fcLOOD CLOTTING 113 



Hemorrhagic Diseases 



In many of the so-called hemorrhagic diseases (acute leuceinia and 

 aplastic anemia) and in the hemorrhagic varieties of diphtheria and 

 smallpox, the platelet count drops from its normal of between 200,000 

 and 800,000 per cubic millimeter to well below 100,000, and indeed in 

 these conditions it is frequently difficult to find any platelets. Samples of 

 blood clot outside the body within the normal time, but the clot is soft 

 and usually fails to retract in the normal manner. It is on account of 

 this, rather than slow clotting that the hemorrhage continues, so that in 

 appraising the gravity of the symptom it is best to measure not the clot- 

 ting time but the time that it takes for bleeding to cease from a small 

 skin wound, as in the lobe of the ear. This can be very accurately done 

 by applying blotting paper at regular intervals to the puncture (Duke 17 ). 



The most interesting and at the same time the most mysterious of all 

 conditions in which blood clotting is interfered with is hemophilia. The 

 clotting time is longer than normal, but even after the clot forms, bleed- 

 ing is likely to continue because the clots are very readily displaced. Both 

 clotting time and bleeding time are increased. So far no change in the 

 clotting factors of the blood has been demonstrated in this disease; the 

 corpuscles and the platelets are normal in numbers, fibrinogen and cal- 

 cium salts are normal, and, as Howell has shown, there is no excess of 

 antithrombin. One significant fact, however, is that the addition of 

 thromboplastin or of its active ingredient, kephalin, greatly shortens the 

 clotting time of the blood when it is removed by venipuncture. In agree- 

 ment with this observation it has been found that hemophilic blood clots 

 much more rapidly, indeed sometimes in the usual time, if it is allowed to 

 flow over cut or damaged tissue and so become mixed with thromboplas- 

 tin. These facts taken together would seem to indicate that the fault 

 must lie in a deficiency in prothrombin, and since this is derived mainly 

 from the platelets, which however are not decreased in number, we must 

 further assume that these elements have undergone some qualitative 

 change preventing their disintegration. An accompanying defect in 

 their agglutinating properties would at the same time explain their fail- 

 ure in hemophilia to clump together at the site of the hemorrhage so as 

 to block the smaller vessels with thrombi; hence the prolonged bleeding 

 time even after clotting has occurred. 



Thrombus Formation 



The first formed portion of a thrombus is paler than those formed later, 

 because it contains excessive numbers of platelets; and it seems clear 

 that it is by agglutination of these into masses, which then stick in the 



