470 
HEMATOLOGY 
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250r 
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FACTOR IX DEF. HUMAN PLASMA 
t 
2 
(a) 
3 4 
TIME 
40 
30 
20 
10 
° t 
(Hrs.) 
2 
(b) 
Figure 6. — a. Splenic factor VIII activities after addition of 5 ml factor IX deficient human plasma as indicated 
by the arrow. Activity of 2 perfusions with CRM(+) hemophilia B plasma (A A); 4 perfusions with 
CRM( — ) hemophilia B plasma (A A); 2 perfusions with CRM(— ) hemophilia B plasma plus factor VIII 
concentrate (X X). b. Splenic factor IX activities of the same perfusion experiments shown in 6a. CRM(+) 
hemophilia B plasma (• •) ; CRM(— ) hemophilia B plasma (O O) ; CRM ( — ) hemophilia B plasma plus 
factor VIII concentrate (X X). 
addition of canine factor VIII and IX deficient 
plasmas demonstrated a parallel inverse rela- 
tionship between the level of coagulation activ- 
ity in perfusates and the subsequent production 
of coagulation factors by the organs perfused.^ 
It is interesting that in the current experi- 
ments, plasma from animals with an artificially 
induced coagulation defect (Figure 3) behaved 
in a manner similar to that obtained from hu- 
mans (Figure 6) or dogs^ with an inherited de- 
fect. 
Although data obtained with deficient human 
plasmas were consistent with the negative feed- 
back hypothesis proposed from studies with an- 
imal plasmas,"' there was an additional more 
interesting finding. The splenic response to 
plasma from patients with CRM ( + ) hemophi- 
lia A was significantly greater than that seen 
with CRM ( - ) hemophilia A or VWD plasmas 
(Figure 5) . A similar but less striking enhance- 
ment was observed with CRM ( + ) hemophilia 
B plasma as compared with CRM ( — ) hemophi- 
lia B plasma (Figure 6). These results sug- 
gested that antigenically detectable but 
nonfunctional molecules accumulate in plasma 
with CRM and can be converted rapidly by the 
spleen to active coagulation factors. Alterna- 
tively, inactive precursors in plasma with CRM 
could stimulate splenic release and/or synthesis 
of coagulation activity. 
It has recently been reported, however, that 
factor VIII antigen is detectable in plasma 
from all patients with hemophilia A but not 
from those with VWD.i^-" These studies em- 
ployed rabbit antibodies to human factor VIII 
in contrast to previous experiments with spon- 
