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The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870–0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868–0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.

Hypofibrinolysis has been demonstrated in several studies in adult sepsis. Although fibrinolysis is an important and integral part of the hemostatic system, few data are available regarding its role in neonatal sepsis. Our purpose was to define fibrinolytic profiles across neonatal sepsis spectrum using rotational thromboelastometry (ROTEM).This study was performed in a Greek tertiary General Hospital during an 18 month-period and included 44 neonates with confirmed sepsis and 22 with suspected sepsis; 110 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM and APTEM assays were performed, clinical findings and laboratory data were recorded.Although most EXTEM parameters were significantly different among the 3 groups, Maximal Lysis (ML) and Lysis Index at 60 min (LI60) levels were similar (p = 0.11 and p = 0.20, respectively). Hyperfibrinolysis, as defined by ROTEM parameters, did not significantly differ among the study populations (p = 0.41). On the contrary, fibrinolysis shutdown, defined as an EXTEM LI60 ≥98%, was more common in septic neonates than in healthy (p 0.001) and neonates with suspected sepsis (p = 0.042). A weak to moderate correlation of LI60 and ML with mortality (Spearman rho = 0.43 and - 0.40, p = 0.005 and 0.007, respectively) and SNAPE score (Spearman rho = 0.35 and - 0.33, p = 0.02 and 0.03, respectively) was noticed in sepsis group.ROTEM, based on fibrinolytic parameters, showed a more frequent fibrinolysis shutdown in neonatal sepsis, but it could neither effectively discriminate septic neonates, nor predict their clinical outcome. The considerable overlap among numerical ROTEM values probably compromises their diagnostic clinical utility in neonatal sepsis.

Perinatal hypoxia is associated with an increased risk of coagulation disorders by enhancing the consumption of platelets and some clotting factors due to the associated severe hypoxemia, acidemia, and compromised oxygen and blood supply to the neonatal liver and bone marrow. Thromboelastometry (TEM), which estimates the dynamics of blood coagulation, may represent an attractive tool for studying the coagulation status of these neonates. We aimed at assessing the hemostatic profile of neonates with perinatal hypoxia using the standard extrinsically activated TEM (ex-TEM) assay. In total, 164 hospitalized neonates with perinatal asphyxia and/or fetal distress comprised the study subjects, and 273 healthy neonates served as controls. Ex-TEM assay was performed, SNAPPE (Score for Neonatal Acute Physiology Perinatal Extension) was calculated, and clinical findings and laboratory results were recorded in all study subjects. Hypoxic neonates expressed a prolonged clotting time (CT) and clot formation time (CFT) and reduced amplitude at 10 minutes (A10), α-angle, and maximum clot firmness compared with healthy neonates. Furthermore, asphyxiated neonates had a significantly prolonged CT and CFT and reduced A10 and α-angle compared with neonates with fetal distress. Hypoxic neonates demonstrate a hypocoagulable ex-TEM profile relative to healthy neonates, indicating a potential role of TEM in the early detection of coagulation derangement in perinatal hypoxia.

Background: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). Methods: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia “Aghios Panteleimon”. Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. Results: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. Conclusions: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates.

The aim of the present study was to assess the coagulation profile in neonatal critical illness using rotational thromboelastometry (ROTEM), and to investigate its association with disease severity and its potential prognostic role in this clinical setting. Over a period of 67 months (July 2014–February 2020) 423 critically ill neonates with confirmed or suspected sepsis, perinatal hypoxia, or respiratory distress syndrome, hospitalized in our neonatal intensive care unit were included in the study. Demographic, clinical, and laboratory data were recorded on admission day and arterial blood was analyzed on ROTEM analyzer using the standard extrinsically activated rotational thromboelastometry assay (EXTEM). Neonatal illness severity scores (Modified NEOMOD [Neonatal Multiple Organ Dysfunction] and SNAPPE [Score for Neonatal Acute Physiology with Perinatal Extension]) were calculated at the same time as ROTEM analysis. Mortality during in-hospital stay was the main outcome measure. Multivariable analyses showed that a 10 mm decrease in EXTEM clot amplitude recorded at 10 minutes (A10) is significantly associated with a higher mortality (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.33–2.08). Higher modified NEOMOD (OR = 1.36, 95% CI: 1.26–1.47) and higher SNAPPE scores (OR = 1.06, 95% CI: 1.04–1.08) were also associated with increased mortality. The CT and A10 variables demonstrated the best prognostic performance among the EXTEM parameters for mortality (area under the curve [AUC] = 0.78; 95% CI: 0.69–0.86 and AUC = 0.76; 95% CI: 0.66–0.85, respectively), showing an optimal cut-off CT ≥63 seconds and A10 ≤37 mm. Using optimal cut-off values of the EXTEM parameters for prediction of mortality, neonates with CT ≥63 seconds were 7.4 times more likely to die (OR = 7.40, 95% CI: 3.50–15.65), while neonates with A10 ≤37 mm were 5.8 times more likely to die (OR = 5.88, 95% CI: 2.94–12.50). An EXTEM hypocoagulable profile on disease onset was shown to be an independent risk factor for in-hospital mortality in neonatal critical illness.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.

"Developmental hemostasis" refers to the dynamic process of gradual hemostatic maturation. Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis, while viscoelastic tests, thromboelastography (TEG), and rotational thromboelastometry (ROTEM) appear very promising as they provide insight more rapidly and accurately into the hemostatic potential. We systematically reviewed the literature in PubMed to examine the use of TEG and ROTEM in neonates. Our search yielded 34 studies, of which 18 concerned healthy neonates and 16 sick neonates. These viscoelastic tests have shown accelerated initiation of coagulation, increased clot strength, and increased fibrinolysis in healthy neonates compared to children and adults. Cord blood leads to a hypercoagulable state as compared to whole blood when testing is performed with TEG. Pre-term neonates have a more hypocoagulable profile, but balanced hemostasis, related to term neonates, that evolves to a more procoagulant phenotype over the first month of life. Critically ill neonates exhibit a more hypocoagulable profile as compared to healthy neonates. TEG and ROTEM have shown predictive value for bleeding events in critically ill neonates and neonates undergoing cardiopulmonary bypass or therapeutic hypothermia.Conclusion: TEG and ROTEM need to become part of the standard coagulation assessment in clinical settings in which hemostatic abnormalities are involved, as they seem to provide more rapid and accurate information regarding the hemostatic profile of the neonates. Their predictive value for bleeding events in critically ill neonates could lead to a more targeted therapy optimizing utilization of blood products. What is Known: • Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis. • TEG and ROTEM delineate more rapidly and accurately the hemostatic potential. What is New: • TEG and ROTEM have shown predictive value for bleeding events. • TEG and ROTEM may lead to a more targeted transfusion therapy optimizing utilization of blood products.

BACKGROUND Our aim was to investigate the role of thromboelastometry (ROTEM) parameters, including maximum clot elasticity (MCE) and platelet component (PLTEM MCE and PLTEM MCF), in early prediction of bleeding events in thrombocytopenic critically ill neonates. MATERIAL AND METHODS This single-center, prospective cohort study included 110 consecutive thrombocytopenic neonates with sepsis, suspected sepsis, or hypoxia. On the first day of disease onset, ROTEM EXTEM and FIBTEM assays were performed and the neonatal bleeding assessment tool was used for the evaluation of bleeding events. RESULTS Most EXTEM and FIBTEM ROTEM parameters significantly differed between neonates with (n = 77) and without bleeding events (n = 33). Neonates with bleeding events had significantly lower PLTEM MCE and PLTEM MCF values compared to those without bleeding events (P

Background: To compare the prognostic accuracy of the most commonly used indexes of mortality over time and evaluate the potential of adding thromboelastometry (ROTEM) results to these well-established clinical scores. Methods: The study population consisted of 473 consecutive term and preterm critically-ill neonates. On the first day of critical illness, modified Neonatal Multiple Organ Dysfunction (NEOMOD) scoring system, Score for Neonatal Acute Physiology (SNAP II), Perinatal extension of SNAP (SNAPPE), and SNAPPE II, were calculated and ROTEM standard extrinsically activated (EXTEM) assay was performed simultaneously. Time-to-event methodology for competing-risks was used to assess the performance of the aforementioned indexes in predicting in-hospital mortality over time. Time-dependent receiver operator characteristics curves for censored observation were compared across indexes. The addition of EXTEM parameters to each index was tested in terms of discrimination capacity. Results: The modified NEOMOD score performed similarly to SNAPPE. Both scores performed significantly better than SNAP II and SNAPPE II. Amplitude recorded at 10 min (A10) was the EXTEM parameter most strongly associated with mortality (A10 &lt, 37 mm vs. ≥37 mm, sHR = 5.52, p &lt, 0.001). Adding A10 to each index apparently increased the prognostic accuracy in the case of SNAP II and SNAPPE II. However, these increases did not reach statistical significance. Conclusion: Although the four existing indexes considered showed good to excellent prognostic capacity, modified NEOMOD and SNAPPE scores performed significantly better. Though larger studies are needed, adding A10 to well-established neonatal severity scores not including biomarkers of coagulopathy might improve their prediction of in-hospital mortality.

Hemostasis is a dynamic age-related process, which gradually evolves from fetal life throughout childhood until adulthood. Although at birth there is a hemostatic deficit of most coagulation factors, studies have shown that this “hemostatic immaturity” is functionally counterbalanced in healthy term or preterm newborns. This delicate hemostatic balance is, however, deranged in sick neonates, resulting in an enhanced risk of hemorrhage and/or thrombosis. In critically ill neonates, conventional coagulation tests do not seem to provide reliable information or indications regarding the functional status of platelets or fibrinolysis. In contrast, viscoelastic tests, namely thromboelastography/thromboelastometry (TEG/TEM) hold promise for rapid assessment of the whole hemostatic potential, allowing immediate intervention should this be required. However, neonatal data are limited due to lack of reference values, especially in premature neonates. In this narrative review, we provide some insights around current knowledge regarding TEG/TEM applications in healthy and sick newborns. Overall, the use of viscoelastic tests in diagnosis and management of coagulation disorders in neonates is definitely worth further exploration. Consideration should be made to include these tests in the routine laboratory investigation of neonates and specific transfusion algorithms should also be developed in order to avoid treatment pitfalls.