Long-Term Storage of Fresh Frozen Plasma at –40 °C. A Multicenter Study on the Stability of Labile Coagulation Factors over a Period of 3 Years

Abstract

Background: Fresh frozen plasma (FFP) is exposed to numerous factors affecting the quality and stability of coagulation factors during blood collection, preparation and storage. In 1995 the European ‘Guide to the preparation, use and quality assurance of blood components’ extended the shelf-life of FFP from 12 to 24 months and concurrently reduced the storage temperature from –30 to –40 °C. Four years later, the European guidelines amended the storage regulations and permitted a 24-month shelf-life at –30 °C. This new regulation of FFP led us to the question whether storage over 3 years at –40 °C could be performed without relevant loss in coagulation factor activity. Due to missing data, a multicenter study was carried out in 7 different quality control (QC) laboratories of the Bavarian Red Cross Blood Transfusion Service. The aim of our study was to obtain selected stability data of the coagulation factors FV, FVIII:C and FXI as well as of the major inhibitor antithrombin III (AT III) over a storage period of more than 3 years at –40 °C. Material and Methods: 12 plasma units – 3 of each ABO blood group – derived from CPD whole blood were processed according to current national and European guidelines. The plasma units were aliquoted and frozen within 18 h after donation at below –30 °C. The storage temperature was held between –38 and –42 °C during the total storage period of 37 months. In the long-term storage, 4 parameters of the coagulation system were determined in aliquots in 7 different QC laboratories. One-stage coagulometric methods were used to determine coagulation factors, and the determination of AT III inhibitor activity was done by a chromogenic method. After the 1st month of storage, each plasma was tested for specific activity. Thereafter, follow-up testing was performed in 4-month periods. Results: The evaluated coagulation parameters show an acceptable stability during the total storage period if ABO blood groups are not taken into consideration. There was no statistically significant loss in activity for FXI and AT III at the end of the storage period in comparison to the initial values, 101.5% for FXI (pFXI = 0.17) and 101% for AT III (pAT III = 0.66). The loss in FV and in FVIII:C activities was 0.6 and 9%, respectively. Both results indicate a statistically significant reduction (t test: pFV = 0.048; pFVIII:C = 0.033). Similar results were obtained taking ABO blood grouping into account, with the exceptions of blood group A where AT III showed an increase of 11% over baseline values and of blood group O where FXI showed an increase of 11.2% over average coagulation activities. There were no differences in the coagulation activities of blood groups B and AB over the storage period. Conclusions: The results show that, under these storage conditions, the recovery of coagulation parameters in FFP is not reduced below 70% of the starting activity and stays in acceptable ranges. For FXI and AT III we did not find any significant reduction. However, for FV and FVIII:C a significant reduction was found, although total activities were not dramatically low. With regard to the guidelines for therapeutic plasma, our findings show that an extended storage for up to 3 years at –40 °C should be possible without clinically relevant loss of efficacy.