468 
HEMATOLOGY 
Figure 4. — a. Splenic factor VIII activities after addition of 5 ml normal human plasma as indicated by the arrow. 
Activity of 4 perfusions in each group. Fresh plasma (A A ); fresh-frozen plasma (A A) ; fresh-frozen 
plasma plus factor VIII concentrate (X X). b. Splenic factor IX activities of the same experiments shown 
in 4a. Fresh plasma (• •); fresh-frozen plasma (O — O) ; fresh-frozen plasma plus factor VIII concen- 
trate (X X). 
istence of low normal factor IX activity in some 
patients and families with VWD.^^ 
Figure 6 shows experiments with factor IX 
deficient human plasma. Interpretation of the 
data obtained with CRM ( — ) and ( + ) factor 
IX deficient plasma, however, is complicated by 
the low levels (45 and 78%, respectively) of 
factor VIII activity present in these frozen 
plasma samples. The consequence of this low ac- 
tivity was to maintain splenic perfusate factor 
VIII activity at a level which permitted subse- 
quent increases in factor VIII production 
(Figure 6a) . As would be predicted, CRM ( - ) 
hemophilia B plasma with 45% factor VIII ac- 
tivity produced a more sustained increase in 
splenic factor VIII activity than CRM ( + ) 
hemophilia B plasma with 78% factor VIII 
activity. This observed increase with CRM 
( — ) plasma could be completely prevented 
by prior mixing of factor VIII concentrate 
with the CRM (-) factor VIII deficient 
samples (Figure 6a). Figure 6b demonstrates 
splenic factor IX production during these expe- 
riments. Data obtained with CRM( — ) hemo- 
philia B plasma were similar to those with 
control perfusions (Figure lb) . There was, how- 
ever, slightly more factor IX activity produced 
with CRM ( + ) hemophilia B plasma as com- 
pared with CRM ( - ) plasma (p = < 0.04) . 
The change in the pattern of activity resulting 
from addition of factor VIII concentrate to 
CRM(-) factor IX deficient plasma (Figure 
6b) is not understood. 
DISCUSSION 
Factor VIII and IX coagulation activities ap- 
pear in liver and spleen perfusates when these 
organs are perfused with fluid devoid of coagu- 
lation activity (Figure 1). The activities gener- 
ated in this system have properties similar to 
plasma coagulation factors VIII and IX,^^ and 
