FAQ: Information for health professionals on pathogen-reduced platelets (PPPT)

Authors: Shuoyan Ning, MD, FRCPC, DRCPSC; Bryan Tordon, MD, FRCPC; Michelle Zeller, MD, FRCPC, DRCPSC; Waseem Anani, MD

NOTE: This information reflects evidence available at time of publication. This information is specific to Pooled Platelet Psoralen-Treated (PPPT) components, which are being implemented nationally one distribution site at a time. See Chapter 19 of the Clinical guide to transfusion for more information including additional resources (slide decks, narrated videos, animations).

General

1. How do component characteristics for pathogen-reduced platelets (specifically pooled platelet psoralen-treated or PPPT) compare to untreated platelets?

See Table 1 for a comparison of component characteristics (this table is excerpted from Chapter 19 of the Clinical guide to transfusion).

Table 1: Component characteristics of PPPT and untreated platelets

2. What is the technology used for pathogen-reduced platelet components, and how does it work?

Canadian Blood Services uses the INTERCEPT Pathogen Inactivation Technology by Cerus to treat platelets. This technology uses a psoralen compound (amotosalen) and UV light to cause irreversible damage to genetic material present in pathogens, rendering them inactive.

3. Will pooled platelets psoralen-treated (PPPT) completely replace untreated pooled platelets?

Once PPPT are implemented at a Canadian Blood Services site, the current untreated pooled platelet component will no longer be produced by that site.

4. Could PPPT be released to my hospital before my production site implements them?

Yes, this is possible. Canadian Blood Services manages a national platelet inventory so hospitals could receive PPPT even though their local Canadian Blood Services site has not yet implemented the manufacturing of this component.

5. Could untreated pooled platelets be released to my hospital after my production site implements PPPT?

Yes, this is possible. Canadian Blood Services manages a national platelet inventory. It is possible that hospitals may receive untreated components to meet inventory demands as PPPT production rolls out across the country.

6. Will PPPT replace untreated apheresis platelets? Will there be a change in available inventory of untreated apheresis platelets?

Untreated apheresis platelets will remain available. However, Canadian Blood Services will be implementing pathogen-reduced apheresis platelets (called apheresis platelet psoralen-treated or APPT) on June 12, 2023 in Ottawa with a national implementation to follow. Non pathogen-reduced platelets (untreated apheresis platelet in PAS-E) will be available for limited indications. For more information, see Canadian Blood Services' Circular of Information and the FAQ on APPT and untreated apheresis platelet in PAS-E.

7. Can we order both units of PPPT originating from the same parent unit?

Yes, a paired dose can be issued to a hospital, if specifically requested and if available. Standard platelet orders will be issued by the oldest expiry, unless otherwise indicated.

8. What post-implementation data collection and analysis is taking place?

Canadian Blood Services will be monitoring for changes in platelet component demand, wastage, and inventory changes.

9. What information is Health Canada monitoring regarding the use of pathogen-reduced platelets?

Health Canada is expected to evaluate the residual leukocyte content, pH, and platelet yield, as well as sterility testing at time of expiration.

10. Do hospitals need to perform isoagglutinin titrations with the PPPT since they are suspended in a combination of PAS and plasma?

While the ABO antibody concentration will decrease due to the removal of approximately 60% of the plasma and addition of Platelet Additive Solution (PAS), Canadian Blood Services cannot make any claims about ABO titres of the final PPPT components. Hospitals can make a segment from the sampling pouch line and use it to prepare a titration if desired.

11. Does the pathogen inactivation process and/or residual psoralen impact any laboratory investigations?

The psoralen added to the platelets is very effectively removed by a compound adsorption device at the end of the manufacturing process. The residual psoralen that may be left (trace amounts) and the pathogen inactivation process has no impact on laboratory investigations.  

Components and administration

12. Will hospitals need to continue irradiating untreated (pooled or apheresis) platelets provided by Canadian Blood Services?

Untreated (pooled or apheresis) platelet components need to be irradiated as per standard practices when clinically indicated. Canadian Blood Services will continue to provide irradiated untreated platelet components to hospitals.  Pathogen reduced platelet components should not undergo irradiation and are safe to use for recipients requiring irradiated blood components.

13. What happens if a pathogen-reduced platelet gets irradiated in error? Can it still be used? 

Pathogen-reduced platelets do not require irradiation, as leukocytes are inactivated by the pathogen inactivation process. However, if a pathogen-reduced platelet is irradiated in error, it may still be transfused as per manufacturer's recommendations. 

14. What will happen to HLA and HPA matched platelets?

At this time, both HLA and HPA matched platelets will continue to be manufactured without pathogen reduction. However, Canadian Blood Services will be implementing pathogen-reduced apheresis platelets (called apheresis platelet psoralen-treated or APPT) on June 12, 2023 in Ottawa with a national implementation to follow. Non pathogen-reduced platelets (untreated apheresis platelets in PAS-E) will be available for limited indications. Moving forward, the majority of HLA and HPA matched platelets will be pathogen inactivated. Untreated apheresis platelets in PAS-E that are HLA or HPA matched are available to order for limited indications. For more information, see the FAQ on APPT and untreated apheresis platelet in PAS-E.

15. Can a PPPT unit be volume-reduced?

No, PPPT unit should not be volume-reduced (centrifuged and supernatant removed) prior to transfusion. Volume reduction may cause aggregation of platelets due to an increased surface area to volume ratio.

16. Can aliquots be obtained from a PPPT unit for transfusion? What is the minimal residual volume of a PPPT unit?

Yes, aliquots can be obtained as long as a minimal residual volume of 135mL remains in the platelet bag. In other words, once there is 135mL or less remaining in the platelet bag, the platelet component can no longer be used and no further aliquots can be obtained.

17. Do untreated (apheresis or pooled) platelet components have the same concentration as PPPT?

No, untreated platelet components are less concentrated than PPPT. The final concentration of the PPPT component is approximately 1.4 times more concentrated than untreated pooled platelets. Please see Table 1.

18. Is the tail on the PPPT unit long enough to allow docking to another bag?

Yes, once the bulb is removed, the remaining tubing length is approximately 8 cm. This should be sufficient for docking another bag depending on the tube welder device used.

19. Can a patient receive both untreated (apheresis or pooled) platelets and PPPT to meet their transfusion requirements?

Yes, patients may receive both untreated platelets and PPPT to meet their transfusion requirements.

20. Can the same line be used for untreated (apheresis or pooled) platelets and PPPT?

Yes, both PPPT and untreated (apheresis or pooled) platelets can be hung in the same line, provided the tubing has not expired.

21. Is there a difference in infusion time with the various platelet components?

No, PPPT can be transfused at the same rate as untreated (apheresis or pooled) platelets. The rate should follow hospital policy.

Clinical use

22. Is premedication required before receiving a PPPT unit?

Premedication is not specifically required for transfusion of PPPT components.

23. What is the adult dose of a PPPT component compared with other platelet components?

For adults, a PPPT component will be equivalent to an untreated (pooled or apheresis) platelet component.

24. What is the neonatal and pediatric dosing for PPPT and untreated platelets?

For both PPPT and untreated platelet components the recommended doses for pediatric and neonatal platelet transfusions are provided in the Canadian Blood Services Circular of Information.

25. Can PPPT components be administered to infants undergoing phototherapy?

PPPT are not indicated for neonatal patients treated with phototherapy devices that emit a peak energy wavelength less than 425 nm or have a lower bound of the emission bandwidth less than 375 nm, due to the potential for erythema resulting from interaction between ultraviolet light and amotosalen. Phototherapy in the blue-green light with peak wavelength of 450-460 nm is the current standard of care for treatment of neonatal hyperbilirubinemia in Canada.¹

26. Can PPPT be administered to patients undergoing extracorporeal photopheresis (ECP) or PUVA light therapy?

There is a theoretical risk of white blood cell inactivation following transfusion of large platelet volumes combined with ECP or PUVA – if patient is exposed to the wavelength ranges with peak energy wavelength less than 425 nm or have a lower bound of the emission bandwidth less than 375 nm. There are no published case reports of harm.

27. Is the count increment expected to be similar following a dose of PPPT compared to untreated platelets?

The current evidence suggests that absolute count increments (ACI) and corrected count increment (CCI) are lower for PPPT components compared with untreated platelets. For 24 hour ACI, mean difference in published studies are -4.1 (95% CI -7.16 to -1.04) and -8.3 (95% CI -9.82 to -6.06) in single and multiple platelet transfusion studies, respectively. There were no differences in bleeding outcomes, and only 7% of hematology oncology patients transfused with pathogen-reduced platelets required additional platelet transfusions compared to patients transfused with untreated platelets.²

28. Will the increased number of donors in PPPT increase HLA alloimmunization?

No, the current evidence does not suggest an increased risk of HLA alloimmunization. There are conflicting data regarding alloimmunization rates due to the varying preparations of pathogen-reduced platelets and technologies deployed in clinical trials. Overall, there appears to be no change in alloimmunization rate with INTERCEPT platelets.³

References

1. Barrington KJ, S.K., Canadian Paediatric Society, Fetus and Newborn Committee. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks' gestation) - Summary. Paediatr Child Health 12, 401-418 (2007).
2. Estcourt, L.J., Malouf, R., Hopewell, S., et al. Pathogen‐reduced platelets for the prevention of bleeding. Cochrane Database of Systematic Reviews 7;7, (2017).
3. McCullough, J., Vesole, D.H., Benjamin, R.J., et al. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial. Blood 104, 1534-1541 (2004).