ABSTRACf. Appropriate animal experimentation can enhance our understanding of thrombotic and hemorrhagic problems in the human neonate. Which newborn animal species' coagulation system most closely resembles the human neonate is unknown. The objective of the study was to assess the newborn coagulation system in four animal species and compare them with the human neonate. Blood samples were drawn on days 1 and 7 of life from lambs (n =10), piglets, (n =12), rabbit pups (n =12), and beagle pups (n = 7). Coagulation screening tests, specific factor assays, and specific inhibitors of the coagulation system were measured. All factor assays were expressed as a percent of the respective species pooled adult plasma. The results from the animals were compared to normal values from our laboratory for healthy full-term infants. The coagulation systems of all species tested, except the rabbit pup, were immmature at birth with most factor levels being lower than the adult of .their species. The coagulation systems were influenced by the postnatal age of the animal and the factor levels reached adult values in fewer days relative to the human. The coagulation system for the piglet most closely approximated the human neonate. The shared characteristics were prolonged screening tests, increased factor VIII:C, generally low levels for the contact and vitamin K-dependent factors, and low antithrombin III levels relative to the adult. The beagle pup also showed many similar characteristics but in contrast to the human neonate factor VIII:C and V were low on day 1 of life and prekallikrein was not measurable in the adult or newborn beagle. These data, especially the low antithrombin III levels, support the use of the piglet to investigate thrombotic problems in the neonate. The sick newborn infant is at risk of developing thrombotic and hemorrhagic problems in the postnatal period. The investigation of thrombotic and hemorrhagic problems in the neonate is often limited by the small size of the infant and the limited forms of investigation that are ethically acceptable in this group of patients. Despite the potential of animal models in investigating hemorrhagic and thrombotic problems in the neonate, there is limited information on the coagulation systems in newborn animals (1,2). The objective of this study was to assess systematically the coagulation system in four newborn animal species and compare them with the human infant in order to determine which animal(s) would be most appropriate for investigation of hemorrhagic and thrombotic problems in the human neonate.
MATERIALS AND METHODSStudy population. Newborn lambs (mixed breed), piglets (mixed breed), rabbit pups (New Zealand White), and purebred beagle pups were studied on days I and 7 oflife. An adult plasma pool was prepared for each species from 20 adult animals of both sexes. Blood was collected directly into 0.13 M sodium citrate (1 part citrate to 9 parts blood except for the piglet for which the ratio was 1.35 citrate to 9 parts blood) from each animal by peripheral v...