Barts c4ts winter 2016 newsletter

C4TS Newsletter Winter 2016 Issue 9 Welcome to the C4TS Winter 2016 newsletter. In this edition, we outline our participation in a UK multicentre clinical trial (E-FIT1) which is evaluating the impact of early administration of fibrinogen concentrate on severely bleeding trauma patients. Research fellow Simon Glasgow explains the results of his award-winning study into the management of blood supplies in mass casualty events, and Zane Perkins summarises his pioneering work on amputation prediction following lower limb vascular trauma. Finally, our outreach team is preparing to hit the road again for the 2016 Seven Oaks school Innovation week to inspire future trauma clinicians and scientists. Enjoy!

Early Fibrinogen Administration

Background Bleeding is the leading cause of preventable death in trauma.

Globally, bleeding following injury is estimated to be responsible for over two million deaths per year.

Fibrinogen is an important blood clotting protein which C4TS has studied for many years. In severe injury and major bleeding, levels of fibrinogen in the blood can fall quickly, increasing bleeding severity.

Although a common transfusion protocol is routinely followed in all UK hospitals, clinicians are not sure whether concentrated fibrinogen as quickly as possible works better than standard practice, improving patient survival and outcomes.

The trial E-FIT 1 is a UK multi-centre, randomised, double blind, placeboCentre for Trauma Sciences

controlled trial evaluating the effects of early administration of fibrinogen concentrate in adults with major traumatic haemorrhage.

The Royal London Hospital has received local approval to run the trial as one of the study centres.

The study will look at the effects of infusing fibrinogen concentrate to adult trauma patients within 45 minutes of admission to hospital. A total of 48 patients will be recruited to the pilot.

It has been shown previously that early treatment of fibrinogen for bleeding has better outcomes. EFIT 1 will evaluate whether it is possible to infuse the drug within 45 minutes of arrival in what is often a challenging clinical environment. It will also look at laboratory and clinical outcomes measures.

As C4TS Clinical Trials Coordinator, I manage the Centre's portfolio of clinical trials, overseeing recruitment and monitoring data quality and integrity to ensure the highest quality of research. The trauma research group adopted a

Newsletter Winter 2016

www.c4ts.qmul.ac.uk

Claire Rourke (Clinical Trials Coordinator)

by Claire Rourke (Clinical Trials Coordinator) 24/7 recruitment rota in January 2016 enabling us to screen all trauma patients for study eligibility and maximise our contribution to the trial. The study commenced in February 2015 and is due to run for 30 months (summer 2018).

Figure 1-structure of fibrinogen protein

Implications Given up to 40% of severely injured trauma patients die from uncontrolled bleeding, improvements in transfusion practice will have a significant impact on global health and mortality. E-FIT1 results will feed into a planned follow-on study that will look at whether fibrinogen concentrate, or similar treatment, will improve death rates.

More information can be found on the E-FIT1 website..

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Blood supplies in Mass Casualty Events

By Simon Glasgow, Research Fellow

Background Traumatic haemorrhage is a leading preventable cause of mortality following mass casualty events (MCEs). MCEs include terrorist attacks of which there has been a ninefold incidence globally since 2000.

This has led to a renewed interest in MCE transfusion planning. The surge in red blood cell (RBC) demand from casualties requiring a Massive Transfusion (MT) has the potential to decimate an individual hospital’s blood bank inventory, severely compromising a unit’s ability to treat bleeding casualties effectively. Examples of in-hospital event modelling have indicated the perceived capacity of hospitals to manage MCEs to be overly-optimistic. The majority of all trauma deaths that occur in the first hour and approximately 50% of deaths in the first 24 hours are due to bleeding. The result is two thirds of an event’s total RBC requirement on the first day is consumed within the first four hours.

Simulating MCE blood supply needs Improving MCE outcomes therefore requires adequate inhospital provision of high volume RBC transfusions (refer Figure 2). Our C4TS research team used simulation modelling to investigate the best strategies for optimizing RBC provision to casualties in MCEs.

Figure 2 – The relationship between the units of RBC held per casualty & the percentage of all bleeding casualties treated within 6 hours.

Centre for Trauma Sciences

Newsletter Winter 2016

We developed a computerized simulation model of a UK major trauma centre (MTC) transfusion system. The model used input data from past MCEs, civilian and military trauma registries. We simulated the effect of varying on-shelf RBC stock hold and the timing of externally restocking RBC supplies on MTC treatment capacity across increasing casualty loads from an event.

Figure 3 – Dr Glasgow’s MCE research won an EAST foundation award in January 2016

Results We found that even limited sized MCEs threaten to overwhelm MTC transfusion systems. Whilst greater and greater stock volumes are able to maintain adequate rates of treatment, the logistical and financial implications of maintaining these volumes of RBCs at MTCs limits the feasibility of this solution long-term. Restocking RBCs early during an event can produce equivocal outcomes compared to an on-shelf stock hold, however, in order to achieve this, a ‘push over pull’ approach needs to be considered to prevent delay and maximise any potential benefits The full article will be published soon in the Journal of Trauma and Acute Care Surgery. The paper won the EAST Foundation’s prestigious Raymond H. Alexander MD Resident Paper Competition at the #EAST2016 conference January 2016.

London’s trauma system was the first of its kind in the UK and has led to dramatic reductions in deaths from injury. Our website now hosts an interactive map which shows the system’s four major trauma networks and contact details for every trauma service.

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When to amputate?

Background

By Zane Perkins, Research Fellow

Lower extremity vascular trauma (LEVT) is a potentially devastating injury that may result in death, profound disability or limb loss. Management priorities are clear: foremost to save the patient's life, and second to salvage the most functional limb possible. Severe LEVT, however, presents some of the most challenging decision-making in trauma surgery. A clear understanding of predictive factors for amputation is

therefore important to inform surgical decision-making, patient counselling and calculating risks. Towards that end, I have been studying predictive factors for amputation following surgical repair of LEVT

Study Methods I undertook a systematic review of the published literature with the objective of developing an understanding of predictive factors for amputation following surgical repair of LEVT. My first aim was to estimate the overall risk of amputation following LEVT repair; second, identify potential patient, injury and treatment predictive factors; and, finally, to measure the strength of association between the identified predictive factors and amputation.

Results Approximately one in ten limbs that undergo vascular repair will require amputation, the rate of which varies depending on specific patient and injury characteristics.

Factors associated with a substantial increase in amputation include: mechanism of injury, injuries to arteries, fracture or major soft tissue injury, duration of ischaemia (restriction in blood supply to tissues) exceeding 6 hours, compartment syndrome (bleeding or swelling within a bundle of muscles) and the surgical method of vascular repair. By comparison, demographic factors, such as older age and female sex, and shock on admission were associated with smaller increases, whereas additional venous or nerve injuries were not associated with an important increase in secondary amputation.

We aim to use this improved understanding of severe lower limb trauma prediction to develop tools that support surgical decision-making, and allow more accurate communication of risk with colleagues, patients and family.

Simon’s paper won the Society of Academic and Research Surgery's (SARS) President's Poster Award at the SARS annual meeting, January 2013.

Centre for Trauma Sciences

Figure 3 – Potential predictive factors identified from the systematic literature review & the evidence supporting an association with secondary amputation (2000-2012)

Newsletter Winter 2016

News and Events Blood management in the news In February, the National Institute for Health and Care Excellence issued 4 new UK guidelines on trauma care. C4TS lead Professor Brohi was quoted in The Guardian newspaper discussing why improved blood transfusion practices are needed to save more lives.

Trauma Team STEM Outreach On 28th Feb, the trauma outreach team will once again pack up the car with platelets, red blood cells, fibrin and the trauma mannequin ready to talk to hundreds of school children at Sevenoaks Innovation Week 2016..

Click here for more information about our education and outreach programs.

New starter!

Yemi Macaulay

“I am a research assistant with a background in infection and immunology.

My role includes working in the Royal London Hospital ED, assisting with the collection and assessment of study patients data and samples. I love what I do because our research contributes to improved survival rates for trauma patients.”

You can contact us via our website or tweet @CommsC4TS

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