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CHAPTER 27  ■  Principles of Hemostasis and Thrombosis: Blood Coagulation Factors and Natural Coagulant Systems                                                         537




                   1. Speci  c Factor Inhibitors                                                                                   e  ication  history  nee    to  be  reviewe  .  A    itiona


                   I  the AP     screening test is   ro onge   with a nor  a  AP    ,                                          with he  arin assay (anti-Xa inhibition assay) can be use   to

                   i    e  iate   ix an   AP     incubate     ix, this in  icates a                                            exc u  e the   resence o  anticoagu ants.

                    actor   e  ciency in the intrinsic or   na  co    on   athway.

                   I  the   ro onge   AP     screen is   ue to the   resence o  an                                             Chrom ogenic Anti-Xa

                   inhibitor,   ixing with an equa  vo u  e o  nor  a    atient                                                T e  chro  ogenic  anti-Xa    etho     or    onitoring   ow–

                      as  a wi   not shorten or correct the   ro ongation o  AP                                                 o ecu ar  weight  he  arin  (LMWH)  an    un ractionate

                   resu ts. T ere is no shortening or correction in the AP                                                     he  arin is another assay. T is auto  ate   assay can re   ace

                   resu t. Inhibitor in the   atient’s    as  a is   resent in excess                                          the AP      or   onitoring un ractionate   he  arin because it

                   an    bin  s  to  coagu ation   actors  or    rotein/  hos  ho i  i                                         e i  inates the variabi ity seen with AP     resu ts.

                   co     exes in both the   atient’s    as  a an   nor  a    atient                                                Chro  ogenic assays use a  actor Xa substrate onto which

                     as  a.                                                                                                    a chro  o  hore has been  inke  . Factor Xa c eaves the chro-

                          o   istinguish the  ocation o  a s  eci  c  actor   e  ciency,                                         ogenic substrate, re easing a co ore   co    oun   that can

                   the AP     resu ts can be ana yze   in conjunction with P                                                   be   etecte   with a s  ectro  hoto  eter an   is   irect y   ro-

                   resu ts. I  the P   is nor  a , this suggests an intrinsic   athway                                           ortiona  to the a  ount o  activate    actor X (FXa)   resent.

                    e  ciency (VIII, IX, XI, XII, PK, HMWK). I  the P   is   ro-                                               When a known a  ount o   actor Xa is a    e   to    as  a con-

                    onge  , this suggests a co    on   athway   e  ciency (  brino-                                            taining he  arin (or LMWH), the he  arin enhances  actor Xa

                   gen, II, V, X).                                                                                             inhibition by antithro  bin ren  ering  ess  actor Xa avai ab e

                        I  the AP     Screen is   ro onge  , with a nor  a  AP                                                 to c eave the substrate. T e test resu ts in the  or   o  a stan-

                   i    e  iate   ix o  an equa  vo u  e o  nor  a    atient    as  a                                            ar   curve with known a  ounts o  he  arin can be use   to

                   but an abnor  a  AP     incubate     ix o  an equa  vo u  e                                                   eter  ine  actor Xa.

                   o  nor  a    atient    as  a, this in  icates the   resence o  a                                                 So  e a  vantages o  the anti-Xa he  arin assay co    are

                    e aye   inhibitor  such  as  s  eci  c   actor  inhibitors,    ost                                         to the AP     are

                   co    on y  actor VIII inhibitor. So  e inhibitors wi     e  -

                   onstrate a   e aye   ty  e inhibitor   attern, with ti  e an  /or                                           ■   Una  ecte   by un  er    e   b oo   co  ection tubes

                   te    erature   e  en  ence.                                                                                ■   Not susce  tib e to inter erence  ro   e evate   concen-

                        A though rare, the   resence o  a  actor inhibitor, such as a                                               trations o   actor VIII or   brinogen  ro   acute-  hase

                    actor VIII inhibitor, wi   increase the risk o   i e-threatening                                                reactions

                   b ee  ing. T e   resence o  a  actor inhibitor can be con  r  e                                             ■   Not inf uence   by  actor   e  ciencies (  ossib e exce  tion

                   by a Bethes  a assay  or that  actor.                                                                            is A     e  ciency)
                                                                                                                               ■   No nee   to estab ish an AP     thera  eutic range

                   2. Nonspeci  c Inhibitors                                                                                        So  e   isa  vantages o  the anti-Xa  he  arin assay co  -


                   I  the AP     Screen is   ro onge   with an AP     i    e  iate                                              are   to the AP     are

                     ix o  an equa  vo u  e o  nor  a    atient    as  a an     ro-

                    onge   with the AP     incubate     ix o  an equa  vo u  e o                                               ■   High cost

                   nor  a    atient    as  a, this suggests a nons  eci  c inhibi-                                             ■   Processing o  s  eci  en within 1 hour to avoi   he  arin

                   tor. T e   resence o   ow- eve  nons  eci  c inhibitors in the                                                   neutra ization  ro   PF4

                    atient’s    as  a   ay   e  onstrate an AP     incubate     ix                                             ■   Questionab e thera  eutic range  i  itations

                   si  i ar to a   e aye   ty  e inhibitor.                                                                    ■   No sa ety an   e  ectiveness   ata on outco  es  or   anag-

                        T e   resence o   u  us anticoagu ants, antibo  ies against                                                 ing thera  y

                     rotein-  hos  ho i  i    co     exes,  wi    increase  the  risk  o

                   thro  boe  bo is  . I  the c inica  history suggests  u  us anti-                                           Classic Assays for Coagulation Factors

                   coagu ant (LA),  urther testing inc u  es   hos  ho i  i  -base                                             Tese assays   ay be con  ucte   in certain circu  stances:

                   screening tests,   hos  ho i  i     e  en  ency assays, an   exc u-

                   sion o  the   resence o  inhibitors in a    ition to the   ixing                                            1.  One-stage quantitative assay  or  actors II, V, VII, an

                   stu  y inc u  ing an incubate   AP    .                                                                          X. T is assay uses age   seru   an   absorbe      as  a in

                                                                                                                                    the P  . Age   seru   contains  actors VII, IX, X, an   XII.
                   3. Anticoagulants                                                                                                Absorbe      as  a contains  actors V, VIII, XI, an   XIII.


                   I  the AP     Screen is   ro onge   with an AP     i    e  iate                                                  Te P   is con  ucte   using s  eci  c  actor–  e  cient    as  a

                     ix o  an equa  vo u  e o  nor  a    atient    as  a an     ro-                                                 with s  eci  c   i utions o    atient    as  a. T e   ercentage

                    onge   with the AP     incubate     ix o  an equa  vo u  e o                                                    o   actor activity is    otte   to construct an activity curve.

                   nor  a    atient    as  a, anticoagu ants are a   ossibi ity.                                               2.  One-stage quantitative assay  or  actors VIII, IX, XI, an

                        T e    resence  o   the  anticoagu ants  such  as  he  arins,                                               XII. T is   roce  ure is base   on the AP     assay. It is base

                    on  a  arinux,   abigatran, or other   irect thro  bin inhibi-                                                  on the resu ts o    atient    as  a to correct s  eci  c  ac-

                   tors can cause   ro ongation o  both the AP     i    e  iate                                                     tor–  e  cient    as  a. T e resu ts are ex  resse   in   ercent

                    ix  an    AP      incubate     ix.  T e    atient’s   e  ica   an                                               activity on an activity curve.
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