FAQ: Solvent detergent (S/D) treated plasma (Octaplasma)

Authors: Johnathan Mack, MD, MSc, FRCPC; Irena Gordon; Rob Romans; Kathryn Webert, MD, FRCPC; Shuoyan Ning, MD, FRCPC, DRCPSC; Michelle Zeller, MD, FRCPC, DRCPSC

Primary target audiences: transfusion medicine physicians, non-transfusion medicine physicians, nurses, medical laboratory technologists in a hospital laboratory 

NOTE: As part of Canadian Blood Services’ transition to a pathogen-reduced blood component inventory, the current restrictions to Octaplasma will be lifted and the product available for ordering as of March 27, 2023. This FAQ was developed in collaboration with Octapharma to support hospitals in transitioning to pathogen-reduced plasma and reflects evidence available at the time of publication. Please also see our publication, Solvent detergent (S/D) treated plasma (Octaplasma). 

General

1. What is Octaplasma?

Octaplasma is blood group specific, pathogen-inactivated human plasma for transfusion. The product is manufactured from US source plasma by Octapharma using solvent/detergent (S/D) pathogen-inactivation method. The resulting product is an alternative to frozen plasma (untreated) components manufactured by Canadian Blood Services (e.g., apheresis frozen plasma [AFP], frozen plasma [FP]) but with reduced risk of transmitting infection from enveloped viruses.

Octaplasma has been available for use in select patient populations in Canada since 2011. Octaplasma has been used widely in Europe for several decades, with some countries (e.g., Norway, Sweden, Finland, United Kingdom, The Netherlands) using Octaplasma as the primary plasma product for transfusion. 

2. Octaplasma is not manufactured by Canadian Blood Services. Where can I get more information about it?

See the Octaplasma product monograph for the product description, and information on labelling, packaging, storage and thawing, as well as other product details. Always refer to the most recent Product Monograph for the most up-to-date product information. Starting end of February, you may also access this information online at www.octaplasma.ca; to receive regular updates, please sign up by visiting this website.

3. Why is solvent detergent treatment performed?

Certain types of infectious disease can be transmitted by transfusion of blood components and plasma-derived products. Donor screening and testing of each blood donation has significantly decreased the risk of transfusion-transmitted infectious diseases. The manufacturing process of Octaplasma employs a number of dedicated steps targeting a variety of pathogens. One of these steps, S/D treatment of plasma, further reduces this risk by inactivating enveloped viruses (e.g., human immunodeficiency virus (HIV), hepatitis B and C) that could be transmitted by transfusion.

While non-enveloped viruses (e.g., hepatitis A, parvovirus B19) are not inactivated by S/D treatment, pooling of plasma reduces possible viral load through dilution and provides neutralizing antibodies. The S/D treatment includes sterile filtration that depletes leukocytes, as well as a column to remove prions—a safety measure considered effective for removing the infectious agent causing variant Creutzfeldt-Jakob disease (vCJD) if present in plasma.

4. How is Octaplasma manufactured? 

Octaplasma S/D pathogen reduction is accomplished by pooling 630–1520 individual plasma donations.¹ The pooled plasma is treated with a combination of 1% tri(n-butyl)-phosphate (TNBP) and 1% octoxynol. The S/D additives are removed using castor oil and solid phase extraction. After sterile filtration, a sterile blood bag is filled with 200 mL of Octaplasma.

5. Are plasma donations, used to make Octaplasma, screened and tested for infectious pathogens?

All plasma donors undergo screening for risk of/history of specific infectious diseases and must meet eligibility criteria in order to donate. Testing for hepatitis B and C, and HIV is done on individual plasma donations. Plasma pools are tested for hepatitis B surface antigen, anti-HIV-1 and anti-HIV-2 antibodies; nucleic acid testing is done for hepatitis A/B/C/E, HIV, and parvovirus B19.

6. Aside from viral inactivation, are there other major differences between Octaplasma and frozen plasma (untreated) components?

The volume of each unit of Octaplasma is 200 mL—lower than the volumes of frozen plasma (untreated) units (approximately 289mL for FP, and 249mL for AFP). There are no current plans for a larger volume format of Octaplasma. Unlike current frozen plasma (untreated), there is no variability across Octaplasma unit size; all have a uniform volume of 200 mL.

Octapharma pools human plasma prior to S/D treatment, so each unit of Octaplasma represents multiple donors. In contrast, frozen plasma (untreated) units manufactured by Canadian Blood Services are derived from a single donor (see Chapter 2).

Each unit of Octaplasma has consistent and standardized clotting factor content compared with single-donor plasma, for which donor-to-donor variation exists. In Octaplasma, all clotting factors are present at a minimum concentration of 0.5 IU/mL. The levels of protein S and plasmin inhibitor (alpha-2 antiplasmin) are lower in Octaplasma than frozen plasma (untreated). The S/D treatment reduces the concentration of lipids and lipoproteins.

7. Will Octaplasma replace frozen plasma (untreated) at Canadian Blood Services?

Frozen plasma (untreated) will initially remain available. All hospitals will be asked to plan at least a partial transition to Octaplasma. Restricted access to Octaplasma will be lifted as of March 2023 and almost full conversion to pathogen-reduced plasma (at least 80% Octaplasma, though hospitals may opt for a higher percentage, up to 100%) will be expected by September 2023. This target will be guided by hospital experience as use of Octaplasma increases.

Ultimately, Canadian Blood Services plans to transition the majority of the plasma inventory towards pathogen-reduced transfusable plasma. This will be done through a combination of Octaplasma and plasma treated with a different pathogen reduction technology (similar to that used for pathogen-reduced platelets). More details on those plans will be shared when they are available.

For hospital technologists

8. What is the shelf life of thawed Octaplasma?

Once thawed, the shelf life of Octaplasma is up to 5 days at 2 to 8°C or for up to 8 hours at room temperature (20 to 25°C) before use.

9. What will happen to the plasma that was previously used by Canadian Blood Services to manufacture plasma for transfusion?

As hospitals transition to Octaplasma, the plasma that would have been used by Canadian Blood Services to manufacture plasma for transfusion will instead be sent to one of Canadian Blood Services’ contracted fractionators. This plasma will be manufactured into plasma protein products that will be available from Canadian Blood Services for Canadian patients.

10. Will Canadian Blood Services have two kinds of pathogen-reduced plasma available for Canadian patients?

Yes. Canadian Blood Services will ultimately have two types of pathogen-reduced plasma available for Canadian patients.

1. Octaplasma, a Health Canada-approved S/D treated plasma product.
2. Plasma collected from our donors will be treated at Canadian Blood Services with a pathogen inactivation technology (similar to that used for pathogen-reduced platelets)

11. Does ABO-group matter with Octaplasma?

The S/D treatment does not remove ABO antibodies. Plasma donations of identical blood type are pooled to manufacture Octaplasma and each bag is labelled with an ABO blood group. To avoid hemolytic transfusion reactions, the ABO blood group of the recipient must be evaluated and only ABO-compatible Octaplasma administered.

12. What are the anti-A and anti-B titres in Octaplasma?

Communication with Octapharma has provided the following information about titres in the different ABO groups of Octaplasma:

The ranges of anti-A and anti-B in Octaplasma are:

• 1:4-1:128 for anti-B in group A Octaplasma
• 1:8-1:128 for anti-A in group B Octaplasma
• 1:64-1:512 for anti-B and 1:128-1:2048 for anti-A in group O Octaplasma
• None detected in group AB Octaplasma for both antibodies²

The manufacturer has no plans to label individual bags with titres.²

The current Octapharma product monograph recommends using group specific Octaplasma or group AB when patient blood group is unknown.

Frozen plasma (untreated) group A components manufactured by Canadian Blood Services will be labelled “Low Anti-A/B” on the label if the component meets low titre criteria. For more information on donor high titre isohemagglutinin (anti-A/anti-B) testing at Canadian Blood Services, see our FAQ.  

13. What if I see visible particulates or clumping in the Octaplasma unit during thawing?

Particulates may be visible as the bag thaws, especially while it still contains an “ice block” of frozen plasma. These particulates should disappear as the plasma warms. We recognize that thawing procedures may vary from site to site and it is recommended to ensure the bag is fully thawed and no visible particulates should be present prior to infusion. Please see Customer Letter 2017-07 and Octapharma communication for more information. See the Octapharma product monograph for options on thawing frozen plasma. 

For clinicians

14. Do frozen plasma (untreated) components and Octaplasma have comparable factor levels?

Pooling of donor plasma standardizes factor units of Octaplasma, resulting in less unit-to-unit variability in factor levels. Factor levels in Octaplasma fall within the ranges measured in fresh frozen plasma (FFP), with the exception of plasmin inhibitor, which is at a reduced concentration. See the table comparing characteristics of Octaplasma with FFP in the product monograph.

15. How is Octaplasma administered? Can the same intravenous line be used for administration of Octaplasma and frozen plasma (untreated) components?

Octaplasma is administered after thawing as an intravenous infusion using a standard infusion set with a filter. The rate of infusion should take patient-specific risk factors for volume overload into account. To avoid citrate toxicity, transfusion rates should not exceed 1 mL/kg/minute. Calcium citrate or gluconate can be administered to treat symptoms of citrate toxicity but must be given into a separate vein from the Octaplasma transfusion to avoid clotting.

Octaplasma can be administered with red blood cell and platelet components. Solutions containing calcium or any other medications should not be mixed or administered into the same vein as Octaplasma transfusion.

Octaplasma and thawed frozen plasma (untreated) can be administered through the same line, provided the tubing has not expired.

Dedicated studies have not been conducted on the use of a rapid infuser for Octaplasma.

Manipulation (e.g., aliquoting or using to prepare reconstituted whole blood) of this product outside of the product monograph should be done in accordance with hospital policies and applicable regulatory requirements.

16. What are the indications for Octaplasma?

Indications are similar to frozen plasma (untreated) components and include:

1. Replacement of complex coagulation factor deficiencies to treat bleeding or prevent bleeding (e.g., prior to invasive procedures, as part of massive hemorrhage protocol)
2. Replacement fluid for therapeutic plasma exchange procedures
3. Emergency replacement of isolated coagulation factor deficiency when precise laboratory diagnosis is not possible, or when a specific factor concentrate is not available
4. Rapid reversal of a vitamin K antagonist (if direct reversal agents are unavailable).

17. What dose of Octaplasma should be prescribed?

A dose of 12–15 mL/kg of recipient body weight is the manufacturer’s recommended starting dose and is anticipated to increase coagulation factor levels by 25%. This is approximately 5–6 units of Octaplasma for a patient weighing 80 kg. The dose should be adjusted according to the clinical situation. Higher doses increase the risk of transfusion-associated circulatory overload (TACO). Response can be monitored using prothrombin time (PT) and activated partial thromboplastin time (aPTT).

18. What are the benefits to Octaplasma?

The S/D treatment inactivates enveloped viruses, enhancing risk reduction offered by routine donor screening and testing.

Pooling of plasma standardizes the concentrations of clotting factors across units of Octaplasma, resulting in a more reliable coagulation profile of each lot of Octaplasma.

Pooling also dilutes antibodies, allergens, and cytokines present in individual plasma donations. Lower rates of allergic reactions have been observed in the literature with Octaplasma compared with frozen plasma (untreated) components.^1,3-5 The risk of transfusion-related acute lung injury (TRALI) may be decreased with use of Octaplasma, although rare cases of TRALI have been observed with Octaplasma.⁶

19. Are there risks to Octaplasma?

The same adverse transfusion reactions associated with frozen plasma (untreated) transfusion can occur with Octaplasma, including minor and severe allergic transfusion reactions, transfusion-associated circulatory overload (TACO), TRALI, hemolytic transfusion reactions and citrate-toxicity. However, current literature suggests that the risk of allergic reactions and TRALI may be decreased with Octaplasma compared with frozen plasma (untreated).^1,3-5,7 

The S/D treatment inactivates enveloped viruses. Non-enveloped viruses are not affected. Since pools of plasma are used in the manufacturing process of Octaplasma, donor exposure is increased but the pooling dilutes individual donations. The presence of neutralizing antibodies against hepatitis A and parvovirus B19 may limit the risk of infection from these non-enveloped viruses. In addition to S/D treatment, Octaplasma undergoes multiple size exclusion filtration steps and ligand chromatography. Clinical use of Octaplasma demonstrated significant reduction in severe adverse reactions (see Krusius et al. 2010).¹

Small amounts of TNBP (<2.0 mcg/mL) and octoxynol (< 5.0 mcg/mL) are present, in addition to sodium dihydrogenphosphate dihydrate (0.06–0.24 g) and glycine (0.80–1.20 g). Animal studies have not demonstrated toxicity of these additives for equivalent Octaplasma doses used in humans.  

20. How should suspected transfusion reactions to Octaplasma be managed?

Management of suspected reactions to Octaplasma transfusions should follow recommendations for adverse reactions to conventional blood components

Canadian Blood Services classifies Octaplasma as a plasma protein and related product. Therefore, in addition to voluntary reporting of suspected or confirmed reactions to the Transfusion Transmitted Injuries Surveillance System (TTISS), under the Food and Drug Regulations hospitals must report a serious adverse drug reaction associated with transfused plasma protein and related products to Health Canada’s Canada Vigilance Program within 30 calendar days from the date of first documentation in the hospital. A report should also be submitted to the manufacturer (Octapharma). Clusters of minor reactions should also be reported to Health Canada and the manufacturer. See the Canadian Blood Services’ Guide to reporting adverse transfusion reactions for more information.  

Adverse reactions should be reported to the Canada Vigilance Program in one of the following 3 ways:

1. Report online at www.healthcanada.gc.ca/medeffect
2. Call toll-free at 1-866-234-2345
3. Complete a Canada Vigilance Reporting Form and Fax toll-free to 1-866-678-6789, or mail to: Canada Vigilance Program, Health Products Surveillance and Epidemiology Bureau, Marketed Health Products Directorate, Health Products and Food Branch, Health Canada, Postal Locator 1908C, Ottawa, Ontario K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect Canada Web site at www.healthcanada.gc.ca/medeffect

21. What unit identifiers will be used during a product recall?

Product recalls issued from Octapharma will reference both the product lot number and the unique ISBT128 unit identification number.

22. Will the eye readable lot number be provided on individual bags with a bar code option?

Octapharma has no current plans to make lot number available as a bar code.

Additional resources

Solvent detergent (S/D) treated plasma (Octaplasma)

• This publication provides information on Octaplasma—blood group specific, pathogen-inactivated human plasma for transfusion—based on its product monograph and evidence available in the literature. 

Octaplasma (S/D plasma): One-page clinical summary 

• This one-page clinical summary can be printed by blood bank staff and provided with Octaplasma units when they are sent to the floor for transfusion.

(Slide deck) Octaplasma (Solvent detergent [S/D] plasma): Clinical overview

• This slide deck may be downloaded for use in presentations. It provides health-care professionals with an overview of Octaplasma, including product characteristics, safety, indications and contraindications, and benefits of pathogen inactivation.

(Slide deck) Octaplasma (Solvent detergent [S/D] plasma): Clinical overview - Short version

• This slide deck may be downloaded for use in presentations. It provides health-care professionals with a shorter version of the clinical overview, highlighting key points about Octaplasma.

  Octplasma - clinical overview (short).pptx

  8.52 MB

  Updated: April 4, 2023

  Download

(Slide deck) Octaplasma: Information for laboratory technologists

• This slide deck may be downloaded for use in presentations. It provides laboratory technologists with an overview of information from the Octaplasma product monograph, including key points about labelling, packaging, storage and thawing. 

NAC recommendations for the use of solvent-detergent plasma in Canada

• This document from the National Advisory Committee on Blood and Blood Products (NAC) provides additional clinical recommendations regarding the indications, dosing and use of S/D plasma in special populations.

References

1. Krusius T AM, Tuimala J. Introduction of Octaplas® in clinical use decreased the rate of severe adverse reactions. Vox Sanguinis 2010;99s1: P-1018
2. Information provided by Octapharma, November 15, 2022.
3. McGonigle AM, Patel EU, Waters KM, Moliterno AR, Thoman SK, Vozniak SO, Ness PM, King KE, Tobian AAR, Lokhandwala PM. Solvent detergent treated pooled plasma and reduction of allergic transfusion reactions. Transfusion 2020;60: 54-61.
4. Saadah NH, Schipperus MR, Wiersum-Osselton JC, van Kraaij MG, Caram-Deelder C, Beckers EAM, Leyte A, Rondeel JMM, de Vooght KMK, Weerkamp F, Zwaginga JJ, van der Bom JG. Transition from fresh frozen plasma to solvent/detergent plasma in the Netherlands: comparing clinical use and transfusion reaction risks. Haematologica 2020;105: 1158-65.
5. Cushing MM, Pagano MB, Jacobson J, Schwartz J, Grossman BJ, Kleinman S, Han MA, Cohn CS. Pathogen reduced plasma products: a clinical practice scientific review from the AABB. Transfusion 2019;59: 2974-88.
6. Klanderman RB, Bulle EB, Heijnen JWM, Allen J, Purmer IM, Kerkhoffs JH, Wiersum-Osselton JC, Vlaar APJ. Reported transfusion-related acute lung injury associated with solvent/detergent plasma - A case series. Transfusion 2022;62: 594-9.
7. Klanderman RB, van Mourik N, Eggermont D, Peters AL, Tuinman PR, Bosman R, Endeman H, Cremer OL, Arbous SM, Vlaar APJ. Incidence of transfusion-related acute lung injury temporally associated with solvent/detergent plasma use in the ICU: A retrospective before and after implementation study. Transfusion 2022;62: 1752-62.

Further reading

1. Octaplasma Product Monograph. Version: October 31, 2022. https://www.octapharma.ca/en/therapies/product-overview. Always refer to the most recent Product Monograph for up-to-date product information.
2. Octapharma. Octaplasma FAQ [Internet]. (2023). Available from: https://www.octaplasma.ca/faq/
3. Al-Abdi S, Dabelah K, Mousa T, et al. Selective prophylactic solvent-detergent plasma and cryoprecipitate transfusion to prevent intraventricular hemorrhage in extreme preterm infants: a case-historical control. J. Neonat. Peri. Med. 11: 241-248 (2018).
4. Camazine MN, Karam O, Colvin R, et al. Outcomes Related to the Use of Frozen Plasma or Pooled Solvent/Detergent-Treated Plasma in Critically Ill Children. Pediatr. Crit. Care. Med. 18:e215-e223 (2017).
5. Chekrizova V and Murphy WG. Solvent-detergent plasma: use in neonatal patients, in adult and paediatric patients with liver disease and in obstetric and gynaecological emergencies. Trans. Med. 16:85-91 (2006).
6. Josephson CD, Goldstein S, Askenazi D, et al. Safety and tolerability of solvent/detergent-treated plasma for pediatric patients requiring therapeutic plasma exchange: an open-label, multicenter, postmarketing study. Transfusion 62:396-405 (2022).
7. Liumbruno GM, Marano G, Grazzini G, et al. Solvent/detergent-treated plasma: a tale of 30 years of experience. Expert Rev. Hematol. 8(3):367-374 (2015).
8. Marietta M, Franchini M, Bindi ML, et al. Is solvent/detergent plasma better than standard fresh-frozen plasma? A systematic review and an expert consensus document. Blood Transfus. 14:277-286 (2016).
9. Spinella PC, Borasino S, Alten J. Solvent/Detergent-Treated Plasma in the Management of Pediatric Patients Who Require Replacement of Multiple Coagulation Factors: An Open-Label, Multicenter, Post-marketing Study. Front. Pediatr. 8:572 (2020).