W. J. DODDS AND L. W. HOYER 
471 
taneous anti-factor VIII anticoagulants.*' '^ More- 
over, new data have shown that the different 
findings with human and rabbit antibodies 
to factor VIII are related to differences in 
antigenic determinants on the molecule with 
which they react, as well as to the divergent 
properties of these two kinds of antibodies. ^- 
The data reported in Figures 5 and 6 of the cur- 
rent studies reveal that the rabbit spleen is 
capable of discriminating between plasmas ob- 
tained from CRM ( — ) and ( + ) hemophiliacs 
in a manner similar to the human antibodies to 
factors VIII and IX. *'-^ In addition, there v/as 
no difference between the activity produced 
after addition of CRM ( — ) and VWD plasmas 
to the splenic perfusion system. There are sev- 
eral possible explanations for the enhanced pro- 
duction of factors VIII and IX in spleens perfused 
with CRM ( + ) plasma but these observations 
require further study. 
SUMMARY 
Production of coagulation factor VIII and IX 
activities by isolated perfused livers and spleens 
was inversely proportional to the coagulation 
activities of the perfusate ; these data suggested 
control by a negative feedback process. 
Enhanced splenic factor VIII production was 
observed with perfusion of CRM ( + ) hemophi- 
lia A plasma as compared with CRM ( - ) and 
von Willebrand's plasmas. 
Similar but less striking enhancement of 
splenic factor IX production occurred with per- 
fusion of CRM ( + ) hemophilia B plasma as 
compared with CRM ( - ) plasma. 
The experiments summarized above demon- 
strated that antigenically detectable but non- 
functional coagulation factors VIII and IX are 
capable of inducing splenic factor VIII and IX 
production, respectively. 
ACKNOWLEDGMENTS 
The authors thank Ann C. Moynihan, Sharon 
L. Raymond, Joanne E, Kull and Carol J. 
Church for their technical assistance. 
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