The thrombus being a blood-clot, it is composed, like the latter, of fibrin and blood-corpuscles. It is presumable that the fibrinous part of a thrombus owes its origin to the same conditions which determine the presence of fibrin in blood removed from the vessels during life or in that within the vessels after death. {57} According to A. Schmidt,[18] the blood and other fluids, in which clotted fibrin makes its appearance, contain two generators, called fibrino-plastic and fibrinogenous. The former is considered to be paraglobulin, a substance contained mainly in the white blood-corpuscles, while the fibrinogenous generator is held in solution in the plasma of the blood. When these materials are acted upon by a third, the fibrin ferment, clotting takes place and fibrin is formed. It is thought that the ferment is intimately connected with the white blood-corpuscles, for with the microscope coagulation is seen to advance as these become destroyed, and where the leucocytes are most abundant, there coagulation advances most rapidly. The elements of clotted fibrin are always present in circulating blood, but Brücke has shown that blood remains fluid, under ordinary circumstances, because of its constant contact with the normal vascular wall. [Footnote 18: Rollett, _Hermann's Handbuch der Physiologie_, Leipzig, 1880, iv. 1, 114.] The general causes of thrombosis are those which produce an abnormal condition of the endothelium, a rapid destruction of the white blood-corpuscles, or a stagnation of the blood. With the presence of one of these causes there is often conjoined another, and the conditions under which they are present are conveniently used in the classification of thrombi. Although stagnation of the blood is often an important immediate cause of its coagulation, it is apparent, from the investigations of Durante[19] and others, that stagnant blood clots in the living vessels only when their endothelium is in an abnormal condition. With the co-existence of abnormal endothelium and stagnant blood, thrombi form with greater frequency and become more voluminous in a given interval of time. [Footnote 19: _Wiener Medizinische Jahrbucher_, 1871, 321.]