476 
HEMATOLOGY 
quential manner, one factor activating the other 
until thrombin is formed. The process starts 
with the activation of the Hageman factor 
(Factor XII) by any surface other than the 
normal vascular endothelium. Then follows the 
activation of Factors XI, IX, VIII in succession. 
Finally, Factor X in the presence of phospho- 
lipids, and Factor V lead to the component that 
converts prothrombin. The details of prothrom- 
bin conversion are becoming increasingly clear. 
The reader is referred to an adjoining paper by 
W. H. Seegers for further information. In the 
presence of tissue factors, through Factor VII, 
a short cut is made for the activation of Factor 
X. The absence, or an abnormal form of any of 
these factors, may lead to bleeding disorders be- 
cause of a delayed thrombin generation, not 
only in man, but in other animals, (hemophilia 
in dogs, for example) . (For a review of the cas- 
cade system in vertebrates, the reader is re- 
ferred to a recent article by Archer.) 
Here I intend to review a previous compara- 
tive study of the interaction of fibrinogen and 
thrombin isolated from various animals.^^ 
It is now well established that when thrombin 
clots fibrinogen, a small portion (3 percent) of 
fibrinogen is split off in the form of two pep- 
tides I'ef erred to as peptides A and B by the 
limited proteolytic action of thrombin.^^ The 
fibrin molecules thus formed join together to a 
network structure, the fibrin clot. 
The chemical composition of the peptides re- 
leased from several different fibrinogens by the 
action of thrombin is now known. Table I shows 
the amino acid sequence of peptide A released 
from the fibrinogens of man, dog, ox, pig, sheep, 
goat, reindeer, rabbit and monkey (Rhesus). 
The following is an examination of how the 
composition of these peptides may affect their 
release by thrombin. 
For these experiments, thrombin and fibrino- 
gen were isolated from eleven different animals. 
The fibrinogens were purified to give 96 % clott- 
able material.-^ For the preparation of throm- 
bin, prothrombin was first adsorbed on barium 
sulfate from the plasma and through further 
purification, the prothrombin was converted to 
thrombin. The thrombin solutions were diluted 
Table I 
The amino acid sequence of these peptides was initiated in the author's laboratory with the determination of the 
sequence of bovine peptide A. The other sequences in the table originate from the work of Blomback and co- 
workers and Doolittle and co-workers. (For references, see Atlas of Protein Sequence and Structure, pp. 165- 
170, 1967-68, M. 0. DayhofF and R. V. Eck, Natl. Biomed. Res. Foundation, Silver Spring, Md.) 
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 
BOVINE GLU ASP GLY SER ASP PRO PRO SER GLY ASP PHE .LEU THR GLU GLY GLY GLY VAL ARG 
EUROPEAN BISON GLU ASP GLY SER ASP PRO ALA SER GLY ASP PHE LEU ALA GLU GLY GLY GLY VAL ARG 
WATER BUFFALO GLU ASP GLY SER ASP ALA VAL GLY GLY GLU PHE ( LEU. ALA . GLU . GLY. GLY. GLY. VAL ) ARG 
SHEEP, GOAT ALA ASP ASP SER ASP PRO VAL GLY GLY GLU PHE LEU ALA GLU GLY GLY GLY VAL ARG 
PRONGHORN ALA ASP GLY SER ASP PRO VAL GLY GLY GLU SER ( LEU. PRO , ASP . GLY. ALA , THR , GLY ) ARG 
REINDEER ALA ASP GLY SER ASP PRO ALA GLY GLY GLU PHE LEU ALA GLU GLY GLY GLY VAL ARG 
MUNTJAK (ALA.ASP.GLY.SER.ASP.PRO.ALA.SER.GLY.GLU)PHE ( LE U. THR . GLU. GL Y. GLY.GLY . V AL ) ARG 
SIKA DEER ALA ASP GL Y ( S E R. ASP . PRO . AL A . S ER . SER . GLU . PHE . LE U. AL A. GLU . GL Y. GL Y . GLY . V AL ) ARG 
RED DEER ALA ASP GLY SER ASP PRO ALA SER SER ASP PHE LEU ALA GLU GLY GLY GLY VAL ARG 
ELK (ALA. ASP. GLY. SER. AS P. PRO. ALA. SER. SER. ASP) PHE { LEU . ALA . GLU . GLY. GLY. GLY . VAL ) ARG 
LLAMA THR ASP PRO ASP ALA ASP LYS GLY GLU PH£ LEU ALA GLU GLY GLY GLY VAL ARG 
VICUNA (THR.ASP.PRO.ASP. ALA.ASP.LYS.GLY.GLU)PHE(LEU. ALA. GLU. GLY . GLY . GLY . VAL ) ARG 
CAMEL THR ASP PRO ASP ALA ASP GLU GLY GLU PHE(LEU. ALA. GLU . GLY . GLY. GLY. VAL ) ARG 
PIG ALA GLU VAL GLN ASP LYS GLY GLU PHE LEU ALA GLU GLY GLY GLY VAL ARG 
•^^^ ALA ASP THR GLY THR THR SER GLU PHE ILUtASP, GLU. GLY. ALA , GLY , I LU ) ARG 
rRcFN MONKEY ''LY GLU GLY ASP PHE LEU ALA GLU GLY GLY GLY VAL ARG 
RHFMiS MONKEY ^^U GLY ASP PHE LEU ALA GLU GLY GLY GLY VAL ARG 
KHtbUi nuiN c ASP THR GLY GLU GLY ASP PHE LEU ALA GLU GLY GLY GLY VAL ART, 
'^^'^'^^^ THR -lYS THR GLU GLU GLY GLU PHE ILU SER GLU GLY GLY GLY VAL ARG 
1^*^^'^ VAL ASP PRO GLY GLU SER THR PHE ILU ASP GLU GLY ALA THR GLY ARG 
THR ASN VAL LYS GLU SER GLU PHE ILU ALA GLU GLY AL A ( ALA. GL Y ) ARG 
n^n^ THR ASP VAL LYS GLU SER GLU PHE ILU ALA GLU GLY ALA VAL. GLY. ARG 
THR ASN SER LYS GLU GLY GLU PHE ILU ALA GLU GLY GLY GLY VAL ARG 
VTj THR ASN SER LYS GLU GLY GLU PHE ILU ALA GLU GLY GLY GLY VAL ARG 
GLY ASP VAL GLN GlU GLY GLU PHE ILU ALA GLU GLY GLY GLY VAL ARG 
^ORSE QLU GLU GLY GLU PHE LEU HIS GLU GLY GLU GLY VAL ARG 
