CURRENT CLINICAL INTERESTS
Evaluation of the effects of platelet dose on transfusion outcomes
CURRENT RESEARCH INTERESTS
·
Evaluate methods of
extending platelet storage times;
·
Assess the effects of
pathogen reduction procedures on platelet viability and function;
·
Determine approaches to
prevent platelet alloimmunization in a dog platelet transfusion model.
·
Puget Sound Blood Center is
a trial site for the Transfusion Medicine/Hemostasis Clinical Trials
Network sponsored by the Heart, Lung, and Blood Institute of the
National Institutes of Health.
Clinical
Trials:
·
Evaluate the effects of
platelet dose on hemostasis – study completed.
·
Effectiveness of
granulocyte transfusions to resolve infections in neutropenic patients
– ongoing.
·
Does the age of red cells
alter clinical outcomes in patients having complex cardiac surgical
procedures – ongoing.
·
Outcomes in patients with
ITP treated at diagnosis with high dose dexamethasone versus standard
of care – initiation in progress
·
Long-term response rates in
patients with TTP treated with Rituximab at diagnosis versus standard
of care – Initiation in progress
RESEARCH DESCRIPTION
Extended
Platelet Storage Studies:
Platelet storage is affected by the method of collection, the storage
bag, and the storage solution. We
have evaluated two different methods of harvesting platelets from
whole blood; the so-called platelet-rich plasma method which involves
a soft centrifugation of the whole blood to separate the blood into
red cells and supernatant platelet-rich plasma.
The platelet-rich plasma is then transferred to another bag
where the platelets are hard-spun concentrating the platelets at the
bottom of the bag, and then most of the supernatant plasma is
transferred to another bag for transfusion as plasma.
The platelets are re-suspended in a small amount of residual
plasma or a storage solution. The
alternate method of preparing platelet concentrates from whole blood
is called the buffy coat method. In
this method, the whole blood is hard-spun producing red cells at the
bottom of the bag, a buffy coat layer that contains the white cells
and platelets in the middle of the bag, and a supernatant plasma
layer. The red cells are
removed through ports in the bottom of the bag, plasma is taken off
the top, and the remaining buffy coats from four to six whole blood
collections are pooled, and a soft centrifugation is done to bring
down the majority of the red and white cells.
The pooled buffy coat platelets are then re-suspended in plasma
or in a storage solution. Studies
to determine how long whole blood prepared platelet concentrates can
be stored are in progress..
In
addition to preparing platelets from whole blood, apheresis procedures
can be used to harvest enough platelets from a single donor to
constitute a transfusion dose. Our
recent studies have indicated that by using a very gentle apheresis
collection procedure, storing the platelets in a specific bag, and in
a storage solution called Plasmalyte rather than residual plasma, we
have been able to extend the storage time of platelets from the
currently licensed five days to 13 days while still meeting FDA
requirements for platelet quality after storage.
Pathogen
Reduction Of Extended Stored Platelets: Because platelets are stored at room
temperature, the risk of bacterial contamination is quite high and is
one of the major reasons for limiting platelet storage time to five
days to reduce the overgrowth of any bacteria which may have entered
the system, usually because of inadequate cleansing of the
venapuncture site. In
order to allow licensing of extended stored platelets, a sensitive and
specific point of release bacterial assay has to be used, and none are
current available. Alternatively,
a method of pathogen reduction can be used.
We have focused our efforts on working with a manufacturer who
has developed a system of pathogen reduction to determine the effects
of pathogen reduction on extended stored platelets.
It is known that there is some damage induced by the pathogen
reduction process, and so it is unlikely that we will be able to
achieve 13 days of storage and still meet FDA post-storage platelet
viability measurements, but we are hopeful that we may be able to
extend platelet storage times to nine to ten days..
Prevention
of Platelet Alloimmunization In a Dog Platelet Transfusion Model: Our prior studies in a dog platelet transfusion
model identified UV-B irradiated platelets as being equivalent to
filter-leukoreduced platelets in preventing platelet alloimmunization.
Our data on UV-irradiation in the dog model was incorporated
into a very large prevention of platelet alloimmunization trial in AML
patients undergoing induction chemotherapy.
This study validated the usefulness of the dog as a
pre-clinical model in identifying methods that were not only
successful in the dog but also in patients in preventing
alloimmunization. In our
most recent studies, we have identified that combining leukocyte
reduction with pathogen reduction resulted in prevention of platelet
alloimmunization in 14 out of 15 recipient dogs who received 8 weekly
platelet transfusions that had been both filter leukoreduced and
pathogen inactivated. This
compares to a 14% incidence of preventing alloimmunization with
standard, non-modified platelets, a 66% protection rate for filtered
leukoreduced platelets, a 45% protection rate for UV-B irradiated
platelets, and a 14% reduction rate using pathogen reduction.
Therefore, it is anticipated that this combined filtration
leukoreduction/pathogen reduction system may be completely effective
in preventing platelet alloimmunization when used in thrombocytopenic
patients who are often immunosuppressed because of their disease or
its therapy.
SELECTED PUBLICATIONS
Slichter
SJ, Fish D, Abrams VK, Gaur L, Nelson K, Bolgiano D.
Evaluation of different methods of leukoreduction of donor
platelets to prevent alloimmune platelet refractoriness and induce
tolerance in a canine transfusion model.
Blood 2005;105(2):847-854.
Slichter
SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, Kickler
T, Lee E, McFarland J, McCullough J, Rodey G, Schiffer C, Woodson R.
Factors affecting post-transfusion platelet increments,
platelet refractoriness, and platelet transfusion intervals in
thrombocytopenic patients. Blood
2005;105(10):4106-4114.
Slichter
SJ, Kaufman R, Assmann SF, McCullough J, Triulzi DJ, Strauss RG,
Gernsheimer TB, Ness PM, Brecher ME, Josephson CD, Konkle BA, Woodson
RD, Ortel TL, Hillyer CD, Skerrett DL, McCrae KR, Sloan SR, Uhl L,
George JN, Aquino VM, Manno C, McFarland JG, Hess JR, Leissinger C,
Granger S. Dose of
prophylactic platelet transfusions and prevention of hemorrhage.
N. Engl J Med 2010;362(7):600-613..
Slichter
SJ, Bolgiano D, Kao K-J, Kickler TS, McFarland J, McCullough J,
Woodson R. Persistence of
lymphocytotoxic antibodies in patients in the Trial to Reduce
Alloimmunization to platelets: Implications
for using modified blood products.
Transfus. Med. Rev., accepted
for publication.
Slichter
SJ, Bolgiano D, Corson J, Jones MK, Christoffel T.
Extended storage of platelet-rich plasma prepared platelet
concentrates in plasma or Plasmalyte.
Transfusion 2010;50;2199-2209.
Marschner
S, Fast LD, Baldwin III WM, Slichter SJ, Goodrich, RP.
White blood cell inactivation with riboflavin and ultraviolet
light. Transfusion
2010;May 28 E-Pub ahead of print.
Dumont LJ, Dumont DF, Unger ZM, Siegel A,
Szczepiorkowski ZM, Corson JS, Jones MK, Christoffel T, Pellham E,
Bailey SL, Slichter SJ for the BEST Collaborative.
A randomized controlled trial comparing autologous radiolabeled
in vivo platelet recoveries and survivals of 7-day stored PRP and
buffy coat platelets from the same subjects.
Transfusion, accepted for publication.
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