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538            PART 7  ■  Principles and Disorders of Hemostasis and Thrombosis




               3.  Factor VIII antibo  ies in he  o  hi iacs. An ELISA tech-                                               assays,  i    uno ogica  assays, an    the    o  i  e    thro  bin

                     nique that uses the bin  ing o  antibo  ies in the    as  a to                                        ti  e.     . T e nor  a  va ue o  200 to 400   g/  L   ay be

                     so i  -  hase antigen, which is subsequent y   etecte   by a                                            ecrease   in  iver   isease or the consu    tion o    brinogen

                     hu  an   o yc ona  IgG  abe e   with the a ka ine   hos  ha-                                          owing to acce erate   intravascu ar c otting. Fibrinogen titers

                     tase-  -nitro  heny    hos  hate substrate syste  .                                                     ay  be  use u .  T e  nor  a   titer  o     brinogen  is  1:128  to

                                                                                                                           1:256; a titer  ess than 1:64 is abnor  a .



                  NOTE: This is a good time to complete Review Questions                                                   Throm bin Tim e

                  related to the preceding content.
                                                                                                                           T e thro  bin ti  e      shou    be   easure   in s  eci  ens

                                                                                                                           with a   ro onge   AP    . I  the      is   ro onge  , a he  arin


               New  Thromboplastins                                                                                        assay  (anti-Xa  inhibition  assay;  by  a  chro  ogenic  assay,
                                                                                                                           that can   istinguish a he  arin e  ect  ro   a   irect thro  bin

               T e new ty  es o  thro  bo   astins  or   easuring the   ro-                                                inhibitor can be use  .

               thro  bin (P  ) are   ixtures o    hos  ho i  i  s an   reco  bi-                                                T e        test    eter  ines  the  rate  o   thro  bin-in  uce

               nant y   erive   hu  an tissue  actor. (  F). Because the new                                               c eavage o    brinogen to   brin   ono  ers an   the subse-

               thro  bo   astins  are    ore  sensitive  (ty  ica   ISI,  1.0)  than                                       quent   o y  erization o  hy  rogen-bon  e     brin   o y  ers

               the tra  itiona  North A  erican ones (ISIs, 1.8 to 3.0), the                                               to  or   an inso ub e   brin c ot. T e nor  a  va ue is  ess than

               P  s  or   atients with inherite   or acquire     e  ciencies o                                             20 secon  s. Pro onge   resu ts wi   be seen i  the   brinogen

               coagu ation  actors wi   be   uch   ore   ro onge   with use o                                              concentration is  ess than 100   g/  L. Abnor  a  resu ts wi

               the new reagents, a though nor  a  va ues   ay change   ini-                                                a so be encountere   in the   resence o  thro  bin inhibitors

                 a  y. However, the thera  eutic range (in secon  s) o  the                                                or substances that inter ere with   brin  or  ation (e.g., he  a-

               P  s in   atients receiving ora  y a    inistere   anticoagu ant                                            rin,    brin    egra  ation    ro  ucts),  or  high  concentrations

               agents is wi  er with the sensitive thro  bo   astins than with                                             o   i    unog obu ins  that  inter ere  with    brin    ono  er

               the tra  itiona  ones. T e INR, however, wi   be the sa  e,                                                   o y  erization such as in cases o    u ti   e   ye o  a.

               as wi   the reco    en  e   ranges o  the INR  or intensity o

               anticoagu ation.                                                                                            Reptilase Tim e

                    Reco  binant  thro  bo   astin  has  the   o  owing                                                    T is assay is si  i ar to the thro  bin ti  e     . T e   i  er-

               a  vantages:                                                                                                ence is that the c otting sequence is initiate   with the snake


               1.  It is   a  e  ro   a hu  an   rotein, not  ro   the   rotein o                                          veno   enzy  e, re  ti ase, which is thro  bin- ike in nature

                     a   i  erent s  ecies.                                                                                an    hy  ro yzes    brino  e  ti  e  A   ro    the  intact    brino-

               2.  T e   ateria  is   ure, an   the concentration can be rea  i y                                          gen   o ecu e. In  contrast to thro  bin, which hy  ro yzes

                     a  juste  , un ike current y avai ab e rabbit brain thro  bo-                                           brino  e  ti  e  A  an    B   ro      brinogen,  re  ti ase  is  not

                       astins. A just  ent wi     ini  ize variation between   i -                                         inhibite   by he  arin. T is assay is use   to screen  or   ys-

                      erent  ots o  the reagent; thus, the nor  a  an   thera  eutic                                         brinogene  ia,  a  coagu ation    isor  er  cause    by  a  vari-

                     ranges o  the P   wi   re  ain the sa  e.                                                             ety o  acquire   or inherite   structura  abnor  a ities in the

               3.  T e reagent is  ree o  conta  ination with noxious viruses                                               brinogen   o ecu e. In the inherite    or  ,  a  i y   e  bers

                     because it is a reco  binant   ro  uct.                                                               wi    exhibit  assay  abnor  a ities.  In  co    arison,    atients

               4.  When the ISI is a    roxi  ate y 1.0, the P  s wi   be the                                              with the acquire    or   o    ys  brinogene  ia wi   not have

                     sa  e as those obtaine   with use o  the Wor    Hea th                                                a  ecte     a  i y    e  bers  an    wi    exhibit  abnor  a    iver

                     Organization re erence thro  bo   astin. T ere ore, the P                                              unction tests.

                     ratio (P   o    atient/  ean nor  a  P  ) wi   be the sa  e as

                     the INR.                                                                                              D-Dim er Testing

               5.  T e new reagents are   ore sensitive to   i      e  ciencies                                            Te D-dimer (Fig. 27.6) is a s  eci  c  rag  ent generate    ro

                     o  coagu ation  actors than are the tra  itiona  thro  bo-                                            two cross- inke     brin   o ecu es a  er a c ot has  or  e  . For

                       astins. Patients with he  ostatica  y a  equate  eve s o                                            d-  i  ers to be  or  e  , three   ajor he  ostatic stages   ust

                     coagu ation  actors II, V, VII, or X (30% to 40% o    ean                                             be  unctioning:

                     nor  a  activity) wi   have INRs o  1.4 or  ess.                                                      1.  Coagu ation to  or   the c ot


                                                                                                                           2.  Cova ent cross- inking o    brin by activate    actor XIII
               Assays for Fibrin Formation                                                                                 3.  Fibrino ysis  to    isso ve  the   ibrin  c ot  into  s  a  er



               Fibrinogen Levels                                                                                                  rag  ent


               Fibrinogen  assays  are  use u   in    etecting    e  ciencies  o                                                A   three o  these stages require a  equate  or  ation o

                 brinogen an   a terations in the conversion o    brinogen                                                 thro  bin. Fo  owing the  or  ation o  a c ot, the   brino ytic

               to   brin. Fibrinogen can be quantitate   by various   eth-                                                 syste   is activate   to regu ate    as  in  or  ation. P as  in

               o  s  inc u  ing   reci  itation  or    enaturation   etho  s,  tur-                                          egra  es  the    brin  c ot  into  s  a  er  s  eci  c    brin   rag-

               bi  i  etric or   brin c ot   ensity   etho  , coagu ab e   rotein                                            ents o  which so  e or a   contain the d-  i  er e  ito  e. On
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