Page 577 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 561

As brinogen is egra e by as in, FSPs or . The Role of Factor VIII

Degra ation occurs whether the as in co es ro DIC or A very c ose re ationshi exists between actor VIII:C ( ro-

ri ary brinogeno ysis. FSPs co ete with regu ar brino- coagu ant) an actor VIII:CAg ( rocoagu ant antigen). In

gen o ecu es or thro bin o ecu es. T is co etitive bin - DIC, it is be ieve that the VIII:CAg is inactivate to a esser

ing akes the thro bin unavai ab e or the conversion o extent than VIII:C by enzy es re ease uring the rocess.

brinogen to brin. In this situation, atients with high FSP It is known that actor VIII:C activity is estroye by in-

eve s have a circu ating anticoagu ant behaving ike he arin. I ute a ounts o thro bin, as in, an activate rotein C

the FSP eve is high, the thro bin c otting ti e is signi cant y (aPC).

ro onge an brinogen quantitation is ow. T e secon e ect It is strong y sus ecte that the in vivo inactivation

is on ate ets. T ese s it ro ucts coat the ate et sur ace, o VIII:C oun in DIC is re ate to the egree o sever-

b ocking the rece tor site nee e or urther ate et activation. ity o DIC. Further ore, ow va ues o actors VIII:C an

When atho ogica brino ysis occurs, not on y are ac- VIIIR:Ag an actors VIII:C an VIIIR:CoF oun in

tors estroye , but, through the estruction o brinogen, atients with irreversib e shock in icate a grave c inica out-

a ro oun antic otting e ect inhibits secon ary he ostasis co e. Discre ancies are a so known to exist between VIII:C

an ate ets. an VIIIR:Ag in atients with thro boe bo ic isease. Such

I the brino ytic syste is activate , it wi contribute to ratios are use u in icators or assessing the severity o DIC.

the consu tion o any coagu ation actors. P as in, the Current thinking in icates that ata on the actor VIII co -

ri ary roteo ytic enzy e o brino ysis, irect y attacks ex show that the og a o a characteristic ecrease o the

an estroys the . T is beco es another or o consu - actor VIII rocoagu ant activity in DIC or u ate in the

tive coagu o athy originating ro an entire y i erent ast is not genera y va i .

source with the sa e en resu t.

When syste ic c otting activation begins, the bo y usu- The Role of Protein C

a y atte ts to sto it. T e two ajor inhibitor syste s o Protein C (PC) is a ajor regu atory echanis o he o-

coagu ation are antithrombin (A ) an the rotein C (PC) stasis. In a ition, PC is now recognize as aying a crucia

an protein S (PS) syste s. T ese inhibitors are consu e ro e in the athogenesis o acute an chronic inf a atory

in the DIC rocess. T ere ore, the co ensatory echa- iseases, or exa e, se sis or asth a. When inf a ation

nis s are o en unab e to stabi ize the consu tive rocess. occurs, coagu ation is a so set in otion an active y artici-

Coagu ation actors an ate ets are consu e ore ra i y ates in enhancing inf a ation.

than they can be re ace , A eve s are e ete , an the PC is a vita in K– e en ent serine rotease that is syn-

i aire ononuc ear hagocytic syste cannot e ective y thesize , re o inant y in the iver, as a sing e o y e ti e

re ove the activate coagu ation roteins. chain o 461 a ino aci s an is a natura anticoagu ant ro-

tein. T e conversion o PC to activate PC (aPC) is enhance
Alternate Form s of DIC by interaction o PC with en othe ia PC rece tor on the ce

Acute DIC resents in one o severa or s in which a sur ace. Activation can a so be triggere by thro bin a one

atient’s c otting an /or brino ytic syste is su en y acti- at a ess e cient rate an is robab y not re evant in the cir-

vate throughout the bo y. In essence, it is a syste ic atho- cu ation. T e unction o aPC as an anticoagu ant is ani-

ogica rocess. Because two ty es o syste s are invo ve , este by its abi ity to inactivate two i ortant co actors o

the c otting an /or the brino ytic syste , severa ty es o the coagu ation casca e: actor V/Va an actor VIII/VIIIa.

2+
DIC can be i enti e c inica y: T ese events are enhance by the resence o Ca , hos ho-
i i s, an co actor rotein S.
1. DIC: C otting an ysis strong y activate ( ost co on Other unctions o aPC in he ostasis are in aintaining

ty e). a f ui state o b oo . aPC has the abi ity to own-regu ate

2. DIC: C otting re o inates with itt e or no ysis ( oor thro bin an su ress the activation o thro bin-activat-

rognosis). ab e brino ytic inhibitor, which in irect y ro otes bri-

3. Pri ary brinogeno ysis: On y ysis activate , but any no ysis. Fibrino ysis is a so sti u ate because o the abi ity

coagu ation actors consu e .
o aPC to inhibit as inogen activator inhibitor-1 (PAI-1).

In the usua or o DIC, the atient’s c otting syste an T e in uction o brino ytic activity by the PC syste

the brino ytic syste are activate . Patients are syste i- ay aci itate the c earance o excess thro bi an generation

ca y or ing thro bin, which, in turn, converts brinogen o FSPs. I aPC is being consu e too ra i y, the regu atory

to brin. In ost instances, the si u taneous generation o abi ity o the PC syste is shar y re uce , which resu ts in

as in wi isso ve the brin. Both the c otting an bri- uncontro ab e thro bosis.

no ytic states are er or ing at abnor a y high rates. I c ot T ro boe bo ic co ications occur in atients with

ysis oes not occur, a i erent or o DIC exists. In this here itary e ciencies o rotein C ( eve s 60% or ess o

case, the rognosis is very oor. A thir ty e is re resente nor a ). Fata neonata purpura eve o s in in ivi ua s

by a state in which the atient re o inant y has brino y- born with a ho ozygous PC e ciency. T e sti u i that can

sis- isse inate intravascu ar brinogeno ysis. Coagu ation in uce DIC ay u ti ate y resu t in abnor a eve s o PC.

actors are egra e by the excess as in being generate . Both nor a an abnor a eve s o PC antigen can be oun ,