Abnormalities of laboratory coagulation tests versus clinically evident coagulopathic bleeding: results from the prehospital resuscitation on helicopters study (PROHS)

Abstract

Background: Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described.

Methods: Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+.

Results: Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 10⁹/L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR.

Conclusion: CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components.

Figure 1

Estimated relative risks and 95% confidence intervals for abnormal TEG parameters versus CC+ in 391 patients. K-time >2.5 min, mA <55 mm, and platelet count <150 × 10⁹/L were independently associated with CC+. ACT, activated clotting time. mA, maximum amplitude. LY30, lysis in 30 minutes. Plt, platelet count. CC, clinically evident coagulopathy.

Figure 2. Proposed mechanisms of TIC

Trauma induces a plethora of biochemical and physiologic changes, including activation of both procoagulant and anticoagulant mechanisms. Several, non-mutually exclusive hypotheses have been proposed as the underlying etiology of TIC, but causative mechanisms are currently unclear. Additionally, the relationship between laboratory-based evidence of TIC, upon which most research efforts are based, and clinically-evident coagulopathic bleeding has not been adequately investigated. TIC, trauma-induced coagulopathy; tPA, tissue plasminogen activator; PAI-1, plasminogen activator inhibitor-1; APC, activated protein C; EGL, endothelial glycocalyx layer. Reproduced from Blood 2016;128(8):1043–9. Used with permission.