Coagulopathy, cryoprecipitate and CRYOSTAT-2: realising the potential of a nationwide trauma system for a national clinical trial

Traumatic-induced coagulopathy (TIC) is often associated with significant bleeding, transfusion requirements, inflammation, morbidity, and mortality. This review considers TIC as a systems failure, not as a single-event manifestation of trauma. After briefly reviewing the meaning of TIC and the bewildering array of fibrinolysis phenotypes, we will discuss the role of platelets and fibrinogen in coagulopathy. Next, we will review the different TIC hypotheses and drill down to a single mechanistic domain comprising (1) thrombin's differential binding to thrombomodulin, (2) the expression of annexin II-S100A10 complex, and (3) the functional integrity of the endothelial glycocalyx. This triad forms the basis of the “switch” hypothesis of TIC. We will next address the potential limitations of current practice in treating a coagulation or fibrinolytic defect, and the next defect, and so on down the line, which often leads to what U.S. surgeon William C. Shoemaker considered “an uncoordinated and sometimes contradictory therapeutic outcome.” The treat-as-you-go approach using sequential, single-target treatments appears to be a by-product of decades of highly reductionist thinking and research. Lastly, we will present a unified systems hypothesis of TIC involving three pillars of physiology: the central nervous system (CNS)–cardiovascular system, the endothelial glycocalyx, and mitochondrial integrity. If CNS control of ventriculoarterial coupling is maintained close to unity following trauma, we hypothesize that the endothelium will be protected, mitochondrial energetics will be maintained, and TIC (and inflammation) will be minimized. The Systems Hypothesis of Trauma (SHOT) also helps to answer why certain groups of severely bleeding trauma patients are still dying despite receiving the best care. Currently, no drug therapy exists that targets the whole system.

Section: Platelet and Fibrinogen Contributions To Early Ticmentioning

confidence: 99%

Traumatic-Induced Coagulopathy as a Systems Failure: A New Window into Hemostasis

Dobson

Morris

Davenport

et al. 2020

“…Specialized, highly centralized, efficient trauma centers in Austria, Germany, and Switzerland have published RCTs demonstrating improved mortality for patients with severe traumatic injuries treated in a goal-directed fashion with concentrates and PRBCs (►Table 3). 27,[78][79][80][81]84,85,90,91 United States' Recent Adoption of WB for Civilian Trauma Resuscitation…”

Section: International Trends In Trauma Resuscitation and The Use Of Wbmentioning

confidence: 99%

“…84 Other studies have failed to show benefit of prehospital administration of blood products in the civilian urban environment. 90,100,101 Rijnhout et al's review reports literature that suggests that prehospital blood transfusion with the simultaneous use of both PRBCs and plasma resulted in a significant reduction in the odds for long-term mortality but not short-term 24-hour mortality. The authors caution that "based on mainly poor-quality evidence no hard conclusion can be drawn about a possible survival benefit for hemorrhagic trauma patients receiving prehospital blood.…”

Section: International Trends In Trauma Resuscitation and The Use Of Wbmentioning

confidence: 99%

Whole Blood for Civilian Urban Trauma Resuscitation: Historical, Present, and Future Considerations

Walsh

Fries

Moore

et al. 2020

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

“…The primary end point is mortality at 28 days. 78 Recruitment will complete in 2020, and the results will directly influence transfusion practice. Until then, fibrinogen replacement is likely to be given to maintain a blood Clauss fibrinogen level of more than 1.5 g/L (or an equivalent VHA threshold) based on observational data and consensus opinion.…”

Section: Fibrinogen Replacementmentioning

confidence: 99%

Surgery in Traumatic Injury and Perioperative Considerations

Curry

Brohi

2019

A severely injured patient presents several unique challenges to an admitting trauma team. Not only must the extent of the patient's injuries, particularly those that are life-threatening, be determined within minutes of hospital arrival, but also the trauma team needs to be able to assess whether the patient is bleeding and/or has an attendant coagulopathy. Early management of trauma patients is dictated by the presence (or absence) of significant bleeding. Standard definitive surgical procedures can be conducted in hemodynamically stable patients, but those in hemorrhagic shock should be treated according to damage control resuscitation (DCR) principles. DCR is a practice that has evolved over the last two to three decades, combining limited surgical techniques, which provide early hemorrhage control, and balanced transfusion resuscitation strategies, which mitigate (and ideally) treat trauma-induced coagulopathy (TIC). This review describes the contemporary perioperative management of trauma patients who have significant bleeding and/or TIC and sets out the evidence around the current approach for hemostatic resuscitation in these patients.