Stability Of Coagulation Factors Research Articles

Stability of coagulation factors in feline fresh frozen plasma intended for transfusion after 1 year of storage.

The most common use of plasma transfusion is for haemostatic purposes, but coagulation factor activities in stored feline plasma are unknown. The concentration and stability of coagulation factors I (fibrinogen), II, V, VII, VIII, IX, X, XI and XII in feline fresh frozen plasma (fFFP) stored for 1 year were studied. Fifty-five units of fFFP were produced from 55 fresh whole-blood donations obtained from indoor healthy blood donor cats. Twenty-one units were stored for <2 weeks (T0) and 34 were stored for 1 year (T1). After the completion of storage, specific coagulation factor activities for factors II, V, VII, VIII, IX, X, XI and XII were tested using modified one-stage activated partial thromboplastin or prothrombin time assays. Fibrinogen was determined using the Clauss method. Significantly decreased activities were observed for factors II (T0: 101.94% ± 19.06%; T1: 73.23% ± 39.06% [P = 0.001]), VII (T0: 102.78% ± 24.69%; T1: 60.08% ± 38.17% [P <0.001]), VIII (T0: 77.52% ± 30.39%; T1: 50.32% ± 23.8% [P = 0.001]), XI (T0: 88.76% ± 22.73%; T1: 66.28% ± 22.2% [P = 0.001]) and XII (T0: 89.50% ± 21.85%; T1: 55.46% ± 23.18% [P <0.001]) when comparing units at time 0 and after 1 year of storage. No significant difference was observed for factors IX (T0: 84.86% ± 29.35%; T1: 71.37% ± 22.23% [P = 0.064]) and X (T0: 96.24% ± 25.1%; T1: 83.91% ± 49.54% [P = 0.236]). Unexpectedly, a significant increase was observed for factor V (T0: 71.94% ± 24.14%; T1: 97.89% ± 62.33%; P = 0.046). Fibrinogen was 2.76 ± 1.09 g/l at T1. Factors VIII, XII and VII had the lowest mean activities after 1 year. Although a decrease in most coagulation factors activities was noted with storage, 1-year-old fFFP was haemostatically active in vitro. The most suitable factors for quality control assessment of fFFP are factors VII and VIII. Approximately 13-20 ml/kg of fFFP is required to administer a minimum of 10 IU/kg coagulation factor activity.

Preparation and Storage of Cryoprecipitate Derived from Amotosalen and UVA-Treated Apheresis Plasma and Assessment of In Vitro Quality Parameters.

Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, cryoprecipitate production in blood centers is a feasible alternative to pharmaceutical fibrinogen concentrate with a high safety profile. In our study, we evaluated the feasibility of the production of twenty-four cryoprecipitate units from pools of two units of apheresis plasma pathogen reduced using amotosalen and ultraviolet light A (UVA) (INTERCEPT® Blood System). The aim was to assess the compliance of the pathogen-reduced cryoprecipitate with the European Directorate for the Quality of Medicines (EDQM) guidelines and the stability of coagulation factors after frozen (≤−25 °C) storage and five-day liquid storage at ambient temperature post-thawing. All pathogen-reduced cryoprecipitate units fulfilled the European requirements for fibrinogen, factor VIII and von Willebrand factor content post-preparation. After five days of liquid storage, content of these factors exceeded the minimum values in the European requirements and the content of other factors was sufficient. Our method of production of cryoprecipitate using pathogen-reduced apheresis plasma in a jumbo bag is feasible and efficient.

Stability of coagulation factors in plasma prepared after a 24‐hour room temperature hold

The manufacture of fresh-frozen plasma (FFP) requires that plasma be frozen within 8 hours of collection and 24-hour frozen plasma requires 1 to 6°C refrigeration before freezing. Manufacture of plasma after a room temperature hold for 24 hours, while convenient, could compromise clotting factor levels. Pairs of FFP and 24-hour room temperature-frozen plasma (PLT-rich plasma [PRP]-24HRTFP) were manufactured from PRP after a room temperature hold for 8 and 24 hours, respectively. Additional whole blood (WB) donations were kept at room temperature for 24 hours before plasma manufacture (WB-24HRTFP). The frozen plasma products were stored at -18°C, thawed, and then stored at 1 to 6°C, with coagulation factor assays performed for up to 7 days. On the day of thaw, Factor (F)VIII was lower in PRP-24HRTFP by 13% (p = 0.002) but not in WB-24HRTFP (p = 0.3) compared to FFP. All other clotting factors were within normal range. During the postthaw period FVIII and FV declined 25 and 6%, respectively, in WB-24HRTFP and 23 to 50% in the paired products; however, the difference between both types of 24HRTFP and FFP is insignificant by Day 7 (p > 0.05). Other clotting factors either were unchanged or showed minimal reduction (< 15%). Plasma manufactured after a 24-hour room temperature hold contains coagulation factors comparable to FFP except for a possible reduction of up to 20% in FVIII. This plasma appears suitable as a transfusable product and extension of liquid storage to 7 days merits consideration.

Effects of collection technique and storage conditions on the stability of coagulation factors in frozen equine plasma

Effects of collection technique and storage conditions on the stability of coagulation factors in frozen equine plasma

Effects of extended storage of whole blood before leucocyte depletion on coagulation factors in plasma

The aim of this study was to evaluate the quality of leucocyte-depleted plasma produced from leucocyte-depleted whole blood, stored for different periods of times before filtration through polyurethane filters. Whole blood was collected, from 48 voluntary donors, into quadruple blood bag sets with integrated whole-blood filters, and stored at room temperature for 1, 2, 6, or 18 h before filtration. Five samples were taken: one directly from the donor; one immediately after collection; one before and one after filtration; and one from plasma units before freezing. All samples were analysed for the following parameters: prothrombin time; activated partial thromboplastin time; prothrombin fragments F1+2; fibrinogen; factors VIII, XI and XII; von Willebrand factor antigen; ristocetin cofactor activity; collagen-binding capacity; multimers; and complement C3a-desArg. Different whole-blood storage times before filtration did not have a significant effect on the stability of coagulation factors. The activity of all investigated coagulation factors in plasma was generally above 90 U/dl, even after 18 h of storage of whole blood before filtration. von Willebrand factor multimeric distribution remained stable throughout the process. However, activation of complement did occur during storage. Leucodepleted plasma originating from leucodepleted whole blood maintains a satisfactory level of coagulation factors, even after the storage of whole blood for 18 h at room temperature before filtration.

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

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.

Refreezing previously thawed fresh‐frozen plasma, Stability of coagulation factors V and VIII:C

With the growth in autologous blood programs and the increased scrutiny of the indications for transfusion of fresh-frozen plasma (FFP), an increase has been seen in the number of occasions on which FFP was requested and thawed but then not transfused. The coagulation properties of FFP units that were refrozen and then rethawed were therefore studied. Fifty-eight units of plasma were studied, with each experimental unit of FFP paired with an identical control unit. Experimental units were frozen, stored at -65 degrees C, thawed, stored at 1 to 6 degrees C for various periods of time up to 24 hours, and then refrozen, stored at -65 degrees C, rethawed, and stored again in the refrigerator for up to 24 hours. Control units were frozen once at the time the experimental units were first frozen and thawed once at the time of the second thaw of the experimental units. Aliquots of plasma were sampled periodically and were later batch-tested for prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor V and VIII:C activity. The results of coagulation testing of the twice-frozen plasmas were always within the normal range. There was a slight but statistically valid prolongation of the PT and aPTT and a decrease in the factor V and VIII:C levels for twice-frozen plasma compared with control plasma. The greatest decline occurred in the level of factor VIII:C. The measured deterioration in coagulation of twice-frozen FFP is unlikely to be of clinical importance. Refreezing FFP may eventually prove useful for rare donor, autologous, and massive transfusion programs.

Stability of Coagulation Factors I and X During Collection and Subsequent Storage of Bank Blood in ACD‐A and CPD Solutions

Abstract. Factors I and X were not significantly altered during the collection of bank blood into ACD‐A and CPD preservative fluids. The factors remained relatively stable on subsequent storage under standard conditions for up to 21 days.

Stability of Coagulation Factors I and X During Collection and Subsequent Storage of Bank Blood in ACD-A and CPD Solutions

Factors I and X were not significantly altered during the collection of bank blood into ACD-A and CPD preservative fluids. The factors remained relatively stable on subsequent storage under standard conditions for up to 21 days.