Page 507 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 25 ■ Principles of Hemostasis and Thrombosis: Vasculature and Platelets 491

bloo n tissue. Electron icroscope ex in tion o the Endothelial Prothrombotic-

en otheliu e onstr tes org nelles such s itochon ri , TABLE 25.1 Antithrombotic Balance*

riboso es, n en opl s ic reticulu .

Prothrombotic Antithrombotic

VASCULATURE PHYSIOLOGY Platelet-activating factor Prostacyclin

Tissue factor Thrombomodulin
The Role of Vasoconstriction in Hemostasis
von Willebrand factor Tissue plasminogen activator

V scul r injury to l rge or e iu -size rtery or vein Plasminogen activator Urokinase

requires r pi surgic l intervention to prevent exs ngui-

n tion. When s ller vessel, such s n rteriole, ven- Inhibitor-1 Heparin-like molecules

ule, or c pill ry, is injure , contr ction occurs to control Other coagulation factors

blee ing. T is contr ction o the bloo vessel w ll is c lle Synthesis of factor V

vasoconstriction. Binding of factors V IXa, Xa
,
V soconstriction is short-live re ex re ction o the

s ooth uscle in the vessel w ll pro uce by the sy p - Activation factor XII

thetic br nches o the utono ic nervous syste . T is n r- *These various endothelial-associated factors and functions contribute

rowing, or stenosis, o the lu en o the bloo vessel ecre ses to a dynamic physiological antagonism or “balance” that determines the

the ow o bloo in the injure vessel n surroun ing v s- status of local hemostatic/thrombotic activity.

cul r be n y be su cient to close severe c pill ries.

Non ptive ch nges in en otheli l structure n unc-

The Role of the Endothelium tion, provoke by p thophysiologic l sti uli, c n result in

loc lize , cute, n chronic lter tions in the inter ctions o
T e en otheliu cont ins connective tissues such s coll -

gen n el stin. T is connective tissue trix regul tes the en otheliu with the cellul r n cro olecul r co po-

per e bility o the inner vessel w ll n provi es the prin- nents o circul ting bloo n o the bloo vessel w ll. T ese

cip l sti ulus to thro bosis ollowing injury to bloo ves- lter tions c n inclu e the ollowing:

sel. T e en otheliu is highly ctive et bolic lly n is ■ Enh nce per e bility to ( n subsequent oxi tive

involve in the clotting process by pro ucing or storing clot- o if c tion o ) pl s lipoproteins

ting co ponents ( iscusse in et il in l ter section o this ■ Hyper hesiveness or bloo leukocytes

ch pter). It is lso rich with pl s inogen ctiv tor, which, i ■ Function l i b l nces in loc l prothro botic n nti-

ppropri tely sti ul te , is rele se n ctiv tes pl s ino- thro botic ctors, growth si ul tors n inhibitors, n

gen, which ensures r pi lysis o f brin clots. A ition lly, v so ctive ( il tor, constrictor) subst nces ( bles 25.1

the en otheliu el bor tes prost cyclin, which is synthe- n 25.2)

size by the en otheliu ro prost gl n in precursors n T e en otheliu is involve in the et bolis n cle r-

strongly inhibits pl telet ggreg tion n hesion. nce o olecules such s serotonin, ngiotensin, n br -

Mini l inter ctions le ing to pl telet ctiv tion or clot

or tion occur between the circul ting bloo n int ct ykinin th t ect bloo pressure regul tion, the ove ent

en otheli l sur ces. However, isrupte en otheli l cells o ui cross the en otheliu , n in tion. With

rele se thro bopl stic subst nces th t c n initi te co gul - respect to bloo co gul tion, one o the b sic ch r cteris-

tion. Coll gen, in p rticul r, initi tes cont ct ctiv tion o tics o nor l, int ct en otheliu is its nonre ctivity with

ctor XII, thereby initi ting bloo co gul tion. pl telets n in bility to initi te sur ce cont ct ctiv tion o

T e en otheliu or s biologic l inter ce between clotting ctor XII ( ble 25.3).

circul ting bloo ele ents n ll the v rious tissues o the

bo y. It is str tegic lly situ te to onitor syste ic s well 25.2 Endothelial Vasoconstrictor-

s loc lly gener te sti uli n to ptively lter its unc- TABLE Vasodilator Balance

tion l st te. T is ptive process typic lly procee s without

notice, contributing to nor l ho eost sis. T e presence o Constrictor Dilator

unique org nelle iscovere by Weibel n P l e in 1964

turne out to be n i port nt rker to i enti y uthentic Endothelin-I Prostacyclin

en otheli l cells. T is org nelle, c lle Weibel-P l e bo y Angiotensin-II Nitric oxide

(WPB), represents the stor ge gr nule or von Willebr n Vasoconstrictor Other “EDRF-like” substances

ctor (vWF), olecule e i ting pl telet hesion. A Prostaglandins

receptor or leukocytes (P selectin) w s oun in WPB e -

br ne. Secretion o these org nelles provi es r pi etho These various endothelial-generated substances contribute to the local
regulation of vascular tone through their effects on smooth muscle
or ctiv te en otheliu to beco e hesive or pl telets contractility.

n leukocytes.