Coagulation Testing in Pediatric Patients: The Young Are Not Just Miniature Adults

Abstract

During the past few decades, great progress has been made toward a better understanding of the development of the hemostatic system. It is now clear that the physiology of hemostasis in pediatric patients differs widely from that in adults, supporting the hypothesis that children might have natural protective mechanisms that justify such variations. However, the correct interpretation of hemostasis test results in young patients, along with a deep understanding of the normal postnatal development in the human coagulation system, are essential prerequisites to the proper investigation of thrombotic and hemorrhagic problems in pediatric patients. Because the hemostatic system is not fully mature by 3 to 6 months of age, it is important to recognize that interpretation of laboratory data in pediatric patients must be accompanied by appropriate age-dependent reference ranges, which should also be specific for the testing system used, to prevent misclassification of children as having defects of factors and inhibitors of the coagulation system.

Age-associated developmental changes in the activated partial thromboplastin time (APTT) and causes of prolonged APTT values in healthy Chinese children

“…This situation necessitates the generation of several appropriate age-dependent reference ranges to interpret laboratory data in pediatric patients and prevent misclassification of children having defects of factors and inhibitors of the coagulation system (7). Since there are differences in the hemostatic system among different racial/ethnic groups (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and also between different analyzer and reagent systems (4), coagulation laboratories should develop age-related reference ranges specific to their own testing systems for the local population (4,7,32). In this study, we analyzed retrospectively the results of preoperative APTT testing in childhood and adult controls undergoing minor elective surgery.…”

“…The hemostatic system of children is significantly different from that in adults. Thus, an understanding of developmental hemostasis and the development of appropriate age-dependent reference ranges are pivotal for prevention, diagnosis, and treatment of hemostatic problems during childhood (4)(5)(6)(7). Physiological reference ranges are available for premature infants, full-term infants and children from 1 to 16 years of age (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

“…Thus, an understanding of developmental hemostasis and the development of appropriate age-dependent reference ranges are pivotal for prevention, diagnosis, and treatment of hemostatic problems during childhood (4)(5)(6)(7). Physiological reference ranges are available for premature infants, full-term infants and children from 1 to 16 years of age (1)(2)(3)(4)(5)(6)(7)(8)(9). However, most reports are relevant to Caucasians (1)(2)(3)(4)(5)(6)(7)(8)(9), while studies on developmental hemostasis in Oriental children is rare.…”

“…There have been several reports concerning age-associated APTT values in healthy children, in which inconsistent conclusions were drawn with respect to values seen in adults (4,6,(29)(30)(31). It is recommended that coagulation laboratories devel-op age-related reference ranges specific to their own testing systems for the local population (4,7,32). In this study, we reviewed retrospectively age-associated evolvement of APTT values in healthy Chinese subjects from birth through childhood.…”

Phase 3, single‐arm, multicenter study of dabigatran etexilate for secondary prevention of venous thromboembolism in children: Rationale and design

“…Adults and children also have differences in their coagulation systems, the maturation of which is not complete until adolescence. Developmental differences in coagulation maturation are exemplified by lower circulating levels of both procoagulant and natural anticoagulant proteins in children versus adults,24, 25 particularly in infants,26 which may affect the way children respond to anticoagulant drugs. In the case of dabigatran, which is primarily renally excreted,27, 28 differences in maturation of renal function are considered important in determining safe and effective pediatric dosages 29.…”