1. Characterization of distinct coagulopathic phenotypes in injury: Pathway-specific drivers and implications for individualized treatment
- Author
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Benjamin M. Howard, S. Ariane Christie, Carolyn S. Calfee, Lucy Z. Kornblith, Amanda S. Conroy, Ryan C. Kunitake, Mary F. Nelson, Mitchell J. Cohen, Rachael A. Callcut, and Carolyn M. Hendrickson
- Subjects
Male ,Resuscitation ,030204 cardiovascular system & hematology ,Cardiorespiratory Medicine and Haematology ,Critical Care and Intensive Care Medicine ,Gastroenterology ,0302 clinical medicine ,Trauma Centers ,2.1 Biological and endogenous factors ,Aetiology ,biology ,medicine.diagnostic_test ,Anticoagulant ,Factor V ,Blood Coagulation Disorders ,Factor VII ,Middle Aged ,Phenotype ,Coagulation ,Female ,Partial Thromboplastin Time ,Fresh frozen plasma ,Partial thromboplastin time ,Adult ,medicine.medical_specialty ,Physical Injury - Accidents and Adverse Effects ,medicine.drug_class ,precision medicine ,Clinical Sciences ,Nursing ,Article ,03 medical and health sciences ,Tissue factor ,Young Adult ,Clinical Research ,Internal medicine ,traumatic coagulopathy ,medicine ,Humans ,Blood Transfusion ,Glasgow Coma Scale ,International Normalized Ratio ,Factor VIII ,business.industry ,030208 emergency & critical care medicine ,Emergency & Critical Care Medicine ,Good Health and Well Being ,biology.protein ,Wounds and Injuries ,Surgery ,business - Abstract
BACKGROUND International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy 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 versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation. METHODS Plasma samples were prospectively collected from 1,262 critically injured patients at a single Level I trauma center. Standard coagulation measures and an extensive panel of procoagulant and anticoagulant 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 Glasgow Coma Scale score than INR-TF (p < 0.001). INR-TF had decreased factor VII activity compared with PTT-CONTACT, whereas PTT-CONTACT had decreased factor VIII activity compared with INR-TF. All coagulopathic patients had factor V deficits, but activity was lowest in BOTH, suggesting an additive downstream effect of disordered activation pathways. Patients with PTT-CONTACT received half as much packed red blood cell and fresh frozen plasma as did the other groups (p < 0.001). Despite resuscitation, mortality was higher for coagulopathic patients; mortality was highest in BOTH and higher in PTT-CONTACT than in INR-TF (71%, 60%, 41%; p = 0.04). CONCLUSIONS Discordant phenotypes demonstrate differential factor deficiencies consistent with dysfunction of contact versus 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/epidemiological study, level II.
- Published
- 2017