Coagulation Profiles of Unexpected DCDD Donors Do Not Indicate a Role for Exogenous Fibrinolysis : Coagulation Profiles of Unexpected DCDD Donors

Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock. This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion. Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI. Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.

Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this. This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1+2, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and D-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high D-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days. Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

Reagent-supported thromboelastometry (TEM) with the ROTEM Whole Blood Haemostasis Analyser is an enhancement of thromboelastography, a method that is increasingly used for the point of care monitoring of acute perioperative bleeding disorders. We investigated the reference ranges of two activated tests (INTEM and EXTEM) and a test analysing specifically the fibrin component of coagulation (FIBTEM) in a multi-centre approach. The reference ranges obtained for the clotting time (CT), clot formation time (CFT), alpha angle (ALP), maximum clot firmness (MCF) and clot lysis parameters were comparable from centre to centre. INTEM: CT equals; 137-246 s, CFT equals; 40-100 s, MCF equals; 52-72 mm. EXTEM: CT equals; 42-74 s, CFT equals; 46-148 s, MCF equals; 49-71 mm. FIBTEM: MCF equals; 9-25 mm. ROTEM whole blood coagulation correlated weakly with a trend towards enhanced coagulation in females compared with males and in advanced age. The repeatability (within-run imprecision) of the results was dependent on the test with the following coefficients of variation: 1-5% (clot firmness, alpha angle), 3-12% (CT, CFT), 6-13% (FIBTEM clot firmness). Citrated blood samples were stable for ROTEM analysis stored within 6 h from drawing. In summary, the data showed that ROTEM thromboelastometry yields consistent values between centres and that providing general orientating reference ranges seems to be possible.