Pathogen Inactivation and Function of Platelets and Red Cells Dr. Dana Devine Professor of Pathology & Laboratory Medicine UBC Centre for Blood Research Chief Medical and Scientific Officer, Canadian Blood Services
Pathogen Inactivation and Function of Platelets and Red Cells Disclosures Research funding received from TerumoBCT, Macopharma and New Health Sciences Member of the medical advisory committee of Fresenius Kabi Deutschland GmbH
Overview • Laboratory investigations of the effect of PI on platelet and RBC function • Clinical assessment of platelet and RBC function after PI • Where do we go from here? 3
Pathogen Inactivation of Platelets and RBC PI technologies • Effective against most transfusion transmissible agents • Dose must balance killing pathogens with killing the transfusion cells • Risk mitigation must consider both infectious risks and risks to product efficacy 4
Laboratory Assessment of Platelet and RBC Function 5
Function of Platelets After PI Abundant laboratory data indicate that all PI treatments damage platelets 100,0 Untreated control platelets Mirasol-treated platelets 10,0 mRNA ing ainin % mR remai 1,0 % 0,1 0 5 10 Klein-Bosgoed C et al. Transfusion, 2016;56:2286-95 . Osman A et al. Platelets 2015; 26:154-63 6
Function of Platelets After PI Numerous studies have demonstrated increased activation with Intercept treatment Johnson L et al. Transfus Med 2013; 23:121 7
Function of Platelets After PI Mirasol treatment related damage to platelets can be modulated by inactivation approach WB… 30,0 80 WB… BC/PC 60 60 20,0 WB CD62P (%) ESC (%) BC/PC 40 CD62P (%) 40 10,0 20 20 0,0 0 d1 d2 d5 d7 d1 d2 d5 d7 0 d1 d2 d5 d7 Platelet concentrates derived from Mirasol-treated whole blood had better quality parameters than Mirasol-treated platelet concentrates on day 7 of storage. Schubert P et al . Transfusion 2015;55:815 – 823 8
Function of Platelets After PI UV-C (Theraflex) also accelerates storage lesions Untreated Gamma irradiated UV-C Tynngard N et al. Transfusion 2015; 55:1169 9
Function of RBC after PI Approaches to PI for RBC vary more than platelet methods • PI treatment protocols differ for Mirasol and Intercept and this is reflected in final product. • Due to wash step (exchange), Intercept-treated RBC have lower hemolysis and higher ATP than control RBCs. (Wiltshire M et al. Transfus Med. 2016;26:208-14) 10
Function of RBC after PI Intercept for RBC (S-303) causes only modest changes 11
Function of RBC after PI RBC quality is negatively affected by Mirasol treatment of WB Assay Week 0 Week 1 Week 3 Week 6 RCC RCC PI-WB RCC RCC PI-WB RCC RCC PI-WB RCC RCC PI-WB 0.04 ± 0.06 ± * 0.12 ± * 0.47 ± 0.27 ± * Hemolysis 0.05 ± 0.01 0.40 ± 0.01 1.04 ± 0.09 0.01 0.01 0.03 0.06 0.06 (%) * * * * 1.1 ± 20.1 ± 28.4 ± Potassium 1.7 ± 0.5 9.6 ± 0.2 27.1 ± 1.3 35.4 ± 1.3 36.7 ± 1.3 0.2 0.9 1.4 (mM) * * * * 4.25 ± 4.51 ± 3.81 ± 3.23 ± 2.67 ± ATP 4.14 ± 0.31 4.15 ± 0.32 2.00 ± 0.37 0.36 0.28 0.29 0.28 0.49 (µmol/g Hb) * * MP count 749 ± 838 ± 1759 ± 19900 ± 6957 ± 765 ± 220 2227 ± 929 89809 ± 39421 ( µL -1 SN) 220 318 512 4819 1860 Pool and split model: RCC prepared from untreated vs. Mirasol treated whole blood. Schubert et al. Transfusion 2015; 55:815-23 12
Clinical Assessment of Platelet and RBC Function
Clinical Assessment of PI treatment Upon careful assessment, effects of PI on platelet transfusions can be seen But do these differences matter? Experience with routine use in European centres would suggest that they do not. Perhaps effects are masked by transfusion practice (high dosing, scheduling). 14
Clinical Assessment of PI treatment RBCs produced from Mirasol treated whole blood have a shortened shelf-life 15
Clinical Assessment of PI treatment Intercept treated RBCs are not exposed to UV and have near normal storage time 16
Pathogen Inactivation of Blood Products Are concerns over use of PI-products in trauma warranted? Hess JR, et al., Transfusion , 2016; 56:1236-41 17
Pathogen Inactivation of Blood Products F i b r i n o g e n s u p p l e m e n t a t i o n I n v i t r o s i m u l a t i o n o f i n v i v o P I - W B t r a n s f u s i o n R i a S T A P 1 µ g / µ L 7 0 * Open symbol: 8 M a x c l o t f o r m a t i o n * WB unit * 6 0 M C F ( m m ) * 6 5 0 Closed symbol: N S m 4 PI treated WB unit m 4 0 2 3 0 2 0 0 0 30% 50% 70% Blood replacement& Blood replacement RiaSTAP suppl. ( ⧯ ) Normal WB (Hct40%) and hemodilution (Hct20%). * n= 8 replicates ±SD, (p < 0.01). ROTEM monitored. Arbaeen A. et al ISBT Copenhagen 2017 18
Pathogen Inactivation of Blood Products Perhaps not…. We need to see publications of the recent clinical studies and await the results of new studies! 19
Where Do We Go From Here?
Pathogen Inactivation of Blood Products Gaps to Fill Using Research Effort • Can we develop strategies to minimize damage to platelets and RBCs? – Different additive solutions or storage conditions? • Will the use of multiple types of PI-treated products in trauma really create a problem? • How do we determine which in vitro parameters should be used for product quality assurance? DAMPS? 21
Thank you for your attention 22
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