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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
Yes. Canadian Blood Services will ultimately have two types of pathogen-reduced plasma available for Canadian patients.
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.
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:
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.
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.
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.
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.
Indications are similar to frozen plasma (untreated) components and include:
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).
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
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.
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
Adverse reactions should be reported to the Canada Vigilance Program in one of the following 3 ways:
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
Product recalls issued from Octapharma will reference both the product lot number and the unique ISBT128 unit identification number.
Octapharma has no current plans to make lot number available as a bar code.
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.
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.
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.
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.