Page 547 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 27 ■ Principles of Hemostasis and Thrombosis: Blood Coagulation Factors and Natural Coagulant Systems 531

ro e in converting actor XIII to XIIIa an in converting

PK brinogen to brin. Fibrin or ation occurs in three hases:
HMWK Kall.
roteo ysis, o y erization, an stabi ization.

Initia y, thro bin, a rotease enzy e, c eaves brinogen,
XII XIIa
Surface which resu ts in a brin ono er, brino e ti e A, an
HMWK brino e ti e B rag ents. In the secon ste , the brin

VIIa VII ono ers s ontaneous y o y erize en to en because o
XI XIa Complex T. Thromboplastin
HMWK Surface Ca2+ hy rogen bon ing. Fina y, the brin ono ers are inke
cova ent y by actor XIIIa into brin o y ers. T ese o y-
IX
CA 2+ IXa ers or a eshy network, an the na brin so ution is

PF 3 converte to a ge when ore than 25% o the brinogen is
converte to brin.

VIII VIIIa Factor XIII is converte to the active or , actor XIIIa, in
X Xa
Ca 2+ two ste s. In the rst ste , thro bin c eaves a e ti e ro

PF 3 each o the two a ha chains o actor XIII with or ation o

V VIIIa an inactive inter e iate or o actor XIII. In the secon
X ste , ca ciu ions cause actor XIII to issociate, or ing
Ca 2+ IIa (Thrombin)

PF 3 actor XIIIa.
Fibrinogen is nor a y resent in the as a as a so ub e

o ecu e. Subsequent to the action o thro bin, brinogen
Fibrinogen Fibrin
is trans or e into brin, an inso ub e ge . T is conversion
FIGURE 27.3 Intrinsic athway o coagu ation. (PK HMWK,

reka ikrein, high– o ecu ar weight kininogen; Ka , ka ikrein; o brinogen to a cross- inke ge occurs in severa stages.

PF3, ate et actor 3.) Factor XIIIa intro uces e ti e bon s within the o y -
erize brin network. T is cross- inking akes the brin

ore e astic an ess susce tib e to ysis by brino ytic agents.

activates rothro bin ( actor II) to thro bin, which in turn Fibrin or s a oose covering over the injure area, rein-

converts brinogen to brin. orces the ate et ug, an c oses o the woun . A er a

Strong negative y charge so i s that can artici ate in the short erio , the c ot begins to retract an beco es s a er

activation o actor XII inc u e g ass an kao in in vitro as we an ore ense. T is retraction rocess is thought to be

as e astin, co agen, ate et sur aces, ka ikrein, as in, an cause by the action o ate ets tra e a ong with eryth-

high– o ecu ar weight kininogen in vivo. Co agen ex ose rocytes an eukocytes in the c ot. As the brin a ents

by b oo vesse injury great y inf uences the rate o reaction. gather aroun the aggregate ate ets, the ate ets sen out

Factor XIIa interacts in a ee back oo to convert reka - cyto as ic rocesses that attach to the brin an u the

ikrein to a itiona ka ikrein. T is reaction is aci itate by bers c oser together. When a c ot or s in a test tube, c ot

the action o HMWK. In the absence o reka ikrein, actor retraction can be observe . T e f ui squeeze ro this c ot

XIIa is generate ore s ow y. is serum.

Ionize ca ciu ays an i ortant ro e in the activa-

tion o certain coagu ation actors in the intrinsic athway. Cell-Based (Physiologic, In Vivo)

Ca ciu is not require or the activation o actor XII, Coagulation

reka ikrein, or actor XI but is necessary or the activation

o actor IX by actor XIa. Cell-based coagulation is regu ate by ro erties o ce sur-

aces. T is o e e hasizes the i ortance o s eci c
Final Com m on Pathway ce u ar rece tors or the coagu ation roteins. A ce -base

Once actor X is activate to Xa, the extrinsic an intrinsic o e ex ains so e as ects o he ostasis that the c assic

athways enter a co on athway. Factor II, rothro bin, casca e, rotein-centric o e oes not.

is activate to thro bin ( actor IIa), which nor a y circu- In contrast to the c assic theory o in vitro c ot-base

ates in the b oo as an inactive actor. coagu ation, a ce -base in vivo o e recognizes that ce s

Fo owing the activation o actor Xa, it re ains ate et with si i ar hos hati y serine content can ay very i -

boun an activates actor V. T e co ex o actors Xa an erent ro es in he ostasis e en ing on their co ection o

Va on the ate et sur ace is or e near ate et-boun ac- sur ace rece tors.

tor II o ecu es. In turn, the ate et-boun Xa/Va co ex In a ition to rocoagu ant an anticoagu ant roteins,

c eaves actor II into thro bin, actor IIa. T e stage is acce - nor a hysio ogic coagu ation requires two ty es o ce s

erate by actor V an ionize ca ciu . or or ation o coagu ation co exes. issue actor ( F)

co es ro a age b oo vesse ce s, an ate et actor
Fibrin Form ation is ex resse by ature ate ets. Because F-ex ressing ce s

C otting is the visib e resu t o the conversion o as a an activate ate ets are essentia or hysio ogic coagu a-

brinogen into a stab e brin c ot. T ro bin ays a ajor tion, b oo c otting is oca ize to the site o injury. Intact