Characterization of distinct coagulopathic phenotypes in injury

Abstract

Background International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy (ATC) but reflect disparate activation pathways. In this study we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact vs. tissue factor pathway perturbations, and that characterization will provide targets to guide individualized resuscitation. Methods Plasma samples were prospectively collected from 1262 critically-injured patients at a single Level-1 trauma center. Standard coagulation measures and an extensive panel of pro- and anti-coagulant factors were assayed and analyzed with demographic and outcome data. Results Fourteen percent of patients were coagulopathic on admission. Among these, 48% had abnormal INR and PTT (BOTH), 43% had isolated prolonged PTT (PTT-CONTACT), and 9% had isolated elevated INR (INR-TF). PTT-CONTACT and BOTH had lower GCS than INR-TF (p<0.001). INR-TF had decreased factor VII activity compared to PTT-CONTACT, while PTT-CONTACT had decreased factor VIII activity compared to INR-TF. All coagulopathic patients had factor V defecits but activity was lowest in BOTH suggesting an additive downstream effect of disordered activation pathways. Patients with PTT-CONTACT received half as much PRBC and FFP as other groups (p<0.001). Despite resuscitation, mortality was higher for coagulopathic patients; mortality was highest in BOTH and higher in PTT-CONTACT than INR-TF (71%, 60%, 41% p=0.04) Conclusions Discordant phenotypes demonstrate differential factor deficiencies consistent with dysfunction of contact vs. tissue factor pathways with additive effects from common pathway dysfunction. Recognition and treatment of pathway-specific factor deficiencies driving different coagulopathic phenotypes in injured patients may individualize resuscitation and improve outcomes. Level of Evidence Prognostic/therapeutic study, level III.

Characterization of organ dysfunction and mortality in pediatric patients with trauma with acute traumatic coagulopathy

“…27 Additional information including demographics, trauma mechanism, and medical interventions were also collected. Injury severity was assessed by the Injury Severity Score (ISS) which was considered as a continuous scale and categorized into mild (0-14), moderate (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and severe (30-75) trauma. [28][29][30] Arterial hypotension was defined as a systolic blood pressure of <60 mm Hg in neonates 0 to 30 days old, <70 mm Hg in infants 30 days to 1 year old, <70 mm Hg + (age in years x 2) mm Hg in children 1 year to 10 years old, and <90 mm Hg in children and adolescents > 10 years old based on reference points established in the Pediatric Advanced Life Support guidelines.…”

Variability in international normalized ratio and activated partial thromboplastin time after injury are not explained by coagulation factor deficits

“…Hence, depletion of clotting elements, assumed in the setting of prolonged CCAs, remains the basis for early transfusion of plasma in trauma patients (7). A recent study evaluating the prevalence of combined or isolated elevations of PT/INR and aPTT revealed discordant phenotypes demonstrating differential factor deficiencies consistent with dysfunction of contact versus tissue factor pathways and additive effects from the common pathway (25). In our patient population, the most common coagulation assay phenotype was a PT/INR of <1.3 and an aPTT of <34 sec followed by elevations in both assays.…”

Goal-directed hemostatic resuscitation for trauma induced coagulopathy: Maintaining homeostasis

“…Interestingly, however, serious injured patients at risk for massive transfusion present with varied profiles of isolated prolongation of the INR, isolated elevated PTT, and a combination of abnormalities. A recent report from the San Francisco General group (26) indicated prolonged INR (>1.3) in 9%, elevated PTT (> 34sec) in 43%, and combined PT and PTT abnormalities in 48 % among coagulopathic patients. In our recent analysis of patients requiring a massive transfusion (>10 RBC/first 6 hours), 2% had a prolonged INR (>1.3), 13% had an elevated PTT (>30 sec), and 72% had combined abnormalities of INR and PTT.…”