that, according to this view, paraglobulin has a very important fibrino-plastic property. On the other hand Hammersten holds that paraglobulin is not an essential in coagulation, or at any rate does not take an active part in the process. He believes that paraglobulin possesses the property in common with many other bodies of combining withor decomposing, and so rendering inert-certain substances which have the power of preventing the formation or precipitation of fibrin, this power of preventing coagulation being well known to belong to the free alkalies, to the alkaline carbonates, and to certain salts; and he looks upon fibrin as formed from fibrinogen, which is either (1) decomposed into that substance with the production of some other substances; or (2) bodily converted into it under the action of a ferment, which is frequently precipitated with paraglobulin. Hammersten's view as to the formation of fibrin from fibrinogen by the action of a second body possibly of the ferment class, is now, very generally held. The presence of a certain but small amount of salts, especially of sodium chloride, is necessary for coagulation, and without it, clotting cannot take place. Sources of the Fibrin Generators.-It has been previously remarked that the colourless corpuscles which are always present in smaller or greater numbers in the plasma, even when this has been freed from coloured corpuscles, have an important share in the production of the clot. The proofs of this may be briefly summarised as follows:-(1) That all strongly coagulable fluids contain colourless corpuscles almost in direct proportion to their coagulability; (2) That clots formed on foreign bodies, such as needles projecting into the interior or lumen of living blood-vessels, are preceded by an aggregation of colourless corpuscles; (3) That plasma in which the colourless corpuscles happen to be scanty, clots feebly; (4) That if horse's blood be kept in the cold, so that the corpuscles subside, it will be found that the lowest stratum, containing chiefly coloured corpuscles, will, if removed, clot feebly, as it contains little of the fibrin factors; whereas the colourless plasma, especially the lower layers of it in which the colourless corpuscles are most numerous, will clot well, but if filtered in the cold will not clot so well, indicating that when filtered nearly free from colourless corpuscles even the plasma does not contain sufficient of all the fibrin factors to produce thorough coagulation; (5) In a drop of coagulating blood, observed under the microscope, the fibrin fibrils are seen to start from the colourless corpuscles. Although the intimate connection of the colourless corpuscles with the process of coagulation seems indubitable, for the reasons just given, the exact share which they have in contributing the various fibrin factors still remains uncertain. It is generally believed that the fibrin-ferment at any rate is contributed by them, inasmuch as the quantity of this substance obtainable from plasma bears a direct relation to the numbers of colourless corpuscles which the plasma contains. Many believe that the fibrinogen too is wholly or in part derived from them, and also that they are the usual source of the paraglobulin present in plasma. According to this view all the fibrin factors are derived from the disintegration of the colourless corpuscles. We have seen that the coloured corpuscles may also under certain circumstances take a share in producing the fibrin generators. Conditions affecting Coagulation.-The coagulation of the blood is hastened by the following means: 1. Moderate warmth,—from about 100° to 120° F. (37·8— 49° C.). 2. Rest is favourable to the coagulation of blood. Blood, of which the whole mass is kept in uniform motion, as when a closed vessel completely filled with it is constantly moved, coagulates very slowly and imperfectly. be 3. Contact with foreign matter, and especially multiplication of the points of contact. Thus, as before mentioned, fibrin may quickly obtained from liquid blood by stirring it with a bundle of small twigs; and even in the living body the blood will coagulate upon rough bodies projecting into the vessels. 4. The free access of air.-Coagulation is quicker in shallow than in tall and narrow vessels. 5. The addition of less than twice the bulk of water. The blood last drawn is said, from being more watery, to coagulate more quickly than the first. The coagulation of the blood is retarded, suspended, or prevented by the following means:— 1. Cold retards coagulation; and so long as blood is kept at a temperature, 32° F. (0° C.), it will not coagulate at all. Freezing the blood, of course, prevents its coagulation; yet it will coagulate, though not firmly, if thawed after being frozen; and it will do so, even after it has been frozen for several months. A higher temperature than 120° F. (49° C.) retards coagulation, by coagulating the albumen of the serum, and a still higher one above 56° C. prevents it altogether. 2. The addition of water in greater proportion than twice the bulk of the blood, also the addition of syrup, glycerine, and other viscid substances. 3. Contact with living tissues, and especially with the interior of a living blood-vessel. 4. The addition of neutral salts in the proportion of 2 or 3 per cent. and upwards. When added in large proportion most of these saline substances prevent coagulation altogether. Coagulation, however, ensues on dilution with water. The time during which blood can be thus preserved in a liquid state and coagulated by the addition of water, is quite indefinite. 5. Imperfect aëration,-as in the blood of those who die by asphyxia. 6. In inflammatory states of the system the blood coagulates more slowly although more firmly. 7. Coagulation is retarded by exclusion of the blood from the air, as by pouring oil on the surface, etc. In vacuo, the blood coagulates quickly; but Lister thinks that the rapidity of the process is due to the bubbling which ensues from the escape of gas, and to the blood being thus brought more freely into contact with the containing vessel. Receiving blood into a vessel, well smeared inside with oil, fat, or vaseline, is said also to retard or prevent coagulation. 8. The coagulation of the blood is prevented altogether by the addition of strong acids and caustic alkalies. 9. It has been believed, and chiefly on the authority of Hunter, that after certain modes of death the blood does not coagulate; he enumerates the death by lightning, over-exertion (as in animals hunted to death), blows on the stomach, fits of anger. He says, "I have seen instances of them all." Doubtless he had done so ; but the results of such events are not constant. The blood has been often observed coagulated in the bodies of animals killed by lightning or an electric shock; and Gulliver has published instances in which he found clots in the hearts of hares and stags hunted to death, and of cocks killed in fighting. 10. The injection of peptones, or of various digestive ferments, e.g., trypsin or pepsin, into the vessels of an animal appears to prevent 77 or stay coagulation of its blood if it be killed soon after. The secretion of the mouth of the leech, and possibly the blood squeezed out of its body when full, also prevents the clotting if added to blood. Cause of the fluidity of the blood within the living body.-Very closely connected with the problem of the coagulation of the blood is the question, why does the blood remain liquid within the living body? We have certain pathological and experimental facts, apparently opposed to one another, which bear upon it, and these may be, for the sake of clearness, classed under two heads : (1) Blood will coagulate within the living body under certain conditions-for example, on ligaturing an artery, whereby the inner and middle coats are generally ruptured, a clot will form within it, or by passing a needle through the coats of the vessel into the blood stream a clot will gradually form upon it. Other foreign bodies, e.g., wire, thread, etc., produce the same effect. It is a well-known fact that small clots are apt to form upon the roughened edges of the valves of the heart when the roughness has been produced by inflammation, as in endocarditis, and it is also equally true that aneurysms of arteries are sometimes spontaneously cured by the deposition within them, layer by layer, of fibrin from the blood stream, which natural cure it is the aim of the physician or surgeon to imitate. (2) Blood will remain liquid under certain conditions outside the body, without the addition of any re-agent, even if exposed to the air at the ordinary temperature. It is well known that blood remains fluid in the body for some time after death, and it is only after rigor mortis has occurred that the blood is found clotted. It has been demonstrated by Hewson, and also by Lister, that if a large vein in the horse or similar animal be ligatured in two places some inches apart, and after some time be opened, the blood contained within it will be found fluid, and that coagulation will occur only after a considerable time. But this is not due to occlusion from the air simply. Lister further showed that if the vein with the blood contained within it be removed from the body, and then be carefully opened, the blood might be poured from the vein into another similarly prepared, as from one test-tube into another, thereby suffering free exposure to the air, without coagulation occurring as long as the vessels retain their vitality. If the endothelial lining of the vein, however, be injured, the blood will not remain liquid. Again, blood will remain liquid for days in the heart of a turtle, which continues to beat for a very long time after removal from the body. Any theory which aims at explaining the normal fluidity of the blood within the living body must reconcile the above apparently contradictory facts, and must at the same time be made to include all other known facts concerning coagulation. We may therefore dismiss as insufficient the following:-that coagulation is due to exposure to the air or oxygen; that it is due to the cessation of the circulatory movement; that it is due to evolution of various gases, or to the loss of heat. Two theories, those of Lister and Brücke, remain. The former supposes that the blood has no natural tendency to clot, but that its coagulation out of the body is due to the action of foreign matter with which it happens to be brought into contact, and in the body to conditions of the tissues which cause them to act towards it like foreign matter. The latter, on the other hand, supposes that there is a natural tendency on the part of the blood to clot, but that this is restrained in the living body by some inhibitory power resident in the walls of the containing vessels. The blood must contain all the substances from which fibrin is formed, and the re-arrangement of these substances must occur very quickly whenever the blood is shed, and so it is somewhat difficult to prevent coagulation. It seems more reasonable to hold, therefore, that the blood has a strong tendency to clot, rather than that it has no special tendency thereto. But it has been recently suggested that the reason why blood does not coagulate in the living vessels, is that the factors which are necessary for the formation of fibrin are not in the exact state required for its production, and that at any rate the fibrin ferment is not formed or is not free in the living blood, but that it is produced (or set free) at the moment of coagulation by the disintegration of the colourless (and possibly of the coloured) corpuscles. This supposition is certainly plausible, and if it be a true one, it must be assumed either that the living blood-vessels exert a restraining influence upon the disintegration of the corpuscles in sufficient numbers to form a clot, or that they render inert any small amount of fibrin ferment which may have been set free by the disintegration of a few corpuscles; as it is certain firstly that corpuscles of all kinds must from time to time disintegrate in the blood without causing it to clot; and, secondly, that shed and defibrinated blood which contains blood corpuscles, broken down and disintegrated, will not, when injected into the vessels of an animal, under ordinary conditions, produce clotting. There must be a distinct difference, therefore, if only in amount, between the normal disintegration of a few colourless corpuscles in the living uninjured blood-vessels and the abnormal disintegration of a large number which occurs whenever the blood is shed without suitable precaution, or when coagulation is unrestrained by the neighbourhood of the living uninjured blood-vessels. The explanation of the clotting of blood which has been given in the preceding pages and which depends chiefly upon the researches of Alex. Schmidt and Hammersten, supposes that it is one of the fermentative actions, so many of which are believed to go on in the living body. Wooldridge ably contests this view of the process. His laborious researches have led him to the belief that coagulation of the blood is a vital process, or rather that it is the last act of vitality displayed by blood plasma, which he considers to be during life, living protoplasm. Some of the results of his experiments may with advantage be here mentioned, as they correct and amplify the informa, |