Health UK (Commonwealth Union) – Severe blood loss poses a significant threat to numerous critically injured patients, accounting for over half of the annual 4.4 million trauma-related deaths worldwide. It stands as the leading preventable cause of death in this particular patient population.
The Center for Trauma Sciences, located at Queen Mary University of London, has a primary goal of reducing fatalities resulting from substantial bleeding in severe trauma cases.
The CRYOSTAT-2 trial, funded by the National Institute of Health and Care Research (NIHR) and Barts Charity, represents the most extensive trial ever undertaken among severely bleeding trauma patients. A collaborative effort between the Center for Trauma Sciences and the NHS Blood and Transplant Clinical Trials Unit, this trial explored the potential benefits of administering additional blood-clotting factors to major trauma patients upon their admission to the hospital, rather than delaying this intervention, as is the current standard practice, with the aim of enhancing survival rates.
Initial research revealed that trauma patients often develop a severe clotting disorder, with a significant component of this disorder being a deficiency in fibrinogen—a fundamental protein required for blood clot formation. When low fibrinogen levels are identified, trauma patients are typically given fibrinogen concentrates to restore their levels and support the coagulation process.
The earlier CRYOSTAT study demonstrated that it was feasible to swiftly provide a substantial dose of fibrinogen (in the form of cryoprecipitate) to all bleeding trauma patients as they entered the emergency department. The results were promising in terms of the capacity to rectify fibrinogen levels, leading to the development of the CRYOSTAT-2 trial.
This extensive trial enrolled over 1,600 patients with life-threatening injuries who were admitted to all 26 major trauma centers in the UK and one trauma center in the US. All participants received the standard, evidence-based treatments for managing critical bleeding, with half also receiving supplementary doses of cryoprecipitate as soon as possible upon arrival.
Unexpectedly, the results of the study, which were published in JAMA recently, had demonstrated that providing additional cryoprecipitate did not lead to an overall improvement in the survival rates of patients. Upon closer examination, it became evident that some patients experienced better outcomes, while others may have had worse results.
According to Karim Brohi, who serves as a Professor of Trauma Sciences at Queen Mary, Co-Chief Investigator of CRYOSTAT-2, and Consultant Surgeon at Barts NHS Trust and the Royal London, the surprising outcomes align with our current understanding that a universal approach doesn’t effectively address the needs of trauma patients. He underscores the importance of bringing early diagnostic tests to the patient, even in the emergency room or ideally at the scene of the injury. This allows for a more precise approach to managing severe bleeding and abnormal clotting. In essence, the aim is to administer fibrinogen promptly to those who require it, while avoiding unnecessary treatment for those who don’t.
Professor Simon Stanworth, CRYOSTAT-2 Co-Chief Investigator, Consultant Haematologist for NHS Blood and Transplant at the John Radcliffe Hospital, Oxford, says “This large national trial answered an important question about whether there was any benefit for patients with major trauma and major bleeding when given a higher dose of blood component called cryoprecipitate as soon as possible after injury and arrival in hospital. Cryoprecipitate is a source of a blood protein called fibrinogen which helps forms clots. The study was delivered across the UK as a collaboration between trauma teams, hospital blood bank laboratories and NHS Blood and Transplant Clinical Trials Unit, but unfortunately found no benefit. We need to understand the reasons for this and whether there might be some types of patients who might be helped by giving cryoprecipitate.”
