Hemostatic Testing in Critically Ill Infants and Children

Abstract

Children with critical illness frequently manifest imbalances in hemostasis with risk of consequent bleeding or pathologic thrombosis. Traditionally, plasma-based tests measuring clot formation by time to fibrin clot generation have been the “gold standard” in hemostasis testing. However, these tests are not sensitive to abnormalities in fibrinolysis or in conditions of enhanced clot formation that may lead to thrombosis. Additionally, they do not measure the critical roles played by platelets and endothelial cells. An added factor in the evaluation of these plasma-based tests is that in infants and young children plasma levels of many procoagulant and anticoagulant proteins are lower than in older children and adults resulting in prolonged clot generation times in spite of maintaining a normal hemostatic “balance.” Consequently, newer assays directly measuring thrombin generation in plasma and others assessing the stages hemostasis including clot initiation, propagation, and fibrinolysis in whole blood by viscoelastic methods are now available and may allow for a global measurement of the hemostatic system. In this manuscript, we will review the processes by which clots are formed and by which hemostasis is regulated, and the rationale and limitations for the more commonly utilized tests. We will also discuss selected newer tests available for the assessment of hemostasis, their “pros” and “cons,” and how they compare to the traditional tests of coagulation in the assessment and management of critically ill children.

Impact of blood sampling technique on reproducibility of viscoelastic coagulation monitor (VCM™) system test results in the neonate

“…The interpretation of neonatal coagulation test results is not an exact science. Developmental haemostasis, pre-analytical and analytical issues and the lack of age, analyzer and reagents appropriate reference ranges for coagulation screening together with the technical challenges associated with blood drawing in neonates have an important impact on both the diagnosis and management of the hemostatic imbalance in infants and may lead to inappropriate transfusions of blood products [11][12][13]. Newer VCT assays assessing the stages of hemostasis including clot initiation, propagation, and fibrinolysis in the whole blood by viscoelastic methods allow for a global measurement of the hemostatic system [1,14].…”

“…The intra-class correlation coefficient (ICC) indicates the inter-patient variance to total variance ratio (11)…”

Thrombosis in Chronic Kidney Disease in Children

“…Platelet function can be assessed by identifying markers of platelet activation and reactivity in plasma and/or on circulating platelets, such as platelet factor 4 and β-thromboglobulin in platelet-poor plasma. This is usually performed by blood flow cytometry, which is used to measure activated platelets, as well as platelet turnover [ 7 ]. Consequently, newer assays that directly measure thrombin generation in plasma, as well as those that assess the stages of hemostasis, including clot initiation, propagation, and fibrinolysis in whole blood by viscoelastic methods, are what may allow a global measurement of the hemostatic system.…”

“…Consequently, newer assays that directly measure thrombin generation in plasma, as well as those that assess the stages of hemostasis, including clot initiation, propagation, and fibrinolysis in whole blood by viscoelastic methods, are what may allow a global measurement of the hemostatic system. Currently available methods for viscoelastic testing include thromboelastography (TEG) and the related rapid thromboelastography (r-TEG) as well as rotational thromboelastography (ROTEM) [ 7 ].…”