Page 557 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 27 ■ Principles of Hemostasis and Thrombosis: Blood Coagulation Factors and Natural Coagulant Systems 541

NORMAL PRO EC IVE MECHANISMS with thro bin. T is co ex is evoi o any thro botic or

AGAINS HROMBOSIS antithro botic activity. A is a so the rinci a hysio ogica
inhibitor o actor Xa. In a ition, it is known to inhibit ac-

In the b oo circu ation, the re is osition to thro bosis tors IXa, XIa, an XIIa.

e en s on the ba ance between rocoagu ant an antico- A is nor a y a s ow inhibitor, but in the resence o

agu ant actors. Severa i ortant bio ogica activities nor- he arin, it ra i y inhibits activate serine roteases such as

a y rotect the bo y against thro bosis. T ese activities activate actors II, IX, X, XI, an XII. T e bin ing o A

inc u e the o owing: an thro bin is increase 1,000- o or greater in the res-
ence o he arin. Initia y, A was esignate he arin co ac-
1. T e nor a f ow o b oo tor. T e enhance ent o the activity o A is consi ere to be

2. T e re ova o activate c otting actors an articu ate the ri ary echanis o he arin’s anticoagu ation e ects.

ateria Nor a y, A accounts or the ajority o the thro bin

3. Natura anticoagu ant syste s known to be o erative in inhibitory activity in as a. T e concentration o A at the

vivo: en othe ia sur ace is rate i iting or inactivation o thro -

a. antithro bin (A ) bin an actor Xa when the as a eve o A a s be ow

b. He arin co actor II (HC-II) 50%.

c. Protein C an its co actor, rotein S A is ra i y re ove ro the circu ation o owing

4. Ce u ar regu ators one-to-one bin ing with an activate coagu ation actor. T e

ha - i e o A in as a is a roxi ate y 70 hours.

Normal Blood Flow
Heparin Cofactor
T e nor a f ow o b oo revents the accu u ation o ro-

coagu ant ateria . T is echanis re uces the chance o He arin is ro uce en ogenous y by ast ce s, an he a-

oca brin or ation. rin- ike o ecu es are oun in the en othe iu . wo he -
arin- e en ent thro bin inhibitors are resent in hu an

as a: A he arin co actor an HC-II, revious y re erre
Removal of Activated Clotting Factors and to as he arin co actor A. T e inhibitory activity o HC-II is

Particulate Material acce erate by he arin. T e inhibition o thro bin by HC-II

Another nor a echanis against ina ro riate thro bo- is not i ite to the activity o thro bin or brinogen; a so

sis is the re ova ro the b oo o activate c otting ac- inhibite are thro bin-in uce ate et aggregation an

tors by he atocytes. T is rocess, a ong with the natura y re ease. In a ition to thro bin, HC-II inhibits chy otry -

occurring inhibitors, i its intravascu ar c otting an bri- sin. It oes not signi cant y inhibit b oo coagu ation actors

no ysis by inactivation o such actors as XIa, IXa, Xa, an IXa, Xa, an XIa or as in.

IIa. Re ova o articu ate ateria by the ce s o the ono- Protein C

nuc ear hagocytic syste is a so i ortant in reventing

the initiation o coagu ation. Protein C an rotein S are invo ve in one o the ajor
natura anticoagu ation syste s in the bo y. De ciency an

The Natural Anticoagulant Systems a teration in either rotein have been c ear y associate with
re is osition to thro bosis.

Te in vivo existence o natural anticoagulant systems is essen- Protein C, a vita in K– e en ent as a rotein synthe-

tia to revent thro bosis. T ese natura anticoagu ant sys- size in the iver, re resents a natura anticoagu ant or e

te s inc u e A , HC-II, an protein C an its co actor, protein in res onse to thro bin generation. Protein C circu ates

S. A an HC-II are serine rotease inhibitors. When acti- in the b oo as a zymogen, an inactive recursor or . T e

vate , rotein C is ca ab e o egra ing activate actors V ajority o as a rotein C exists as a two-chain zy ogen

(Va) an VIII (VIIIa) in the resence o the co actor rotein ( o ecu ar weight, 62,000) be ore activation. A sing e-chain

S. or an a inor beta or have a so been e onstrate .

Protein C requires roteo ytic c eavage to beco e active
Antithrom bin (Fig. 27.8). It is converte by thro bin to its enzy atica y

Antithrombin (AT) is consi ere the ajor inhibitor o coagu a- active or . A or s can be activate . T ro bin activates

tion. A is one o the ser in su er a i y o serine proteinase rotein C in the resence o the en othe ia ce –associate

inhibitors that a so inc u es a ha-1 antitry sin, C1 inhibi- i o rotein co actor thrombomodulin. T is reaction con-

tor, a ha-2 anti as in, HC-II, an as inogen activator verts the zy ogen or into the serine rotease, activate

inhibitor. rotein C (APC). T ro bin activation o rotein C is a so

A is an a ha-2 g obu in g yco rotein that circu ates in enhance by activate actor V, a though consi erab y ess

the as a. It is synthesize by he atocytes, egakaryo- e cient y.

cytes, an vascu ar en othe iu . A is the rinci a hysi- T e rotein C anticoagu ant athway is recognize as a

o ogica inhibitor o thro bin that s ow y an irreversib y ajor b oo coagu ation regu atory echanis . APC is a

inhibits thro bin by or ing a stab e one-to-one co ex otent as a anticoagu ant. Once activate , APC—in the