Fibrinogen Has a Rapid Turnover in the Healthy Newborn Lamb

ABSTRACT: The half-lives for coagulation factors in the healthy newborn infant are not known and may be different than for the adult. We measured the half-life for fetal sheep fibrinogen and compared it to the half-life of adult sheep fibrinogen. Fibrinogen was purified from adult and fetal sheep plasma and radiolabeled with either 125I or 131I. The half-lives for these fibrinogens were determined in the adult sheep and newborn lamb. In addition, the fetal and adult sheep fibrinogens were compared by reptilase time, thrombin clotting time, sialic acid content, and the behavior of the N-glycans derived from these fibrinogens on the immobilized lectin, Sepharose-concanavalin A. Finally, the in vivo response of coinjected radiolabeled fibrinogens to increasing doses of infused thrombin was determined. The fetal sheep fibrinogen differed from the adult as indicated by a prolonged reptilase time and an increased sialic acid content (fetal: 10–11 residues/340 Kd versus adult: 8–9 residues/340 Kd). The latter was also reflected in differing chromotographic profiles for the N-glycans on Sepharose-concanavalin A. The half-lives for both the adult and fetal fibrinogen were significantly more rapid in the newborn lamb (fetal: 47 ± 2.0 h; adult: 46 ± 2.4 h, mean ± SEM) than in the adult (fetal: 116 ± 6.5 h; adult: 121 ± 6.9 h). Finally, the adult and fetal sheep fibrinogen responded to thrombin in an identical fashion in the intact animal. In summary, both adult and fetal fibrinogen have faster half-lives in the lamb compared to the adult, despite a higher sialic acid content for the fetal fibrinogen. We speculate that the more rapid turnover of coagulation proteins in the newborn may be of significance when planning replacement therapy for congenital or acquired coagulopathies.