Recommendations for in vitro evaluation of blood components collected, prepared and stored in non-DEHP medical devices.

BACKGROUND AND OBJECTIVES: DEHP, di(2-ethylhexyl) phthalate, is the most common member of the class of ortho-phthalates, which are used as plasticizers. The Medical Device Regulation has restricted the use of phthalates in medical devices. Also DEHP has been added to the Annex XIV of REACH, "Registration, Evaluation, Authorisation and Restriction of Chemicals" due to its endocrine disrupting properties to the environment. As such, the sunset date for commercialisation of DEHP-containing blood bags is May 27th 2025. There are major concerns in meeting this deadline as these systems have not yet been fully validated and/or CE-marked. Also, since DEHP is known to affect red cell quality during storage, it is imperative to transit to non-DEHP without affecting blood product quality. Here, EBA members aim to establish common grounds on the evaluation and assessment of blood components collected, prepared and stored in non-DEHP devices. MATERIALS AND METHODS: Based on data as well as the input of relevant stakeholders a rationale for the validation of each component was composed. RESULTS: The red cell components will require the most extensive validation as their quality is directly affected by the absence of DEHP, as opposed to platelet and plasma components. CONCLUSION: Studies in the scope of evaluating the quality of blood products obtained with non-DEHP devices, under the condition that they are carried out according to these recommendations, could be used by all members of the EBA to serve as scientific support in the authorization process specific to their jurisdiction or for their internal validation use.

Antioxidants in single methylene-blue-treated plasma units cannot be used to predict pathogen inactivation treatment success.

BACKGROUND AND OBJECTIVES: Measurement of antioxidant power (AOP) can be useful to validate the execution of the pathogen inactivation (PI) treatment of plasma units. The aim of this study was to evaluate the Theraflex technology for plasma units routinely used in Belgium. MATERIALS AND METHODS: AOP was tested on plasma units treated by Theraflex with various non-complete treatment scenarios. AOP was quantified electrochemically using disposable devices and was expressed as equivalent ascorbic acid concentration. RESULTS: During a complete PI treatment, AOP rose from 195 ± 32 to 230 ± 42 µmol/L eq. ascorbic acid after addition of methylene blue (MB), and decreased to 192 ± 30 µmol/L eq. ascorbic acid after illumination and finally to 177 ± 27 µmol/L eq. ascorbic acid after final filtration. Without MB, the final filtration had no effect on the plasma AOP (197 ± 22 µmol/L eq. ascorbic acid before filtration and 194 ± 22 µmol/L eq. ascorbic acid after filtration). With no MB and no illumination, there was no significant difference between the plasma AOP at the beginning (188 ± 23 µmol/L eq. ascorbic acid) and at the end of the process (179 ± 21 µmol/L eq. ascorbic acid). CONCLUSION: AOP measurement may not indicate the effectiveness of the PI treatment.

Evaluation of the hemostatic capacity of methylene blue-treated liquid (not frozen) plasma stored up 14 days at 2° to 6°C.

BACKGROUND: Early plasma transfusion for management of bleeding, particularly trauma, is associated with better outcomes. Improving the availability/safety of plasma transfusion for patients is essential for transfusion services. The aim of this study is to evaluate the hemostatic capacity of methylene-blue (MB) liquid (not frozen) plasma over time. MATERIALS AND METHODS: Twenty whole blood-derived plasma units collected from male donors were separated and processed within 18 h of collection. Individual plasmas were treated with MB and stored in liquid status at 2-6°C for 14 days. A range of coagulation assays, including thrombin generation, rotational thromboelastometry (ROTEM), and Thrombodynamics were tested at different time-points, together with bacterial growth. RESULTS: Apart from Factor (F)XII, other coagulation factors (fibrinogen, FV, FVIII, FXI) reduced significantly after MB treatment, with levels remaining stable except for FVIII afterward. By day 14, most clotting factors were >0.7 IU/ml, apart from FVIII. There was a disproportionate decrease in Protein S (PS) activity compared to free PS antigen and by day 14 its value was ~50%. There was no significant difference in maximum clot formation (ROTEM) and clot-density (Thrombodynamics) over time. Endogenous thrombin potential (Thrombin-Generation), clot-size, and velocity index (Thrombodynamics) decreased significantly over time consistent with clotting factor reduction. There was no bacterial growth. CONCLUSIONS: MB-treated liquid plasma stored at 2-6°C can be used for up to 14 days: the long shelf-life, the liquid status, and the MB treatment will improve its availability for management of bleeding as well as providing a safe component from pathogens.

Antioxidant power measurement in platelet concentrates treated by two pathogen inactivation systems in different blood centres.

BACKGROUND AND OBJECTIVES: The antioxidant power measurement can be useful to validate the execution of the pathogen inactivation treatment of platelet concentrates. The aim of this study is to evaluate the technology on different blood preparations including INTERCEPT and Mirasol treatments that are in routine use in Belgium and Luxemburg. MATERIALS AND METHODS: The antioxidant power measurement was tested on 78 apheresis platelet concentrates and 54 pools of buffy-coats-derived platelet concentrates before and after INTERCEPT treatment. In addition, 100 Reveos platelet pools were tested before and after Mirasol treatment. The antioxidant power was quantified electrochemically using disposable devices and was expressed as equivalent ascorbic acid concentration. RESULTS: Mean results for apheresis platelet concentrates were of 90 ± 14 and 35 ± 10 µmol/l eq. ascorbic acid before and after INTERCEPT treatment, respectively. The mean results for pools of buffy-coats-derived platelet concentrates were of 81 ± 10 and 29 ± 4 eq. µmol/l ascorbic acid before and after INTERCEPT treatment, respectively. For buffy-coats-derived platelet concentrates treated by Mirasol technology, the mean results were of 98 ± 11 and 32 ± 10 µmol/l eq. ascorbic acid before and after illumination, respectively. CONCLUSION: The antioxidant power significantly decreases with pathogen inactivation treatments for platelet concentrates treated by INTERCEPT or Mirasol technologies.

Influence of platelet preparation techniques on in vitro storage quality after psoralen-based photochemical treatment using new processing sets for triple-dose units.

BACKGROUND: The INTERCEPT Blood System (IBS) for platelets (PLTs) uses a combination of psoralen and ultraviolet-A light to inactivate pathogens that may contaminate PLT concentrates (PCs). However, no data are available on the quality of IBS-treated PLTs from different apheresis and buffy-coat PC preparation platforms using the new triple storage (TS) set. STUDY DESIGN AND METHODS: The objective of this study was to evaluate the TS set on three different preparation platforms compared with the large-volume (LV) set, as control. PLT in vitro metabolic and activation parameters were studied over 7 days. RESULTS: Several statistical differences are observed between the two sets, particularly for pH, oxygen pressure (pO2 ), carbonic gaz pressure (pCO2 ), and bicarbonate. The three different preparation techniques influence PLT parameters, and the difference is statistically significant for all the studied parameters, except for pCO2 . The TS set has the advantage of shorter compound adsorption device time, higher PLT recoveries, and less PLT activation. CONCLUSION: Results from the measured metabolic parameters and PLT variables obtained from PCs treated by LV and TS sets indicated good PLT function preservation up to 7 days of storage. The in vitro assessment results demonstrated acceptable PLT function for transfusion.