Thromboelastometry Variables in Neonates with Perinatal Hypoxia.

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.

Clinical Application of Thromboelastography/Thromboelastometry (TEG/TEM) in the Neonatal Population: A Narrative Review.

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.

Cancer-Associated Thrombosis: Pathophysiology, Laboratory Assessment, and Current Guidelines.

Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Conventional coagulation tests (PT/aPTT) are more accurate in detecting a hypocoagulable rather than a hypercoagulable state; thus, their contribution to CAT management is limited. Traditionally, D-dimer levels have been the most common laboratory study for the evaluation of thrombotic risk. However, D-dimer levels only display a snapshot of the coagulation cascade, and they cannot provide a dynamic evaluation of evolving clot formation. Non-conventional assays, such as viscoelastic methods and microparticle formation are promising tools for the identification of patients at risk for developing CAT. Recent guidelines from the American Society of Clinical Oncology counsel against the estimation of thrombotic risk through a single test and recommend the use of scoring systems that take into account several risk factors. The present review outlines the current insights into the pathophysiological mechanisms of CAT and provides a comprehensive review of the latest advances in the laboratory assessment of CAT and the recent guidelines for the management of patients at risk for developing thromboembolic complications.

Nucleated Red Blood Cells: Could They Be Indicator Markers of Illness Severity for Neonatal Intensive Care Unit Patients?

BACKGROUND: We aimed to assess whether nucleated red blood cells (NRBCs) count could serve as a diagnostic and prognostic biomarker for morbidity and mortality in critically ill neonates. METHODS: The association between NRBCs count and neonatal morbidity and mortality was evaluated in an observational cohort of critically ill neonates hospitalized in our neonatal intensive care unit over a period of 69 months. The discriminative ability of NRBCs count as diagnostic and prognostic biomarkers was evaluated by performing the Receiver Operating Characteristics (ROC) curve analysis. RESULTS: Among 467 critically ill neonates included in the study, 45 (9.6%) of them experienced in-hospital mortality. No statistically significant difference was found with regards to NRBCs count between survivors and non-survivors, although the median value for NRBCs was sometimes higher for non-survivors. ROC curve analysis showed that NRBCs is a good discriminator marker for the diagnosis of perinatal hypoxia in neonates with area under the curve (AUC) [AUC 0.710; 95% confidence interval (CI), 0.660-0.759] and predominantly in preterm neonates (AUC 0.921 (95% CI, 0.0849-0.0993)) by using a cut-off value of ≥11.2%, with 80% sensitivity and 88.7% specificity. NRBCs also revealed significant prognostic power for mortality in septic neonates (AUC 0.760 (95% CI, 0.631-0.888)) and especially in preterms with sepsis (AUC 0.816 (95% CI, 0.681-0.951)), with cut-off value ≥ 1%, resulting in 81.6% sensitivity and 78.1% specificity. CONCLUSION: NRBCs count may be included among the early diagnostic and prognostic markers for sick neonates.

Coagulation Profiles of Pulmonary Arterial Hypertension Patients, Assessed by Non-Conventional Hemostatic Tests and Markers of Platelet Activation and Endothelial Dysfunction.

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.