What is fibrinogen?
Fibrinogen is an inactive, soluble protein which normally circulates in the blood and is essential to stemming bleeding from damaged tissues, a process known as haemostasis.
The first stage of haemostasis involves activation of tiny cells called platelets which form a plug at the site of injury. At the same time, a series of rapid enzymatic reactions occur which breaks fibrinogen into insoluble strands of fibrin. These fibres aggregate and wind around one another to form a meshwork which acts as a platform for a strong clot to form at the site of injury and prevent further blood loss. In healthy people, there is normally 2.5g of fibrinogen in every litre of blood circulating. However, these levels can become rapidly depleted in times of major bleeding, such a severe injury, as the body fights to keep blood within the arteries and veins.
Our discoveries
In a large observational study conducted at the Centre for Trauma Sciences (C4TS), involving over 500 trauma patients, we showed that low levels of fibrinogen level on admission to the Emergency Department are an independent predictor of mortality. This important finding provided the impetus to develop and carry out a randomised controlled trial at C4TS and John Radcliffe Hospital (Oxford). In a pilot study (CRYOSTAT-1) we were able to evaluate the feasibility and potential effectiveness of early fibrinogen replacement with cryoprecipitate which are blood transfusions rich in fibrinogen. Results reported in 2015 suggested that early use of cryoprecipitate improved survival from major bleeding in trauma but that a larger definitive study was required to fully answer the question.
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) across the UK. C4TS European partners in the TACTIC study will also participate, as well as four trauma centres in the US. More information can be found on the CRYOSTAT-2 trial website.
More information about fibrinogen in trauma can be found in this article
