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CHAPTER 25  ■  Principles of Hemostasis and Thrombosis: Vasculature and Platelets                                           499




                                                                                 ADP                                             ADP                                                           PGI
                                                                                                                                                                                                    2
                                                                                                A3P5PS                                         Clopidogrel

                                                                                                MRS2179                                        Ticlopidine
                                                                                                                                               Cangrelor



                                                                                 P2  Y                                          P2  Y                                                           IP IP IP
                                                                                                                                P2
                                                                                                                                P2Y
                                                                                 P2Y
                                                                                     Y
                                                                                 P2
                                                                                                                                    Y
                                                                                       1 1 1                                           12
                                                                                                                                        2
                                                                                                                                        2
                                                                                                                                       122
                                                                                                                                       12
                                                                                                                                        2
                                                                 GTP
                                                                 G GTPP                          g                     g                       G GTP                         GTP                               g
                                                                                                                                                                               TP
                                                                                                                                               GTP
                                                                                                                                                                             G G
                                                             GG        a                          b                      b                            a                            a                            b
                                                               q q
                                                                                                                                                                            G
                                                                                                                                                           G G              GG
                                                                   PLCb
                                                                   PL
                                                                   PLCb                                                                                       i2 i2            s s
                                                                     L
                                                                          b
                                                                          b
                                                                       C
                                                                       C
                                                                                                                       PI3K
                                                                                                                       PI3K
                                                     IP 3  DAG              PIP  2
                                                                                                       GTP
                                                                                                              Rap1
                                 Ca  2+  Ca 2+                                                                       ON                                                            AC
                                     Ca  2+                    PKC                                                              Akt


                                                      PLA                                                                                                                ATP                      cAMP
                                                            2



                                          PC          Arachidonic                        PH  Pleckstrin PH

                                                           Acid

                     FIGURE 25.9  Pl  telet   ctiv  tion by ADP.   wo receptors th  t c  n be   ctiv  te   by ADP h  ve been i  entif e   in pl  telets. P2Y1   n   P2Y12,

                     which   re couple   to   i  erent G proteins   n   there ore   e  i  te   i  erent responses. Gq couples P2Y1 receptors to the   ctiv  tion o  PLCβ.

                     T e Gi      ily   e  ber, Gi2, couples P2Y12 to the inhibition o  cAMP  or    tion (vi   Gi2 α)   n   to e  ector p  thw  ys th  t inclu  e PI3K

                       n   R  p1B (vi   G βγ). (Fro   M  r  er VJ, Air   WC, Bennett JS, et   l. Hemostasis and T rombosis, 6th e  , Phil    elphi  , PA: Lippincott

                     Willi    s & Wilkins, 2012.)




                    gents— or  ex    ple,  eptif b  ti  e,     nonpepti  e    nt  gonist.                                      Bleeding Tim e With and Without Aspirin

                   Abcixi    b  inhibits  the  f n  l  co    on  p  thw  y  o   pl  telet                                      T e blee  ing ti  e test is now   n in requently per or  e   in

                     ggreg  tion where f brinogen bin  s to GP IIb/III   receptor.                                             vivo   e  sure  ent o  pl  telet     hesion   n     ggreg  tion on

                        Neutr  lizing   ntibo  ies to   bcixi    b c  n  or  , there ore,                                      loc  lly injure   v  scul  r suben  otheliu  . T is test provi  es

                   the   rug c  n only be use   once. GP IIb/III     nt  gonists c  n                                            n esti    te o  the integrity o  the pl  telet plug   n   thereby

                   c  use severe blee  ing,   n   it c  n t  ke over 12 hours  or pl  te-

                   let  unction to be restore       er stopping   n in usion.



                   Other Agents                                                                                                     BOX  25.2


                   Another   ntipl  telet   rug is tic  grelor. It is license    or use with

                    spirin in preventing  therothro  botic events. T e newer P2Y12

                    nt gonists pr  sugrel  n   tic  grelor h ve   ore pre  ict  ble ph r-                                        Laboratory Assessment of Platelet Function

                       cokinetics   n   ph  r    co  yn    ics th  n clopi  ogrel.
                                                                                                                                 Peripher  l bloo   s  e  r

                                                                                                                                 Pl  telet count
                   Laboratory Assessment of Platelets
                                                                                                                                 Petechio  eter

                   A pl  telet count is     un      ent  l co  ponent in the ev  lu  -                                           Pl  telet   ggreg  tion

                   tion o     p  tient. Ex    in  tion o  the peripher  l bloo   s  e  r                                         A  enosine   iphosph  te (ADP)

                    or pl  telet nu  ber   n     orphology is critic  l bec  use     ny                                          Epinephrine

                   clinic  l clues     y be obt  ine    ro     n ev  lu  tion o  pl  te-                                         Coll  gen

                   let qu  ntity   n     orphology. A     nu  l pl  telet count   n                                              Ristocetin

                   peripher  l s  e  r ev  lu  tion is    b  sic   ssess  ent. Except  or                                        Ar  chi  on  te

                   extre  ely low pl  telet counts, tot  l pl  telet counts   re per-                                            T ro  bin

                    or  e   on   uto    te   equip  ent.                                                                         Pl  telet lu  i  ggreg  tion (rele  se)

                                                                                                                                 Pl  telet   ntibo  ies (IgM   n   IgG)
                   Qualitative Assessm ent of Platelets                                                                          Pl  telet   e  br  ne glycoproteins (  ow cyto  etry)


                   I     pl  telet count is nor    l but    p  tient h  s    suggestive                                          Pl  telet    ctor IV

                   blee  ing history,   n   ssess  ent o  pl  telet  unction shoul   be                                          (Bet  )-thro  boglobulin

                   con  ucte  . Metho  s o  ev  lu  tion (Box 25.2) inclu  e   ggre-                                             T ro  box  nes

                   g  ting   gents,   n   lu  i  ggreg  tion.
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