Page 548 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )
P. 548
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

