474 
HEMATOLOGY 
of the plasma into a plug by an enzyme present 
in muscle tissues. 
If we view hemostasis in the animal kingdom, 
we can discern four systems : (1) vasoconstric- 
tion, (2) thrombocyte system, (3) transami- 
dase system, and (4) cascade system. 
In man and in most vertebrates, all these four 
systems operate simultaneously, occasionally 
one or the other dominating the picture. It 
would be impossible for me to deal adequately 
with these systems in the animal kingdom; 
therefore, I will restrict myself to illustrating 
them with examples choosing those where our 
knowledge is on sufficiently solid ground. 
THROMBOCYTE SYSTEM 
For the illustration of the thrombocyte sys- 
tem, I would like to discuss briefly the clotting 
of the horseshoe crab (Limulus polyphemus) . 
This animal actually is not a crab but is related 
to the arachnid and thus belongs to the arthro- 
pods. The hemolymph of this arthropod contains 
one type of a circulatory cell called amoe- 
bocytes or hemocytes. In case of injury, these 
cells break up and release the clotting material. 
The amoebocytes are very sensitive to the ubiq- 
uitous endotoxin and when these cells come into 
contact with even trace amounts of this mate- 
rial, they disintegrate. The disintegrating cells 
release the clotting material which, in turn, in 
the presence of endotoxin, forms the clot. 
Levin and Bang^'^ discovered that if the 
blood of Limuhis is drawn in the presence of 
N-ethyl maleimide, the cells are protected from 
the disruptive effect of the ever present endo- 
toxin and can be separated from the plasma by 
centrifugation. The isolated cells may be lysed 
to obtain a cell-extract. This extract clots upon 
addition of endotoxin. Since the cell-free plasma 
does not clot and the clotting material in the 
cells represents the total clotting material, it is 
quite obvious that the amoebocytes alone are re- 
sponsible for the clotting. 
The time course of the clotting material iso- 
lated from the cells indicates an enzymatic 
process similar to clotting of fibrinogen by 
thrombin or transglutaminase. The endotoxin 
bringing about the clotting is viewed as an 
agent which activates a clotting enzyme or con- 
verts it to an active enzyme from a precursor. 
Solum recently reported the purification of 
the clotting material which turned out to be a 
protein.* The molecular weight of this clottable 
protein appears to be about one-tenth of that of 
bovine fibrinogen.'' 
Vertebrates and a large number of inverte- 
brates contain hemostatic cells. In some of the 
invertebrates, these cells function similar to 
what we see in Limulus blood. In others, the 
main purpose of the circulating cells is to form 
aggregates at the site of injury. 
The thrombocytes and the platelets apparent- 
ly carry out both of these functions. According 
to Levin and Bang^ and Solum,^ the hemo- 
cytes of the Limulus are the prototype of the 
thrombocytes and platelets. The thrombocytes 
are nucleated cells, while platelets are devoid of 
nucleus and are derived from the megakary- 
ocytes. Platelets, similar to the hemocytes of 
Limulus, also contain fibrinogen or profibrin-like 
material which forms micro-clots when the plate- 
lets disintegrate.^ The micro-clots generated 
from platelets are especially predominant in the 
so-called Shwartzman'^ reaction when the disin- 
tegrating platelets can cause fatal clots. 
In the Shwartzman reaction, the disintegra- 
tion of platelets is attributed to endotoxin. The 
involvement of endotoxin in platelet disintegra- 
tion further emphasizes the analogy between 
the amoebocytes of the Limulus and the plate- 
lets. It appears that during the evolutionary 
process, the thrombocyte cells lost their sensi- 
tivity towards endotoxin, but when the sensitiv- 
ity is regained, as in the generalized Shwartzman 
reaction, these cells behave as the hemocytes 
of the primitive invertebrates. The analogy 
of the platelets to the hemocytes of the in- 
vertebrates underlines the importance of the 
study of these primitive organisms for the un- 
derstanding of the behavior of platelets in ver- 
tebrates and man. 
TRANSAMIDASE SYSTEM 
As an illustration of the operation of this sys- 
tem, I am citing the clotting of lobster's blood. 
Lobster (Homarus) is a crustacean, one of the 
most primitive representatives of the arthro- 
pods. The clot in the lobster's blood, in contrast 
to Limulus where it is strictly of cellular origin, 
