Diagnosis and Treatment of Hyperfibrinolysis in Trauma (A European Perspective)

Abstract

Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. The mechanistic drivers and dynamics of fibrinolytic activation in response to injury and trauma resuscitation are currently unclear. Furthermore, therapeutic triggers are compounded by the lack of a sensitive and rapid diagnostic tool, with discrepancy between hyperfibrinolysis diagnosed by viscoelastic hemostatic assays versus biomarkers for fibrinolysis. Rotational thromboelastometry and thromboelastography appear capable of detecting the severest forms of hyperfibrinolysis but are relatively insensitive to moderate, yet clinically significant fibrinolytic activation. Rapid evaluation of the current status of the fibrinolytic system remains a challenge and therefore the decision whether to administer an antifibrinolytic agent should be based on available evidence from clinical trials. In line with current European guidelines, we recommend that all bleeding trauma patients, and in particular, severely injured patients with evidence of hemorrhagic shock, should receive early empiric tranexamic acid. This review explains our current knowledge of the pathophysiological pathways which induce hyperfibrinolysis in trauma hemorrhage, evaluates the available diagnostic modalities, and describes current treatment strategies.

Measuring fibrinolysis: from research to routine diagnostic assays

“…Significantly for fibrinolysis, the reduction in clot firmness generated by the ROTEM as lysis index at 30 min LI(30) is calculated in a different way from LY30 in TEG, so the results are not interchangeable. Different definitions of hyperfibrinolysis as detected by VMs used in various studies have been reviewed and summarized elsewhere , and efforts are underway to standardize how diagnosis is performed, and to identify the best parameters to guide therapeutic interventions. For example, research is being carried out by the European TACTIC consortium to develop data‐driven algorithms for the management of hemorrhage .…”

Defining trauma‐induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH

“…Fibrinolytic systems bring about dynamic two‐phase changes: increased fibrinolysis due to shock‐induced t‐PA release at an early stage, and the inhibition of fibrinolysis due to persistent expression of PAI‐1 at a later stage of trauma . These imbalances are predictors of mortality in observational studies, and importantly, those patients with physiologic levels of fibrinolysis on admission have been shown to have the lowest mortality . However, depending on the mechanism of injury, and the type and speed of resuscitative measures imparted, the evolution from hyperfibrinolytic‐type to hypofibrinolytic‐type can occur in minutes to hours .…”

“…51,71,72 These imbalances are predictors of mortality in observational studies, and importantly, those patients with physiologic levels of fibrinolysis on admission have been shown to have the lowest mortality. [8][9][10][11] However, depending on the mechanism of injury, and the type and speed of resuscitative measures imparted, the evolution from hyperfibrinolytic-type to hypofibrinolytic-type can occur in minutes to hours. 10 Increased fibrinolysis accelerates bleeding, thus leading to uncontrolled hemorrhage.…”

“…As a result of the difficulty in defining clinical TIC, the underlying biochemical mechanisms of TIC are unclear. Factors contributing to a hypocoaguable state include impaired thrombin generation, impaired platelet function, deficient or defective fibrinogen, increased fibrinolysis, and endothelial dysfunction, while those contributing to hypercoagulability include excessive thrombin generation, endothelial injury, platelet hyperactivity and exhaustion, hyperfibrinogenemia, and impaired fibrinolysis …”

“…Factors contributing to a hypocoaguable state include impaired thrombin generation, impaired platelet function, deficient or defective fibrinogen, increased fibrinolysis, and endothelial dysfunction, while those contributing to hypercoagulability include excessive thrombin generation, endothelial injury, platelet hyperactivity and exhaustion, hyperfibrinogenemia, and impaired fibrinolysis. [6][7][8][9][10][11][12][13][14][15][16] In recent years, multiple definitions of the hemostatic disturbances in trauma have been published. [17][18][19][20] The unstandardized nomenclature and definitions (ATC, acute traumatic coagulopathy; TIC, trauma-induced coagulopathy; ACoTS, acute coagulopathy of trauma-shock; CoT, coagulopathy of trauma; DIC, disseminated intravascular coagulation; endotheliopathy of trauma and hemorrhagic blood failure; 21 SHINE, shock-induced endotheliopathy 5,6 ) used to describe these derangements in trauma has led to a considerable degree of confusion within the field.…”