Developmental haemostasis

Abstract

Developmental haemostasis is a concept, now universally accepted, introduced by Andrew et al. in the late 1980's. However, coagulation analysers and reagents have changed significantly over the past 15 years. Coagulation testing is known to be sensitive to changes in individual reagents and analysers. We hypothesised that the reference ranges developed by Andrew et al. may not be appropriate for use in a modern coagulation laboratory. Our study was designed to determine whether a current day coagulation testing system (STA Compact analyser and Diagnostica Stago reagent system) was sensitive to age-related changes in coagulation assays. This is the first large scale study since Andrew et al. to determine the age associated numerical changes in coagulation proteins. Our results confirm the concepts of developmental haemostasis elucidated by Andrew et al. However, our results clearly demonstrate that the absolute values of reference ranges for coagulation assays in neonates and children vary with analyser and reagent systems. The results confirm the need for coagulation laboratories to develop age-related reference ranges specific to their own testing systems. Without this, accurate diagnosis and management of neonates and children with suspected bleeding or clotting disorders is not possible. Finally we present age related reference ranges for D-dimers, TFPI, and endogenous thrombin potential, previously not described.

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

“…The concept of developmental hemostasis introduced by Andrew et al (1)(2)(3) in the late 1980s has been universally accepted (4). The hemostatic system of children is significantly different from that in adults.…”

“…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.…”

“…Shortened APTT values may be associated with hypercoagulability and appear to be significantly associated with increased risk of VTE (28). 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).…”

Developmental Changes in Soluble CD40 Ligand

“…During childhood and adolescence many platelet and coagulation functions become more like those of adults so that higher sCD40L during this period is not as easily ascribed to compensating hemostatic abilities. When considering developmental changes in coagulant and inhibitor levels, Monagle and colleagues hypothesized that these proteins might have additional functions that dictate age-related differences in concentration (24). It could be that there is a greater necessity at birth and during the early years of life for certain non-hemostatic CD40L activities, mandating higher levels during these periods.…”