W. J. DODDS AND L. W. HOYER 
467 
WARFARIN -TREATED RABBIT PLASMA 
lOOr 
75 
> 
o 50 
< 
25 
A SPLEEN 
LIVER 
100 
75- 
50- 
25 
t 
0 
• SPLEEN 
o LIVER 
t 
(a) 
TIME (Hrs.) 
2 
(b) 
Figure 3. — a. Factor VIII activities of 4 spleen and liver perfusions after addition of 5 ml fresh plasma from war- 
farin-treated rabbits as indicated by the arrow, b. Factor IX activities of the same experiments shown in 3a. 
served with fresh plasma (p = < 0.02), indi- 
cating a possible inverse relationship betv^^een 
initial perfusate activity and subsequent pro- 
duction. Similarly, this concept of negative 
feedback is supported by the data obtained fol- 
lov^^ing addition of factor VIII concentrates to 
normal plasma (Figure 4a). Factor VIII levels, 
in this instance, were sufficiently elevated to 
minimize any further increases. Figure 4b 
shows splenic factor IX activity during the 
same experiments with normal human plasma. 
In contrast to the data with regard to factor 
VIII, the relatively low levels of perfusate fac- 
tor IX activity achieved were high enough to in- 
hibit further production by the spleen. These 
findings were consistent despite the use of 
fresh, fresh-frozen, or frozen plasma with 
added factor VIII concentrate (Figure 4b) . The 
data are plausible if one considers that little 
difference exists between the relative activities 
of human and rabbit factor IX. 
Figure 5 presents data obtained after addi- 
tion of factor VIII deficient human plasma to 
rabbit spleen perfusates. As would be expected 
by a system regulated by negative feedback, 
factor VIII production continued (Figure 5a) 
while factor IX production ceased (Figure 
5b). The factor VIII activity produced with 
CRM ( - ) factor VIII deficient and VWD plas- 
mas was similar to that observed in control per- 
fusions (Figure la). However, an unexpected 
finding was the significantly greater effect on 
splenic factor VIII production after addition of 
CRM ( -I- ) factor VIII deficient plasma. The dif- 
ferences shown in Figure 5a between CRM ( — ) 
and ( + ) plasmas and between CRM ( -I- ) and 
VWD plasmas are statistically significant with 
p = < 0.01. As shown in Figure 5b, there was 
a tendency for factor IX activity to increase 
somewhat after addition of VWD plasma in 
contrast to plasmas from either CRM ( — ) or 
( -I- ) classic hemophiliacs. These findings are 
not understood, but might be related to the ex- 
