The hemostatic status of pediatric recipients of adult liver grafts suggests that plasma levels of hemostatic proteins are not regulated by the liver

Abstract

Plasma levels of coagulation factors differ profoundly between adults and children, but are remarkably stable throughout adulthood. It is unknown which factors determine plasma levels of coagulation factors in a given individual. We hypothesized that the liver, which synthesizes coagulation factors, also controls plasma levels. We measured a panel of coagulation factors in samples taken from either adults or young children who underwent a liver transplantation with adult donor livers. Samples were taken 1-3 months after transplantation, when the patients were clinically stable with adequate graft function. After liver transplantation, the hemostatic profile of the pediatric group was remarkably different from that of the adult group, and resembled the hemostatic profile of normal children. Thus, children transplanted with an adult liver graft maintain a pediatric hemostatic profile after transplantation despite receiving an adult liver graft. These findings suggest that plasma levels of hemostatic proteins are not controlled by the liver. IntroductionThe liver plays a central role in hemostasis because it synthesizes many of the plasma proteins involved in coagulation and fibrinolysis. 1 Although plasma levels of the various proteins vary between individuals, levels of these proteins within an individual are remarkably stable throughout adulthood, 2 although subtle elevations in coagulation factors are observed with increasing age. 3 In young children, the hemostatic system is still in development, and plasma levels of various hemostatic proteins in young children are profoundly different from that of adults. [4][5][6][7][8] Although levels of many coagulation factors increase toward values found in adults in the first year of life, striking differences between infants and adults are still present in children at 6 months of age. 6 More subtle differences between children and adults are still observed between the ages of 1 and 16 years. 4 It is not known which factors control the levels of coagulation factors in a given individual, but it appears plausible that the liver may be involved.Children with end-stage liver disease may undergo liver transplantation. These children will frequently obtain a split-liver graft from an adult donor. In these children undergoing transplantation, a unique situation occurs in which liver mass is not significantly different from children who do not, but liver tissue is of adult origin. Here we investigated whether transplantation of an adult (split) liver graft into very young children would convert the pediatric hemostatic status to a hemostatic profile similar to that of adults. Methods PatientsEleven children who underwent a primary (n ϭ 10) or second (n ϭ 1) liver transplantation for biliary atresia (n ϭ 10) or metabolic disease (n ϭ 1) with a mean of age 8.5 months (range, 4.2-11.7 months) and 9 adults with a mean age of 56 years (range, 46-65 years) who underwent transplantation for cirrhosis of various etiology (primary sclerosing cholangitis, 2 [one of which was a retrans...

The impact of perioperative transfusion of blood products on survival after pediatric liver transplantation

“…In addition, this study identified also intraoperative transfusion of three units of FFP and postoperative transfusion of one unit of FFP as a risk factor, respectively, for patient and graft survival after LT. There are no data on the negative effect of FFP transfusion on patient and graft survival after LT. A recent study (27) suggested that the hemostatic status of pediatric recipients transplanted with adult liver grafts is not regulated by the new liver; this result may induce the pediatric intensivist to reconsider a different strategy of FFP transfusion in the early phase post‐LT.…”

“…Most of the information on blood product transfusion in critically ill pediatric patients has come from studies in adults, but the pathophysiology, developmental stage, size, blood volume, and remaining life span of pediatric patients differ from adults (24)(25)(26)(27). Risks of RBC transfusion have been recently investigated in critically ill children (28)(29)(30), but the influence of various blood products on mortality has not been well studied in children undergoing LT (4,31,32).…”

Postoperative complications in cirrhotic pediatric deceased donor liver transplantation: Focus on transfusion therapy

“…A better understanding of coagulation disorders and hemostasis in pediatric liver disease is needed . Recently, a physiologic study showed that the hemostatic status of pediatric recipients transplanted with adult liver grafts is not regulated solely by the new liver …”

The circulating platelet count is not dictated by the liver, but may be determined in part by the bone marrow: analyses from human liver and stem cell transplantations

“…Next to the platelet count, also levels of most coagulation proteins have a wide between‐individual variation, whereas the intra‐individual variations in these proteins are narrow. In a recent study we provided evidence that the liver, which synthesizes most coagulation proteins, is not involved in determining circulating levels of coagulation factors [20]. Similar to this, regulation of the platelet count thus appears to take place outside of the liver.…”