% dextrose, pH 4.5), to make the
PIC.15
Software used for data analysis.
Winplate, version 1.1 (Idexx Corp, Westbrook, ME), and
Sigma Plot for Windows, versions 2.01 and 3.0 (Jandel
Corp, Chicago, IL) were used. Sigma Stat for Windows,
versions 1.0 and 2.0 (Jandel Corp), was used for the comparative
analyses (paired t-test). A P value less than .05 was
considered to be significant.
Methods
General principles for kininogen assays using particle concentration
fluorescence immunoassay (PCFIA).
PCFIA was performed, in triplicate, in 96-well assay plates fitted with
a 0.45-µm membrane. Microspheres were placed in each well followed by
diluted reference plasma (ranging from 1:50 to 1:3,200).15
The surrounding plasma from the platelet concentrates, after
centrifugation to sediment the cells, were diluted 1:100 in PCFIA
diluent (see above), and the same diluted sample was used for all 3 kininogen determinations. PCFIA diluent was used as the blank. After 20 minutes, 20 µL of tracer (composed of anti-HK labeled with FITC) was
added and the mixture was incubated for an additional 20 minutes. The
plate was then placed in a fluorescence concentration analyzer (FCA),
where it was evacuated at 20 mm Hg and then washed twice, under vacuum,
with 10 mmol/L sodium phosphate, pH 7.0, containing 0.5 mol/L NaCl and
0.02% NaN3 (wt/vol). The plate was read on the FCA and the
data were analyzed by Winplate software using an IBM compatible
486DX-100 computer, equipped with Windows 95 software (Microsoft Corp,
Redmond, WA). The curves were fitted by the Winplate software and the
values for the triplicate determinations were automatically calculated
from the standard curve. For HK, no antibody is used on the
microspheres for capture, because we demonstrated that HK, and not LK,
specifically adsorbs to the carboxylate-modified latex microsphere
surface.15 LK is specifically attached to the microspheres
via its unique light chain by a monoclonal antibody,
LKL-1,16 which is covalently bound to specially modified
microspheres.15 TotK, the sum of LK plus HK, is measured by
the capture of LK and HK heavy chains by the monoclonal antibody,
2B5,17 covalently bound to specially modified
microspheres.15 It is the capture that makes each of the
kininogen determinations specific, because unbound proteins are
completely removed during the washing phase.15 The same polyclonal detector antibody is then used to detect the kininogen that
is bound to the microspheres. The calculated kininogen values from the
Winplate software for HK, LK, and TotK were copied to Sigma Plot for
Windows, where transforms were created to calculate HK plus LK, CKI
(see below), and specific kininogen concentrations (see
below).15 The interassay coefficients of variation (CV) for
HK, LK, and TotK were 3.34%, 5.45%, and 3.47%, respectively, for a
sample containing 1 U/mL kininogen (where 1 U is defined as the amount
in 1 mL of normal, pooled plasma) and 5.23%, 6.59%, and 7.48%,
respectively, for a sample containing 0.1 U/mL. The intraassay
coefficients of variation were 4.79%, 5.49%, and 4.18% for HK, LK,
and TotK, respectively, for a sample containing 1 U/mL kininogens and
3.76%, 1.69%, and 3.23%, respectively, for a sample containing 0.7 U/mL. Both activation and destructive cleavage of kininogens are easily
detected by this assay method.15 HK, LK, and TotK in our
normal pooled plasma was assayed against highly purified HK and
LK.15
Determination of cleaved kininogen index (CKI).
To determine the CKI, the LK concentration (as measured by its light
chain) was subtracted from the concentration determined for TotK
(measured by the sum of the heavy chains of LK and HK), and this became
the denominator in the equation. The numerator in the equation was HK
that was measured by PCFIA (see above). The equation is listed
below15: CKI = HK/(TotK  LK).
The theoretical value for intact kininogen is 1.0. A significant shift
in value upward indicates activation of HK to HKa5 and
indicates contact activation,15 whereas a downward shift below 1.0 indicates a destructive cleavage of HK and/or LK.
Determination of total protein.
Protein was determined with Coomassie Plus Protein Assay Reagent
(Pierce Chemical Co, Rockford, IL). The samples were
diluted 1:100 in phosphate-buffered saline (PBS)-Tween and
the standard curve was constructed from bovine serum
albumin.15
Samples for leukocyte filtration.
Twenty batches of single-donor platelet concentrates, from 2- to
4-day-old apheresis units, were divided and used for each side by side
filtration using the Pall (filter A) or Asahi (filter B) filters. The
apheresis units were obtained using Cobe Spectra and Fenwal CS3000
machines and then stored at 22°C with agitation. A 900 µL prefiltration sample (influent) was taken before each filtration,
placed in a polypropylene tube containing 100 µL PIC (see the
Materials and Methods), and set aside for processing. Influent
leukocyte concentrations ranged from 0.5 to 1,000 white blood cells
(WBC)/µL. Influent platelet concentrations ranged from
1.1 to 1.9 × 106 platelets/µL. Typical bedside flow
rates (7 to 10 mL/min) were maintained using a roller clamp for both
filters. The WBC residuals and platelet recoveries for both filters
were consistent with their respective manufacturers' claims. A sample
was withdrawn after the first 5 mL passed through the filter (5 mL),
and another sample was withdrawn after all of the platelet concentrate
was filtered and combined (pool). All withdrawn samples (900 µL) were immediately placed into polypropylene microcentrifuge tubes containing 100 µL of PIC (see the Materials and Methods) to prevent subsequent activation of kininogen from occurring. All samples were then centrifuged at 10,000g for 15 minutes and the supernatants were harvested and centrifuged a second time under the same conditions. The
second supernatant was then frozen at 70°C until the time of
assay.
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RESULTS |
Assessment of HK After Filtration of Platelet Concentrates
An initial sample was removed before filtration (influent). A second
sample was removed after 5 mL of platelet concentrate passed through
each filter (5 mL). The remainder of the material was collected into a
bag and, after the remainder of the platelet concentrate passed through
the filter, a sample was taken (pool). Influents, 5-mL samples and
pools were all assayed for HK by PCFIA.15 The 5-mL samples
as well as the pools were compared with the influents (Table 1). There was a slight decrease in
HK after the first 5 mL was filtered on filter A that was not
statistically different from the influent by paired t-test
(Fig 1A). This decrease in HK after
filtration on filter A returned to prefiltration levels by the end of
the experiment (Table 1). There were no changes in HK during filtration
through filter B. These data suggest that a small amount of HK may
initially adsorb to filter A but desorbs by the end of the filtration.
When each platelet concentrate was normalized to its baseline level, to
correct for variation in initial HK concentration (Fig 1), the results
were very similar to the data in Table 1.
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| Fig 1.
Effect of filters A and B on HK from platelet
concentrates. HK was measured in 20 platelet concentrates, subjected to
filtration by filter A and filter B, and compared with the initial
starting material (influent). The data are expressed as the percentage of initial HK. (A) The first 5 mL of filtrate collected. (B) The final
pooled filtrate. Error bars are the ± SEM for the 5 mL and final
samples.
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We then looked at the specific HK values (ie, HK divided by the total
protein concentration) and found that they were all within the normal
limits for plasma HK.15 It is, therefore, unlikely that a
major contribution of platelet HK to the total HK found in the
platelet-rich plasma had occurred. When we related specific HK to the
influents, we observed a small (<5%) nonsignificant decrease in
specific HK with filter A after 5 mL of filtration did not occur with
filter B (Fig 2A). This value returned to
the baseline value by the end of the experiment (Fig 2B).
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| Fig 2.
Effect of filters A and B on specific HK from platelet
concentrates. Specific HK was measured in 20 platelet concentrates, subjected to filtration by filter A and filter B, and compared with the
initial starting material (influent). Total plasma protein was also
measured in each sample. The data are expressed as the percentage of
initial specific HK. (A) The first 5 mL of filtrate collected. (B) The
final pooled filtrate. Error bars are the ± SEM for the 5 mL and
final samples.
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Assessment of LK After Filtration of Platelet Concentrates
LK concentration in the samples was measured by PCFIA15
(Table 2). There was a slight,
nonsignificant decrease by paired t-test in LK concentrations
with both filters A and B after the first 5 mL of the filtration
process that returned to baseline by the end of the filtration process
(Table 2). Specific LK values did not change significantly from the
influent, although there was a slight decrease using filter A
(Fig 3A). In contrast, there was a slight,
nonsignificant increase in specific LK at the end of filtration using
filter B (Fig 3B).
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| Fig 3.
Effect of filters A and B on specific LK from platelet
concentrates. Specific LK was measured in 20 platelet concentrates, subjected to filtration by filter A and filter B, and compared with the
initial starting material (influent). Total plasma protein was also
measured in each sample. The data are expressed as the percentage of
initial specific LK. (A) The first 5 mL of filtrate collected. (B) The
final pooled filtrate. Error bars are the ± SEM.
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Assessment of TotK After Filtration of Platelet Concentrates
There were no significant differences in absolute TotK concentrations
after filtration on filter A or B (data not shown). However, specific
TotK measurements showed a slight, significant decrease (P < .05) after the first 5 mL of platelet concentrates was filtered with
filter A that was not observed with filter B (Fig 4A). By the end of the filtration
process, specific TotK returned to the prefiltration level (Fig 4B).
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| Fig 4.
Effect of filters A and B on specific TotK from platelet
concentrates. Specific TotK was measured in 20 platelet concentrates, subjected to filtration by filter A and filter B, and compared with the
initial starting material (influent). Total plasma protein was also
measured in each sample. The data are expressed as the percentage of
initial specific TotK. (A) The first 5 mL of filtrate collected. (B)
The final pooled filtrate. Error bars are the ± SEM.
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Effect of Filtration of Platelet Concentrates on the CKI
The combined heavy chains of HK and LK were measured so that we could
calculate the CKI.15 A CKI equal to 1.0 indicates that HK
and LK are totally intact.15 The CKI for each influent, 5-mL aliquot sample, and postfiltration sample was determined. We
compared 5 mL aliquot values and the postfiltration samples to their
respective influents and found no significant differences by paired
t-test with either the 5-mL samples
(Fig 5A) or postfiltration samples (Fig 5B)
when either filter A or filter B was used. There was a slight,
nonsignificant increase in the CKI at the end of filtration by filter
A. These data suggest that neither HK nor LK was significantly cleaved
as a result of passage of platelet concentrates through either filter A
or B.
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| Fig 5.
Effect of filters A and B on CKI after filtration of
platelet concentrates. The CKI was calculated after 20 platelet
concentrates were subjected to filtration by filters A and filter B. They were compared with the CKI of each initial sample (influent). (A)
The first 5 mL of filtrate collected. (B) The final pooled filtrate. Error bars are the ± SEM.
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DISCUSSION |
The kallikrein-kinin system not only contributes the vasodilatory
peptide, bradykinin, but also generates factor XIIa that cleaves the
first component of the classical complement pathway,18 resulting in its activation. Thus, it is clinically relevant to know if
the kallikrein-kinin system becomes activated as a result of platelet
concentrate filtration, as was recently reported.12-14,19 Because HK is the contact system cofactor1 as well as the
substrate for cleavage by both plasma kallikrein and factor XIIa, a
small change in the concentration of HK can signify a substantial
amount of contact system activation in addition to bradykinin release. Although it is true that there is a sensitive, direct enzyme
immunoassay for bradykinin,20 it should be noted that
bradykinin can be released and/or degraded in plasma simply due
to handling and processing of the sample, particularly if appropriate
proteinase inhibitors are not included. This manipulation can result in
either spurious increases or decreases of the actual amount of
bradykinin measured in the sample. In our study, we used a combination
of kininogen determinations that can distinguish between intact and cleaved kininogens using samples that were immediately placed into
proteinase inhibitor cocktail to prevent additional cleavage from
occurring during the processing.15 We observed a slight, nonsignificant decrease in HK after the first 5 mL of platelet concentrates were filtered using filter A. The decrease in HK was not
the result of activation because activation results in an apparent
increase in HK concentration when measured by PCFIA and
clotting.15 Therefore, it appears that some HK was
initially adsorbed to the filter and later desorbed because, by the end of the filtration process, the HK level was similar to baseline values
(Table 1). In contrast to HK, LK appeared to initially adsorb to both
filters A and B (Table 2) after the first 5 mL was filtered. When the
HK data were expressed as the percentage of the influent (Fig 1), a
process that corrects for the initial variation of HK concentration in
the platelet concentrates, the picture looked very similar to the data
in Table 1.
The measurements of specific kininogens (ie, kininogen concentrations
divided by total plasma protein concentrations in each sample) have
proven to be the best assessment of the behavior of kininogens in
systemic inflammatory response syndrome (SIRS) and
polytrauma.21,22 In this study, calculation of specific kininogens allowed us to see subtle changes in kininogens that would
have otherwise been missed. Whereas the decrease in HK and LK, after
the first 5 mL of platelet concentrates was filtered, was not
significant, the addition of the two kininogens, as assessed by the
heavy chain assay (specific TotK), showed a slight, significant decrease with filter A (Fig 3). This decrease in high and low molecular
weight kininogens returned to the baseline value by the end of the
filtration. The CKI, a sensitive measurement of HK
activation,15 was not significantly changed by filtration with either filter A or B, indicating that substantial cleavage of
kininogens had not resulted (Fig 5). Because HK and/or LK must be cleaved to release bradykinin, we conclude that significant levels
of bradykinin are not generated during filtration by either filter A or
filter B. In addition, because the less than 4% decrease in specific
HK and specific LK observed with filter A after 5 mL of platelet
concentrates was filtered (Figs 2A and 3A) was not accompanied by a
significant change in the CKI (Fig 5A), these data suggest that the HK
and LK that initially adheres to filter A subsequently desorbs,
primarily intact, after additional platelet concentrate passes through
the filter. From these results we conclude that the kallikrein-kinin
system is not substantially activated by either filter A or filter B.
It was recently suggested by Takahashi et al14,19 that,
because filter A's surface has a net negative charge, it would increase the amount bradykinin generated via contact activation and,
perhaps, cause the hypotensive reactions that are observed when some
patients are transfused. However, in the samples examined in their
previous study, the highest concentration of bradykinin released, at
the half-way point of filtration, was 8,000 pg/mL,19 which
amounts to only 0.1% of the total bradykinin in the sample that can be
released via contact activation of HK. In our study, we observed no
significant change in the CKI (Fig 5), which is sensitive to more than
5% of the total cleavage of HK and LK.15 Considering the
amount of plasma typically in platelet concentrates (150 to 300 mL),
there would be less than 6 to 12 µg bradykinin generated (40 to 80 ng/mL) if 5% of the bradykinin were released from the HK. Typically,
platelet concentrates are infused at a rate of 7 to 10 mL/min. However,
the clearance rate of bradykinin from the circulation is very rapid.
Approximately 95% of the bradykinin is removed by a single passage
through the lungs.23 If 6 to 12 µg bradykinin was infused
as a bolus into a patient, it might cause hypotension in patients
receiving ACE inhibitors. According to Bönner et
al,24 approximately 3.5 µg bradykinin (50 ng/kg) was
required to decrease the mean arterial pressure by 15 mm Hg in humans
receiving ACE inhibitors, whereas that same concentration had no effect
on mean arterial pressure in humans not receiving ACE inhibitors.
However, the chances of such a high concentration of bradykinin being
infused into a patient during a platelet concentrate transfusion are
unlikely, because the concentrates are usually administered over a
30-minute period. Takahashi et al19 found a maximum of 200 pg/mL bradykinin at the end of the filtration process using filter A
that translates to 60 ng bradykinin in 300 mL of platelet concentrate.
Because of the limitation of our assay, we could have missed the low
levels of bradykinin that were reported in Takahashi et
al.19 However, the concentration of bradykinin reported by
Takahashi et al19 was more than 50-fold less
than the concentration needed to produce clinical hypotension in
patients receiving ACE inhibitors.24 Shiba et
al25 described a case of a patient with low ACE activity
who received platelet concentrates filtered with filter A. Even though
there was a small increase in bradykinin from 20 to 80 pg/mL, the
patient did not become hypotensive or exhibit other adverse
reactions.25 Shiba et al25 also state that they
cannot conclude that the increased bradykinin levels are a major cause
of hypotensive reactions, because severe, adverse reactions were also
reported during platelet concentrate transfusions using non-negatively
charged filters similar to filter B. In agreement with Shiba et
al,25 we did not find significant changes in HK levels with
either filter. However, Shiba et al25 also observed a
decrease in prekallikrein and concluded that to be an indication of
contact activation. Because the assay they used does not distinguish
between prekallikrein and kallikrein, it is more likely that the
decreased levels of prekallikrein they observed resulted from
adsorption of the prekallikrein to the filter, rather than
activation.25 If prekallikrein were actually activated to
the extent reported in Shiba et al,25 they would have
observed a great deal more bradykinin than what was reported. Because
kallikrein is the enzyme in the reaction that releases bradykinin from
HK, a few molecules of kallikrein would have been able to cleave many
molecules of HK. Also, it is not surprising that filter A did not
induce a great deal of contact activation, because the rate of contact
activation is dependent on the surface area that the plasma contacts.
The surface area of filter A is only 30.68 cm2, which is
small when compared with the surface area of a membrane oxygenator (450 cm2) used in cardiopulmonary bypass.
Dextran sulfate has a strong negative charge and is a potent activator
of the contact system.26 Infusion of dextran sulfate into
rabbits produces acute hypotension.27 However, Wiggins et
al27 demonstrated that the hypotension was not the result of contact activation and release of bradykinin (which did occur), but
rather the hypotension was mediated by serotonin released from the
platelets. Upon storage, platelets have been shown to release serotonin
from their dense granules.28 In a recent report, Masayuki
et al29 demonstrated increased bradykinin formation in red
blood cell concentrates upon prolonged storage. After filtration of the
red blood cell concentrates through negatively charged filters, they
observed additional bradykinin.29 However, Masayuki et
al29 point out that hypotensive reactions are rare in
patients receiving red blood cell transfusions and conclude that
bradykinin is not likely to be the main cause of hypotensive reactions.
These data, in conjunction with the reports of Bönner et
al24 and Takahashi et al,19 suggest that
bradykinin, even if present in platelet concentrates, is not
responsible for the hypotension that is associated with transfusion
reactions. To date, there has been no direct correlation of the use of
filter A and/or bradykinin concentrations with severe
hypotension in patients experiencing transfusion reactions.
Transfusion reactions continue to be a moderate to serious complication
for many patients receiving blood products, with the majority of these
reactions occurring when platelet products are transfused.30 These reactions may include hypotension,
fever, rigors, and, more seriously, anaphylaxis.31
Filtration of platelet concentrates to remove leukocytes is practiced
in many institutions to prevent transmission of cytomegalovirus
(CMV),32 to remove HLA
alloantigens,33 and to minimize
immunosuppression.34 Muylle et al35 observed a
correlation with febrile transfusion reactions and the concentrations
of interleukin-6 (IL-6) and tumor necrosis factor  (TNF) in the
platelet concentrates. Stack and Snyder36 found that (day
1) leukofiltration of platelet concentrates drastically decreases the
generation of IL-8 that normally accumulates during storage of platelet
products, ostensibly due to the removal of cytokine-producing
leukocytes. These reports suggest that patients transfused with
platelets that are not leukodepleted before storage may receive
substantial concentrations of IL-8 and other biological response
modifiers (ie, TNF and some fragments of complement) that can lead
to febrile, nonhemolytic reactions.30 It is possible that
these cytokines are also a major cause of severe hypotensive reactions
during transfusion of platelet concentrates. In addition to the
aforementioned mediators, histamine is another biological mediator of
hypotension that is known to accumulate upon storage of platelet
concentrates.37,38 In a blood bank environment, platelet
concentrates are stored from 1 to 4 days before they are filtered and
administered to patients. This practice of not leukodepleting platelets
before storage allows mediators to be released from the leukocytes and
most of these harmful mediators are not removed by leukocyte filters
when used immediately before transfusion. In contrast, immediate
filtration before storage dramatically decreases the concentration of
cytokines in platelet concentrates that are released by
monocytes.36 Even with this knowledge, the immediate
filtration of platelets before storage is not a common practice. It is
interesting to note that a benefit of using the negatively charged
leukocyte removal filter is a reduction of harmful anaphylotoxins after
platelet concentrates are filtered with filter A, as was reported by
Shimizu et al.39 Careful clinical studies must be performed
to correlate the incidence of transfusion reactions with various
biological mediators such as cytokines, complement components,
histamine, and serotonin in addition to bradykinin. Only then will
questions be appropriately answered and solutions found for the ongoing
problem of transfusion reactions.
| |
FOOTNOTES |
Submitted October 15, 1996;
accepted March 3, 1998.
Support for this research was provided by National Institutes of Health
Program Project No. HL 56914.
Address reprint requests to Robert W. Colman, MD, Temple University
School of Medicine, The Sol Sherry Thrombosis Research Center, 3400 N
Broad St 300A-OMS, Philadelphia, PA 19140; e-mail: colmanr{at}astro.temple.edu.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
| |
ACKNOWLEDGMENT |
The authors thank Dr Jingqiu Yao (Temple University School Of Medicine)
for her excellent technical assistance and Dr Jay Herman (Director of
Transfusion Medicine, Temple University School Of Medicine) and Dr
Walter H. Dzik (Director of Transfusion Medicine, Deaconess Hospital of
Harvard Medical School, Boston, MA) for their critique of this
manuscript.
| |
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Abstract
Introduction
Abstract