=Causes.=--The underlying _cause_ of all _thrombi_ is, then, _alteration of the endothelium_. In consequence, when it is desirable to produce coagulation artificially, advantage may be taken of this fact, and mechanical injury to the vessel walls may be quickly followed by the desired results. Advantage is also taken of this fact in surgery, especially in certain methods of treating aneurysm, by rude handling, by needling, by the introduction of horsehairs, fine wire, etc. A venous thrombosis is certainly favored by the thinness of the venous walls, by which poorer protection is afforded to their lining endothelium, and infection more easily occurs. Arterial thrombosis is favored when cardiac vigor is impaired and vessel walls are thickened so as to obstruct the blood current. This occurs particularly in syphilitic endarteritis, where the intima suffers most, and final occlusion is due to the thrombus thus formed. Arteriosclerosis does not, by itself, often produce this trouble; it comes rather with atheromatous and calcareous degenerations. The local ischemia which is occasioned by ergotism, by pellagra (due to use of certain kinds of maize), by the vasomotor spasm of Raynaud’s disease (see under _Gangrene_), by too long-continued constriction, or by frostbite, causes results comparable to those produced experimentally in parts supplied by a terminal artery, _e. g._, in the kidney after temporary occlusion of its artery. All the tissues involved undergo profound alterations, in which thrombosis figures very largely and may lead to gangrene. While such endothelial lesions are essential, there are, nevertheless, numerous other accessory causes which should be mentioned. These comprise: A. _The presence of foreign bodies_, as, for example, needles, hooklets of echinococci, parasites, particles of tumors, fragments from the heart valves, and, most of all, that which is essentially a foreign body, a clot which has come from some other point. Around such foreign particles will quickly group themselves a relatively large number of leukocytes, thus affording another example of phagocytosis, soon to be described. Mere slowing of blood stream without some such mechanical irritation is not sufficient to produce coagulation. If, for instance, a section of vein is isolated between two ligatures, the ligation being aseptically done and the surroundings of the vein wall disturbed as little as possible, the blood thus shut up within the vein remains fluid indefinitely. If, however, the vessel wall is separated from its surroundings, so that its nourishment is compromised, the contained fluid quickly coagulates. B. _Necrosis_, _gangrene_, etc., lead to quick involvement of the endothelium of the vessels contained within the involved part, and consequently to quick coagulation of the blood which they contain.