FAQ

A: Octaplasma^® is standardized human plasma for intravenous administration. It is a Health Canada regulated medicinal product for human use.

Octaplasma^® is made from pooled plasma collected from donors in the United States.¹ The Octaplasma^® manufacturing process ensures that each bag of plasma has standardized content of clotting factors and proteins. It is devoid of antibodies implicated in transfusion-related acute lung injury (TRALI) pathogenesis and employs multiple dedicated steps to eliminate transfusion-transmissible infectious agents, allergic and citrate reactions.² Octaplasma^® is manufactured by Octapharma AB in Stockholm, Sweden.³

A: Octaplasma^® manufacturing employs a process called Solvent/detergent (S/D) treatment. S/D treatment was pioneered by Octapharma and is an established virus inactivation technology that has been industrially applied for manufacturing plasma derived medicinal products for almost 30 years. It is considered as the gold standard for pathogen inactivation of lipid enveloped viruses. Many clinical studies have confirmed its safety and efficacy in the setting of congenital as well as acquired bleeding disorders.²

The manufacturing process ensures pathogen inactivation in three ways – solvent/detergent (S/D) viral inactivation, volume dilution and antibody neutralization.4 In addition, pathological prion proteins are removed by using an affinity ligand chromatography step.5,6 This significantly reduces the risk of potential pathogen transmission with Octaplasma^® as in contrast to single donor controlled, untreated frozen plasma (FP).⁷

A: The transition to Octaplasma^® from FP ensures enhanced safety from pathogens including enveloped and non-enveloped viruses and prions,²² lower rates of transfusion reactions as seen in countries like the UK ²⁴, and lower allergic and citrate reactions.²³

The transition, as observed in other countries, could additionally result in a decrease in overall plasma utilization with no significant difference being observed in terms of bleed control.⁸

A: Protein S and Plasmin inhibitor levels have been found to be below the range for normal human plasma but within the final product release limits of ≥ 0.4 IU/ml and ≥ 0.2 IU/ml, respectively, and in line with the European Pharmacopoeia (Ph. Eur.) regulations.^11,12

There is no impact on the clinical efficacy of the product.13,14 However, appropriate protection against thromboembolism should be employed when S/D treated plasma is used for large volume exchange, and patients should be monitored for thromboembolic events.³

The decrease in alpha2-antiplasmin concentration may lead to elevated fibrinolysis. Accordingly, Octaplasma^® should not be used to correct hyperfibrinolysis caused by a deficiency of the plasmin inhibitor.³

A: Each 200 mL of Octaplasma^® contains between 0.88 – 1.48 g of sodium citrate dihydrate.3 Thus, citrate levels in Octaplasma^® are comparable to that in single-donor FFP.¹⁰

In a study evaluating Octaplasma^® for large volume plasma exchange in acute TTP, the rate of citrate reactions with Octaplasma^® was 50% lower than CSP. .²²

As with frozen plasma, high infusion rates may drive citrate elevation and lower ionized plasma calcium levels, especially in patients with liver dysfunction. It is therefore recommended that the infusion rate should not exceed 0.020-0.025 mmol citrate/kg body weight/min, which equals to 1 mL Octaplasma^®/kg body weight/min.³

A:  Octaplasma^® is indicated for complex deficiencies of coagulation factors such as consumption coagulopathy e.g., disseminated intravascular coagulation (DIC) or coagulopathy due to severe hepatic failure, massive transfusion, or repeated large volume plasma exchange (especially in patients with impaired liver function). It may be used for emergency substitution therapy in coagulation factor deficiencies, when situations, e.g., hemorrhage, do not allow a precise laboratory diagnosis, or when a specific coagulation factor concentrate is not available. It is also indicated for rapid reversal of effects of oral anticoagulants when vitamin K is insufficient in emergency situations, or in patients with impaired liver function.³ These indications are like those for frozen plasma.¹⁹

 Octaplasma^® is pharmaceutically treated plasma that contains standardized clotting factor levels¹⁶ and can be used in all clinical settings where plasma usage is deemed appropriate as per the discretion of the treating physician.

A: Since the introduction of Octaplasma^® in Canada over 10 years ago, more than 91000 bags have been infused into more than 1000 patients in clinical settings such as high volume or chronic plasma transfusions such as TTP, atypical Hemolytic Uremic Syndrome (aHUS), when FP is not effective and for clotting factor deficiencies where licensed concentrates are not available²⁸ etc.

In a study where Canadian patients were treated with Octaplasma^® for TTP, aHUS, secondary TMA, C3 glomerulonephritis and antibody-mediated transplant rejection, 80% of the 89% who were switched post allergic reaction to FFP or CSP, had stable or improved disease with Octaplasma^® with no severe allergic reactions being reported.²⁹

Octaplasma^® is approved by Health Canada to be used for complex coagulation deficiencies as in DIC, repeated large volume plasma exchange, severe hepatic failure; emergency substitution such as in hemorrhage and for rapid reversal of oral anticoagulants in case of insufficient vitamin K or impaired liver function.³

A: Since the introduction of Octaplasma^® in Europe in 1992, more than 12 million units have been infused into approximately 3.9 million patients.³ Octaplasma^® has been used in all clinical settings where plasma usage is indicated .³⁰

 In the UK, Octaplasma^® is the preferred product for all patients with TTP. ³¹

A: 1 bag of Octaplasma^® contains 200 ml of S/D plasma. The volume of an FP bag varies with the mean ± 1SD volume being 289 ± 16 ML.³²

The difference in volume between an Octaplasma^® and FP bag however does not translate into any difference in efficacy for the approved indications.^3,23 In a study, bleed control was found to be effective for Octaplasma^®   and FFP despite lower volume infused.⁸

 The volume of plasma administered in clinical settings depends on the patients’ underlying disorder, with the volume needed being the same as that of FP for large volume exchanges and for other settings, may vary on a case-by-case basis.

A:  The infusion rate should not exceed 1 mL Octaplasma^®/kg body weight/min which equates to 0.020-0.025 mmol citrate/kg body weight/min as high infusion rates may cause cardiovascular effects as a result of citrate toxicity (fall in ionised calcium), especially in patients with liver function disorders. Patients should be observed for at least 20 minutes after the administration.³

A: The standard protocol for plasma transfusion is use of normal saline to flush the infusion lines.

A: Octaplasma^® must not be mixed with other drugs as inactivation and precipitation may occur. Interactions with other drugs are unknown. To avoid the possibility of clot formation, solutions containing calcium must not be administered by the same intravenous line as Octaplasma^®.³

Due to the risk of activation/inactivation of Octaplasma^®, the concomitant administration of other blood products should be avoided as much as possible, except for emergency situations. However, the product can be mixed with red blood cells and platelets.³

A: Octaplasma^® is contraindicated in patients with IgA deficiency with documented antibodies against IgA as it may cause anaphylactic and anaphylactoid reactions, in patients with severe deficiency of protein S as it may result in an increased risk of developing blood clots and in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.³

Recently thawed Octaplasma at a temperature of +37°C does not need to be infused through blood warmers.

Blood warmers are often used for rapid blood transfusion at a volume load of > 50 mL/kg/hr in hypothermic patients or for rare conditions where cold fluid delivery is problematic (e.g., cold agglutinins), as well as for massive transfusion to avoid hypothermia.

When blood warmers are used, for instance, in the case of previously thawed but refrigerated plasma, they should not bring any blood component to a temperature above the normal body temperature of +37°C, at which all the constituents of blood have their optimal quality and function. Higher temperatures may have a negative impact on the quality and efficacy of the product infused as well as the patients’ safety, e.g., with an increased coagulation time which is observed at temperatures of +40°C.

Most blood warmers have a free setting of the temperature between +37 and 41°C based on 0.5°C steps.

Octapharma does not have data regarding the use of a blood warmer device to administer Octaplasma^®. Therefore, Octapharma cannot recommend the use of Octaplasma^® for thawing or administration using devices that exceed +37 °C. If you are unsure about the temperature of a blood-warming device, do not use it to warm Octaplasma^®.

Octaplasma can be mixed with red blood cells and/or platelets. Octaplasma can be infused into the patient at the same time as red blood cells and/or platelets, but for all these blood products – however, they must be infused through separate infusion lines and not mixed together simultaneously through a Y-aggregate. Neither red blood cells nor platelets activate or inactivate Octaplasma.

Concomitant administration of other blood products with plasma is a common and accepted clinical practice. Patients with multiple intravenous lines could receive blood products simultaneously as happens in trauma settings. We also know from the PROPPR trial that blood products administered within minutes of arrival using a transfusion ratio of 1:1:1 was associated with more patients achieving hemostasis and decreased hemorrhage-related deaths over the first 24 hours.

Octaplasma should NOT be mixed with other drugs/medicinal products and solutions, as inactivation and precipitation may occur. For instance, Octaplasma must not come in direct contact with calcium-containing solutions as calcium promotes clot formation by reacting with the citrate present in Octaplasma as an anticoagulant agent.

According to the approved Canadian product monograph, the Octaplasma® infusion rate must not exceed 1 mL Octaplasma/kg body weight/min or 60 mL Octaplasma/kg/hr. This infusion rate is recommended to avoid the potential risk of citrate toxicity (0.020-0.025 mmol citrate/kg/min) which may result in other health complications.

The recommended rate of infusion rate applies to most patients in receipt of any coagulation active plasma. Most plasma infusions are normally performed with an infusion rate of 10-20 mL/kg/hr, therefore the recommended rate is adequately rapid. If you are using a rapid infuser device, ensure the recommended rate is not exceeded and observe signs of citrate toxicity.

A: Octaplasma^® should be stored and maintained frozen until use (< -18 °C).³

In the event of a temperature excursion, hospitals will need to contact Canadian Blood Services who will then forward the case to Octapharma Canada for assessment. The assessment will be done by Octapharma QA team and will determine next steps on a case-by-case basis.

A: Octaplasma^® can be thawed using either a water bath or a dry tempering system such as SAHARA-III. ³

If using a water bath, thaw with the outer wrapper intact for no less than 30 minutes in a circulating water bath at +30 °C to +37 °C. The minimum thawing time is 30 minutes at 37 °C. The thawing time depends on the number of bags in the water bath. If more plasma bags are thawed in parallel, the thawing time can be prolonged, but should not be longer than 60 minutes.

If using a dry tempering system such as the SAHARA-III, place the Octaplasma^® bags on the agitation plate according to the manufacturer instructions and thaw plasma using the fast-tempering function. When +37 °C blood component temperature is indicated on the temperature display, terminate the tempering process, and remove the bags. It is recommended to use the protocol printer to record the course of the blood component temperature and, error messages in event of failure.

Other thawing systems for frozen Octaplasma^® can be used on the condition that the methods are validated for that purpose.

A: Octaplasma is approved and available in over 30 countries globally. Different countries around the world use different thawing devices, and the thawing time differs significantly based on the device used and the number of bags thawed in parallel. In contrast to FP, Octaplasma^® has a secondary overwrap, and thawing is performed in this outer wrapper. This may influence the thawing time.

Octaplasma^® product monograph recommends 30 minutes thawing time at 37°C, since this time is valid for all devices.

It is suggested that hospitals use their judgment based on the thawing device used locally and the number of bags being thawed. Transfuse only fully thawed bags of Octaplasma^® which is a clear, yellow solution without cloudiness or precipitates.

A:  After thawing Octaplasma^®, it can be stored for up to 5 days at +2-8 °C or for up to 8 hours at room temperature (+20-25°C) before use.³ Thawed Octaplasma^® must not be refrozen.³

 Studies have demonstrated comparable clotting factor activities within thawed and stored Octaplasma^® in the refrigerator for up to 5 days.^33,34,35

A: Four blood type groups of Octaplasma^® are available through CBS, which include A, B, AB, and O. Administration of Octaplasma^® must be based on ABO-blood group specificity, otherwise incompatibility reactions between antibodies contained in Octaplasma^® and antigens on the recipient’s red blood cells can result in immediate or delayed type hemolytic transfusion reactions.³

 In emergency cases, where a specific blood group type is not available, Octaplasma^® blood group AB can be regarded as universal plasma since it can be given to all patients.³

A: Each bag of Octaplasma^® has fixed and variable barcodes.

The fixed barcodes do not change from lot to lot and are based on product code and blood group. They help Octapharma for internal tracing of the lot.

The variable barcodes enable tracing of the bag via ISBT 128 standards. The upper variable barcode denotes bag number, and the lower variable barcode denotes expiry date and donor name with collection time, which may be helpful especially for safety reporting and quality issues.

The objective of thawing any kind of plasma for transfusion is not just to get frozen FFP or Octaplasma to their respective liquid states.

Plasma comprises about 90% water. A cocktail of over 1,000 individual proteins plasma makeup 6-8% of plasma; mostly albumin (55-60%), (α, β and γ) globulins (35-38%) and fibrinogen (4-7%). There are also a number of vital regulatory proteins and coagulation factors (<1%) – as well as electrolytes (e.g., Na+ and Cl-), nutrients [e.g., sugars (glucose) and amino acids], fat (e.g., lipids), hormones (e.g., cortisol and thyroxine), wastes (e.g., urea), and dissolved gasses (e.g., O2 and CO2). Therefore, plasma is a complicated, natural, and multifunctional solution.

Plasma proteins have a primary, secondary, and tertiary structure, shaping molecules with specialized functions under different physical conditions. In frozen plasma, these special functions of plasma proteins are in a static state and need to be regained through thawing, being eventually natural and optimal at around +37°C.
Inadequately thawed plasma can result in the aggregation of plasma proteins (precipitate formation). The recommended thawing temperature helps plasma protein maintain its normal folding.

Therefore, Octaplasma must be allowed to be brought to ‘at or around +37°C’. This is true for frozen products as it is for products in a liquid but a refrigerated state. Octaplasma is a high-quality medicinal product. Thaw it adequately at +37°C, use it quickly, thereafter, and it is best not to under- or overheat the product at any time.

Octaplasma can be stored at ≤ -18°C for up to 4 years after manufacturing. All coagulation-active products, including Octaplasma, should ideally be thawed shortly before use (within 1-2 hours) to ensure the best quality. If however, the product cannot be administered after thawing, it can be stored at +2-8°C for up to 5 days or at +20-25°C for up to 8 hours. Pre-thawed, long-term-stored Octaplasma should therefore be used only as an exception in cases where time plays a crucial role, such as e.g., massive transfusions caused by major trauma.

If the thawed product cannot be used immediately, it is important to let the product reach +37°C, and then let the product rest for some time at room temperature and slowly cool it down to +2-8°C for up to 5 days of storage. This reduces the chance for protein precipitates to form later – especially after 3-5 days.

A:  Six clinical studies with Octaplasma^® have been conducted by Octapharma. In total, 229 patients have been enrolled, and the patients were exposed to a total number of about 1,200 treatment courses with Octaplasma^®.³ These studies were conducted in various types of clinical settings including intensive care patients with DIC, hereditary or acquired isolated or combined coagulation factor deficiency, patients undergoing open heart surgeries and extracorporeal surgery, patients suffering from coagulopathy due to liver disease, liver toxicity ,Thrombotic Thrombocytopenic Purpura (TTP), sepsis among others and covered a wide range of patients aged from 0  to 96 years. In all these studies, Octaplasma^® has been demonstrated to be safe and effective.³

A:  The safety and efficacy of Octaplasma^® in children was demonstrated in two post-marketing studies– LAS-212 and LAS-213.³  

 In the LAS 212 study,²⁰ Octaplasma^® was evaluated in 50 pediatric patients aged between 0 to 16 years in the perioperative setting. Investigators assessed overall safety in this study as ‘excellent’ for all 50 patients. No ADRs were reported including no hyper-fibrinolytic events or treatment-related thromboembolic events. Hemostatic parameters were within the expected ranges after using Octaplasma^®.

In the LAS 213 study,²¹ the safety of Octaplasma^® was evaluated in 41 patients requiring therapeutic plasma exchange (TPE) aged 2 to 20 years. No thrombotic or thromboembolic events or any other treatment-related serious adverse events were reported. Overall safety was assessed by investigators as excellent for >90% of patients 24 hours after each TPE throughout the study.

The studies support the use of Octaplasma^® in managing perioperative or bleeding pediatric patients who require replacement therapy and for TPE in the plasma exchange.

A: The safety of Octaplasma^® for use in human pregnancy and during lactation has not been established in controlled clinical trials.

Although no harmful effects on mother, embryo, fetus, or child are to be expected, Octaplasma^® should be used in pregnant and lactating women when benefit outweighs the potential risk.³

A: The common side effects of Octaplasma^® include nausea, rash, pruritus, pyrexia and chills; similar to fresh frozen plasma and other blood and blood products.^2,19 However, the pooling and immune neutralization, sterile cell filtration,the solvent detergent treatment process and ligand chromatography utilized in manufacturing of Octaplasma^® makes it devoid of antibodies implicated in serious adverse events such as transfusion-related acute lung injury pathogenesis,¹ reduces risk of pathogen transmission¹ and reduces incidence of allergic reactions as compared to fresh frozen plasma.²²

 In a single- center study comparing Octaplasma^® to Cryosupernatant plasma (CSP) for large volume plasma exchange in acute TTP, citrate reactions decreased by >50% and allergic reactions decreased > 60% with use of Octaplasma^®.²³

Data from the UK between 2012-2021 showed the lowest risk of transfusion reactions for SD Plasma as compared to all other plasma products.²⁴

A:  In a single-center study comparing Octaplasma^® to Cryosupernatant plasma (CSP) for large volume plasma exchange in acute TTP, allergic reactions decreased > 60% with use of Octaplasma^®.²³

 Pooling plasma and viral immune neutralization utilized in manufacturing of Octaplasma^® reduces allergic reactions by diluting and reducing antibody titres against blood cells and plasma proteins^25,26 and by eliminating the highest molecular weight forms of vWF. ²⁷ The risk of alloimmunization or other cell-related reactions is further reduced by size-exclusion and ligand chromatography, a sterile cell filtration process used in Octaplasma^® manufacturing.^20,28