A principal component analysis of postinjury viscoelastic assays: Clotting factor depletion versus fibrinolysis

Abstract

Introduction The mechanisms driving trauma-induced coagulopathy (TIC) remain to be defined and its therapy demands an orchestrated replacement of specific blood products. Thrombelastography (TEG) is a tool to guide the TIC multicomponent therapy. Principal component analysis (PCA) is a statistical approach that identifies variable clusters, thus, we hypothesize that PCA can identify specific combinations of TEG-generated values that reflect TIC mechanisms. Methods Adult trauma patients admitted from September 2010 to October 2013 for whom a massive transfusion protocol was activated were included. Rapid TEG values obtained within the first 6 hours postinjury were included in the PCA analysis. PCA components with an eigenvalue >1 were retained, and, within components, variable loadings (equivalent to correlation coefficients)>|60| were considered significant. Component scorings for each patient were calculated and clinical characteristics of patients with high and low scores were compared. Results Of 98 enrolled patients, 67% were male and 70% suffered blunt trauma. Median age was 41 years (IQR:28-55) and median Injury Severity Score was 31.5 (IQR: 24-43). PCA identified three principal components (PC) that together explained 93% of the overall variance. PC1 reflected global coagulopathy with depletion of platelets and fibrinogen whereas PC3 indicated hyperfibrinolysis. PC2 may represent endogenous anticoagulants such as the activation of protein C. Conclusions PCA suggests depletion coagulopathy is independent from fibrinolytic coagulopathy. Furthermore, the distribution of mortality suggests that low levels of fibrinolysis may be beneficial in a select group of injured patients. These data underscore the potential of risk for concurrent presumptive treatment for preserved depletion coagulopathy and possible fibrinolysis.

An International Normalized Ratio–Based Definition of Acute Traumatic Coagulopathy Is Associated With Mortality, Venous Thromboembolism, and Multiple Organ Failure After Injury

“…The INR alone cannot distinguish between potential ATC mechanisms. Recent studies employing both conventional (60) and viscoelastic (28) measures suggest, however, that the PT/INR captures the most important type of coagulopathy for adverse trauma outcomes.…”

“…As a result, we evaluated two risk-adjusted models for each outcome, differing as to the ATC definition but otherwise containing the same covariates. We selected the two candidate ATC definitions, INR >1.2 or INR >1.5, based on the INR thresholds most frequently used in published literature to define ATC (9, 10, 20-28). We compared the fit of the two competing models for each outcome using the Akaike information criterion (49).…”

“…While the INR meets these laboratory criteria, it is unclear (1) whether INR as a single test measured on emergency department admission and reflective of extrinsic coagulation pathway abnormalities is independently associated with adverse outcomes and (2) which of the two most common INR-based ATC definitions — INR >1.2 (equivalent to PT, Quick's value or INR outside the normal range (9, 10, 20-24) or INR >1.5 (25-28) — is most clinically meaningful. To address these issues, we investigated the independent association of INR with mortality and morbidity in a prospective multicenter cohort of severely injured trauma patients.…”

Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock

“…Appreciation that the two components of TIC (hypocoagubility and hyperfibrinolysis) are not necessarily linked (7, 8) warrants a re-evaluation of how to design animal models with the objective of identifying specific TIC phenotypes. We found that tissue injury and shock have opposing actions on clot stability.…”

“…Principal component analyses suggest that hyperfibrinolysis does not correlate with impaired clot formation (7, 8). In a human study, patients with non-traumatic cardiac arrest had a high prevalence of hyperfibrinolysis (9).…”