Achievements

The aim of this study was to collect data on supernatant potassium data in standard adult red cell components (RCC) early in storage, with or without irradiation.

This is to aid the response to queries from hospitals regarding expected levels of potassium at varying point in shelf-life with or without irradiation, which is known to increase potassium leakage from red cells.

These data will be used to increase our data base on expected values in blood for transfusion.

We performed laboratory studies to assess the feasibility of cryoprecipitate stored cold (2-6 °C) for 5 days following thawing to increase its shelf-life from the current maximum of 4 hours.

A provisional specification for an extended post-thaw shelf-life cryoprecipitate component was subsequently approved by JPAC.

This will allow NHSBT to trial the extended shelf-life with a small group of hospitals to better evaluate its feasibility and benefits in routine use, including time to administration and reduction in wastage.

In a study that will be published later in 2021, we compared the equivalence of gamma and x-irradiation on red cell components, a process required for certain transfusion recipient groups.

This followed a national incentive to move away from gamma sources in order to improve biosecurity.

CDL’s work on the effect of x-ray irradiation on red cells has been included in a Public health England (PHE) white paper on safer alternatives to gamma irradiation.

The paper includes a decision tree with a recommendation that x-irradiation can be used as an alternative. The process is now in routine use in NHSBT.

• PHE: Alternatives to caesium irradiators for biological sciences and blood transfusion services (PDF 758KB)

NHSBT were required to collect convalescent plasma in response to the COVID-19 pandemic. This required validation of a novel plasmapheresis device as part of the overall project to produce convalescent plasma at scale.

We rapidly performed a laboratory validation study, evaluating plasma quality of units collected on the new device, and stored in two different blood packs.

This enabled this device to be used routinely from December 2020. As part of this process a provisional trial specification ‘Convalescent Plasma (COVID-19), FFP, Leucocyte Depleted’ was agreed by SACBC and JPAC.

This has been incorporated onto the ‘Guidelines for the Blood Transfusion Services’ website.

During the initial stages of the COVID-19 pandemic, we reviewed and summarised internal and external data to support an extension in shelf-life from 35 to 42 days.

The output of this work was an agreed new component specification in Annex 5 of the UK blood transfusion Guidelines – Blood Components for Contingency Use.

Thankfully, red cell stocks remained above critical levels and NHSBT weren’t required to utilise the increase in shelf-life.

Nevertheless, this work will allow the shelf-life of red cells to be extended in the future should the need arise.

In the early stages of the COVID-19 pandemic, we led a national review of options to enhance the platelet supply in case of excess demand – particularly options that could be implemented quickly and easily.

We quickly undertook a laboratory validation that confirmed acceptable quality of apheresis platelets in plasma split into smaller doses than standard, potentially allowing production of more units of platelets for a given number of donations.

This study was the basis for a specification for the product approved for use as contingency if needed by JPAC in September 2020.

Alongside work on extending the shelf-life of red cells (below), this was recognised by a Royal College of Pathologists Achievement Award.

In 2020, we validated an alternative platelet additive solution for the manufacture of washed platelets (Platelets in Additive Solution, Leucocyte Depleted) due to the planned withdrawal from the market of the existing additive solution.

A revised component was produced and validated by CDL and rolled out operationally in routine production.

Some further work may be required in 2021/22 to resolve any remaining teething issues.

During the manufacture of platelets and plasma components, red blood cells (rRBCs) may also end up in the product to a varying degree.

Due to their potential to cause adverse clinical effects, enumeration of rRBCs is required to ensure compliance with quality monitoring (QM) guidelines, but there is no standard method to do this.

Similarly, the specific role of rRBC-platelet interactions on platelet quality is unknown.

Using a Sysmex XN-series analyser with the Blood Bank (BB) mode software we have been able to assess a simple and robust method to enumerate rRBCs, and to examine their effect on the quality of PCs. 

Assessment of the BB mode rRBC counting technology demonstrated performance characteristics acceptable for use in NHSBT’s QM environment. 

This work will enable assessment of levels of RBC in components to aid risk assessment as part of our work on Universal Platelets.

The aim of this study was to validate the delayed manufacture of leucocyte depleted whole blood for up to five days after venepuncture (VP), in order to allow more operational flexibility in routine manufacturing.

The data supported the conclusion that blood should be processed as soon after collection as possible, but that - if necessary - this could be extended to Five days.

Paediatric red cell components are currently produced from whole blood that is placed in cold storage (4±2ºC) within 12 hours from venepuncture – the ‘12-hour rule’. This creates a considerable operational constraint and therefore we undertook a study to consider whether this timeframe could be safely extended to 16 hours. 

The study concluded that the data did not support changing current policy at present, and that further work is needed to fully understand the risks associated with extending this time limit.

In collaboration with Sysmex UK, Europe and Japan, we have investigated whether a novel software development linked to a haematology analyser can be used to accurately measure residual white (rWBC) in blood components.

Flow cytometry is the current standard method used in the UK to routinely monitor blood for transfusion.

Our work aimed to ascertain whether we could improve the efficiency of these measurements – both in terms of lowering the cost and creating less operator workload – whilst increasing the amount of data obtained per test.

We undertook initial studies to establish the accuracy and sensitivity of the rWBC measurements, before establishing a two-month field trial in Manchester’s NHSBT routine quality monitoring laboratory.

Our seminal study was published in the journal Transfusion in January 2020, and was in the top ten percent of the journal’s downloaded articles for 2019/20.

Platelets are routinely tested at the end of their shelf-life for pH, a marker of platelet quality.

Routine quality data from NHSBT had indicated that maintaining compliance with standards for pH for platelets produced for neonates had become increasingly challenging.

To alleviate this issue, we developed and validated a new neonatal platelet product by adding a small amount of an artificial platelet storage solution to improve platelet quality.

We summarised the data to allow the UK Standing Advisory Committee on Blood Components to approve the use of the product in the UK, and translated our knowledge to routine manufacturing to enable the implementation and routine use of this product in January 2020.

NHSBT Quality monitoring data has shown < 90% compliance for neonatal platelet pH at expiry. It is unclear as to the cause of this decrease in compliance and a number of operational changes have occurred which may have contributed.

This CDL study was designed to investigate whether the volume of the neonatal split PC affects the quality of the component, as demonstrated by its pH. 

Double dose apheresis platelets in plasma were divided into splits of different volumes and were tested over storage to assess quality. Data indicated that a neonatal PC with a larger volume than current would have improved quality (including pH) at the end of storage (day 8) and that reducing the shelf life of neonatal PC would ensure a component with a higher pH at end of storage.

NHSBT are currently considering options to obviate this issue based on the data, including moving to a shorter shelf life for neonatal platelets, or reducing the number of splits made from a single apheresis platelet.

Transfusion with multiple components in different bags within the pre-hospital setting and/or trauma environment is challenging.

To facilitate better provision of blood components and improve management of major haemorrhage, NHSBT are collaborating with Barts Health Trust and London Air Ambulance (LAA) to re-establish a whole blood component (red cell, plasma and platelets in one bag).

In Phase One, CDL performed the in vitro studies to validate storage of a red cell and plasma component, for use in an 18-month feasibility study on board the LAA.

This work was accepted for publication in Transfusion.

We were part of the small task force that reviewed and updated this guideline, and co-authors of the final published version (see publications). We incorporated a revision to the shelf-life of plasma from 24 to 120 hours, based on validation studies in CDL

We led this work as part of our contribution to the UK Standing Advisory Committee on Blood Components (SACBC). This includes specifying the level of microbial kill expected from these systems and validation of blood component quality.

We consulted with manufacturers of PI systems in the development of this guidance, and the final version was reviewed and approved by the UK Joint Professional Advisory Committee, and will be posted on their website so that this is publicly available and transparent.

In conjunction with research colleagues in Prof Anstee’s group, and the NIHR Cambridge Bioresource, CDL have performed a number of studies to assess the impact of a rare genetic variant that causes red cells to release more potassium when they are stored in the cold (familial pseudohyperkalemia - FP).

Other than increased rate of potassium leakage, red cells from these donors appear to function normally and the variant does not have any impact on the health of the donor. However, there is the potential for adverse effects from these red cells when they are transfused in large volumes to neonates.

In collaboration with Dr Helen New, we have undertaken a clinical risk assessment which has led to the UK wide recommendation (via JPAC) that where such donations are identified, they are not used to manufacture red cells for neonates and infant large volume transfusion.

Following concerns regarding consistently out of consensus results in the full blood count scheme of UK NEQAS, we carried out detailed analysis of QC data and of NEQAS sample results obtained on our XN-1000 and XN-450 Sysmex Haematology analysers.  

As a direct result of our work and discussion with UK NEQAS, they have changed how they group analysers for analysis of results for full blood counts.

As part of a project investigating the potential use of pathogen inactivation (PI) of platelet concentrates, The Component Development Laboratory (CDL) optimised the production of an 8 buffy coat (BC) ‘double dose’ platelet concentrate that could be PI treated and subsequently split into two adult therapeutic doses. This would improve the cost-effectiveness of such treatment.

As part of an agreement between NHS Blood and Transplant (NHSBT ) and Haemonetics, data was provided to Haemonetics to enable them to update the CE mark for their leucodepletion filter for used with up to 8 buffy coats, and their platelet storage bag to contain a double dose platelet concentrate (up to 8 BCs), for up to 6 hours with agitation.

This CE mark change would facilitate an easier transition should PI treatment of platelets be implemented by NHSBT in the future.

Intra-uterine transfusion (IUT) red cell units are provided to foetuses and therefore have high specification and a 5-day shelf life to reduce risk to the recipient. This study validated the re-manufacture of unissued IUT units into standard red cells for neonates and adults to reduce wastage as a result of consolidation of manufacturing activity in the North of England. The study results showed that IUT units not issued for transfusion can be re-manufactured on day 7 into standard red cells for adult or neonates and stored up to 35 days post-donation. The re-manufactured adult-sized red cells can be irradiated but not the re-manufactured neonatal-sized red cells. This work has enabled a change in practice that will reduce the wastage of high specification red cells (estimated to cost £30,000 per annum).

These components are transfused to patients who have severe allergic reactions to standard red cell components. The Component Development Laboratory validated alternative methods for preparing washed red cells which improved the quality and content of the red cells. The selected new method (manual wash with SAGM) also offers a significant cost reduction (£180,000 per annum) compared to the previous method (Automated ACP215).

Red cells are stored in the fridge within a controlled temperature range to ensure that their quality is preserved, and to reduce the risk of bacterial growth which can occur at higher temperatures. Hospitals limit the time red cells are removed from a controlled temperature environment to 30 minutes or they must be discarded - the '30 minute rule'. This results in around 10,000 units of red cells being discarded annually in England. A systematic review of the literature conducted by NHS Blood and Transplant concluded that the evidence base to support the 30 minute rule was poor, and that there may be scope to extend it if further studies were conducted. A survey commissioned with the Blood Stocks Management Scheme suggested that if the 30 minute rule could be extended to 60 minutes, a large proportion of the 10,000 units currently discarded might be saved and be able to be transfused.

Changes in clinical guidelines in 2015 recommended that transfusion laboratories should consider having pre-thawed plasma on standby to allow it to be immediately available for the management of major bleeding associated with trauma. This led to practical difficulties, including increased fresh-frozen plasma (FFP) wastage due to the shelf-life of pre-thawed FFP being only 24 hours. The Component Development Laboratory evaluated two options for ameliorating this issue: either to extend the shelf life of frozen plasma following thawing or to have a never frozen liquid plasma component.  This led to a change in UK guidelines to allow the shelf life to be increased from 24 to 120 hours. Many hospitals are now pre-thawing plasma for unexpected major haemorrhage with a 5 day shelf-life and this has reduced the wastage of plasma.

Historically NHS Blood and Transplant have received a relatively large number of complaints from hospitals regarding precipitated matter in cryoprecipitate (lumpy cryo). Work within The Component Development Laboratory on pathogen inactivated cryoprecipitate has looked at a new centrifugation profile (reduced time and speed). This study revealed that the new spin profile would not only be quicker for manufacturing sites but also produced cryoprecipitate that was as least as good as the current component and contained less visible precipitate.

Short term deviations in the normal storage temperature of frozen plasma can occur and can result in the requirement to discard units of plasma. The Component Development Laboratory performed a large study to determine the effects of short-term deviations in freezer temperature on fresh-froxen plasma (FFP) quality. This work has lead to 1000s of units of FFP not being discarded as evidence is now available to inform risk assessments.

A small number of hospitals had a policy of ordering washed red cells for renal transplant recipients to prevent human leucocyte antigen (HLA) sensitisation as this process was thought to reduce the amount of leucocytes in the component. The Component Development Laboratory undertook a study which demonstrated that washing red cells was unlikely to be beneficial in this respect, enabling a change in practice.

Combined laboratory studies and platelet recovery and survival studies in healthy subjects assessing platelets treated using the Theraflex UVC system. Performed in collaboration with the manufacturers (Macopharma) enabling them to CE mark the process and proceed to phase II/III clinical studies.

Production of a new pooled granulocyte component and its validation in laboratory studies. Prior to this hospitals were offered individual buffy coats. The new component contains fewer contaminating red cells and is available as a pooled component that is operationally easier for hospitals administering the component. This component has been issued as a standard component since 2012.

Validation of re-manufacturing red cells originally intended for neonatal exchange transfusion if not issued by the end of their shelf-life (day 5), to red cells suitable for transfusion to adults, to reduce wastage of these precious red cells. This work was later repeated to allow remanufacture of units up to the end of day 7.

Validation of the methylene blue pathogen inactivation system to produce cryoprecipitate. This enabled NHS Blood and Transplant to produce a pathogen inactivated cryoprecipitate product to improve blood supply.