Development of the human coagulation system in the healthy premature infant

Abstract

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.

Reference intervals for common coagulation tests of preterm infants (CME)

“…First, identifying a coagulation value as “abnormal” depends on having accurate reference intervals for comparison. Reference intervals for late preterm and term infants are available, but meager data are found for preterm infants . This is due, in part, to the large amount of blood needed for these tests relative to the patient's blood volume and the difficulty in obtaining blood samples that are reliably uncontaminated by heparin.…”

“…Thus, our impression that cord blood coagulation tests do not identify the neonates who will go on to have bleeding problems is tentative and subject to modification when thousands of preterm neonates have been similarly screened. The problems of small sample size is common to all previous reports of coagulation tests in preterm neonates . To lessen this problem, we attempted (Table ) to estimate the relevant reference intervals using data from the present plus previous studies and to propose tentative recommendations for management of preterm neonates.…”

Association of ABO(H) and I blood group system development with von Willebrand factor and Factor VIII plasma levels in children and adolescents

“…The aim of our study was to investigate the influence of the ABO(H) blood group system on Factor (F)VIII activity (FVIII : C) and von Willebrand factor (VWF) variables in children, with specific consideration of the first year of life and to establish age‐, reagent‐, and analyzer‐specific pediatric reference intervals for several coagulation parameters. Two decades ago, Andrew and colleagues 1‐3 reported age‐dependent features of the coagulation system in children. These studies concluded that the physiologic system of hemostasis is immature at birth and subjected to continuous maturation.…”

Early fresh‐frozen plasma transfusion decreases the risk of retinopathy of prematurity

“…Coagulation tests were considered abnormal during the first week of life when APTT was more than 50 seconds and INR was 1.4 or more. The literature does not report strict recommendations for the diagnosis and treatment of bleeding disorders in the preterm infant, and the classical values reported by Andrew and coworkers were determined in infants who were healthy and more mature than ours (they were born at 30‐36 weeks of gestation) and using coagulation analyzers and reagents not appropriate for use in a modern coagulation laboratory. Therefore, we developed these reference values (which are very almost equal to those of Andrew et al.)…”