Pathogen-reduced Amatosalen-treated/ Intercept Plasma.

Introduction :
Several technologies can reduce pathogens that may be present in donated transfusable plasma. Canadian Blood Services plans to provide almost all transfusable plasma as a pathogen-reduced (PR), using either solvent/detergent plasma (Octaplasma®, Octapharma) or plasma treated with Amotosalen followed by ultraviolet light illumination called Amotosalen-treated/ INTERCEPT Plasma.

The method of pathogen reduction may have some impact on plasma protein levels. Below is a table highlighting the differences between products. Only protein levels where there is a 15% or greater difference when compared to untreated frozen plasma, as per the product monograph, are shown. 

*Plasma protein composition (only proteins where >15% difference exists compared to untreated FP are shown)

**from the INTERCEPT or Octaplasma monograph.

For various reasons, some hospitals maintain a mixed inventory of solvent/detergent plasma (S/D plasma) and frozen plasma. Pediatric & neonatal hospitals vary in ordering practices (some hospitals order smaller volumes of Frozen Plasma called FP divided directly from Canadian Blood Services, while some hospitals aliquot the required dose from a thawed plasma unit).

Survey Intent : 

A. to better understand the demand and preferred volume of Amatosalen-treated/ INTERCEPT Plasma for pediatric/ neonatal use.

B. to determine if there are patient populations/ clinical indications where untreated FP is preferred (provided equivalent thaw time with both INTERCEPT & frozen plasma)

Please note that the feedback received on the volume preference is subject to further exploration.

French translation :

Plasma INTERCEPT à teneur réduite en agents pathogènes

Introduction :

Différentes technologies permettent de réduire la teneur en agents pathogènes présents dans le plasma donné pour la transfusion. La Société canadienne du sang prévoit que presque tout le plasma offert pour les transfusions sera à teneur réduite en agents pathogènes en proposant du plasma traité par solvant/détergent (Octaplasma®, Octapharma) ou encore du plasma traité à l’amotosalène activé par l’illumination aux rayonnements ultraviolets appelé plasma traité à l’amotosalène/INTERCEPT. La méthode employée pour réduire la teneur en agents pathogènes pourrait avoir une incidence sur les taux de protéine du plasma. Le tableau ci-dessous souligne les différences entre les produits. Il n’inclut que les protéines pour lesquelles une différence d’au moins 15 % existe par rapport au plasma congelé non traité, conformément à la monographie de produit.

*Composition de la protéine plasmatique (seules les protéines pour lesquelles une différence >15 % existe par rapport au plasma congelé non traité y figurent)

**Tiré de la monographie du produit INTERCEPT ou Octaplasma.

Pour différentes raisons, certains hôpitaux maintiennent des stocks mixtes de plasma congelé et de plasma traité par solvant/détergent (plasma S/D). Les pratiques de commande des hôpitaux offrant des soins pédiatriques et néonataux varient, c’est-à-dire que certains hôpitaux commandent des volumes moins élevés de plasma congelé divisé en aliquotes directement auprès de la Société canadienne du sang, alors que d’autres ne commandent que l’aliquote nécessaire d’une unité de plasma décongelée.

Buts du sondage :

1.  Mieux comprendre la demande et le volume préféré dans le cas du plasma traité à l’amatosalène/INTERCEPT destiné à un usage pédiatrique ou néonatal.
2.  Déterminer si le plasma congelé non traité est préférable pour certaines populations de patients ou selon certaines indications cliniques (temps de décongélation équivalent entre le plasma INTERCEPT et le plasma congelé).

Veuillez noter que les commentaires reçus concernant le volume préféré sont susceptibles d’être examinés plus en profondeur.

Objective:

This survey seeks to gain a comprehensive understanding of Canadian transfusion medicine practitioners' awareness and perspective on OctaplasLG Lyo, a solvent detergent freeze-dried plasma, with the ultimate goal of enhancing patient care in Canada.. 

 Introduction: 

Freeze-dried plasma is a product obtained by freeze-drying a batch of plasma units and can typically maintain its hemostatic properties for up to two years when kept at room temperature, as demonstrated by consistent coagulation factor profiles. Furthermore, FDP can be easily reconstituted using sterile water and is not affected by forceful shaking during reconstitution. In addition to its practicality in prehospital and early hospital settings where fresh plasma may not be available, FDP can be used within minutes. It is important to note that FDP is not a recent development, as it has been used in military settings since World War II to treat hemorrhagic shock. 

Canadian Blood Services is currently exploring the possibility of using Octaplasma® Lyo-Powder and solvent for infusion. This substance is a freeze-dried version of Octaplasma®, a type of human plasma treated with S/D for transfusion. Octaplasma® Lyo-Powder is provided in a glass vial and contains 9-14g of ABO-blood group-specific human plasma proteins. Once mixed with 190ml of solvent (WI), the solution contains 45-70mg/ml of ABO-blood group-specific human plasma proteins, similar to a unit of solvent detergent S/D plasma. OctaplasLG is available in different presentations based on the relevant blood groups.

• Blood group A

• Blood group B

• Blood group AB

• Blood group O

Octaplasma® Lyo has a shelf life of two years. Once reconstituted, the solution is physically and chemically stable for up to 8 hours at room temperature (maximum +25°C). Using the product immediately after reconstitution is recommended to ensure microbiological safety. It is crucial to avoid freezing or refrigerating the reconstituted solution. Any partially used bottles must be discarded.

Clinical Indications for the use of Octaplasma® Lyo :

• Complex deficiencies of coagulation factors such as coagulopathy due to severe hepatic failure or massive transfusion.

•  Substitution therapy in coagulation factor deficiencies occurs when a specific coagulation factor concentrate (e.g., factor V or factor XI) is not available for use or in emergencies when a precise laboratory diagnosis is not possible.

•  Rapid reversal of the effects of oral anticoagulants (coumarin or indanedione type) when a prothrombin complex concentrate is unavailable for use or administration of vitamin K, is insufficient due to impaired liver function or emergencies.

• In patients who fail to respond to conventional measures, potentially dangerous hemorrhages during fibrinolytic therapy, e.g., tissue plasminogen activators.

• Therapeutic plasma exchange procedures include thrombotic thrombocytopenic purpura (TTP).

Dosage:

Determining the appropriate dosage of OctaplasLG depends on the specific clinical situation and underlying disorder. The recommended starting dose is typically 12-15 ml per kilogram of body weight. This initial dose should increase the patient's plasma coagulation factor levels by approximately 25%.

It is crucial to closely monitor the patient's response both clinically and through measuring activated partial thromboplastin time (aPTT), prothrombin time (PT), and/or specific coagulation factor assays.

Dosage for coagulation factor deficiencies:

For patients with coagulation factor deficiency experiencing minor or moderate hemorrhages or undergoing surgery, an infusion of 5-20 ml octaplasLG per kg of body weight is usually sufficient to achieve an adequate hemostatic effect. This infusion should increase the patient's plasma coagulation factor levels by approximately 10-33%. However, in the case of major hemorrhages or surgery, it is recommended to seek the expert advice of a hematologist.

If undergoing therapeutic plasma exchange procedures, it is also recommended to seek the expert advice of a hematologist. The entire plasma volume exchanged should be replaced with octaplasLG in TTP patients.

Method of administration

The administration of octaplasLG must be based on the ABO-blood group specificity. In emergencies, octaplasLG blood group AB can be considered universal plasma as it can be given to all patients, regardless of their blood group.

OctaplasLG should be given through intravenous infusion after reconstitution, as described in section 6.6, using a vented infusion set with a filter. An aseptic technique must be maintained throughout the injection.

The reconstituted solution appears clear to slightly opalescent. Citrate toxicity can occur when more than 0.020-0.025 mmol citrate per kg per minute is administered, so the infusion rate should not exceed 1 ml of OctaplasLG per kg per minute. The toxic effects of citrate can be minimized by giving calcium gluconate intravenously into another vein.

The reconstituted product should be administered at a tolerable temperature to prevent hypothermia, but it should not be above 37°C.

Contraindications

•  IgA deficiency with documented antibodies against IgA.

•  Hypersensitivity to the active substance or any excipients listed in section 6.1 or residues from the manufacturing process, as stated in section 5.3.

• Severe deficiencies of protein S.

Note: There is limited data on children and adolescents (0-16 years)

Please note that all the above-mentioned platelet storage alternatives are activated and get rapidly clear from the circulatory system and hence are not interchangeable with room-temperature platelets.