Am.  jour,  Pharm.  )        Theories,  of  Blood-Coagulation  705 
fact  affords  a  possibility  of  detecting  whether  a  given  thrombin  has 
been  produced  quite  recently  or  some  time  ago.  Several  experi- 
ments, as  we  shall  see,  require  such  a  determination. 
Contact  is  also  necessary  to  coagulation.  How  does  it  operate? 
I  showed  with  Gengou,  many  years  ago,  that  contact  is  in  a  way 
analogous  to  calcium,  or  in  other  words,  that  contact  with  a  foreign 
solid  body  (paraffin  of  course  excepted)  is  necessary  to  the  appear- 
ance of  thrombin,  but  is  not;  requisite  for  the  coagulating  influence 
of  the  latter.  When  blood  is  received  into  a  paraffined  vessel,  throm- 
bin is  not  formed;  when  received  into  a  glass  vessel,  thrombin  is 
produced  in  the  zone  of  contact,  a  fact  which  explains  why  coagula- 
tion begins  along  the  wall.  But  when  serum  yielded  by  previously 
clotted  plasma  is  added  to  blood  or  plasma  kept  in  a  paraffined  ves- 
sel, the  entire  mass  rapidly  solidifies  the  paraffin  no  longer  exerting* 
any  inhibiting  influence.  This  experiment  explains  why  blood 
freshly  drawn  and  placed  in  a  glass  vessel  coagulates  in  a  mass 
much  more  rapidly  when  shaken. 
What  then  is  the  origin  of  thrombin?  It  does  not  exist  as  such 
in  the  circulating  blood,  although  the  latter  contains  everything 
requisite  for  its  production.  The  circulating  blood,  therefore,  con- 
tains the  mother-substance,  or  mother-substances,  of  thrombin, 
which,  for  convenience,  may  be  called  prothrombin,  and  which  in  the 
early  stages  of  coagulation  is  converted  into  thrombin.  What  is 
prothrombin  ? 
Sixteen  years  ago  Morawitz  made  an  important  discovery  in 
this  connection.  He  found  that  if  crushed  tissue,  muscle  for  exam- 
ple, is  added  to  serum  yielded  by  normal  coagulation,  the  coagulat- 
ing power  of  this  serum  towards  oxalated  plasma  is  considerably  in- 
creased. And  yet,  the  extract  of  tissue  by  itself  does  not  contain  any 
thrombin,  since  without  the  help  of  serum,  it  is  incapable  of  coagu- 
lating oxalated  plasma.  Hence,  we  are  forced  to  conclude  that  the 
tissue  extract  contains  something  which  is  not  thrombin,  but"  which 
reacts  with  the  serum  so  as  to  produce  this  active  principle.  Thence 
follows  at  once  the  hypothesis  that  thrombin  is  derived  from  the 
interaction  of  two  different  substances,  the  one  furnished  by  the 
tissue  cells,  the  other  by  the  serum.  Undoubtedly,  even  before  the 
introduction  of  the  tissue  extract,  a  certain  amount  of  thrombin 
existed  in  the  serum,  but  it  seems  as  if  this  fluid  contained  also  an 
excess  of  the  mother-substance,  the  latter  being  capable  of  reacting 
