702  Theories  of  Blood-Coagulation        \ Amucu!'imarm' 
modern  conceptions  which  seem  to  afford  the  best  explanation  of 
this  complicated  process,  and  which,  therefore,  especially  deserve  our 
attention. 
It  is  hardly  necessary  to  remind  you  that  coagulation  is  noth- 
ing else  than  the  aggregation,  into  meshes  of  fibrin,  of  particles  of 
fibrinogen,  a  substance  which,  as  Fredericq  showed  43  years  ago, 
pre-exists  as  a  dispersed  colloid  in  the  circulating  plasma.  When  the 
blood  flows  from  a  wound,  the  first  determining  factor  which, 
through  successive  modifications  of  the  plasma,  assures  the  solidi- 
fication of  fibrinogen,  is  not  infrequently  the  mixture  of  the  blood 
with  very  active  principles  liberated  by  the  bruised  tissues,  or  in 
other  words,  the  addition  to  the  blood  of  tissue  extract.  But  such 
an  influence  is  an  additional  one,  foreign  to  the  blood  itself ;  hence, 
limiting  the  problem,  I  shall  consider  here,  exclusively,  the  coagula- 
tion that  the  blood  is  capable  of  showing,  solely  by  means  of  its 
own  substances. 
A  most  important,  even  a  decisive  factor  of  this  automatic  coag- 
ulation, is  the  contact  of  a  foreign  solid  body  (glass,  for  instance), 
which  acts  only  physically  by  its  presence,  since  it  does  not  liberate 
any  soluble  substance.  The  contact,  external  factor,  brings  into  ac- 
tivity the  internal  factor,  belonging  to  the  blood,  and  that  is  the 
process  through  which  the  principle  directly  and  immediately  respon- 
sible for  the  coagulation,  the  fibrin-ferment  or  thrombin,  is  pro- 
duced. In  fact,  the  thrombin,  which  is  found  in  large  quantities  in 
the  clot  or  in  the  serum,  does  not  exist  (as  Schmidt  showed  many 
years  ago),  in  the  circulating  blood.  Consequently,  several  stages 
are  to  be  distinguished  in  the  total  process,  the  most  important  one 
being  the  period  in  which  the  thrombin  appears,  the  fibrinogen  it- 
self playing  merely  a  passive  role.  Fibrinogen  can  be  extracted  by 
special  methods  and  obtained  in  a  fairly  pure  condition, -but  it  must 
be  kept  in  mind  that  the  essential  problem  presented  to  the  physiolo- 
gist is  the  coagulation,  not  of  pure  fibrinogen,  but  of  the  blood  con- 
sidered as  a  whole,  that  is,  of  a  very  complex  medium,  cellular  and 
plasmatic,  having  a  definite  reaction  and  definite  osmotic  pressure, 
containing  numerous  constituents,  and  especially  colloids,  which) 
presumably  are  apt  to  influence  each  other  through  molecular  ad- 
hesion. Coagulation  could  not  be  studied  without  taking  into  con- 
sideration every  influence  apt  to  interfere  in  the  phenomenon. 
Since  the  blood  of  mammals,  as  a  rule,  clots  promptly,  it  seemed 
