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Education and Training:

B.A., Mathematics, Cum Laude, Washington State University, Pullman, Washington (1959)

M.D., George Washington University, Washington, DC (1963)

Rotating Internship, Mount Sinai Hospital, New York, New York (1963-64)

Resident in Medicine, Mount Sinai Hospital, New York, New York (1964-65)

Resident in Medicine,
Parkland Memorial Hospital, Dallas, TX (1965-67)

Senior Fellow in Medicine (Hematology/Oncology), University of Washington, Seattle, WA (1967-68)

Sherrill J. Slichter, M.D.
Professor of Medicine, Division of Hematology
University of Washington School of Medicine

Director, Platelet Transfusion Research,
Puget Sound Blood Center

Office Address:
Puget Sound Blood Center
Box 359190
921 Terry Avenue
Seattle, WA 98104-1256

Phone:   (206) 292-6541
Fax:       (206) 292-8030
E-mail:   sjslichter@psbc.org


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.