Author:
Coleman Julia R.,Moore Ernest E.,Kelher Marguerite R.,Jones Kenneth,Cohen Mitchell J.,Banerjee Anirban,Silliman Christopher C.
Abstract
BACKGROUND
The mechanisms underlying trauma-induced coagulopathy remain elusive. Hyperfibrinolysis has been linked to increased plasminogen activation and antiprotease consumption; however, the mechanistic players in its counterpart, fibrinolysis shutdown, remain unclear. We hypothesize that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a major role in fibrinolytic shutdown after injury.
METHODS
As part of this observational cohort study, whole blood was collected from trauma activation patients at a single, level 1 trauma center. Citrated rapid thrombelastography and the following enzyme-linked immunosorbent assays were conducted: thrombin, antithrombin, thrombin-antithrombin complex, TAFI, plasminogen, antiplasmin, plasmin-antiplasmin (PAP), tissue plasminogen activator, plasminogen activator inhibitor 1, and tissue plasminogen activator–plasminogen activator inhibitor 1 complex. Univariate and cluster analysis were performed.
RESULTS
Overall, 56 patients (median age, 33.5 years; 70% male) were included. The majority (57%) presented after blunt mechanism and with severe injury (median New Injury Severity Score, 27). Two clusters of patients were identified: Group 1 (normal fibrinolysis, n = 21) and Group 2 (fibrinolysis shutdown, n = 35). Group 2 had significantly lower fibrinolysis with a median LY30 of 1.1% (interquartile range [IQR], 0.1–1.9%) versus 2.1% (IQR, 0.5–2.8%) in Group 1; while the median LY30 was within physiologic range, 45% of patients in Group 2 were in shutdown (vs. 24% in Group 1, p = 0.09). Compared with Group 1, Group 2 had significantly higher PAP (median, 4.7 [IQR, 1.7–9.3] vs. 1.4 [1.0–2.1] μg/mL in Group 1; p = 0.002) and higher TAFI (median, 152.5% [IQR, 110.3–190.7%] vs. 121.9% [IQR, 93.2–155.6%]; p = 0.04). There was a strong correlation between PAP and TAFI (R
2 = 0.5, p = 0.0002).
CONCLUSION
The presented data characterize fibrinolytic shutdown, indicating an initial plasmin burst followed by diminished fibrinolysis, which is distinct from hypofibrinolysis (inadequate plasmin burst and fibrinolysis). After an initial thrombin and plasmin burst (increased PAP), fibrinolysis is inhibited, mediated in part by increased TAFI.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Critical Care and Intensive Care Medicine,Surgery
Cited by
3 articles.
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