Abstract

Objective: To identify whether coagulation profiles using thromboelastometry are associated with outcomes in pediatric septic shock. The primary outcomes were the development of disseminated intravascular coagulation (DIC) and the severity of the pediatric intensive care unit (PICU) existing scoring systems, while the secondary outcome was hospital mortality. This study aimed to contribute to current findings of the limitations of conventional tests in determining the optimal timing of anticoagulation in sepsis.Design: A prospective, observational study conducted between August 2019 and August 2020.Setting: PICU at a pediatric tertiary hospital in Hanoi, Vietnam.Patients: Fifty-five pediatric patients who met the septic shock criteria were enrolled.Measurements and Main Results: Fifty-five patients with septic shock were recruited. At the time of diagnosis, thromboelastometry revealed normocoagulability, hypercoagulability, and hypocoagulability in 29, 29, and 42% of the patients, respectively (p > 0.05); however, most patients in the overt DIC and non-survival groups progressed to hypocoagulability (82 and 64%, respectively). The overt DIC, PELOD-2 > 8, PRISM-III > 11, and non-survival group had a significant hypocoagulable tendency according to thromboelastometry parameters [prolonged clotting time (CT) and clot formation time (CFT); and reduced α-angle (α), maximum clot firmness (MCF), thrombodynamic potential index (TPI)] compared to the non-overt DIC, PELOD-2 ≤ 8, PRISM-III score ≤ 11 and survival group (p < 0.05). Conventional parameters between the normocoagulable and hypercoagulable groups were not different (p > 0.05). Hypocoagulability was characterized by lower platelet count and fibrinogen level, higher prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), and higher D-dimer level than in hypercoagulability (p < 0.05). Hypocoagulable tendency on thromboelastometry had a higher hazard at a PT > 16.1 s [area under the curve (AUC) = 0.747, odds ratio (OR) = 10.5, p = 0.002], INR > 1.4 (AUC = 0.754, OR = 6.9, p = 0.001), fibrinogen <3.3 g/L (AUC = 0.728, OR = 9.9, p = 0.004), and D-dimer > 3,863 ng/mL (AUC = 0.728, OR = 6.7, p = 0.004).Conclusions: Hypocoagulable tendency using thromboelastometry is associated with the severity of septic shock. Conventional coagulation tests may fail to detect hypercoagulability, which is crucial in determining anticoagulation timing.

Highlights

  • Sepsis-induced coagulopathy (SIC) is initially triggered by the combination of procoagulant upregulation, endogenous anticoagulant downregulation, and fibrinolytic impairment

  • As external pathway activation plays a crucial role in SIC, our study focused on EXTEM parameters, including clotting time (CT)—time to thrombin generation, clot formation time (CFT), and αangle (α)—fibrin polymerization and clot formation, maximum clot firmness (MCF)—the measure of maximum clot amplitude describing clot stability and thrombodynamic potential index (TPI) calculated by 30∗(100∗MCF)/CFT∗(100-MCF) describing global coagulation

  • 31% presented with positive blood cultures, and the most prevalent organisms isolated were Streptococcus pneumonia, Staphylococcus aureus, and Escherichia coli

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Summary

Introduction

Sepsis-induced coagulopathy (SIC) is initially triggered by the combination of procoagulant upregulation, endogenous anticoagulant downregulation, and fibrinolytic impairment. The current standards for hemostatic assessment are generally based on conventional parameters with several limitations As they are performed using plasma, the function of cell components (such as the contribution of platelets to thrombosis) in the coagulation system is bypassed. These parameters are not reflective of the in vivo hemostatic process and do not provide qualitative or functional data [1, 14]. Methodological improvements in thromboelastography (TEG) or rotational thromboelastometry (ROTEM) have been widely utilized as point-of-care tests for optimal hemostatic resuscitation in patients with sepsis These tests measure dynamic global clotting and overcome limitations of the conventional assay in discriminating between hyper- and hypocoagulability [10,11,12, 17]. We aimed to contribute to the current findings on the limitations of conventional coagulation tests in optimal anticoagulation timing in sepsis

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