THE COAGULATION OF THE BLOOD. 
Bv FREDERICK P. HENRY, M.D., Philadelphia. 
The coagulation of the blood, although invariably treated of in 
physiological text-books, is in no sense of the term a physiological 
process, being a product of abnormal conditions. The blood cir- 
culating in the living, healthy vessels, never coagulates, but no 
sooner is the vessel-wall injured, however slightly, by a needle 
puncture or an escharotic, than a thrombus begins to form at the 
site of injury. This local coagulation may be regarded as a con- 
servative effort to repair the lesion, but, if so, the remedy is fre- 
quently worse than the disease, for the thrombus may be swept 
away by the blood-current, and >if finally arrested in a terminal 
artery-such, for example, as the arteria centralis retinae-may 
work irreparable mischief. The coagulation of albuminous fluids, 
whether it take place within or without a cell-body, is a necrosis, 
the importance of which in pathological processes is just beginning 
to be recognized, and the time is probably not far distant when 
the recently introduced term, coagulation necrosis, will be consid- 
ered tautological. Hayem speaks of the coagulation of the blood 
as a kind of rigor mortis-une espice de rigiditd cadavdrique,-and 
this manner of regarding it is justified not only by the change in 
its physical properties, but also by the fact that coagulation never 
occurs without the destruction of some of the morphological ele- 
ments of the blood. Nevertheless, the act of coagulation furnishes 
most important data for the study of the physiology of the blood, 
for it is a spontaneous analysis, the thoroughness of which de- 
Reprinted from the Archives of Medicine, Vol. xii., No. 3, Dec., 1884. COAGULATION OF THE BLOOD. 
2 
pends upon the slowness with which it takes place. For this 
reason, horses' blood, which coagulates very slowly, is much em- 
ployed in physiological researches. In such blood, before the 
clot has begun to form, the red corpuscles have gravitated to the 
bottom of the vessel, while the white remain at the top and form 
the buffy coat, and it has always been a matter of observation 
that, in such blood, the clot becomes gradually firmer as its upper 
layers are approached ; and, further, that a relation exists between 
the density and color of coagula. In the upper layers, where the 
color is lightest, the density is greatest, and vice versa. In other 
words, coagulation is most perfect where the white corpuscles are 
most abundant. 
It would serve no practical purpose to give a history of the rise 
and progress of the various theories that have been upheld with 
regard to the coagulation of the blood, and their subsequent de- 
cline and fall; but no paper on the subject can be regarded as 
complete, that does not contain some reference to the experiments 
made by Dr. Andrew Buchanan, of Glasgow, in 1831. This ob- 
server found that certain animal fluids, such as lymph-liquor 
pericardii-and non-inflammatory effusions, such as the fluids of 
hydrocele, hydrothorax, and ascites, which do not coagulate spon- 
taneously, may be made to coagulate by the addition of the fluid 
obtained by squeezing a blood-clot in a linen cloth. He subse- 
quently found, that the most effective method of causing the 
above-named liquids to coagulate was by adding to them what he 
called washed blood-cloi. This he made by mixing blood with from 
six to ten parts of water and stirring for five minutes. The mix- 
ture was allowed to stand for from twelve to twenty-four hours, 
and then filtered through a coarse linen cloth ; the residue left 
upon the filter was then washed with water. This substance, 
mixed with a little spirit of wine to prevent putrefaction, retained 
its coagulative power for many months. This washed clot is a 
mixture of fibrin and white corpuscles, the red corpuscles having 
been dissolved in water and removed by filtration, and the ques- 
tion that presented itself to the mind of Buchanan was : Upon 
which of these ingredients does this coagulative power depend ? FREDERICK P. HENRY. 
3 
He concluded that it was due to the white corpuscles, from the 
facts, that the upper layers of a clot, in which these bodies are 
most numerous, possessed a much greater coagulative power than 
portions taken from the lower layers, and that this coagulative 
property was unusually powerful in thebuffy coat of horses' blood, 
which is almost entirely composed of white corpuscles. From 
these researches Buchanan concluded that fibrin exists in solution 
in serous fluids and in the liquor sanguinis, and that it has no 
spontaneous tendency to coagulate, but does so when brought in 
contact with a substance derived from the white corpuscles, which 
substance he considered to be of the nature of a ferment, for he 
compared its action to that of rennet upon milk. 
These facts attracted little attention, and were almost entirely 
forgotten when Prof. A. Schmidt, of Dorpat, re-discovered them 
in 1861. He endeavored to isolate from blood the substance on 
which its coagulative power depends, and believed that he had 
identified it with serum-globulin, which he accordingly called the 
fibrinoplastic substance. He precipitated serum-globulin from 
serum by diluting it with waler and passing through it a stream 
of CO2, and demonstrated that serum from which the so-called 
fibrinoplastic substance had been thus precipitated had lost its 
coagulative power. Schmidt considers that there is little or no 
serum-globulin in the circulating blood, but that it is the product 
of the white corpuscles, which, according to him, undergo rapid 
destruction when the blood is withdrawn from the vessels. He 
found that plasma, from which the white corpuscles had been 
separated by filtration, was very poor in serum-globulin ; while 
the white corpuscles remaining on the filter yielded a large per- 
centage of this substance. 
He next endeavored to ascertain upon what the coagulating 
property of transudates depends, and identified it with a substance 
belonging also to the class of globulins, to which he gave the 
name of fibrinogen. Transudates from which this substance had 
been precipitated no longer coagulated on the addition of the 
fibrinoplastic substance, and, on the other hand, when these two 
substances were isolated and mingled in alkaline solution con- 4 
COAGULATION OF THE BLOOD. 
taining a certain proportion of salts, the result was the formation 
of fibrin. Coagulation, Schmidt then supposed, was due to the 
interaction of these two bodies in saline solutions. He subse- 
quently ascertained that the two bodies may be present in a fluid 
-that of hydrocele, for instance, which may contain considerable 
quantities of serum-globulin-without coagulating, but that a clot 
will form on the addition of blood or blood serum. It then ap- 
peared evident that a third factor was necessary to the act of co- 
agulation, and this he named fibrin ferment. He obtained this 
substance from blood, or, preferably, serum, by mixing it with 
twenty times its volume of alcohol, and setting it aside for a con- 
siderable period of time-two weeks to three months. The 
alcohol coagulates all the proteids of the serum, which are col- 
lected on a filter, dried and pulverized, and the powder dissolved 
in water. Such a solution, when added to a mixture of fibrinogen 
and fibrinoplastin, that does not coagulate spontaneously, will 
often cause the prompt formation of a clot. Schmidt derives the 
ferment, as well as the serum-globulin (fibrinoplastin), from the 
white corpuscles ; for he found that plasma, from which these 
bodies had been separated by filtration, when subjected to the 
process for obtaining ferment, yielded a very inactive solution of 
this substance, and that blood received directly from a vessel into 
absolute alcohol-by which means the destruction of the white cor- 
puscles is supposed to be prevented-yielded no ferment whatever. 
He also demonstrated, by actual counts of the white corpuscles, that 
a large number of these bodies disappear in the act of coagulation, 
presumably partly in the formation of fibrin ferment. He counted 
the leucocytes in the plasma of horses' blood, and found that they 
numbered 14,909 per cubic millimetre in an average of eleven 
counts ; he then allowed the plasma to coagulate and counted the 
leucocytes of the serum, and found that they numbered, in an aver- 
age of nine counts, but 4,222 per cubic millimetre, 71.7 per cent, 
having disappeared in the coagulum. He also counted the red 
corpuscles before and after its defibrination, and found the differ- 
ence to be only thirty per cent. He therefore argues that the 
disappearance of the leucocytes is not a mechanical entanglement FREDERICK P. HENRY. 
5 
in the meshes of the fibrin, for, were this the case, there would be 
no such difference in the percentage of disappearance between the 
red and white corpuscles. Besides, on examining a clot with the 
microscope, the red corpuscles may be seen entangled in the 
meshes of the fibrin, while of the white, not a trace remains but a 
few greatly altered cells, the majority having entirely disappeared 
in the formation of the clot. 
Schmidt's theory of coagulation, therefore, is that it is due to 
the union of two substances, fibrinogen and serum-globulin, under 
the influence of a ferment, and that the fibrinogen exists as such 
in the circulating blood, while the serum-globulin and ferment are 
formed after the blood is withdrawn from the vessels. 
The researches of Hammarsten tend to prove that serum-globulin 
is an unnecessary factor in the formation of fibrin, which, accord- 
ing to him, is derived solely from fibrinogen under the influence 
of the ferment. He has prepared fibrinogen free from all traces 
•of serum-globulin, and has caused the formation of a clot by the 
addition of the ferment only. He admits that coagulation may 
be produced by the addition of serum-globulin to a transudation 
that will not coagulate in the presence of the ferment alone, but he 
has shown that other substances, such as calcium chloride and 
■casein, have the same effect. He has also shown that, from fluids 
which do not coagulate on the addition of ferment, fibrinogen may 
be obtained which does coagulate when the ferment is added. In 
such a case the fluid evidently contained substances that prevent 
coagulation. Such substances are free alkalies, alkaline carbon- 
ates, and certain salts. For example, in a hydrocele fluid con- 
taining very little fibrinogen, that does not coagulate on the 
addition of the ferment and does coagulate on the further addition 
of calcium chloride, it is possible that this salt may decompose an 
alkaline carbonate that held the fibrin in solution. He claims 
also that when coagulation is produced by adding serum-globulin 
to a non-coagulating mixture of fibrinogen and ferment, the effect 
is due to impurities mingled with the serum-globulin, for when he 
repeated the same experiment with pure serum-globulin, coagula- 
tion did not take place. 6 
COAGULATION OF THE BLOOD. 
Hammarsten, therefore, attributes the formation of fibrin to 
one substance, fibrinogen, which exists as such in the blood, under 
the influence of a ferment derived from the white blood corpuscles 
The above-named observers agree in regarding fibrin as a pre- 
cipitate caused by the union of soluble substances in the liquor 
sanguinis. 
Later observations by Wooldridge, Norris, Hayem, and Bizzo- 
zero attribute the formation of fibrin, in great part, to a direct 
transformation of morphological elements of the blood. 
In the Proceedings of the Royal Society for June 18, 1881, is 
an important contribution to the subject by Mr. L. C. Wooldridge. 
He obtained leucocytes from lymphatic glands, by a process de- 
scribed in his paper, and washed them thoroughly with a half-per- 
cent. solution of common salt, after which he found that their 
normal microscopic appearance was unaltered. He then found 
that if to one volume of suspended cells an equal volume of ten-per- 
cent. solution of common salt were added, the whole was immedi- 
ately converted into a " peculiar semi-transparent jelly " which 
behaved chemically precisely like fibrin, while, under the micro- 
scope, he found that the cells, as such, had entirely disappeared. 
" Only nuclei imbedded in a distinctly fibrous ground-substance " 
were visible. Similar results were obtained on adding distilled 
water or a solution of magnesium sulphate. He then studied the 
behavior of leucocytes toward plasma. The most convenient way 
of obtaining plasma is by injecting peptone into the blood of an 
animal. If the animal be bled a few minutes after the injection, 
the blood does not coagulate, and by means of the centrifugal 
machine the corpuscles may be entirely separated from the 
plasma. Wooldridge obtained a specimen of this peptone plasma 
which presented the following characters : 
It was totally uncoagulable : i. On dilution with water. 2. On 
passing a current of CO2 through it. 3. On addition of Schmidt's 
fibrin ferment. 4. On addition of serum-globulin. 5. On addi- 
tion of normal serum. 6. On standing till it was foul. 
Nevertheless, on adding leucocytes to such plasma, coagulation 
promptly followed, of which the completeness was in direct ratio FREDERICK P. HENRY. 
7 
to the number of leucocytes added. As additional facts in favor 
of his view that the plasma changes the leucocytes directly into 
fibrin, he gives : 
1. The weight of the coagulum is, as near as may be, in such 
observations, identical with that of the cells that have been added. 
2. The percentage of albumins in peptone plasma before coagu- 
lation is identical with the percentage after coagulation with 
cells. 
3. The protoplasm of the cells has completely disappeared and 
has been converted into a partly fibrous, partly granular, ground- 
substance ; the nuclei remain. 
4. If to a very large quantity of suspended cells (say 50 cubic 
centims.) a very small quantity (1 cubic centim.) of peptone plasma 
be added, the whole clots firmly. 
Wooldridge does not deny that Hammarsten's theory of coagula- 
tion is partly true, for he concludes his paper with the statement 
that there are " two essential processes in the coagulation of the 
blood, one of which has been hitherto entirely wrongly appreciated 
or overlooked." This latter process is that the "dead" plasma 
converts the white corpuscles directly into fibrin. At the same 
time, however, that this occurs, a substance is liberated from the 
cells which converts the fibrinogen also into fibrin. This is the 
other process. The substance which is liberated from the cells is 
fibrin ferment. 
Later observations by Norris, Hayem, and Bizzozero associate 
the formation of fibrin with changes in certain morphological 
elements of the blood : by the first, to changes in what he terms 
the invisible corpuscle or advanced lymph disc ; by the two latter, 
to similar changes in bodies termed by Hayem hamatoblasts, from 
their supposed share in the formation of the red corpuscle, by 
Bizzozero., Blutpldttchen. At the present time, the subject has 
assumed such a controversial aspect that it is somewhat difficult 
to arrive at an exact understanding of it. Thus Norris claims 
that the blood-plates1 are nothing but products of disintegration 
1 This term is used for both the " hsematoblasts " of Hayem and the " blut- 
plattchen of Bizzozero, which are identical. 8 
COAGULATION OF THE BLOOD. 
of his colorless corpuscle, while Hayem and Bizzozero maintain 
that the corpuscle of Norris is nothing but a red corpuscle 
decolorized by manipulation. Certain it is, however, that the 
blood-plates may be seen in the circulating blood. These bodies 
(as shown by Osler) are the component constituents of Schultze's 
granule masses seen in blood by all microscopists. They are the 
elementary corpuscles of Zimmermann, the globulins of Donne, 
the grains sarcodiques of Vulpian,- and the granulations libres 
of Ranvier. The latter regarded them as particles of fibrin 
which serve as centres of coagulation, just as a crystal of sodium 
sulphate, dropped into a solution of the same, will serve as a 
centre of crystallization. 
If a cover glass be firmly fastened to a slide with parafine, as 
directed by Hayem, and blood dropped at its edge, it will run be- 
neath by capillarity, and in the islets free from red corpuscles 
may be readily seen, with a power of from 400 to 500 diams., the 
bodies described as blood-plates. They are exceedingly delicate, 
colorless bodies, with a diameter from two to three times less than 
that of the red corpuscles, and, according to Hayem, exist in the 
blood in health, to the number of 255,000 per cubic millimetre. 
They are scarcely under observation than they begin to alter in 
shape in a variety of ways, but in each instance a division of the 
blood-plate into two portions may be detected-namely, the one 
central, vitreous-like, and strongly refractive ; the other peripheral, 
granular, and of a gray color. The latter is extremely viscous, and 
causes the formation of groups of blood-plates, from the borders 
of which may be seen to proceed a number of exceedingly fine 
filaments that cross each other in every direction, thus forming an 
irregular network. These changes are exactly coincident with 
the formation of a coagulum, and the agents which prevent these 
alterations in the blood-plates are precisely the ones that prevent 
the formation of fibrin. Among these may be mentioned a tem- 
perature of 0° C., certain saline solutions, liquor amnii, and 
dropsical effusions. 
Hayem does not absolutely claim that fibrin is derived directly 
from his " haematoblasts, " for, in referring to the viscous matter p. 9 missing