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532            PART 7  ■  Principles and Disorders of Hemostasis and Thrombosis




                                                                                                                                                                             TF-bearing cell

                                                                                                                                                                                                      1
                                                                                                                                                                IXa


                                                                                                                                                        II                          VIIa           Initiation


                                                                                                                                                                     Xa
                                                                                                                                                                                   IIa                 V, VIII plts





                                                                                                                                                   Plt              VIIIa
                                                                                                                                                                                           3      Propagation
                                                                                                                                                                  2
                                                                                                                                                         IXa         Amplification


                                                                                                                           FIGURE  27.5  Ce  -base     o  e  o  he  ostasis. Ce  u ar he  o-

                                                                                                                           stasis is thought to occur in three stages: initiation, a     i  cation,

                                                                                                                           an     ro  agation. T e initiation stage (1) takes    ace on   F-bearing

                                                                                                                           ce  s (ce  s such as   onocytes that can bin     F an     resent it to a
                                                                                                                            igan  ), which co  e into    ay when en  othe ia  injury occurs an

                                                                                                                             F is ex  ose  . T e initiation stage is characterize   by   resentation

                                                                                                                           o    F to its  igan    actor VII an   the subsequent activation o   ac-

                                                                                                                           tors IX an   X on the   F-bearing ce  . T e activation o   actor X
                                                                                                                           to Xa causes thro  bin   ro  uction an   activation. Once generate  ,

                                                                                                                           thro  bin  ee  s back to activate  actors VIII, V, an      ate ets. T e

               FIGURE 27.4  Initiation, a     i  cation,   ro  agation, an   stabi iza-                                    a     i  cation stage (2) then occurs on the sur ace o  the activate

               tion o  he  ostasis an   c ot  or  ation. T is   escribes the co     ex-                                      ate et, which ex  oses sur ace  hos ho i  i  s that act as rece  -

               ity o  the c otting   rocess an   i  ustrates the interaction between                                       tors  or the activate    actors VIIIa an   IXa. T e    ate et sur ace

               coagu ation  actors an   the ce   sur aces o     ate ets in what has                                        a  ows  or  urther thro  bin  or  ation an   hence the a     i  cation
               been   escribe   as the ce  u ar   o  e  o  he  ostasis. Four sequentia                                     o  coagu ation. Continue   generation an   activation o  thro  bin

               an   interre ate   stages inc u  e initiation, a     i  cation,   ro  aga-                                  causes  urther   ositive  ee  back   echanis  s (3) to occur that u ti-

               tion, an   stabi ization as shown. T is   o  e  a so co  bines   u ti   e                                     ate y ensure the  or  ation o  a stab e c ot, inc u  ing c eavage o

               as  ects o  the c assic water a  /casca  e   o  e  an    urther ex   ains                                     brinogen to   brin, re ease an   activation o   actor XIII  or   brin
               a    itiona  as  ects o  he  ostasis that the c assic ace  u ar   o  e                                      cross- inkage, an   the re ease o  a thro  bin-activatab e   brino y-

                oes not. (Fro   Stoe ting R, F oo  P, Rath  e   JP. Steven Sha er                                          sis inhibitor. (Fro   Hens ey FA, Grav ee GP, Martin DE. Practical

               Stoelting’s Handbook o  Pharmacology and Physiology in Anesthetic                                           Approach to Cardiac Anesthesia, 5th e  , Phi a  e   hia, PA: Li    incott

               Practice, 3r   e  , Phi a  e   hia, PA: Li    incott Wi  ia  s & Wi kins,                                   Wi  ia  s & Wi kins, 2012.)
               2014.)


                                                                                                                           thro  bin generate   is not su  cient, but nu  erous   ositive

               en  othe iu   an     rotease inhibitors   revent c otting  ro                                                ee  back  oo  s are   resent that bin   thro  bin with    ate ets.

               s  rea  ing to other   arts o  the bo  y.                                                                   T ro  bin that is generate   in the initiation   hase  urther

                    A ce  -base   coagu ation   rocess has the  o  owing   hases                                           activates  actor V an    actor VIII, which serves as a co ac-

               (Figs. 27.4 an   27.5):                                                                                     tor in   rothro  binase co     ex an   acce erates the activa-

                                                                                                                           tion o   actor II by  actor Xa an   o   actor Xa by  actor IXa,
               1.  Initiation                                                                                              res  ective y.
               2.  A     i  cation                                                                                              C eavage o    brino  e  ti  es occurs at the en   o  the ini-


               3.  Pro  agation                                                                                            tiation   hase an   beginning o  the next   ro  agation   hase.
               4.  Stabi ization (  er  ination)
                                                                                                                           In   ost c ot-base   coagu ation assays, this is the visua  en

                                                                                                                             oint o  the assay which occurs with a    roxi  ate y 3% o  the
               Initiation Phase                                                                                            tota  thro  bin generate  .


               Initiation  occurs  on  a  tissue   actor  (  F)-bearing  ce  .  It

               begins  when    F ro      a  age    b oo    vesse s  bin  s   actor                                         Propagation

               VIIa to activate  actor IX an    actor X. T is activation o   ac-                                           In  the    ro  agation    hase  o   in  vivo  coagu ation,   arge

               tor IX by   F-VIIa co     ex serves as the bri  ge between c as-                                            a  ounts o  thro  bin are generate   on the    ate et sur ace.

               sica  extrinsic an   intrinsic   athways. Factor Xa then bin  s                                             Te  accu  u ate    enzy  e  co     exes  (tenase  co     ex  an

               to  actor II to  or   thro  bin ( actor IIa). T ro  bin genera-                                               rothro  binase co     ex) on the    ate et sur ace   ro  uces

               tion through this reaction   ro  uces 3% to 5% o  the tota                                                  95% or   ore o  the tota  a  ounts o  thro  bin generation

               thro  bin generate   an   can be ter  inate   by   F   athway                                               an      ate et activation. T is ensures continuous generation

               inhibitor.                                                                                                  o  thro  bin an   subsequent y   brin to  or   a  arge c ot.



               Am pli  cation                                                                                              Stabilization


               In this   hase,    ate ets an   co actors are activate   to set the                                         T ro  bin generation  ea  s to activation o   actor XIII (  brin

               stage   or   arge-sca e  thro  bin  generation.  T e  a  ount  o                                            stabi izing   actor),  which  cova ent y   inks    brin    o y  ers
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