28-day thawed plasma maintains α -antiplasmin levels and inhibits tPA-induced fibrinolysis.

Introduction: Evidence supports the use of plasma-first resuscitation in the treatment of trauma-induced coagulopathy (TIC). While thawed plasma (TP) has logistical benefits, the ability of plasma proteins to attenuate fibrinolysis and correct TIC remain unknown. We hypothesize that TP retains the ability to inhibit tissue plasminogen activator(tPA)-induced fibrinolysis at 28-day storage.

Do not drink and lyse: alcohol intoxication increases fibrinolysis shutdown in injured patients.

Introduction: High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients.

Increase in post-reperfusion sensitivity to tissue plasminogen activator-mediated fibrinolysis during liver transplantation is associated with abnormal metabolic changes and increased blood product utilisation.

Background: Increased systemic fibrinolytic activity can occur in liver transplant recipients after the donor graft is reperfused. However, it remains unclear whether this is related solely to tissue plasminogen activator (t-PA) levels or whether unique metabolic changes can alter t-PA activity and enhance fibrinolytic activity. We hypothesise that an increase in sensitivity to t-PA-mediated fibrinolysis (StF) following liver reperfusion is associated with specific metabolic abnormalities.

Empiric transfusion strategies during life-threatening hemorrhage.

Background: Resuscitation guided by thrombelastography improves survival after injury. If bleeding is rapid, however, or if no thrombelastography data are available, the optimal strategy remains controversial. Our current practice gives fresh frozen plasma and red blood cells (1:2) empirically in patients with life-threatening hemorrhage, with subsequent administration based on rapid thrombelastography.

Thrombin stimulates increased plasminogen activator inhibitor-1 release from liver compared to lung endothelium.

Background: Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of the fibrinolytic system, covalently binding to tissue plasminogen activator and blocking its activity. Fibrinolysis shutdown is evident in the majority of severely injured patients in the first 24 h and is thought to be due to PAI-1. The source of this PAI-1 is thought to be predominantly endothelial cells, but there are known organ-specific differences, with higher levels thought to be in the liver.

Thrombin Provokes Degranulation of Platelet α-Granules Leading to the Release of Active Plasminogen Activator Inhibitor-1 (PAI-1).

Background: The balance of fibrinolytic mediators is crucial to the survival of the critically ill patient, with tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) playing significant roles. While elevated levels of PAI-1 are associated with increased morbidity and mortality, the source of this PAI-1 remains elusive. Platelets contain 90% of circulating plasma PAI-1, however, their ability to release active PAI-1 is controversial.

Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator.

Background: Fibrinolysis shutdown (SD) is an independent risk factor for increased mortality in trauma. High levels of plasminogen activator inhibitor-1 (PAI-1) directly binding tissue plasminogen activator (t-PA) is a proposed mechanism for SD; however, patients with low PAI-1 levels present to the hospital with a rapid TEG (r-TEG) LY30 suggestive SD. We therefore hypothesized that two distinct phenotypes of SD exist, one, which is driven by t-PA inhibition, whereas another is due to an inadequate t-PA release in response to injury.

14-Day thawed plasma retains clot enhancing properties and inhibits tPA-induced fibrinolysis.

Background: Plasma-first resuscitation attenuates trauma-induced coagulopathy (TIC); however, the logistics of plasma-first resuscitation require thawed plasma (TP) be readily available due to the obligatory thawing time of fresh frozen plasma (FFP). The current standard is storage of TP for up to 5 days at 4°C, based on factor levels at outdate, for use in patients at risk for TIC, but there remains a 2.2% outdated wastage rate.

Targeting resuscitation to normalization of coagulating status: Hyper and hypocoagulability after severe injury are both associated with increased mortality.

Introduction: The prevalence and impact of hypercoagulability (hypo) in severely injured patients early after injury remains unclear. We hypothesize that the predominant phenotype of postinjury coagulopathy is hypercoagulability (hyper) and it is associated with increased mortality.

Material And Methods: Blood samples from 141 healthy volunteers assayed with thrombelastography (TEG) were used to identify thresholds of hypo and hypercoagulability (above 95th/below the 5percentile) in four TEG indices.

Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion.

Background: Thrombelastography platelet mapping is a useful assay to assess antiplatelet therapy. Inhibited response to the adenosine diphosphate receptor on platelets occurs early after injury, but recent work suggests this alteration occurs even with minor trauma. However, the utility of thrombelastography platelet mapping, specifically the percent of adenosine diphosphate receptor inhibition, in predicting outcomes and guiding platelet transfusion in trauma-induced coagulopathy remains unknown We assessed the role of percent of adenosine diphosphate-inhibition in predicting survival, requirement for massive transfusion or platelet transfusion in patients at risk for trauma-induced coagulopathy.

Tranexamic acid is associated with increased mortality in patients with physiological fibrinolysis.

Background: Tranexamic acid (TXA) administration after trauma has not been proven to improve survival in the United States. Trauma patients were presented to the hospital with a spectrum of fibrinolytic activity, in which physiological levels of fibrinolysis are associated with the lowest mortality. We hypothesize that trauma patients who present to the hospital with physiological levels of fibrinolysis will have increased mortality if they receive TXA.

Tranexamic Acid Use in Prehospital Uncontrolled Hemorrhage.

The use of tranexamic acid (TXA) in the treatment of trauma patients was relatively unexplored until the landmark Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage-2 (CRASH-2) trial in 2010 demonstrated a reduction in mortality with the use of TXA. Although this trial was a randomized, double-blinded, placebo-controlled study incorporating >20,000 patients, numerous limitations and weaknesses have been described. As a result, additional studies have followed, delineating the potential risks and benefits of TXA administration.

Viscoelastic Tissue Plasminogen Activator Challenge Predicts Massive Transfusion in 15 Minutes.

Background: Coagulopathy is associated with massive transfusion in trauma, yet most clinical scores to predict this end point do not incorporate coagulation assays. Previous work has identified that shock increases circulating tissue plasminogen activator (tPA). When tPA levels saturate endogenous inhibitors, systemic hyperfibrinolysis can occur.

Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the presence of tissue plasminogen activator similar to pooled liquid plasma.

Background: Systemic hyperfibrinolysis is an integral part of trauma-induced coagulopathy associated with uncontrolled bleeding. Recent data suggest that plasma-first resuscitation attenuates hyperfibrinolysis; however, the availability, transport, storage, and administration of plasma in austere environments remain challenging and have limited its use. Freeze-dried plasma (FDP) is a potential alternative due to ease of storage, longer shelf life, and efficient reconstitution.

Early intubation in the management of trauma patients: indications and outcomes in 1,000 consecutive patients.

Background: The Eastern Association for the Surgery of Trauma Practice Management Guidelines identify indications (EI) for early intubation. However, EI have not been clinically validated. Many intubations are performed for other discretionary indications (DI).