Fibrinolytic Impairment and Mortality in Pediatric Septic Shock: A Single-Center Prospective Observational Study.

OBJECTIVES: Fibrinolytic shutdown is associated with poor prognosis in adult sepsis, but data in the pediatric population are sparse. This study aimed to identify the association between impaired fibrinolysis and mortality in pediatric septic shock. DESIGN: A prospective, observational study conducted between August 2019 and August 2020. SETTING: PICU at a pediatric tertiary hospital in Hanoi, Vietnam. PATIENTS: Fifty-six pediatric patients who met septic shock criteria were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Conventional coagulation tests and rotational thromboelastometry were performed at diagnosis. The fibrinolytic activity on extrinsic pathway thromboelastometry was negatively correlated with the Vasoactive-Inotropic Score at 24 hours post-PICU admission, peak lactate level during the first 24 hours, Pediatric Logistic Organ Dysfunction-2 score, and Pediatric Risk of Mortality-III score (all p < 0.05). Compared with patients with nonovert disseminated intravascular coagulation, dysfunction of less than two organs, and who survived, patients with overt disseminated intravascular coagulation, dysfunction of greater than two organs, and who died showed significantly lower fibrinolytic activity, represented by significantly higher lysis indexes (%) and lower maximum lysis (%) (all p < 0.05). The threshold values for prediction of mortality were lysis index 60 minutes greater than 97.5 (area under the curve = 0.86; sensitivity = 73%; specificity = 90%), maximum lysis less than 6.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 87%), and lysis index 45 minutes greater than 99.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 85%). Hypofibrinolysis was associated with prolonged PICU length of stay in survivors and with early mortality in nonsurvivors. CONCLUSIONS: Fibrinolytic shutdown in pediatric septic shock is associated with an increase in disease severity and mortality. This highlights the need for further investigations regarding whether fibrinolytic therapy improved the outcome of pediatric septic shock.

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study.

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.