Pathogen Inactivation and Function of Platelets and Red Cells Dr. - - PowerPoint PPT Presentation

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Pathogen Inactivation and Function of Platelets and Red Cells Dr. - - PowerPoint PPT Presentation

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


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  • 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

  • f Platelets and Red Cells
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Disclosures

Pathogen Inactivation and Function of Platelets and Red Cells

Research funding received from TerumoBCT, Macopharma and New Health Sciences Member of the medical advisory committee of Fresenius Kabi Deutschland GmbH

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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?

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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

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Pathogen Inactivation of Platelets and RBC

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Laboratory Assessment of Platelet and RBC Function

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Abundant laboratory data indicate that all PI treatments damage platelets

Function of Platelets After PI

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0,1 1,0 10,0 100,0 5 10

% % mR mRNA remai ainin ing

Untreated control platelets Mirasol-treated platelets Klein-Bosgoed C et al. Transfusion, 2016;56:2286-95. Osman A et al. Platelets 2015; 26:154-63

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Numerous studies have demonstrated increased activation with Intercept treatment

Function of Platelets After PI

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Johnson L et al. Transfus Med 2013; 23:121

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Mirasol treatment related damage to platelets can be modulated by inactivation approach

Function of Platelets After PI

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20 40 60 80 d1 d2 d5 d7 CD62P (%)

WB…

20 40 60 d1 d2 d5 d7 CD62P (%)

WB BC/PC

0,0 10,0 20,0 30,0 d1 d2 d5 d7 ESC (%)

WB… BC/PC

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

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UV-C (Theraflex) also accelerates storage lesions

Function of Platelets After PI

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Tynngard N et al. Transfusion 2015; 55:1169

Untreated Gamma irradiated UV-C

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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)

Function of RBC after PI

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Intercept for RBC (S-303) causes only modest changes

Function of RBC after PI

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RBC quality is negatively affected by Mirasol treatment of WB

Assay Week 0 Week 1 Week 3 Week 6

RCC RCCPI-WB RCC RCCPI-WB RCC RCCPI-WB RCC RCCPI-WB Hemolysis (%) 0.04 ± 0.01 0.05 ± 0.01 0.06 ± 0.01 * 0.40 ± 0.01 0.12 ± 0.03 * 0.47 ± 0.06 0.27 ± 0.06 * 1.04 ± 0.09 Potassium (mM) 1.1 ± 0.2 * 1.7 ± 0.5 9.6 ± 0.2 * 27.1 ± 1.3 20.1 ± 0.9 * 35.4 ± 1.3 28.4 ± 1.4 * 36.7 ± 1.3 ATP (µmol/g Hb) 4.25 ± 0.36 * 4.14 ± 0.31 4.51 ± 0.28 * 4.15 ± 0.32 3.81 ± 0.29 * 3.23 ± 0.28 2.67 ± 0.49 * 2.00 ± 0.37 MP count ( µL-1 SN) 749 ± 220 765 ± 220 838 ± 318 2227 ± 929 1759 ± 512 * 19900 ± 4819 6957 ± 1860 * 89809 ± 39421

Function of RBC after PI

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Pool and split model: RCC prepared from untreated vs. Mirasol treated whole blood.

Schubert et al. Transfusion 2015; 55:815-23

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Clinical Assessment of Platelet and RBC Function

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Upon careful assessment, effects of PI on platelet transfusions can be seen

Clinical Assessment of PI treatment

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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).

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RBCs produced from Mirasol treated whole blood have a shortened shelf-life

Clinical Assessment of PI treatment

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Intercept treated RBCs are not exposed to UV and have near normal storage time

Clinical Assessment of PI treatment

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Are concerns over use of PI-products in trauma warranted?

Pathogen Inactivation of Blood Products

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Hess JR, et al., Transfusion, 2016; 56:1236-41

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2 0

3 0 4 0 5 0 6 0 7 0 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 M a x c l o t f o r m a t i o n m m

* * * *

(⧯) Normal WB (Hct40%) and hemodilution (Hct20%). * n= 8 replicates ±SD, (p < 0.01). ROTEM monitored.

2 4 6 8

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 R i a S T A P 1 µ g / µ L  M C F ( m m )

N S

Pathogen Inactivation of Blood Products

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Blood replacement 30% 50% 70% Blood replacement& RiaSTAP suppl.

Open symbol: WB unit Closed symbol: PI treated WB unit Arbaeen A. et al ISBT Copenhagen 2017

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Perhaps not….

Pathogen Inactivation of Blood Products

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We need to see publications of the recent clinical studies and await the results of new studies!

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Where Do We Go From Here?

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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?

Pathogen Inactivation of Blood Products

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Thank you for your attention

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