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From the Transactions of the Glasgow Philosophical Society, January, 1844. 



NOTE 



STATE IN WHICH FIBRIN EXISTS IN THE BLOOD. 



ANDREW ANDERSON, M.D., 

ANDEKSONIAN ^ROPESSOIl OP THE INSTITUTES OP MEDICINE. 



It has for some time been the general opinion among physiologists, 
that the fibrin of the blood is liquid during life, and becomes solid 
onlj when that fluid dies ; and this opinion is based on the well-known 
experiment, first performed by Miiller, of filtering frog's blood before 
its coagulation, and thus obtaining the clot separate from the globules, 
which remain behind on the paper. At the meeting of the British 
Association at Glasgow, Dr. A. Buchanan exhibited a method of show- 
ing the same thing in human blood, by receiving it from the vein into 
a vessel of serum, in which the globules subside before coagulation. 

The common notion of the change which takes place on coagulation 
has been well expressed as follows : — 

T3ioc*v,« i Fluid Serum 

T winn. Wn.^ / I Fibrin \ VDead blood. 

Livmgblood|^j^^^l^^^ _ J 

From this opinion there have recently dissented M. Mandl* and 
Dr. A. Buchanan.! These gentlemen hold, that while of the cor- 
puscles of the blood the red take no part in the coagulation, and 
are merely engaged as it were by accident in the clot, from which, by 
the above mentioned means, they may be artificially excluded ; yet 
the white corpuscles and the molecules which exist in the fiuid, really 

* Anat. Microscopique, Art. Sang. 1842. 
t Proceedings of the Glasg. Philos. See. 1843, p, 131. 



2 Dr. Anderson on the state in which Fibrin exists in the Blood. 

constitute the fibrin : and that the coagulation consists simply in the 
aggregation of these previously isolated bodies. Dr. Buchanan's 
opinion to this effect is based, not upon the direct examination of the 
process of coagulation in the blood, but upon what he conceives to occur 
in the case of the fluid of blisters and of serous cavities, and to furnish 
an analogical argument of considerable weight. 

Now, it is true that the fluid of blisters contains corpuscles like the 
white globules of the blood, and also that it coagulates on standing ; 
and it may be likewise true, that the number of the corpuscles is in 
the ratio of the size of the clot : but I have carefully watched the fluid 
of a recent blister coagulating under the microscope, and find that 
the delicate clot forms independently of the corpuscles, as it is seen to 
occupy the whole area of the field of view, while at most two or three 
corpuscles may be scattered over it. 

Again, it is true that in the very curious experiment which we owe 
to Dr. Buchanan, the mixture of the serum of blood and of that of 
hydrocele, exhibits after standing for some time a marked coagulum ; 
but I submit that neither is this a proof that that coagulum is derived 
from the corpuscles existing in the fluid in which it forms ; for I have 
divided such a mixture into two equal parts, and while leaving one 
untouched have separated by filtration all the corpuscles from the other, 
while still fluid, and tested their absence by the microscope, and yet the 
eye could detect no difference between the coagula subsequently formed 
in the two portions — nor, when aided by the microscope, any corpuscles 
newly formed. 

But the experimentum crucis is the examination of the changes 
which occur in the plasma of the blood itself ; and this may be effected 
by removing with a spoon a portion of the incipient buffy coat, (the 
whitish fluid which floats before coagulation on the surface of inflam- 
matory blood,) and placing it under the microscope. This fluid is the 
blood mifius the red corpuscles, which, as Mr. Wharton Jones has 
shown,* attract one another more strongly in inflammatory than 
in healthy blood, and sink rapidly in the fluid. Our view, then, 
of the changes which occur being no longer obscured by their pre - 
sence, we watch the plasma swarming with molecules and white cor- 
puscles, the latter always most abundant in inflammation, as may 
be seen even by placing a drop of the just abstracted blood 
under the microscope between two plates of glass, to which the 
white corpuscles stick because of their greater size, while the red 
(known by their smooth outline, their central nuclei, elongated profile, 
and, even under the microscope, pale yellowish colour,) rush beauti- 
fully past them, like fragments of floating things carried against a 

* Ed. Med. and Surg. Journal, 1842. 



Dr. Anderson on the state in which Fibrin exists in the Blood, 



3 



buoy moored in a strong tideway. As we watch the plasma it has be- 
come partly solid, but no visible change appears ; the corpuscles re- 
main quite still, and it is only by drawing across the glass a needle, 
which carries the whole in a mass along with it, that we find that 
they are engaged in a thin coagulum. There is then no running 
together of the corpuscles ; but so far we are still in doubt whether 
the clot may not be formed by their cohesion : the doubt is resolved 
by simply continuing to look : we have drawn aside the forming clot 
before its solidification was complete ; and have left a clear fluid per- 
fectly free from corpuscles of any kind, and yet in this again the coagu- 
lation takes place ; it must, therefore, be from a solidification of the 
previously fluid fibrin. 

So far my observations agree with those of Dr, Addison,* published 
after mine had been made ; but he states that the fibrin solidifies 
in the form of fibres, and figures these of a somewhat stellate or 
spiculate appearance. In the existence of this sort of crystallisa- 
tion I wholly disbelieve. I have repeatedly seen the whole field of 
view occupied uniformly by the extremely delicate clot, so fine and 
transparent as to be distinctly visible only when its edge was 
drawn across the glass with a needle, and thus contrasted with the 
remaining limpid fluid ; and of which the structure was so faintly 
fibrous, that with the greatest difficulty, in a carefully modified 
light, there could, with a power of 600 diameters, be just traced, 
distributed equally over the whole surface, a most delicate striated 
appearance. It is true that afterwards the coagulum becomes 
fibrous, but this is the consequence of a subsequent contraction, the 
nature of which has not been satisfactorily explained, but of which I 
can say only this, that save its lessened size, and a slight increase of 
the fibrous appearance, no change, by motion or otherwise, could be 
observed in a coagulum prepared as above, and allowed to remain for 
twenty-four hours in a covered glass cell under the microscope, till 
it had fully contracted, and squeezed out all the serum from its 
interstices. 

Moreover, I must differ in opinion from Dr. Addison, when he 
advances it as ascertained, that the fibrinous spontaneously coagulable 
liquid is formed within the white corpuscles, and appears on their rup- 
ture only : there is no doubt some inseparable connexion between the 
presence of these corpuscles and the existence of the fibrin of the 
blood, for in determination of blood, and in inflammation, the increase 
of the one keeps pace with that of the other : and it is possible that 
the corpuscles may have the function of converting the "reduced 
albumen"! of the food, and of the effete parts of the tissues, 

* Trans, of the Prov. Med. Assoc. 1843. f Prout. 



4 Dr. Anderson on the state in which Fibrin exists in the Blood. 

into organizeable fibrin, which appears first in the chyle along with 
these corpuscles, after that fluid has passed the mesenteric glands ; 
and in all likelihood, first in the lymph after it has passed the lym- 
phatic glands. Yet we find that in the mixed serums already spoken 
of, the solidification goes on for days gradually increasing, in the utter 
absence of corpuscles of any kind, and must, it hence appears probable, 
be owing to the progressive formation of fibrin, and not to the mere 
coagulation of that already formed ; for that, as we see in the blood, is 
finished within a short time of the death of the fluid. Another proof 
of the essential difference between the white corpuscles of the blood, 
and its coagulable matter, is afforded by an elegant experiment, de- 
scribed by M. Donne.* This consists in agitating the blood during 
coagulation: the fibrin is thus separated in stringy morsels, and 
on leaving the remaining part to stand for some time in a tall glass 
vessel, the white corpuscles are found forming a thin pale layer 
between the red globules below and the clear fluid, to the bottom of 
which they have subsided. The mode in which the change in the 
mixed fluids takes place is yet unexplained. 

I believe with Dr. Buchanan, that the increased formation of fibrin 
in an inflamed part, takes place within the vessels, and therefore in 
the pure plasma of the blood itself ; but that it is in all likelihood 
effected by the agency of the white corpuscles, which during inflamma- 
tion become more numerous in the capillary blood-vessels, and adhere to 
their walls even more firmly than, in the state of health, they are wont 
to do ; and thus throw an obstruction in the way of the red globules, 
which in health form a rapid current in the centre of the vessels.! 
Mere stasis does not produce the change, for in simple congestion, 
however much the blood may be delayed, there is no increase of 
fibrin — and in determination there is more fibrin formed, though 
there may be no obstruction, but rather a more rapid flow of blood : 
in the latter case, however, the vital nutritive action of the part is 
increased, in the former diminished, and this I take to be the true 
explanation of the increase of fibrin ; holding it to be produced within 
the vessels by a greater activity of whatever organ (be it the white 
corpuscles or no) is in health charged to convert the " reduced albu- 
men " to organizeable fibrin ; an activity called into play by the in- 
creased demand for that material in the excited and over active part. 

Thus, then, I think we must still believe that the coagulation of the 
blood forms an exception to the generality, contended for by Dr. Barry 
and otherSjJ of the law that the living tissues are formed directly from 
cells. 

* Cours de Microscopie, p. 84. 1843. 
t Williams ; Princ. of Medicine, p. 213. Travers ; Pathology of Inflammation, &e. 1343. 
X Various Papers, Phil. Trans. 1838, 1842, <fcc. 



Dr. Anderson on the state in which Fibrin exists in the Blood. 5 

How the corpuscles of serous effusions are formed we cannot jet 
surely say : not, probably, as Dr. Addison * supposes, by the 
actual passage through the walls of the capillaries of the white cor- 
puscles of the blood. The simplest effusion which takes place from 
vessels is pure water, as from the Malpighian bodies of the kidneys.f 
When there is more pressure or excitement, serum is effused, being 
water with albumen in solution, as in dropsy, or renal congestion ;J if 
the local excitement still increase, fibrin is thrown out, and coagulates 
spontaneously when withdrawn from the body, as in the fluid of 
blisters ; § and a yet higher action of the part results in the throw- 
ing out of " lymph," or coagulable matter full of active cells, which, 
as in the inflammations of serous membranes, becomes rapidly 
organized. Dr. Addison would say that these cells are the white 
corpuscles of the blood, which have traversed the coats of the 
vessels, and go to form the plastic fibrin of the effusion ; but then 
its plasticity ought to be in the ratio of their number, which is noto- 
riously not the case : for pus, the most aplastic of all effusions, actually 
swarms with distinct corpuscles, very like those found in the blood, 
and yet contains no coagulating fibrin at all. 

The opinion of Gendrin,|| that the pus corpuscle is formed from- 
the red blood globule, can scarcely now be held, except it be by Dr. 
M. Barry ; and it is extremely improbable that bodies such as the 
white corpuscles, which are larger than the red globules of the blood, 
as l-2600th to l-3500th of an inch, should traverse the unruptured 
capillary walls while the latter are retained. 

The nutrition of nonvascular tissue is effected** by the transu- 
dation of nutritive matter through the coats of the looped capillaries 
which encroach upon its edges ; and we cannot suppose that white 
corpuscles, even if they too transuded, should make their way 
onwards to the centre of a solid mass of cartilage, for instance: we 
must suppose that it is the plasma alone which the tissue imbibes, 
and by which its living cells are nourished ; and so in the case of 
effusion it seems most probable that what really occurs is simply 
a transudation of that plasma, nourished by which the corpuscles 
grow, whether they be descended from "germinal granules," or *'cy- 
toblasts," or in whatever way they originate. 

The "molecules" and "granules," formed so abundantly in the 
buffy coat, exist also in healthy blood, in the serum of which they can 
be seen by the microscope ; and in " milky" serum, such as occurs in 
renal inflammation, they are very abundani;. Simon has shown ft 

* Loc. Cit. + Bowman, Phil. Trans. 1842. X Robinson, Med. Chir. Trans. 1843. 
§ Dr. Buchanan, loc. cit. p. 133. || Sur les Inflam. ii. 472. 

** Toynbee, Phil. Trans. 1842. ft Beitraege, &c. Lief. 1. 



6 



Dr. Anderson on the state in which Fibrin exists in the Blood. 



that it is in part to an albuminous, and not, as Prout and Christison* 
supposed, wholly to a fattj matter that such serum owes its opacity ; 
and by the microscope it can be seen to swarm with particles resem- 
bling the molecules of the blood, rather than with the chyle globules 
which Gulliver describes,! though no doubt these may in certain 
cases exist. Dr. Andrew Buchanan J has discovered a method of 
separating this albuminous matter, and causing it to float on the sur- 
face of the fluid, when it puts on all the appearance of the amorphous 
substance found in what Hodgkin § calls the nonplastic serous effu- 
sion. Do such effusions depend on the superabundance of this 
matter in the blood, as the more plastic forms are owing to increase 
in the coagulable fibrin, and is the well known action of mercury in 
making the plastic become the aplastic effusion, owing to some " re- 
ducing" action by which it tends to make the protein compounds of 
the blood less fibrinous, and more like common albumen ? 

It is evident that in the blood we have several forms of these com- 
pounds, deserving of much separate investigation, as : — 

1. Albumen — coagulable by heating the serum. 

2. " Serolin " remaining in the solution, mixed with urea, salts, &c. 
— and which Mulder, with what truth I know not, avers || to be a trit- 
oxide of protein. 

3. Fibrin — procured by agitating fresh blood. 

4. White molecules — procurable by Dr. Buchanan's method from 
" milky" serum. 

5. White corpuscles — probably procurable by a like method from 
the yet fluid buffy coat. 

6. Hematosin dissolved out by water from the red globules. 

7. " Globulin," or the coats and nuclei of these globules, which sub - 
side to the bottom when hematosin remains dissolved. 

All these substances must be separately analysed, if we would per- 
fect our knowledge of the blood : but it were an error to fancy that 
they must needs be exactly the same in all cases — even if in the same 
way procured. Mulder** tells us that the buffy coat is not pure 
fibrin, but a mixture of the deutoxide and tritoxide of protein : I 
cannot tell how this may be ; but I know that it is not in the globules 
alone that we find a varying attractive or cohesive power. In in- 
flammation, as Jones has shown,tt the mutual attraction of the 
red corpuscles is increased, so that they withdraw from the floating 
plasma ; but the solidifying fibrin of that plasma contracts too with a 

* On Granular Degen. of the Kidney, 
t Notes to Gerbcr's Anat. J Proceedings of Glas. Phil. Soc. 1844. 
§ On Serous Membranes. |1 Annalcn der Ch. und Ph. 1843. ** Loo. cit. 

ft Loc. cit. 



Dr. Anderson on the state in which Fibrin exists in the Shod. 7 



varying power : iu sthenic inflammation, when the system is otherwise 
in health, the coagulnm shrinks during many hours, and the huffy 
coat forms a tough leathery covering to the clot. In asthenic or 
specific inflammation, as for example in the "ophthalmitis post- 
febrilis,"* occurring as a too frequent sequela of the fever lately 
epidemic in Glasgow, we have still the increased formation of fibrin 
and white corpuscles, still the greater mutual attraction of the red 
globules, and still the buffy coat ; but it does not contract much, but 
maintains a gelatinous appearance, a state obviously owing to a vital 
power of the fibrin in some way diminished. 

It remains for chemistry to tell whether the ultimate analysis of 
such a buffy crust differ from that of the more common kind ; but 
from the difficulty of procuring material, it is probable the question 
may remain long unsolved. 

But we have more : the red blood corpuscles have always a certain 
mutual attraction, clinging closely in death to one another ; inflamma- 
tion increases this, and likewise the quantity of fibrin and white cor- 
puscles, and so the buffy coat is formed. But this takes place within 
a very few minutes : the subsequent contraction of the clot, by which 
the serum is squeezed from its interstices, is the work, not of the globules 
hut of the fibrin ; hence we find in one case a clot much contracted, 
though without a buff ; in another buffy blood, of which the clot and 
even the buff itself are loose and soft ; in still another the coagulum is 
soft and presents no buff ; while there are also cases where the clot is 
small and dense, as well as clothed with a firm leathery coating. 

The first occurs in sthenic states, where the fibrin is highly vitalised, 
but no inflammation is present — in plethora for instance : the second, 
where we have inflammation with an asthenic state of the system— -as in 
the postfebrile ophthalmitis: the third, where much debility exists, with- 
out any local inflammation — as in fever : and the fourth, where, as in 
sthenic acute inflammation, there is a local disease, and an active state 
of the system besides. 

These differences point at some element of the doctrine of the pro- 
perties of blood, which it will go hard if chemistry alone can explain. 

* Mackenzie. 



Dr. Anderson on the state in which Fibrin exists in the Blood. 




Explanation of the Figures. 



Pig^ 1.— Three white corpuscles (a, a, a,) are seen sticking to the glass in the field of 
view, while the red corpuscles rush rapidly past. (Inflammatory blood before its death.) 

Pig, 2. ^The coagulation of the buffy coat : a, the white corpuscles and molecules ; 

6, a few red corpuscles ; c, the striated coagulum, formed after the removal of the cor- 
puscles ; the clear space containing serum. 



BELL AND BAIN, PRINTERS, GLASGOW.