Universal plasma quality and coagulation parameter stability during storage

Plasma isoagglutinins require ABO blood group compatibility. We have developed a GMP-compliant method to deplete the isoagglutinin titer of fresh frozen plasma (FFP) units of groups A, B and O based on isoagglutinin adsorption on added red cells from red cell concentrates (RCC). We performed an extensive validation study to assess the effect of plasma treatment of blood group A plasma on coagulation and immune parameters directly after manufacture and after storage at ≤30°C for at least 6 months.

We have developed a bag system that facilitates the pooling of three units of FFP, addition of the appropriate volume of RCC, and subsequent removal of the isoagglutinin red cell sediment in a closed system. After incubation at 20-24°C for two hours, the isoagglutinin red cell sediment was separated from the plasma pool by centrifugation (4,000g, 10min). We compared plasma units from 12 production processes (totaling 36 units) with and without the addition of RCC for isoagglutinin adsorption, focusing on the following parameters: anti-B titer, hemoglobin, residual erythrocytes, factors II-XIII, fibrinogen, vWF antigen + activity, protein C + S, antithrombin, ADAMTS13, aPTT, Quick value, lactate dehydrogenase, and complement activation immediately after production and after storage at ≤-30 °C for 8.6±1.5 months.

From peaks of 1:16 in the plasma pools, total anti-B titers were reduced to < 1:1 in all units in the treatment arm. The coagulation factors II to XIII of the plasma units analyzed were largely within reference ranges even after 6 months of storage, except for factor VIII in both the treatment and control arm. Factor VIII decreased on average by 21.4% (treatment group) and 14.9% (control group) after 6 months of storage, thus fulfilling the requirements of the hemotherapy guidelines. Other as parameters C3 and C4 complement activity, ADAMTS13, INR, vWF antigen and activity and lactate dehydrogenase were within reference ranges after storage. There was no difference between the control and treatment groups.

We introduce a fully automated GMP-compliant method for producing universal plasma suitable for blood group-independent transfusion. Our method maintains the quality and safety of universal plasma, as demonstrated by the preservation of all coagulation and immunological parameters even during storage for at least 6 months below -30°C.

Macopharma kindly provided the bag systems.