2.5 million People a year bleed to death as the result of severe physical injury (i.e. Trauma). Trauma patients develop a problem with coagulation within a few minutes of injury that impedes normal blood clot formation, leading to more bleeding and more deaths. These ‘coagulopathic’ trauma patients develop an immediate deficiency of the fundamental blood clotting protein ‘fibrinogen’. The CRYOSTAT study was conceived and implemented to determine the feasibility and effectiveness of early (i.e. hyperacute) delivery of fibrinogen therapy to bleeding and severely injured trauma patients. Specifically can we safely deliver fibrinogen therapy to trauma patients in the emergency environment and does fibrinogen therapy rapidly improve blood clotting, thereby reducing blood loss and death in critically-bleeding trauma patients?  
Aims, Progress & Future Plans
CRYOSTAT was a feasibility study for a multi-centre, randomised controlled trial (RCT) evaluating the effects of early administration of high-dose cryoprecipitate (i.e. a source of fibrinogen) in adults suffering major traumatic haemorrhage.  This 1-year study aimed to recruit 40 patients by September 2013, with all study patients completing a subsequent 3-month follow-up visit. We were able to demonstrate the feasibility of delivering early cryoprecipitate in 43 patients at two major trauma centres (Royal London Hospital and John Radcliffe, Oxford). This study also constituted the UK’s first co-developed civilian-military RCT which was conducted in parallel at Camp Bastion, Afghanistan. Although a definitive RCT is required to evaluate clinical outcomes associated with hyperacute administration of fibrinogen, the preliminary results of CRYOSTAT suggested that early cryoprecipitate therapy maintained acceptable blood fibrinogen levels during active bleeding, with a signal for reduced mortality (3 deaths vs. 6 deaths) in the treatment arm of the study. This feasibility trial has emphasised the importance of pragmatic inclusion criteria and a simple case report form for focused outcome and adverse event data collection. Results from the trial will be published in a peer-reviewed journal and presented at appropriate educational conferences. Preliminary data from the CRYOSTAT study will be used to inform the design and sample size of an international multi-centre trial focusing more on efficacy and safety outcomes.
1. Phase 2a study: CRYOSTAT. Available at: http://www.controlled-trials.com/ISRCTN55509212
Impact on human health
Major haemorrhage is the most common preventable cause of death in the trauma population. Whilst we have shown that low fibrinogen levels on admission to hospital are independent predictors of early mortality in trauma patients 2, larger definitive studies are required to evaluate the use of fibrinogen replacement in major trauma haemorrhage. There are two sources of fibrinogen for use in major blood loss; cryoprecipitate and fibrinogen concentrate. Despite being a fifth of the cost (per gram of fibrinogen) compared with fibrinogen concentrate, cryoprecipitate is a pooled blood component with high but variable fibrinogen concentration and contains other plasma proteins which may confer additional clotting benefit.
This study has proven the feasibility of conducting multi-centre trauma trials focusing on the efficacy and safety outcomes of hyperacute administration of fibrinogen therapy. CRYOSTAT will greatly facilitate the design and implementation of further clinical trials (including CRYOSTAT-2 as an international definitive Phase 2a trial) that will answer the question: does early fibrinogen reduce mortality in adult patients with trauma haemorrhage. These will inform clinical practice, may improve the treatment of many patients in the future and have the potential to save the lives of patients who sustain major trauma haemorrhage.