Presentation is loading. Please wait.

Presentation is loading. Please wait.

Current Status of Pathogen Reduction Methods James P. AuBuchon, MD President & Chief Executive Officer Puget Sound Blood Center Professor of Medicine and.

Similar presentations


Presentation on theme: "Current Status of Pathogen Reduction Methods James P. AuBuchon, MD President & Chief Executive Officer Puget Sound Blood Center Professor of Medicine and."— Presentation transcript:

1 Current Status of Pathogen Reduction Methods James P. AuBuchon, MD President & Chief Executive Officer Puget Sound Blood Center Professor of Medicine and of Laboratory Medicine University of Washington Seattle, Washington

2 SAFETY Transfusion safety is like an onion… R V O L U N T E E R D O N O T S I N T G E T R A N O O O N D E C U D I A O E T H G P N T T A C N V I A I I O N

3 Modified from: Morens DM et al. Nature 2004;430: Chikungunya virus; Dengue fever Emerging Pathogens Ocean virus

4 Photoactive compounds: Genomic disruption Psoralen derivatives (amotosalen) Riboflavin Methylene blue Chemicals: Physical disruption Solvent/detergent technology Direct radiation effect Genomic disruption UVC Chemicals: Short-term activation Genomic disruption S-303 (FRALE: Frangible Anchor Linker Extender) Currently Under Investigation or in Use Pathogen Inactivation Methods

5 Methods: Available or Approaching Plasma Quarantined plasma Solvent/detergent treatment Methylene blue + light Amotosalen + UV Riboflavin + UV UVC alone Platelets Amotosalen + UV Riboflavin + UV UVC alone Red cells/Whole blood S-303 Riboflavin + UV

6 PI Plasma: The Similarities Reduction in procoagulant activity:10-20% Effect of implementation:Clinical utility Rock G. Vox Sang 2011;100;

7 PI Plasma: The Differences SD Plasma Allergic reactions (1/50,000 units) TRALI [0 ?] NAT for non-enveloped viruses (HAV, B19) Reduction in HMW vWF + ADAMTS-13 retention Reduction in anticoagulant proteins thrombosis [?] MB Plasma Slightly greater fibrinogen + F VIII reduction

8 Cardigan R et al. Transfusion 2009;49: Evaluation MB Plasma Clots by Thromboelastometry THROMBIN GENERATION CLOT FORMATION MAXIMUM CLOT FIRMNESS Less thrombin Slower Strength OK

9 PI Plasma: The Differences SD Plasma Allergic reactions (1/50,000 units) TRALI [0 ?] NAT for non-enveloped viruses (HAV, B19) Reduction in HMW vWF + ADAMTS-13 retention Reduction in anticoagulant proteins thrombosis [?] MB Plasma Slightly greater fibrinogen + F VIII reduction France: 11 severe allergic reactions (1 death) UV ± Photosensitizer Plasma UVC alone: F XI (no clinical trials) Implementation Increased use [?] Reduced TTP response Reduced TTP response Nubret K et al. Transfusion 2011;51:125-8.

10 PI Platelets: The Similarities Some loss of platelets through process (small; manageable) UV light Identifiable platelet damage Increased metabolic rate Increased activation during storage (mt DNA transcription)

11 Using UVC to Inactivate Walker WH et al. Vox Sang 2007;93(suppl 2):69. Control Treated Platelets 9.4± ±1.3 x 10 8 /mL HSR 68±1 61±8% pH7.29± ±0.05 Aggr: Collagen 62±7 69±7% Glucose 63±9 41±8 mg/dL Lactate12.5± ±1.0 mM Illumination: 0.4J/cm 2 Testing: Day 8

12 Picker SM et al. Transfusion 2009;49: Fibrinogen receptor expression, MFI Control Intercept Mirasol Control Intercept Mirasol TRAP-6 aggregation response,, % In vitro Assessment of Functional Properties

13 Picker SM et al. Vox Sang 2009;97: Lactate, mM Storage time, days Treatment Effect: Metabolic Changes

14 PI Platelets: The Similarities Some loss of platelets through process (small; manageable) UV light Identifiable platelet damage Increased metabolic rate Increased activation during storage Reduced recovery Reduced survival 15-25%

15 Van Rhenen D et al. Blood 2000;96:819a. Treated Control Treated Control Units transfused/patient p > 0.05 Count increment (10 9 /L) : 1h post-transfusion p < h post-transfusion p = Corrected count increments: 1h post-transfusion 13, , p = h post-transfusion , p = 0.02 Clinical Trial: Amotosalen-Treated Platelets The euroSPRITE Trial

16 McCullough J et al. Blood 2001;98:450a. WHO Grade 2, 3 or 4 bleeding: No difference between groups Platelet content of treated units: 7.5% less Post-transfusion counts: 22-26% lower in treated group French/Belgian experience: No increase in usage Loss: 8% Clinical Trial: Amotosalen-Treated Platelets The SPRINT Trial Murphy S et al. Transfusion 2006;46: Comparison by dose: Equivalent effect from similar dose

17 Clinical Trial: Riboflavin-Treated Platelets The MIRACLE Trial n = 110 CCI 1h : 31% decrease (primary outcome measure) CCI 1h : 31% decrease (primary outcome measure) Transfusion 2010;50: ,000 40,000 30,000 20,000 10, ,000 CCI Mirasol Control Mirasol Control MAX75% MEAN 50% 25% MIN CCI 1h CCI 24h

18 Clinical Trial: Riboflavin-Treated Platelets The MIRACLE Trial n = 110 CCI 1h : 31% decrease (primary outcome measure) CCI 1h : 31% decrease (primary outcome measure) No differences observed Clinical bleeding assessment Clinical bleeding assessment Inter-transfusion interval Inter-transfusion interval Transfusion 2010;50: CCI 1h : 31% decrease (primary outcome measure) CCI 1h : 31% decrease (primary outcome measure)

19 Pathogen-Inactivated Platelets in Routine Use Osselaer JC et al. Transfusion 2007;47:19A. 3 yr before 3 yr after adoption of INTERCEPT platelets (Used in place of bacterial detection and gamma irradiation) BeforeAfter Patients Transfusions Transfusions/patient Platelets collected/unit6.6x x10 11 Storage period 5d 7d Outdating 9.1% 1.2%

20 PI Platelets: The Similarities Some loss of platelets through process (small; manageable) UV light Identifiable platelet damage Increased metabolic rate Increased activation during storage Reduced recovery Reduced survival Interaction with leukocytes DNA Interaction with leukocytes DNA Reduction in alloimmunization Consideration of replacement of γ-irradiation

21 Marschner S et al. Transfusion 2010;50: Prevention of Alloimmunization MECHANISM INHIBITED BY PHOTINACTIVATED PI MECHANISM NOT INHIBITED BY PHOTINACTIVATED PI

22 Prevention of Graft versus Host Disease Adducts: Amotosalen + UV1/83 base pairs Gamma irradiation1/37,000 base pairs R Dodd Vox Sang 2002;83(Suppl 1): Osselaer JC et al. Blood 2007;110:849a. Prevention of GvHD in murine model Inhibition of APC function Inhibition of cytokine production

23 PI Platelets: Concerns SPRINT Trial (FDA) Respiratory distress: 5 test vs. 0 control (n=671) Independent, blinded review of all (148) pulmonary events No association with PI platelets No association with PI platelets Corash L et al. Blood 2011;117:

24 PI Platelets: Concerns HOVON Trial Kerkoffs J-LH et al. BJH : Heme/Onc pts (n=295) Expected: 2 plt transfusions Plasma (n=99) 357 transfusion events 292 per protocol PAS III (n=94) 381 transfusion events 278 per protocol PR – PAS III (n=85) 391 transfusion events 257 per protocol Primary endpoint:CCI 1hr Secondary endpoints:CCI 24hr, bleeding, transfusion needs and intervals, reactions Early cessation: Lower CCI 1hr Increased bleeding

25 PI Platelets: Concerns HOVON Trial Heme/Onc pts (n=295) Expected: 2 plt transfusions Plasma (n=99) 357 transfusion events 292 per protocol PAS III (n=94) 381 transfusion events 278 per protocol PR – PAS III (n=85) 391 transfusion events 257 per protocol Primary endpoint:CCI 1hr Secondary endpoints:CCI 24hr, bleeding, transfusion needs and intervals, reactions SPONTANEOUSLY REPORTED; UNBLINDED TRIAL Kerkoffs J-LH et al. BJH :

26 PI Platelets: Concerns Kerkoffs J-LH et al. BJH Maximum grade of bleeding (%) PlasmaPAS IIIPR – PAS III Grade 1 12% 11% 19% Grade 2 6% 4% 7% Grade 3 1% 0 6% CLINICAL SIGNIFICANCE? APPROPRIATE TO COMBINE?

27 6-7d Storage of Amotosalen-Treated Platelets Lozano M et al. ISBT UntreatedPI Platelets Patients CCI 1hr 9,383 8,163 CI 1hr 21,600 19,400/μL CI 24hr 15,200 11,100 Interval d HSCT: 67% p < 0.05 Δ = 17% (<30%) 6d: 20% 7d: 80% p < 0.05 NSNS

28 Antimicrobial Peptides Studied Mohan KVK et al. Transfusion 2010;50: Bacterial Reduction by Antimicrobial Peptides

29 Mohan KVK et al. Transfusion 2010;50: Bacterial Reduction by Antimicrobial Peptides

30 Methods: Available or Approaching Plasma Quarantined plasma Solvent/detergent treatment Methylene blue + light Amotosalen + UV Riboflavin + UV Platelets Amotosalen + UV Riboflavin + UV UV alone Red cells S-303 Riboflavin + UV

31 S-303 Mechanism of Action Similar to amotosalen but no UV activation required t 1/2 = 25 min S NO NUCELIC ACID INTERACTIONS pH ACIDIC NEUTRAL ACTIVATION ACTIVATION

32 Effect of S-303 on RBC Recovery and Survival 35d storage Rios et al. Transfusion 2006;46: Treated Control Treated Control 24h Recovery % %p = Survival d dp > 0.05 n = 29, paired 11 full-unit reinfusions

33 Problems with RBC Pathogen Inactivation NEOANTIGEN Y ACRIDINE Y No Monocyte Mononuclear Assay activity. North A et al. Vox Sang 2007; 93(suppl 1):167-8.

34 Problems with RBC Pathogen Inactivation Modified S-303 Process: Glutathione: 2 20mM at neutral pH Y ANTI-ACRIDINE

35 S-303 Treatment and Immunogenicity Augmented Rabbit Model RBCRecovery (log scale) Time Rabbits immunized with S KLH S-303 TRMT UNTREATED RBCs mS-303TRMT Recently completed: Blinded crossover autologous reinfusion trial North A et al. Vox Sang 2007; 93(suppl 1):168.

36 Riboflavin Treatment and Immunogenicity Baboon Model RBCRecovery(%) Time (h) Quinacrine mustard trmt Goodrich RP et al. Transfusion 2009;49: Riboflavin + UV Control RBCs Unlabeled infusions: Days 0, 21, 42, Cr infusion: Day 56 Ab demonstrated No Ab demonstrated

37 Current Status of Pathogen Reduction Methods But can the system accommodate? Yes, PI works.

38 Osselaer JC et al. Transfusion 2009;49: All PatientsHematology Patients Platelet Transfusions Required Impact of Conversion to PI Platelets Before PI After PI

39 If someone says its not about the money, its about money! Intercept Platelet conversion experience - Strasbourg Cazenave JP et al. Vox Sang 2007; 93(suppl 1):51-2. Kit cost:75/apheresis unit Personnel time: 3 Costs avoided: Bacterial detection:30 Per new test:10 For France: Cost neutral with apheresis proportion 85% 55%

40 Reduction of Economic Impact APHERESIS PLATELET WHOLE BLOOD Plt DOUBLE POOL TREATED POOLED PLTS TREATED POOLED PLTS TREATED APHERESIS PLATELET APHERESIS PLATELET TREATED APHERESIS PLATELET

41 Pathogen Inactivation Technologies An opportunity to improve patient safety and simplify blood banking.

42


Download ppt "Current Status of Pathogen Reduction Methods James P. AuBuchon, MD President & Chief Executive Officer Puget Sound Blood Center Professor of Medicine and."

Similar presentations


Ads by Google