1. Pathogen Reduced Platelets: The Next Big Thing in Transfusion Safety
Elizabeth S. Allen, MD

2. Outline Platelets Problems with Platelets Pathogen Reduced Platelets
UCSD Implementation Strategy

3. Objectives Understand the risks of conventional platelet transfusion
Describe the mechanism and effects of pathogen reduction technology
Identify the pathogen reduced components available for transfusion and discuss key elements of a policy for the use of pathogen reduced components
Describe the steps necessary for implementation of pathogen reduced products in the Transfusion Service

4. Platelets Collection Storage environment & duration
Minimum number of platelets in one unit
Antigens on the platelet surface

5. Platelet Transfusion Prophylaxis to prevent bleeding
In stable patients with platelet count <10K
In patients undergoing procedures with platelet counts K
Central line placement: 20K
Surgery: 50K
Neurosurgery: 100K
Treatment for active bleeding
In thrombocytopenic patients
During massive transfusion

6. The Problems with Platelets
Bacterial contamination  septic transfusion reactions
Existing & emerging infectious diseases that affect the safety of the blood supply

7. FDA, Transfusion/Donation Fatalities 2015

8. FDA, Transfusion/Donation Fatalities 2015

9. Current Process Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Collection
Draw sample for culture
Day 2
Release culture-negative products into inventory
Day 3
Available for transfusion
Day 4
Day 5
Discard at end of day

10. Existing Pathogens Do we test donated blood for malaria?
Do we test for babesia?

11. Emerging Pathogens 1982: HIV 1985: Testing for HIV 1989: HCV 1992:
Testing for HCV
2002:
West Nile Virus
2003: Testing for WNV
2015:
Zika Virus
2016:
Testing for Zika Virus
1981: CDC confirms new disease HIV
1982: HIV confirmed to be transfusion-transmitted
1999: first outbreak of WNV in the US
2002: first confirmed transfusion transmission of WNV in the US
Pattern: we are chasing the pathogens with a reactive approach. Why not take a proactive approach?

12. Enter pathogen reduction…
An FDA approved process in which platelet products are treated to inactivate pathogens and any white blood cells present.

13. Pathogen reduction
At the blood collection center, a compound called amotosalen is added to the platelets
The product is exposed to UVA light. This causes the amotosalen to intercalate in the DNA or RNA
The DNA and RNA cannot replicate
Any bacteria or viruses are permanently inactivated and cannot multiply
Any white cells are permanently inactivated and cannot multiply

14. The operating principle for the INTERCEPT Blood System for platelets is illustrated below (Figure 1). Platelets collected by apheresis in a container are sterile connected to the Platelet DS Processing Set [INT2510]. The platelets flow through the amotosalen container into the illumination container. The illumination container is placed into the INT100 illumination device for UVA treatment while being mixed with horizontal agitation. Inactivation of potential pathogen or leukocyte contaminants in platelet components is achieved through a photochemical treatment process. Amotosalen (S-59, psoralen derivative), a chemical capable of binding to nucleic acids is added to platelets. UVA illumination (320 – 400 nm wavelengths) of amotosalen-treated platelet components induces covalent cross-linking of any nucleic acids to which amotosalen is bound; thereby, preventing further replication.1 Treated platelets are then transferred to the CAD container to reduce the levels of residual amotosalen and free photoproducts. Finally, the platelet components are transferred through the in-line March 15, SPC AW, V3.1
filter to the storage container for use or storage at 20-24°C with continuous agitation for up to 5 days from the time of collection.

15. Pathogen reduction Amotosalen Some pathogens are not inactivated
Positives
Negatives
Decreased risk of transfusion reactions from bacterial contamination
Decreased risk of transmitting viruses—those we know about, and those we don’t yet know about
Inactivation of lymphocytes, just like irradiation. These products are considered equivalent to irradiated.
Inactivation of any potential CMV virus. These products are equivalent to CMV seronegative products.
Amotosalen
Toxicity?
Allergy?
Some pathogens are not inactivated
Smaller transfusion increments, more frequent transfusions
Increased cost

16. Not inactivated
Certain non-enveloped viruses (Hepatitis A, Hepatitis E, poliovirus)
Bacillus cereus spores

17. Effectiveness

18. Debilitating blood loss
†,‡ Non-inferiority method. PCT not inferior to control
WHO bleeding scale
No bleeding 1
Petechiae 2
Mild blood loss 3
Gross blood loss 4
Debilitating blood loss

19. PCT = Photochemically treated

20. Pathogen Reduction
What is your overall assessment of pathogen-reduced platelets?
Do you think they are worth implementing?
Do you need any other information to make your decision?

21. UCSD Approach
Gained approval and funding from medical executive committee and hospital administration
Gained support from key stakeholders, such as hematology/oncology and NICU physicians
communication to all physicians and staff before initiation
Training
Live training for nurses in the outpatient cancer center and inpatient BMT ward
Electronic training document provided to other nurses.

23. Laboratory Management
Updated 5 SOPs
Platelet Transfusion
Neonate and Infant Transfusion
Receipt and Inspection of Blood Components
Adding Special Messages
Irradiation Policy  Prevention of Transfusion-Associated GVHD

24. Informatics Updated product codes
Created 2 new product attributes, “IRRPR” and “CMVPR”
Created 2 new patient requirements, “IRRPR” and “CMVPR”
All patients with the requirement for “IRR” products were manually updated to “IRRPR”

25. Patient GP

26. Phased Implementation
Remaining areas of UCSD Health
Inpatient BMT ward
Outpatient Cancer Center (Infusion Center)

27. Blood, 2016; 127, 4

28. Outpatient cancer center Inpatient BMT ward Entire health system
Phase 1
Days 1-45
Requested 5 PRP daily
(3 daily on weekends)
Inpatient BMT ward
Phase 2
Days 46-59
Requested 15 PRP daily
(8 daily on weekends)
Entire health system
Phase 3
Day 60 and on
Requested 20 PRP daily

29. Platelets issued throughout the health system

30. PRP requested & received from the blood center

31. PRP issued to areas not yet phased-in

32. Outcomes No complaints received Challenges
Avoiding wastage: when selecting products, should technologists select the product about to expire, or a PR product?
Not yet reached 100% PR products

33. Phased implementation is a practical and ethical way to introduce pathogen reduced platelets

34. Thank You
UCSD Transfusion Medicine Pat Kopko Pat Whitacre Lily Mejia Aaron Harding Amie Erese Eileen Licuanan
Cerus Corporation Medical Science Liaison Kent Carter Hospital Implementation Expert Buddy Nguyen

35. Questions?