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

Outline Platelets Problems with Platelets Pathogen Reduced Platelets UCSD Implementation Strategy

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

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

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

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

FDA, Transfusion/Donation Fatalities 2015

FDA, Transfusion/Donation Fatalities 2015

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

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

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?

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

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 https://intercept-usa.com/resources

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, 2016 2 SPC 00336-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. https://intercept-usa.com/resources

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

Not inactivated Certain non-enveloped viruses (Hepatitis A, Hepatitis E, poliovirus) Bacillus cereus spores https://intercept-usa.com/resources

Effectiveness

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

PCT = Photochemically treated

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?

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 Email 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.

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

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”

Patient GP

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

Blood, 2016; 127, 4

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

Platelets issued throughout the health system

PRP requested & received from the blood center

PRP issued to areas not yet phased-in

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

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

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

Questions?