Pediatric Thromboelastograph 6s and Laboratory Coagulation Reference Values

Abstract

Context.— Specific reference intervals (RIs) facilitate accurate interpretation of results. Coagulation assay results may vary by demographics and also between reagents and analyzers used. Current Thromboelastograph 6s (TEG 6s) Hemostasis Analyzer RIs were generated from adult samples. Objective.— To generate reagent analyzer-specific pediatric RIs for TEG 6s and coagulation parameters. Design.— A prospective, observational, single-center study of healthy children undergoing general anesthesia (January 3, 2017 to January 3, 2019). Venous blood samples were obtained for TEG 6s (Kaolin, Kaolin-Heparinase, Rapid and Functional Fibrinogen assays) and coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time, Echis time, antithrombin activity, and fibrinogen concentration using Instrumentation Laboratory ACL-TOP analyzers). Differences between activated partial thromboplastin time and prothrombin time reagents were investigated using mixed-effects regression, comparing maximum coefficients-of-variation with assay-specific allowable variation. RIs (lower/upper limits 2.5th of 97.5th percentiles) were generated using the following 2 methods: within discrete age-groups (neonates [<1 month], infants [1 month–1 year], young children [1–5 years], older children [6–10 years], and adolescents [11–16 years]), and modeled as functions of age and/or sex using quantile regression, including significant fractional polynomial and interaction terms. Results.— Variation between prothrombin time and activated partial thromboplastin time assays using different reagents was clinically significant. Reagent-analyzer specific pediatric RIs were generated using data from 254 children. Discrete and model-based RIs varied by age for all coagulation parameters and TEG 6s variables in all assays. Conclusions.— We report reagent-analyzer specific pediatric RIs for TEG 6s and coagulation parameters. Observed variation reinforces recommendations for laboratory-specific RIs. These findings improve accuracy of interpretation of clinical results, provide a foundation for comparison and validation of tests in pathology and illustrate feasibility and advantages of model-based RI approaches.

Age-related changes in thromboelastography profiles in injured children

“…A bimodal age distribution for VTE rates has been described previously with peaks around ages 0 to 2 years and 13 to 17 years, and risk factors may include traumatic brain injury (TBI), critical care, blood transfusions, central line placement, mechanical ventilation, and surgery. 12,30 While healthy children with a hypercoagulable profile did not have increased VTE risk in previous studies, [7][8][9] the above injured cohort had additional risk factors that increased thromboembolic risk and could be mitigated with timely interventions. The results of this study suggest there is more nuance in the TIC response in the diverse group treated as "children" that may necessitate differential treatment algorithms, for example, more frequent use of DVT prophylaxis in infants or consideration of more widespread use of hemostatic adjuncts in adolescents.…”

“…In total, 726 subjects were identified (Fig. 1); 69% were male, median (interquartile range [IQR]) ISS was 12, [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] and 83% sustained a blunt mechanism. There were multiple differences identified in demographics and injury characteristics across age groups.…”

“…[4][5][6][22][23][24][25][26][27] Multiple studies have shown young children have decreased levels of proteins involved in coagulation, fibrinolysis, and natural inhibitors of coagulation without increases in bleeding or thrombosis. 6,8,24,28 However, injured children are often managed uniformly despite these developmental and physiologic differences.…”

“…6 Studies in healthy children have identified sig-nificant differences in conventional coagulation tests and viscoelastic monitoring (i.e., thromboelastography [TEG] and rotational thromboelastometry [ROTEM]) based on age, especially during their first year of life, without an increased tendency toward bleeding or thrombosis. [7][8][9] In addition, differences in development may result in age-based differences in treatment response. Therefore, understanding developmental hemostasis is critical to ensure optimal prevention, diagnosis, and treatment of hemorrhagic and thrombotic disease in children.…”

“…Therefore, understanding developmental hemostasis is critical to ensure optimal prevention, diagnosis, and treatment of hemorrhagic and thrombotic disease in children. [7][8][9] There is increasing utilization of TEG in assessing and treating injured children across trauma centers. In pediatric trauma literature, TEG results have predicted the need for blood product resuscitation, including massive transfusion, 10,11 life-saving interventions, 11 development of deep venous thrombosis (DVT), and death and disability.…”