02 
II.  THE  RELATION  OF  HAEMOLYSINAEMIA  TO  THE 
HAEMOGLOBINURIA  OF  BLACKWATER  FEVER. 
In  no  single  instance,  up  to  the  present  time,  has  the  mechanism 
of  production  of  haemoglobinuria  in  blackwater  fever  been 
established,  though  assertions  respecting  its  mode  of  production  are 
constantly  to  be  met  with  in  text-books  and  in  clinical  articles. 
The  only  form  of  haemoglobinuria,  of  which  the  mechanism  is  in 
part  known,  is  paroxysmal  haemoglobinuria,  and  before  proceeding 
further  it  will  be  of  advantage  briefly  to  recapitulate  the  facts  which 
have  recently  been  establi.shed  in  connection  with  the  mechanism 
of  production  of  this  condition.  In  1904  Donath  and  Landsteiner- 
showed  that,  in  the  intervals  between  the  attacks  of  haemoglobinuria, 
if  the  blood  rendered  fluid  by  potassium  oxalate,  or  a  mixture  of  the 
patient’s  serum  and  the  patient’s  washed  red  blood  cells,  was  cooled 
and  then  warmed  to  body  temperature,  a  marked  haemolysis  occurred, 
which  was  not  observed  if  the  blood  was  kept  at  body  temperature, 
without  previous  cooling.  The  red  blood  cells  of  the  patient  were 
found  to  be  normal,  and  might  be  replaced  by  foreign  human  red 
cells  ;  only  the  serum  or  plasma  is  changed,  and  the  haemolysin  could 
be  extracted  in  the  cold  from  the  serum  by  red  blood  cells,  which 
became  dissolved  when  the  serum  of  the  patient  or  normal  human 
serum  was  added,  the  reaction  being  completed  by  the  addition  of 
complement.  The  minimum  time  of  cooling  required  in  ice  cold 
water  was  five  to  ten  minutes  (in  one  case  two  minutes).  Cooling  to 
10°  C.  for  half  an  hour  was  followed  by  partial  haemolysis.  This 
condition  was  not  met  with  in  health,  nor  in  patients  suffering  from 
any  disease  other  than  paroxysmal  haemoglobinuria,  with  the 
exception  of  general  paralysis,  in  which  affection  it  was  found  that 
in  six  out  of  sixty-six  cases  the  same  reaction  was  Qbtained. 
Donath's  and  Landsteiner's  results  were  confirmed  and  their 
conclusions  disputed  by  Widal  and  Rostaine.t  who  have  arrived  at  a 
somewhat  different  interpretation  of  the  reaction  in  question.  These 
*  Uber  paroxysmale  Hamoglobiiiurie.  Miinch.  nieil.  Wocbensclir.,  1904,  No.  36.; 
Uber  paro.xysmale  Plamoglobiiuin'e,  Zeit.schr.  1.  Idiii.  jMediziii,  lyo6,  Bd.  58,  S.  173. 
t  Insufiisance  de  raatisensibilisatrice  dans  le  sang  de.s  liaemoglobinuriques.  Compte; 
reiidus  de  la  Societe  de  Biologie,  1905,  T.  1,  p.  321  ;  Insufiisance  de  rantiscnsibilisatiice 
dans  le  sang  d’un  haemoglobiiniiiqiie.  ibid.,  p.  372  ;  Serotherapie  prevenlive  de  I'aUaqiie  tie 
rh^tnoglobimiria  |)aroxystique,  ibid.,  p.  397. 
