Source of platelet concentrates FACHBEREICH MEDIZIN

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Vincent Clarke
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FACHBEREICH MEDIZIN Efficacy and safety of platelet concentrates from platelet apheresis donations or whole blood donations Gregor Bein Institute for Clinical Immunology and Transfusion Medicine

1 FACHBEREICH MEDIZIN Efficacy and safety of platelet concentrates from platelet apheresis donations or whole blood donations Gregor Bein Institute for Clinical Immunology and Transfusion Medicine Justus-Liebig-University Giessen Source of platelet concentrates Source of platelet concentrates (PCs) Single donor: Apheresis (A-PC) 4-6 donors (Pool-PC): USA Platelet Rich Plasma (PRP) PC Europe Buffy Coat (BC) PC 1

2 Preparing platelets from whole blood soft spin PRP RBC Pool 4-6 BCs (+ PPP) hard spin PPP BC RBC hard spin soft spin Pool 4-6 PCs (+ PPP), filter PRP-PC PPP PC PC RBC PRP, Platelet Rich Plasma RBC, Red Blood Cells PPP, Platelet Poor Plasma PC, Platelet Concentrate BC, Buffy Coat filter BC-PC Efficacy Efficacy of platelet transfusion Bleeding Time to next transfusion Surrogate outcomes Corrected platelet count increments (CCIs) Platelet recovery CCI = increment [10 9 /l] x body surface area [m 2 ] number of platelets transfused [10 11 ] normal value: > ( ) 2

Comparing different platelet concentrates Product related factors affecting

content, additive solution Storage period ABO compatibility Comparing different

The properties of apples, oranges and pears can be compared The study design must

transfusion: storage time Clinical effectiveness of leukoreduced, pooled donor

3 Comparing different platelet concentrates Product related factors affecting efficacy and safety Platelet source: A-PC, PRP-PC, BC-PC Leukocyte count Plasma content, additive solution Storage period ABO compatibility Comparing different platelet concentrates comparing apples, oranges and pears? The properties of apples, oranges and pears can be compared The study design must exclude or control confounding variables Confounding variables in platelet transfusion: storage time Clinical effectiveness of leukoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction Kerkhoffs JH et al.; Br J Haematol,

4 Comparing the efficacy and safety of apheresis and whole blood derived platelet transfusions: a systematic review 1-6 hour CCI hour CCI Heddle NM et al.; Transfusion, 2008 Summary, systematic review, 2008 A-PCs were associated with significantly higher CCIs than Pool-PCs at both 1 hour and 18 to 24 hours No significant difference between A-PCs and BC-PCs No studies addressed outcomes of time to next transfusion or bleeding Heddle NM et al.; Transfusion, 2008 Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage (PLADO-Trial) Hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy n = 1272 patients with 6031 PC transfusions 1.1x10 11 plts per m 2 BSA LD group 2.2x10 11 plts per m 2 BSA MD group 4.4x10 11 plts per m 2 BSA HD group Prophylactic platelet transfusion when morning platelet counts were /µL Primary endpoint: bleeding grade 2 or higher (WHO criteria) Slichter SJ et al.; N Engl J Med,

5 Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage (PLADO-Trial), primary and key secondary endpoints Characteristic Low Dose n = 417 Medium Dose n = 423 High Dose n = 432 Grade 2 bleeding PC transfusions Median Days until next transfusion Total # of plts transfused (x ) Median Slichter SJ et al.; N Engl J Med, 2010 Time from platelet transfusion to first grade 2 bleeding for each platelet characteristic. Secondary analysis of the PLADO trial Triulzi DJ et al.; Blood, 2012 Effects of platelet dose, source, storage duration, and ABO matching status on 4-hour corrected platelet count increment. Triulzi DJ et al.; Blood,

6 Effects of platelet dose, source, storage duration, and ABO matching status on 24-hour corrected platelet count increment. Triulzi DJ et al.; Blood, 2012 Summary, secondary analysis of the PLADO trial Dose strategy, platelet source, ABO compatibility, and duration of storage did not predict bleeding Platelet increments were higher for transfusions of A-PC compared to PRP-PC, ABO-identical platelets, and platelets stored 3 days versus 4 to 5 days. Triulzi DJ et al.; Blood, 2012 Safety 6

$(leukoreduced A-PCs and Pool-PCs do not differ for transfusion reactions, allosensitization / refractoriness, and bacterial contamination; data not shown) HIV incidence in blood donors stratified by$

7 Safety Are pool-pcs from 4 whole blood donations associated with a 4-fold risk of virus transmission? (leukoreduced A-PCs and Pool-PCs do not differ for transfusion reactions, allosensitization / refractoriness, and bacterial contamination; data not shown) HIV incidence in blood donors stratified by sex, age, and residence Offergeld R et al.; DGTI-Meeting, Graz 2012 Safety: documented virus transmissions (German haemovigilance system) Platelet product HCV HIV HBV A-PC BC-PC Hämovigilanz-Bericht des Paul-Ehrlich-Instituts 2010 ( 7

8 Summary, Pool-PC versus A-PC Efficacy A-PCs are associated with significantly higher CCIs than PRP-PCs (meta analysis, PLADO trial) Platelet source does not predict bleeding (PLADO trial) No significant difference of CCIs between A-PCs and BC- PCs (two small scale studies) Safety No difference for transfusion reactions, allosensitization / refractoriness, and bacterial contamination (data not shown) Pool-PC: calculated fold higher risk of HIV window period donation No difference for documented transmissions in Germany

Management of platelet refractory patients, why does your patient keep on bleeding? Dr Colin Brown, H&I Dept, NHSBT Colindale

$Management of platelet refractory patients, why does your patient keep on bleeding? Dr Colin Brown, H&I Dept, NHSBT Colindale$ Management of platelet refractory patients, why does your patient keep on bleeding? Dr Colin Brown, H&I Dept, NHSBT Colindale Pooled Platelets (Buffy Coat Derived) Adult dose from 4 ABO-identical donors