Page 549 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 27 ■ Principles of Hemostasis and Thrombosis: Blood Coagulation Factors and Natural Coagulant Systems 533

an rovi es strength an stabi ity to brin incor orate

in ate et ug. In a ition, thro bin activates thro bin BOX 27.1

activatab e brino ysis inhibitor ( AFI) that rotects the c ot

ro brinolysis.
Components of the Plasma Fibrinolytic

Im plications of Cell-Based Coagulation System

A ce -base o e o coagu ation a ows or a ore thor- PLASMINOGEN ACTIVATORS

ough un erstan ing o how he ostasis works in vivo an En ogenous

ex ains the atho hysio ogica echanis s behin certain issue-ty e as inogen activator (t-PA)

coagu ation isor ers. Patients acking actor XII, reka - Urokinase

ikrein, or high- o ecu ar weight kininogen o not b ee Exogenous

abnor a y. Secon , atients with on y trace quantities o Stre tokinase

actor XI can withstan ajor trau a without unusua Acy - as inogen stre tokinase activator co ex

b ee ing. Patients who co ete y ack actor XI exhibit i (APSAC)

he orrhagic isor er.

PLASMINOGEN INHIBITORS

A ha-2 as in inhibitor

NOTE: This is a good time to complete Review Questions issue as inogen activator inhibitor

related to the preceding content.

Thrombin-Mediated Reactions P as in igests brin an brinogen by hy ro ysis to ro-

Nu erous athways exist that u ti ate y ea to the gen- uce rogressive y s a er rag ents. T is s ow-acting ro-

eration o thro bin an consequent y brin or ation o - cess gra ua y isso ves away the c ot as tissue re air is taking

owing vascu ar injury. T e categories o essentia thro bin ace, with the articu ate atter being hagocytize by the

bioregu ation o he ostasis are ononuc ear hagocytic syste .
Inactive plasminogen circu ates in the as a unti an

1. Procoagu ant injury occurs. T e activators o as inogen consist o

2. Coagu ation inhibitor en ogenous an exogenous grou s (Box 27.1). P as inogen

3. issue re air activation to as in is the resu t o the activity o a nu -

ber o roteo ytic enzy es. T ese enzy es, the kinases, are

Procoagulant re erre to as the plasminogen activators. P as inogen activa-

tors are oun in various sites, such as the vascu ar en o-
Acting as a rocoagu ant, thro bin in uces ate et activa-

tion an aggregation. In a ition, thro bin activates co ac- the iu or ysoso a granu es, an bio ogica f ui s. At east

tor VIII to VIIIa, converts brinogen to brin, an activates two or s o tissue activators have been escribe : those

actor XIII to XIIIa. It converts rothro bin to thro bin via that see re ate to urokinase, a urinary activator o as-

autocata ysis. inogen, an those unre ate to urokinase. T e activators
unre ate to urokinase inc u e thro bin, bacteria ro ucts

Coagulation Inhibitor such as stre tokinase ro beta-he o ytic stre tococci, an
sta hy okinase. P as a activators o as inogen inc u e
Te coagulation inhibitor activity is aye by thro bin is the

bin ing o antithro bin (A ) to inhibit serine roteases an as a ka ikrein, activate as a thro bo astin antece -

bin ing to thro bo o u in to activate rotein C. In a i- ents ( actor XI), an activate Hage an actor ( actor XIIa).

tion, the other activity in this category is the ro otion o It is esti ate that 1.5 i ion A ericans have a heart

en othe ia ce re ease o t-PA. attack each year. Most are cause by c ots that cut o b oo
f ow to the heart usc e. issue-ty e as inogen activator

Tissue Repair (t-PA) is resent in inute quantities in the vascu ar en o-

T ro bin e iates tissue re air by in ucing ce u ar che o- the iu . When t-PA encounters a b oo c ot, t-PA trans-

taxis an sti u ation o ro i eration o s ooth usc e an or s as inogen to as in, an as in then egra es

en othe ia ce s. the c otte brin network. As a resu t o biotechno ogy
(reco binant DNA), a synthetic tissue-ty e as inogen

Fibrinolysis has been eve o e an is use c inica y to treat ost– yo-
car ia in arction an u onary e bo i. t-PA is consi ere

Fibrin c ots are te orary structures that sea o a a age by any to be ore s eci c an twice as e ective as stre -

area unti hea ing can take ace. Fibrino ysis is the hysi- tokinase in isso ving c ots an has cause ewer si e e ects.

o ogica rocess that re oves inso ub e brin e osits by T rough its ysis o brin or brinogen, as in is res on-

enzy atic igestion o the stabi ize brin o y ers. As sib e or or ing egra ation or brin split products consisting

hea ing occurs, the c ots the se ves are isso ve by as in. o inter e iate rag ents X an Y, an rag ents D an E.