Primary Objective: To identify the clinically significant mechanisms and pathways by which coagulation and inflammation are activated immediately following major trauma and how these result in the observed clinical sequelae of this in terms of bleeding, transfusion requirements, organ injury, multiple organ failure and death. 1. On coagulation: Aim: • To identify the key derangements in coagulation and fibrinolysis following trauma • To identify and characterize the subsequent hypercoagulable state (although trauma patients are more likely to bleed initially, they subsequently develop a state where they are more likely to form blood clots, leading to deep venous thrombosis, pulmonary embolism and death). A four channel thromboelastometry (RoTEM and TEG) will be used to detect coagulopathic derangements and fibrinolysis and determine the response to blood component therapy. • To validate the effectiveness of RoTEM or TEG for guiding transfusion practice after trauma. • To develop a prediction model for massive transfusion requirements and the development of organ injury following trauma. This will allow us to identify patients who might benefit for early intervention to prevent these complications and reduce the death rate following severe injury. Hypothesis on coagulation: • Acute traumatic coagulopathy is caused by tissue hypoperfusion through the systemic activation of anticoagulant and fibrinolytic pathways (the body’s anticlotting mechanisms) and can be detected by RoTEM and TEG. • Early coagulopathy leads to exhaustion of the anticoagulant system andup−regulation of antifibrinolytic systems, resulting in a hypercoagulable state. • Subsequent transfusion of red cells and blood component therapy has specific effects on the acute coagulopathy, which may be beneficial or harmful dependent on the current clinical state. • Massive transfusion requirements (the need to replace a person’s entire volume of blood, or more than 10 units of blood) can be predicted by initial physiological variables and immediate analysis of coagulation parameters by RoTEM. Conversely, the requirement for blood component therapy might be reduced by targeted measurement of coagulation function and biomarkers during transfusion, as it can be guided by RoTEM.• Coagulation is linked to innate immunity cellular responses, which may include (neutrophil derived) nucleosomes and serine proteases, as well as microvesicles 2. On Inflammation: Aim: • To elucidate the effect of derangements in coagulation, fibrinolytic and endothelial cell function on the inflammatory response and the development of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), Acute Kidney Injury (AKI), multiple organ failure (MOF), and death. Hypothesis on inflammation: • There is a dose−dependent effect of the severity of trauma on coagulation, fibrinolytic and endothelial cell function. These correlate with activation of a pathological systemic inflammatory response which leads to ALI, ARDS, AKI & MOF • There is a dose-dependent effect of the degree and duration of tissue hypoperfusion on coagulation, fibrinolytic and endothelial cell function. These correlate with activation of a pathological systemic inflammatory response which leads to ALI, AKI & MOF. • While tissue trauma and cellular hypoperfusion are different initiators, the resulting activation of the coagulation and inflammatory systems is identical and is the final common pathway in acute lung injury. Tissue trauma and cellular hypoperfusion have an additive effect on the development of ALI, AKI & MOF. • ALI, AKI & MOF can be predicted in the first hours after trauma based on trauma severity scores, tissue damage, severity and duration of tissue hypoperfusion, with biochemical markers of coagulation or inflammation.