Plasma factor VIII synthesis and control as revealed by canine organ transplantation.

WEBSTER, WILLIAM P., CHARLES F. ZUKOSKI, PETER HUTCHIN, ROBERT L. REDDICK, STANLEY R. MANDEL, AND GEORGE D. PENICK. Plasma factor VIII synthesis and control as revealed by canine organ transplantation. Am. J. Physiol. 220(5) : 1147-1154. 1971.The synthesis and control of factor VIII (antihemophilic factor, AHF) have been studied by transplanting livers, spleens, and kidneys into hemophilic and normal dogs. The results indicate that the liver is the primary site of synthesis as evidenced by the establishment of normal levels of factor VIII within the circulating blood of a hemophilic recipient of a normal liver allograft. Extrahepatic sites of synthesis were revealed by replacing the livers of normal dogs with hemophilic livers. Factor VIII levels in such recipients never fell below 14y0. Normal splenic transplants failed to elevate the levels of factor VIII in hemophilic dogs for longer than 96 hr. A transplanted normal kidney failed to raise the levels of circulating factor VIII in a hemophilic recipient, but normal canine kidney autografts produced wide variations in postoperative levels. A hypothesis is presented that relates hepatic and extrahepatic synthesis, splenic storage, and effective hemostatic protection.