FAQ: Apheresis frozen plasma, psoralen-treated 

1. What is apheresis frozen plasma, psoralen-treated? 

Apheresis frozen plasma, psoralen-treated is plasma that has been pathogen-reduced using psoralen treatment (INTERCEPT) technology. The INTERCEPT Blood System (Cerus Corporation) for pathogen inactivation reduces the risk of transfusion-transmitted infections and was approved by Health Canada in 2016. This technology inactivates a broad spectrum of enveloped and nonenveloped viruses, Gram-positive and -negative bacteria, spirochetes, and parasites, in addition to potentially harmful donor residual white blood cells in whole blood-derived or apheresis plasma. Treating plasma with Cerus’ INTERCEPT technology enhances the safety profile of this blood component. 

This blood group specific, pathogen-reduced human plasma component will be available through Canadian Blood Services beginning in Fall 2025 in Ottawa and gradually rolled out nationally. 

2. How is apheresis frozen plasma, psoralen-treated collected? 

Apheresis frozen plasma, psoralen-treated is produced from human plasma that is collected from donors in a Canadian Blood Services donation centre using apheresis techniques, which include leukoreduction. The donated plasma is collected in acid citrate dextrose – Solution A (ACD-A) anticoagulant (contains sodium citrate 22.0 g/L, citric acid 8.0 g/L, dextrose 24.5 g/L).  

The component may be collected from a donor with a history of pregnancy.   

3. How is pathogen reduction performed? 

Pathogen reduction is achieved with the Cerus INTERCEPT Blood System for plasma,  which includes the addition of 15 mL of 6 mM amotosalen solution (a synthetic psoralen), illumination with 3 Joules/cm² of UVA light (wavelength 320 to 400 nm), exposure to a compound adsorption device for the removal of residual amotosalen and free photoproducts, and splitting of the pathogen-reduced component into three single transfusion units (See Figure 1).  

This is the same pathogen inactivation system that is used for platelets. 

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Figure 1. Pathogen reduction process for apheresis frozen plasma, psoralen-treated at Canadian Blood Services. 

4. Are plasma donations used in the production of apheresis frozen plasma, psoralen-treated screened and tested for infectious pathogens?

Prior to making blood components available for transfusion, blood samples collected from the donor at the time of donation are tested for ABO group, RhD type, anti-A and anti-B titres and clinically significant antibodies against red cell antigens. 
The sample must test non-reactive for: 

• Human immunodeficiency virus (HIV-1 and HIV-2): anti-HIV-1 and anti-HIV-2 antibodies, HIV-1 and HIV-2 RNA  
• Hepatitis C virus (HCV): anti-HCV antibodies, HCV viral RNA  
• Hepatitis B (HBV): Hepatitis B core antigen (HBcore), hepatitis B surface antigen (HBsAg), presence of HBV viral DNA 
• Human T-cell lymphotropic virus, type I and II (HTLV-I/II): anti-HTLV-I/II antibodies 
• Syphilis 

In some cases, a donor sample is tested for the presence of IgA, antibodies to Trypanosoma cruzi (T. cruzi or Chagas Disease) and West Nile Virus RNA. For more information on donor testing, read Chapter 6 of the Clinical Guide to Transfusion. 

In addition to viral testing, pathogen inactivation treatment is used to inactivate a broad range of pathogens, including viruses, bacteria, and protozoan parasites, thus reducing the risk of transfusion-transmitted infections.  

In some emergency situations, with the approval of both Canadian Blood Services and recipient’s physician, partially tested or untested blood may be released for transfusion.

 
5. How is apheresis frozen plasma, psoralen-treated packaged?

A typical unit of apheresis frozen plasma, psoralen-treated will be manufactured in the volume of 200 mL ± 10% (see Table 1). While the bags are different, it is similar in appearance to a unit of apheresis, untreated plasma (see Figure 2). The label contains all the relevant information about the product. (See Figure 3)

Apheresis frozen plasma, psoralen-treated is stored in bags using a plastic film that is made of a copolymer of ethylene and vinyl acetate (EVA).^1-4 This component has been in contact with DEHP plasticizer during their collection and manufacturing. DEHP plasticizer can leach from DEHP-plasticized medical devices into blood and blood components. Currently, there is no conclusive scientific evidence that DEHP exposure via medical treatments has harmful effects in humans. However, it is recognized that the potentially high-risk exposure during medical treatment may raise a concern for harmful effects in humans. Reducing DEHP exposure in neonatal patients has been recommended. 

^†Volume includes approximately 35 mL of ACD-A anticoagulant 

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Figure 2. Comparison of apheresis frozen plasma, psoralen-treated, and apheresis plasma not treated when both components are frozen. a) Apheresis frozen plasma, psoralen-treated; b) Apheresis plasma

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Figure 3. Example label for apheresis frozen plasma, psoralen-treated. Visit blood.ca to find a list of the new codes in customer letter #2025 - 26.

6. How is apheresis frozen plasma, psoralen-treated stored?

Apheresis frozen plasma, psoralen-treated components are stored at -18°C or colder for a maximum period of 12 months. The component should be thawed in a watertight protective plastic overwrap using gentle agitation in a water bath at 30–37°C (thawing may take up to 30 minutes) or in a microwave specifically manufactured for this use. Once thawed, plasma components should not be refrozen. If stored at 1–6°C, the component should be transfused within 5 days. 

A visual inspection of the component should be performed according to the individual facility’s policies. For more information on variability in blood components, please see the Visual Inspection Tool (VIT).  

7. What is the shelf-life of thawed apheresis frozen plasma, psoralen-treated?

If stored at 1–6°C, the component should be transfused within 5-days. Once thawed, plasma components should not be refrozen. 

8. Does apheresis frozen plasma, psoralen-treated have to be ABO-compatible?

Yes, apheresis frozen plasma, psoralen-treated must be ABO-compatible, or as defined by individual facility’s policies. RhD need not be considered. 

9. Does our hospital have to stock all three transfusable plasma products that Canadian Blood Services carries?

No. It is the hospital’s decision on what products they stock.

Canadian Blood Services will continue to maintain manufacturing capability for untreated frozen plasma.
 
Ultimately, Canadian Blood Services aims to transition to a 100% pathogen-reduced plasma inventory across Canada, which will result in a combination of solvent detergent treated and psoralen-treated plasma available to hospitals. Untreated frozen plasma will still be available, but only for rare clinical circumstances and business continuity. There is no definitive timeline for this transition, however, hospitals will be kept informed of any changes.

10. Will apheresis frozen plasma, psoralen-treated be available in all blood groups?

At present, Canadian Blood Services will produce apheresis frozen plasma, psoralen-treated from donors who are non-Group O only (i.e., Group A, B and AB donors).

11. Will Canadian Blood Services still have Octaplasma available for patients in Canada?

Yes, Canadian Blood Services will continue to supply Octaplasma, a Health Canada-approved solvent detergent treated plasma product alongside apheresis frozen plasma, psoralen-treated. Canadian Blood Services will also maintain an inventory of untreated frozen plasma.

12. How do I order apheresis frozen plasma psoralen-treated?

Due to limited availability, hospitals will not be able to specifically request apheresis frozen plasma, psoralen-treated. When a hospital places an order for “Frozen Plasma”, the Canadian Blood Services shipment may contain a mix of untreated frozen plasma and apheresis frozen plasma, psoralen-treated. 

Hospital orders for solvent detergent plasma are not anticipated to be impacted by the implementation of apheresis frozen plasma, psoralen-treated.

13. Will there be enough available inventory of apheresis frozen plasma, psoralen-treated for my hospital to replace its existing stock of plasma?

During the gradual roll out of apheresis frozen plasma, psoralen-treated, there will be extremely limited quantities of this new component. It is unlikely that Canadian Blood Services will be able to fulfill a medium to large hospitals’ transfusable plasma needs with apheresis frozen plasma, psoralen-treated alone.

14. Will Canadian Blood Services offer Group AB apheresis frozen plasma, psoralen-treated in the smaller volume units (e.g., 100 mL ped-packs)?

Smaller volume units (e.g., 100 mL ped-packs) of Group AB will not be part of Phase One of Canadian Blood Services’ pathogen-reduced plasma project (apheresis derived pathogen-reduced plasma). Smaller volume pathogen-reduced plasma units may be in scope for the next phase of this project as whole blood derived pathogen-reduced plasma is introduced.
 

15. How is apheresis frozen plasma, psoralen-treated administered?

The volume of apheresis frozen plasma, psoralen-treated transfused depends on the clinical situation and recipient size. Common dosing is 10–15 mL per kg body weight.   

Serial laboratory assays of coagulation function may be of assistance in planning the dose. A standard blood administration set containing a 170–260-micron filter or a filter of equivalent efficacy, approved by Health Canada, must be used for infusion.

No medications or solutions may be added to or infused through the same tubing simultaneously with blood or blood components, unless the solution has been approved for this use by Health Canada or there is documentation available to show that addition of the solution to the blood component involved is safe. Please refer to the Circular of Information for Plasma components for further information.
 
Transfusion rate is dependent on clinical factors. For more information, refer to the Clinical Guide to Transfusion. All transfusions should be complete within 4 hours of removal from storage. Recipients should be under observation during transfusion with close observation during the first 15 minutes and in accordance with institutional guidelines. 

16. What are the indications for apheresis frozen plasma, psoralen-treated?

Apheresis frozen plasma, psoralen-treated shares the same indications as fresh plasma and may be useful in the management of: 

• Bleeding patients or patients undergoing invasive procedures with high bleeding risk who require replacement of multiple plasma coagulation factors. 
• Patients receiving massive transfusion with clinically significant coagulation abnormalities. 
• Patients on warfarin who are bleeding or need to undergo a high bleeding risk invasive procedure before vitamin K could reverse the warfarin effect, and where prothrombin complex concentrate is not available or is contraindicated.^5,6
• Patients with selected coagulation factor or with rare specific plasma protein deficiencies for which a more appropriate alternative therapy is not available. 
• Preparation of reconstituted whole blood for exchange transfusion in neonates. 
• Patients with thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) undergoing plasma exchange. 

17. Are there any contraindications in using apheresis frozen plasma, psoralen-treated?

Patients with known anaphylaxis to plasma components should only receive plasma components under appropriate medical supervision. Recipients with known anti-IgA should receive IgA deficient plasma.   
Plasma components should not be used to treat hypovolemia. 

Apheresis frozen plasma, psoralen-treated should not be used for: 

• Patients with a history of hypersensitivity reaction to amotosalen or other psoralens. 
• Neonatal patients treated with phototherapy devices that emit a peak energy wavelength less than 425 nm, and/or have a lower bound of the emission bandwidth <375 nm, due to the potential for erythema resulting from interaction between ultraviolet light and amotosalen. 

18. How should suspected reactions to apheresis frozen plasma, psoralen-treated be managed?

Management of suspected reactions should follow recommendations for adverse reactions to conventional blood components. See Reporting adverse-transfusion reactions for more information.
Potential adverse events related to a blood transfusion range in severity from minor with no sequelae to life-threatening. All adverse events occurring during a transfusion should be evaluated to determine whether the transfusion can be safely continued/restarted. All adverse events suspected to be related to a transfusion (whether during or after a transfusion) should be reported to your local transfusion service and, when required, the hospital/regional hemovigilance network. Health Canada’s Blood Regulations requires reporting of adverse events that may be attributed to the manufacturing process (e.g., associated with blood component quality) to Canadian Blood Services.^7-10 

Reporting of suspected cases of transfusion-related infections such as HIV, HCV, HTLV, HBV, West Nile Virus and other transfusion-related infections is described in Chapter 1 of the Clinical Guide to Transfusion and in the publication, A guide to reporting adverse transfusion reactions. 

19. What are the benefits of using pathogen-reduced plasma?

Pathogen inactivated plasma has an added layer of protection against bacterial contaminants (gram-positive and gram-negative), viruses (enveloped and non-enveloped), protozoa parasites and white blood cells (leukocytes).  

In addition to a reduction in the risk of pathogen transmission, other adverse transfusion reactions also decrease with use of pathogen reduction technology such as solvent detergent plasma. These include a reduction in allergic reactions and febrile non hemolytic transfusion reactions; however, these reductions may reflect pooling of plasma and subsequent dilution of potential allergens or reactants rather than the pathogen-reduction process.  

20. Can apheresis frozen plasma, psoralen-treated be used to treat neonatal and pediatric patients?

There are limited data available for the use of pathogen-reduced plasma for transfusion among pediatric and neonatal patients. However, the available hemovigilance data suggests the product is safe and well tolerated in this population.  

Preliminary animal studies of pathogen-reduced plasma reported no adverse impacts with transfusion in neonatal rats. Specifically, there were no amotosalen-related adverse effects found in the neonatal rats despite the exposure to amotosalen concentrations being as high as 48 times the standard exposure in adult patients.¹¹ 

Human clinical trials have similarly reported no or low-grade adverse events among pediatric and neonatal populations. An open label clinical trial conducted in Belgium and France reported that pathogen-reduced plasma transfusion was well tolerated in routine clinical use for children and infants.¹² The study assessed 160 children (aged 1–-18 years) and 188 infants (aged < 1 years) from 2007–2011, constituting 11% of the total mixed hematology, medical and surgical patients in the study (n=3, 232). Results for pediatric patients were not reported separately from the adult patients, but overall adverse transfusion reactions were reported in 0.11% (8/7483) of transfusions, with 5 being of Grade 1 severity and 3 serious adverse events; all adverse events occurred in adult patients in this study. There were no reported TRALI events.  

Another hemovigilance study assessing the safety profile of pathogen-reduced platelets and pathogen-reduced plasma in 11 countries over an 8-year period reported infrequent transfusion reactions among patients (0.4% of transfusions). The study assessed 440 infants (aged < 1 years) and 355 children (aged 1–18 years), and the pediatric data was not reported separately from adult patients. A subsequent post-marketing hemovigilance study of 3, 179 pathogen-reduced plasma and platelet transfusions in 11 countries found that these components were well tolerated by a pediatric population with only low-grade transfusion reactions reported. The sample included 540 children (aged 1–18 years) and 499 infants (aged < 1 year) with mixed clinical indications for transfusion, including medical (45%), hematology-oncology (34%) and surgical (20%). Three of the 795 pediatric patients experienced a transfusion reaction. Symptoms were characterized by rash (n=2), urticaria (n=1), and chills (n=1) without serious consequences, TRALI, or transfusion associated sepsis.¹³  

From a hemostasis perspective, a single-arm open label study of pathogen-reduced plasma reported good clotting factor kinetics post-transfusion and hemostatic efficacy when used for both prophylactic and therapeutic indications. The study included 34 patients who received 107 transfusions; a portion of the participants were pediatric patients (ages ranged from 3 to 77 years) but data for pediatric patients were not reported separately from adult patients.¹⁴   

Currently, there is limited safety data for apheresis frozen plasma, psoralen-treated when used for intrauterine transfusion.¹⁵   

21. What dose of apheresis frozen plasma, psoralen-treated should be prescribed?

The volume of apheresis frozen plasma, psoralen-treated transfused depends on the clinical situation and recipient size. Common dosing is 10–15 mL per kg body weight. 
Serial laboratory assays of coagulation function may be of assistance in planning dose.

22. How does apheresis frozen, plasma psoralen-treated compare to solvent detergent plasma and untreated frozen plasma regarding factor levels?
 

^†Alpha-2 antiplasmin and ADAMTS-13 were determined using kits designed for research purposes. The other parameters were tested on Stago Coagulation Analyzer. All methods are designed for clinical diagnostic samples; however, we are using them “off label” to measure coagulation related parameters in plasma components (n = 33 for all the parameters).
^‡Data were gathered from development data at Canadian Blood Services.
^§All parameters taken from product monograph (n = 12),¹⁶ except for ADAMTS-13 (n =18) taken from https://www.octaplasma.ca/standardization-of-plasma-protein-levels-in-octaplasma/ 
^||There are currently no defined acceptance criteria listed by CSAZ902-25² specifically for pathogen reduced plasma.
^¶Reference ranges were taken from Erickson et al.¹⁷ and were established on fresh frozen, normal donor plasma samples by Machaon Diagnostic Laboratory
^#The percentage of activity and the IU/mL unit are directly proportional (i.e., if the activity is 50%, it would be 0.5 IU/mL).
^**Data from Heger et al.¹⁸  

23. Can apheresis frozen plasma, psoralen-treated be used for alternative treatments?

Apheresis frozen plasma, psoralen-treated should not be used when coagulopathy can be more appropriately corrected with specific therapy, such as vitamin K or specific factor replacement. For example, replacement of the vitamin K-dependent coagulation factors (i.e., factors II, VII, IX and X) can be achieved with prothrombin complex concentrates. 

Hemophilia A and B and von Willebrand disease are more appropriately treated with recombinant or virally inactivated fractionation products or 1-deamino-8-D-arginine vasopressin as initial treatment. For replacement of fibrinogen and factor XIII, commercial virally inactivated concentrates are also available. Some products are only available through the Special Access Programme of Health Canada. 
Solvent detergent plasma is also available as an alternative to apheresis frozen plasma, psoralen-treated.