112 THE BLOOD AND THE LYMPH 



ficient clotting of blood in diseased conditions or for the formation of 

 intravascular clots (thrombi) are little understood. According to How- 

 ell's theory of the nature of the process, which is the most satisfactory at 

 the present time, abnormal clotting might be due to the following 

 causes: (1) A diminished amount of fibrinogen. This occurs when the 

 hepatic cells are greatly damaged, as in poisoning by chloroform or 

 phosphorus and in such diseases as acute yellow atrophy and yellow 

 fever. In many cases of chronic cirrhosis of the liver, as Whipple, etc., 15 

 have shown, the blood also clots feebly because of deficient fibrinogen. 

 It should be pointed out that it is not so much the clotting time that is 

 increased in such cases, as the firmness or consistency of the clot that 

 is affected. 



2. A deficiency in prothrombin. In the condition known as "melena 

 neonatorum," undoubted benefit is derived from intravenous injections 

 of blood serum or by direct blood transfusions, probably because throm- 

 bin or prothrombin is thus furnished. 



3. A deficiency of thromboplastin. Since this substance is derived from 

 both blood cells and tissue cells, it does not seem likely that a deficiency 

 could ever occur. Certain observers, however Morawitz, for example 

 lay great stress on this as an important factor in hemorrhagic diseases. 



4. An excess of antithrombin. The undoubted increase in this substance 

 that can be brought about experimentally by injecting hirudin or pep- 

 tone into animals, has stimulated careful search for a similar increase in 

 the blood in clinical conditions in which abnormal blood clotting is one 

 of the symptoms (Whipple 16 ). Antithrombin is said to be increased in 

 septicemia, pneumonia, miliary tuberculosis, etc. 



5. A deficiency of calcium ions. Although at one time it was supposed 

 that this might be responsible for the feeble clotting in hemophilia, it 

 has not been found, after very extensive trials, that the exhibition of 

 Ca salts in any way relieves the condition. It is said, however, that the 

 slow coagulation seen in obstructive jaundice is decidedly shortened by 

 treatment with calcium salts. 



One thing stands out prominently in connection with the whole problem, 

 and that is the close relationship of the blood platelets to the clotting 

 process. From these cells are derived, according to Howell, not only the 

 prothrombin but also, as from other cells, thromboplastin. It is not sur- 

 prising therefore to find that decided alterations in the platelet count 

 occur in cases of faulty blood clotting, and that local accumulations of 

 these elements within the blood vessels, produced by their clumping to- 

 gether or agglutinating, is followed by a formation of local clots, as in 

 thrombosis. 



