Background
Isoagglutinins in plasma require for ABO blood group compatibility. We developed a GMP conform procedure to deplete the isoagglutinin titer of fresh frozen plasma (FFP) units group A, B, and O. The method is based on isoagglutinin adsorption onto added red cells. A requirement for the approval of isoagglutinin depleted plasma from blood group A units was an extensive validation study to be able to assess the impact of the plasma treatment on coagulation and immune parameters.
Methods
We developed a bag system, which enables pooling of three FFP units, addition of the adequate RCC volume and subsequent removal of isoagglutinin red cell sediment in a closed system. After incubation at 20-24°C for two hours the isoagglutinin red cell sediment was removed from the plasma pool by centrifugation (4,000g, 10min) and separation. Within the validation study we compared plasma units of 12 production processes (=36 units) with or without the addition of RCC for isoagglutinin adsorption with regard to the following parameters: anti-B titer, free hemoglobin, residual red cells, factors II–XIII, fibrinogen, vWF antigen+activity, protein C + S, antithrombin, ADAMTS13, aPTT, Quick value, lactate dehydrogenase and complement activation.
Results
Starting from maximum values of 1:16 in the plasma pools, total anti-B titers were reduced to < 1:1 in all units of the treatment arm. Free hemoglobin was similar between the control and treatment group (24.8±19.7 µM vs 22.9±15.4 µM; p>0.5). No residual red cells were found by microscope counting. All other coagulation and immune parameters showed no significant differences between the control and treatment arms (Table 1).
Conclusion
We present a fully automated GMP conform procedure for the production of isoagglutinin depleted plasma without any impact on a large set of coagulation and immune parameters.
Offenlegung Interessenkonflikt:
Macopharma kindly provided parts of the bag system used.