TY  - CHAP
M1  - Book, Section
TI  - Control of Coagulation Reactions
A1  - Mosnier, Laurent O.
A1  - Griffin, John H.
A2  - Kaushansky, Kenneth
A2  - Lichtman, Marshall A.
A2  - Prchal, Josef T.
A2  - Levi, Marcel M.
A2  - Press, Oliver W.
A2  - Burns, Linda J.
A2  - Caligiuri, Michael
PY  - 2015
T2  - Williams Hematology, 9e
AB  - SUMMARYThe  blood  coagulation  system,  like  a  powerful  idling  engine,  is  always  active  and  generating  thrombin  at  very  low  levels,  poised  for  explosive  thrombin  generation.  Positive  feedback  activation  of  factors  V,  VII,  VIII,  and  XI  imparts  special  threshold  properties  to  blood  coagulation,  making  the  coagulant  response  nonlinearly  responsive  to  stimuli.  Overt  blood  coagulation  represents  a  threshold  system  with  apparent  all-or-none  responses  to  various  levels  of  stimuli,  and  an  ensemble  of  opposing  reactions  determines  the  ultimate  upregulation  and  downregulation  of  thrombin  generation  both  locally  and  systemically.  Cellular  and  humoral  anticoagulant  mechanisms  synergize  with  plasma  coagulation  inhibitors  to  prevent  massive  thrombin  generation  in  the  absence  of  a  substantial  procoagulant  stimulus.  This  chapter  highlights  mechanisms  that  inhibit  blood  coagulation,  with  an  emphasis  on  defects  of  plasma  proteins  that  cause  hereditary  thrombophilias.  Major  thrombophilic  defects  involve  the  anticoagulant  protein  C  pathway,  comprising  multiple  cofactors  or  effectors  that  additionally  include  thrombomodulin,  endothelial  protein  C  receptor,  protein  S,  high-density  lipoprotein,  and  factor  V.  Activated  protein  C  exerts  multiple  protective  homeostatic  actions,  including  proteolytic  inactivation  of  factors  Va  and  VIIIa,  as  well  as  direct  cell-signaling  activities  involving  protease  activated  receptors  1  and  3,  endothelial  cell  protein  C  receptor,  integrin  CD11b/CD18,  and  apolipoprotein  E  receptor  2.  The  factor  V  Leiden  variant  causes  hereditary  activated  protein  C  resistance  by  impairing  the  ability  of  the  protein  C  pathway  to  inhibit  coagulation  because  it  cannot  properly  cleave  factor  Va  Leiden.  Plasma  protease  inhibitors  are  also  key  to  block  coagulation.  Antithrombin  inhibits  thrombin  and  factors  Xa,  IXa,  XIa,  and  XIIa,  in  reactions  stimulated  by  physiologic  heparan  sulfate  or  pharmacologic  heparins.  Tissue  factor  pathway  inhibitor  neutralizes  the  extrinsic  coagulation  pathway  factors  VIIa  and  Xa.  Other  plasma  protease  inhibitors  can  also  neutralize  various  coagulation  proteases.Control  of  coagulation  reactions  is  essential  for  normal  hemostasis.  As  part  of  the  tangled  web  of  host  defense  systems  that  respond  to  vascular  injury,  the  blood  coagulation  factors  (Chap.  113)  act  in  concert  with  the  endothelium  and  blood  cells,  especially  platelets,  to  generate  a  protective  fibrin-platelet  clot,  forming  a  hemostatic  plug.  Pathologic  thrombosis  occurs  when  the  protective  clot  is  extended  beyond  its  beneficial  size,  when  a  clot  occurs  inappropriately  at  sites  of  vascular  disease,  or  when  a  clot  embolizes  to  other  sites  in  the  circulatory  bed.  For  normal  hemostasis,  both  procoagulant  and  anticoagulant  factors  must  interact  with  the  vascular  components  and  cell  surfaces,  including  the  vessel  wall  (Chap.  115)  and  platelets  (Chap.  112).  Moreover,  the  action  of  the  fibrinolytic  system  must  be  integrated  with  coagulation  reactions  for  timely  formation  and  dissolution  of  blood  clots  (Chap.  135).  This  chapter  on  control  of  coagulation  highlights  the  major  physiologic  mechanisms  for  downregulation  of  blood  coagulation  reactions  and  the  plasma  proteins  that  inhibit  blood  coagulation,  with  an  emphasis  on  those  mechanisms  whose  defects  are  clinically  significant  based  on  insights  gleaned  from  consideration  of  the  hereditary  thrombophilias  (Chap.  130).  Chapter  113  provides  a  complete  description  of  blood  coagulation  factors  and  hemostatic  pathways.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - hemonc.mhmedical.com/content.aspx?aid=1121102711
ER  -