544 
Blood  Coagulants. 
5  Am.  Jour.  Pharm. 
I     August.  1921. 
The  clotting  of  blood  is  not  as  simple  an  operation  as  it  ordi- 
narily seems.  A  substance  exists  in  the  blood  stream,  which  is 
known  as  prothrombin.  The  latter  reacts  with  the  calcium  salts  to 
form  an  enzyme  known  as  Thrombin  or  the  So-Called  Fibrin 
Ferment.  During  bleeding,  the  fibrin  ferment  (which  does  not 
seem  to  be  a  ferment  at  all)  acts  at  once  on  the  fibrinogen  (a  protein 
material  normally  present  in  blood  plasma)  to  form  an  insoluble 
substance  known  as  Fibrin.  This  forms  in  shreds  within  which  are 
held  the  elements  of  the  blood,  this  mass  in  turn  giving  rise  to  what 
is  commonly  termed  a  blood  clot. 
If  this  theory  would  be  accepted  as  it  stands,  the  question  may 
arise  why  blood  does  not  clot  spontaneously  in  the  tissues. 
Howell  (American  Jour.  Phys.}  29,  187,  191 1)  has  advanced  a 
modification  of  this  theory,  which  is  as  fully  and  firmly  founded  as 
any  theory  as  yet  brought  forth.  He  claims  that  in  addition  to 
fibrinogen,  prothrombin  and  calcium  salts,  normal  blood  contains 
another  constant  element  which  he  calls  antithrombin.  The  latter 
possesses  the  property  of  preventing  the  changing  of  prothrombin 
into  thrombin  in  the  circulating  blood.  During  bleeding,  however, 
the  broken  down  blood  cells  (especially  blood  platelets)  or  tissue 
cells  seem  to  furnish  a  substance  (called  Thrombo  Plastic  Sub- 
stance or  Thromboplastin)-,  which  unites  with,  neutralizes  or  in- 
activates the  Antithrombin  thus  liberating  the  prothrombin.  The 
latter  in  the  presence  of  the  calcium  salts  forms  thrombin  which  re- 
acts with  fibrinogen,  producing  the  blood  clot. 
In  many  cases  of  all  types  of  hemorrhage,  an  individual  may 
bleed  to  death  due  to  a  defective  power  of  coagulation.  Lack  of 
coagulating  properties  may  be  due  to  many  reasons,  the  important 
one  being,  a  deficiency  in  prothrombin  (due  to  its  absence  or  on 
account  of  its  complete  neutralization  by  antithrombin).  The  prin- 
ciple of  the  normal  serum  treatment  consists  in  supplying  the  active 
ferment  (present  in  the  latter)  to  such  patients,  lacking  the  active 
coagulating  principle,  or  as  thought  by  some,  its  value  may  be  due 
to  the  presence  of  thromboplastic  substance. 
Horse  serum  loses  its  efficiency  upon  standing.  It  was  also 
found  to  be  harmful  at  times  due  to  pronounced  anaphylatic  reac- 
tions, which  may  result  in  severe  shock  and  even  terminate  fatally. 
Investigators  were  therefore  let  to  isolate  the  clotting  principle 
or  produce  a  substance  which  would  assist  in  coagulation. 
As  soon  as  Howell  put  forth  his  theory,  a  new  thought  was  ad- 
