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.
Highlights
Hemostatic dysfunction and resultant pathologic bleeding and/or thrombosis is a common complication of critical illness in children
Platelets are recruited to areas of vascular injury and adhere to endothelial cells and subendothelial structures via specific receptors on these structures, a process augmented through binding to von Willebrand factor, thereby forming a platelet plug (Figure 3A)
These studies show that most coagulation parameters are highly dependent on age and undergo the greatest changes during the 1st year of life. These changes require the use of age-specific reference intervals in the clinical assessment of hemostasis and the diagnosis of pediatric bleeding and thrombotic disorders. Despite these age-dependent differences, the changing coagulation system throughout infancy, childhood, and adolescence should be viewed as physiologic, i.e., “balanced,” with decreased factor levels and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in infants compared to normal adolescents and adults not necessarily reflecting an increased risk for hemorrhage
Summary
Reviewed by: Genny Raffaeli, IRCCS Ca ’Granda Foundation Maggiore Policlinico Hospital, Italy Paul Monagle, The University of Melbourne, Australia. 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.” 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 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.
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