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THE

NATURAL HISTORY REVIEW:

A

QUARTERLY JOURNAL OF BIOLOGICAL SCIENCE.

Reviews and Notices.

XXIV. - THE COAGULATION OF THE BLOOD.

(1) RICHARDSON, W.B., M.D.-The Cause of the Coagulation of the Blood. 1857.

(2) BRÜCKE, E., M.D.-An Essay on the Cause of the Coagulation of the Blood. British and Foreign Medico-Chirurg. Review.

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(3) SCHMIDT, Alex.-Ueber den Faserstoff und die Ursachen seiner Gerinnung. Arch. für Anat, u. Physiol. 1861, p. 545 et seq. (4) SCHMIDT, Alex.-Weiteres über den Faserstoff. u. Physiol. 1862, p. 428 et seq.

Arch. für Anat.

The Croonian

p. 580.

(5) LISTER, J.-On the Coagulation of the Blood. Lecture. Proceedings of the Royal Society, XII. Br the spontaneous coagulation of any fluid, be it of blood, lymph, chyle, secretion of serous membrane, or vegetable juice, is meant the appearance in that fluid of a solid body having definite characters, and bearing the name of fibrin. Whenever we meet with spontaneous coagulation, we find the substance fibrin as a result; whenever we see fibrin, either in the fluids above mentioned, or elsewhere, we say that a spontaneous coagulation laid it there. Before inquiring, therefore, into the causes of spontaneous coagulation, before investigating the special problems why any fluid coagulates spontaneously as we say, under certain circumstances and not under others, it seems fit first of all to seek some further knowledge of the essential nature of this process that we call spontaneous coagulation, to learn something more of what fibrin is, of what its relations to other bodies are, of what its antecedents in the coagulating fluid are, in short, to study the natural history of fibrin. The term "natural history" seems preferable to "chemical history," because it is at

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least possible that some other name than chemical may be hereafter adopted to designate the relations of that class of bodies to which fibrin belongs, bodies the phenomena of which chemists and physiologists alike strive to grasp, and alike fail to master, bodies to which Mr. Graham has given the name colloid, and which he says ought to have a chemistry, that is to say a science, to themselves.

There have been two chief theories in vogue about the immediate antecedents of fibrin. The one most generally adopted maintains that coagulation is merely the passing into a solid state of previously existing liquid fibrin, a substance which has all the characteristics of ordinary fibrin except its solidity, a substance which, though belonging to the protein group, and therefore in some respects similar to liquid albumin, is yet perfectly distinct from that body, and probably pursues quite a different course in the path of life, having come about in a different way, and tending to a different end. The other theory is that fibrin only exists in the solid form, and is produced fresh from albumin during the very act of coagulation, made out of it in some way or other, and can only be said to pre-exist in any coagulable fluid in the same sense as hydrochloric acid may be said to pre-exist in common salt. Both these theories have been for the most part mere theories, unsupported by any satisfactory array of facts and experiments.

Virchowt has especially adopted the former view, working it in with his general pathological doctrines. He adds to it, as a sort of corollary, that in lymph and chyle, in the spontaneously coagulating effusions (hydrops lymphaticus, and to some extent in blood in certain conditions, fibrin does not exist as such but in a preparatory stage; fibrinogen he calls it, requiring oxydation by the atmosphere before it becomes perfect fibrin, and plays the coagulating part. Zimmermann, experimenting on blood kept fluid by mixture with various salts, built on very unsafe foundations a theory that fibrin existed in the blood before coagulation, in a fluid state as a distinct and separate body, and that a spontaneous decomposition of the complex secretion produced in it some kind of ferment, which acting in a catalytic manner changed the molecular arrangement of the fibrin and so brought it into a solid condition.

Babington. Med. Chir. Trans. vol. xvi. p. 301 et alibi.

† Cell. Path. Lect. viii., Chance, p. 156 et seq.

Moleschott, Untersuch. I. 2. Henle and Meissner, 1856, p. 197.

The laborious researches of Denis* led him to believe that, beside the fibrin forming the clot, a large quantity of the same substance remained behind in the serum, together with some globulin and the albumin, or, as he calls it, serin. This fibrin soluble in the serum he holds to be identical in the main with the fibrin of the spontaneous clot, and with that obtained by whipping, though he recognises modifications either caused by the mode of generation, or due to the source (arterial or venous) from whence it was obtained. He calculated the amount of fibrin dissolved in the serum to be four times greater than that obtained from the clot. This fact gave rise in his mind to the idea that there existed in fluid blood a substance which he proposed to call sero-fibrin, standing somewhere between serin and fibrin, and one-fifth more soluble in blood than fibrin. Coagulation was the conversion of sero-fibrin into fibrin, whereupon one-fifth of the latter was precipitated, the remaining four parts being still held in solution. All this was purely hypothetical, no demonstration of the sero-fibrin being advanced.

Brücket having ascertained that the whole of the protein constituents of blood-plasma, (the coagulation of which had been delayed by the action of acetic acid and ammonia,) might be precipitated by heat as one apparently homogeneous mass, inferred that fibrin did not pre-exist before coagulation as such, but was formed anew from albumin during that process. Other experiments brought him to the view that coagulation might be a separation in some way of some of the albumin from the alkali by which it was held in solution. both his facts and reasoning are wanting in clearness.

But

Synthetical attempts to convert albumin into fibrin by simple direct processes as oxydation, electrical action, &c. have as yet always failed. The latest is that by Mr. A. H. Smee. We know at present nothing, or at the very best next to nothing, though recent researches seem to promise much, about the various soluble and insoluble derivatives and modifications of albumin. We cannot say that any derivative ought to be called fibrin merely because it seems to show a fibrillated structure under the microscope. In order to claim for any artificially prepared substance the right to be called fibrin, we must show that it has all the characters, exhibits all the phenomena, goes through the same performances as natural fibrin.

* Nouvelles Études chimiques, &c Paris, 1856. Henle et Meissner, 1856. p. 19.
† Op. Cit. p. 207.
Proc. Roy. Soc. xii. 399.

Every specimen of natural fibrin gives us a group of facts occurring in its life, whereby we can make our diagnosis. There is first the viscid plasma, and then the gelatinous clot with its subsequent contraction and ultimate fibrillation. We are too far away in colloidal chemistry to be able to lean much on atomic analysis. It is on physical, or, if you will, physiological features that we must chiefly rely.

In the course of some experiments performed during the years 1831-45, Dr. A. Buchanan of Glasgow observed that when blood strained from a kneaded clot was mixed with hydrocele fluid, the mixture in a short time set into a coagulum so firm that the vessel holding it might be turned upside down without fear of spilling. After a while the artificial clot, for such it was, contracted and exuded a sérum. The same result was obtained by mixing with hydrocele fluid blood serum, washed blood-clot, and buffy coat, the latter even after having been dried and preserved for several months. The clot thus produced closely resembled ordinary blood clot in all important points.

There was evidently here the making of solid fibrin in a fluid which had hitherto been supposed to contain nothing of the kind. Dr. Buchanan's view of the matter was that there existed both in hydrocele fluid and in blood a certain amount of fibrin in a liquid state, but that the latter contained what the former lacked-a something which caused the fibrin to coagulate just as suitable re-agents will cause albumin and casein to coagulate. That something he believed was mainly seated in the colourless corpuscles. Influenced by the rising theories about cell-power, he was led to the idea that the coagulating force was possessed only by protein-substance, which had "acquired more or less of the organized vesicular shape."t Hence he was not surprised to find that muscle, skin, connective tissue, mucus, and spinal marrow, also caused the hydrocele fluid to clot. The primary cell endued with power from the mother solidified the fibrin of its surrounding plasma. The solid fibrin thus gained, became in time organized, and so acted in turn upon fresh plasma.

These researches striking in their nature seemed destined, as able editors said at the time, to throw great light on the processes of nutrition and growth. That light unhappily never shone either on

*Lond. Med. Gazette, 1845, p. 617.

† His views here approximate somewhat to those of Wharton Jones and others, on the function of the corpuscles as fibrin-elaborating glands.

nutrition or on coagulation. The facts never obtained the attention they deserved, and the general feeling seemed to be that in such cases as the hydrocele fluid, fibrin was present in a latent form, and that the serum, or washed clot, acting in some kind of catalytic manner, brought it forth into palpable existence. The observations of Schroeder van der Kolk and J. Davy,* that fibrin, added to fresh blood, will quicken its coagulation, were interpreted as instances of a similar catalytic action. Mr. Gulliver, however,† both satisfied himself of the truth of Dr. Buchanan's discoveries, and recognized their importance. He also clearly saw that the mystic influence of cells had nothing at all to do with the matter, but that on the contrary the production by artificial means of a delicate sac of fibrin, reminding one irresistibly of the tender tissues of the Coelenterata, was in itself a protest against cellular theories.

In 1861, Mr. Alexander Schmidt of Dorpat, unaware apparently at that time of the labours of the Scotch Physiologist, entered upon the same line of investigation. His results corroborated in the main Dr. Buchanan's facts, though not his theories. He found that he could artificially, by the addition of blood freed from its clot, produce a coagulum identical in all its chief features with that of blood, not only in hydrocele fluid, but also in pericardial, peritoneal, and other so-called serous fluids and effusions, which have of themselves, as a general rule, no power of spontaneous coagulation. The same treatment quickened and increased the coagulation of chyle and lymph.

Mr. Lister bears testimony to the same effect. Indeed there is no doubt about it. Any one who makes the experiment will meet with the same result. Blood-serum, which is free from fibrin, which will not of itself coagulate, or blood-clot, which has completed its coagulation, will, when joined with serous fluid, which has of itself not any, or scarcely any power of spontaneous coagulation, produce a clot of the substance we call fibrin. The fact is beyond cavil. How is it to be explained?

Does the fibrin thus formed arise from the union of two bodies, two substances, the one pre-existing in the serum, the other in the exudation, which apart are neither of them fibrin, but which joined together become it? Or does it exist in a kind of latent form,

* Quoted in Nasse, Wagner's Handwörterbuch, I. p. 161.

† Vide Lectures, Med. Times and Gazette, 1683, Vol. I. p. 155.

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