FAQ

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

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

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

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.

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

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

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.

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

Octaplasma^® is associated with reduced risk of pathogen transmission,⁷ a lower risk of TRALI¹ and a lower risk of non-hemolytic transfusion reactions when compared to FFP, particularly allergic reactions and citrate reactions.^18,22

 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.

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

 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

 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

The fixed barcodes (in black in the above image) 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 (highlighted in purple in the image above) 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.

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.

Below is a guide on the appearance of thawed Octaplasma ® bags and when a bag would be considered safe to transfuse:

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.

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

 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

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.

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.

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^®.

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.

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.