Uncontrolled haemorrhage remains a leading cause of preventable mortality and morbidity. The LMTS is leading or collaborating on a number of research projects aimed at better understanding the coagulation systems response to injury.


Within minutes of injury, up to 1 in 4 severely injured patients develop a clotting dysfunction, termed Acute Traumatic Coagulopathy (ATC) that exacerbates bleeding and increases transfusion requirements, morbidity and mortality. ACIT is designed to identify the clinically significant mechanisms by which the body’s inflammation and coagulation pathways are activated immediately following major trauma. It also allows the monitoring of any change in functional blood coagulation, during the course of treatment with blood components and procoagulant agents. The study is revealing how trauma leads to coagulopathy and a perturbed inflammatory response, which leads to increased transfusion requirements and adverse outcome in terms of organ failure and death.


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, 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.


CRYOSTAT-1 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 recruited 43 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 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.

CRYOSTAT-1 suggesed 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. More information about the trial can be found in this article and also here.


In 2017, C4TS and NHS Blood & Transplant were awarded £2.4m from the National Institute for Health Research Health and Bart’s Charity to carry out a large multi-centre Randomised Controlled Trial (RCT) to evaluate early cryoprecipitate in major traumatic haemorrhage (CRYOSTAT-2).

The trial will test the effect of early cryoprecipitate (within 90 minutes of admission) compared to standard blood transfusion therapy, on 1568 severely bleeding trauma patients from each Major Trauma Centre (MTC) in London and across the UK. C4TS European partners in the TACTIC study will also participate, as well as four trauma centres in the US.

Patient recruitment commenced in July 2017 and the trial will run for 36 months.  The study will provide the answer as to whether early cryoprecipitate transfused for major traumatic bleeding saves lives.

This will be the first national transfusion study in the UK since trauma networks were established in England and Wales. Improved transfusion practices have the potential to save millions of lives globally.

CRYOSTAT-2 has it's own website with more information for clinicians and patients.

For any queries, please contact principal Investigator: Dr Ross Davenport


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