Page 513 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 25 ■ Principles of Hemostasis and Thrombosis: Vasculature and Platelets 497

pl telets re e i te by the bin ing o l rge soluble cro- Primary wave Secondary wave

olecules to istinct GP receptors nchore in the pl telet (a)

e br ne. T is incre se in hesiveness c uses circul ting

pl telets to here to those lre y tt che to the coll gen.

Te result is cohesive pl telet ss th t r pi ly incre ses in n

size to or platelet plug. o i
s t
T e tr ns or tion o the pl telet ro isc to sphere s h ) i

with pseu opo s pro uces sur ce e br ne reorg niz - (% m g Li s

tion. Intern l contr ction o the pl telet results in rele se o n a Tr (b)

gr nul r contents o the lph n ense gr nules n the

lysoso l contents. T is process rese bles the secretory

ctivities o other cells. Shape change

Pl telets here t sites o ech nic l v scul r injury n (c)

then un ergo ctiv tion n express unction l GP IIb/III

receptors ( lso re erre to s integrin lph bet ) or circu- Time (minutes )
IIb
3
l ting hesive lig n proteins (pri rily f brinogen). T ese FIGURE 25.8 Pl telet ggreg tion stu ies. Pl telet ggreg tion stu -

unction l GP IIb/III receptors e i te the recruit ent o ies involve the ition o gonists (coll gen, thro bin, ADP, r chi-

loc l pl telets by or ing f brinogen bri ges between pl te- onic ci , or epinephrine) to suspension o pl telet-rich pl s
(PRP); the gonist in uces ggreg tion o pl telets n llows tr ns-
lets— process c lle pl telet cohesion. Although unction l ission o light through the pl s co ponent o the PRP. (a) In

GP IIb/III receptors bin with other circul ting hesive the nor l scen rio, the bin ing o n gonist to its pl telet receptor

olecules in pl s (inclu ing vWF, f bronectin, vitronec- initi tes sh pe ch nge th t te por rily ecre ses light tr ns ission;

tin, n thro bospon in), f brinogen is the pre o in nt subsequently, pri ry w ve o pl telet ggreg tion is recor e ( s

lig n bec use o its rel tively high concentr tion. T e pep- incre se light tr ns ission) s f brinogen bin s its receptor, GPIIb/

ti e recognition sequence rginine-glycine- sp rtic ci III , n begins to cross-link pl telets. Unlike the other gonists, col-

present in these i erent hesive olecules e i tes bin - l gen oes not in uce pri ry w ve. A secon ry w ve occurs s

ing with expresse GP IIb/III receptors. Glycoprotein IIb/ sign l tr ns uction events (resulting ro pl telet ctiv tion) eventu-

III is specif c or pl telets. Pl telet recruit ent epen s te in ug ente bin ing o GPIIb/III by f brinogen n rele se o

l ost exclusively on the f n l ph se o glycoprotein IIb/ pl telet gr nules, whose contents re ble to in uce urther ggreg -

III – epen ent pl telet cohesion. Glycoprotein IIb/III is tion. (b) In stor ge pool ise se (SPD), pl telet ggreg tion to ADP
n other gonists typic lly shows n initi l w ve o ggreg tion, but
the ost bun nt pl telet e br ne protein (with pproxi- the ggreg tes subsequently issoci te bec use o re uce or bsent

tely 50,000 receptors per pl telet). rele se o pl telet gr nule contents. Bec use rele se o gr nules is

l rgely epen ent on thro box ne, the spirin e ect pro uces

Platelet Aggregation si il r pl telet ggreg tion prof le to th t o SPD when ADP or epi-
nephrine is use , but stronger gonists such s thro bin n coll -

Observ tion o pl telets by electron icroscopy e on- gen c n circu vent the thro box ne p thw y n pro uce nor l

str tes inhibition o org nelle centr liz tion th t nor lly ggreg tion curve. (c) Bec use o l ck o GP IIb/III expression on the

ollows pl telet sti ul tion by coll gen. Platelet aggrega- pl telet sur ce, pl telets ro p tients with Gl nz nn thro b sthe-

tion ss ys with spirin-tre te pl telets shows ecre se ni show bsent ggreg tion to ll gonists except ristocetin. (Fro

responses to coll gen n n bsence o the secon ry w ve Ro gers GP, Young NS. Bethesda Handbook o Clinical Hematology,

o ggreg tion (Fig. 25.8) th t is nor lly in uce by epi- 3r e , Phil elphi , PA: Lippincott Willi s & Wilkins, 2013.)

nephrine n low concentr tions o ADP, which is re ecte

by rke re uction in the rele se o ( elt ) gr nule ADP, A v riety o gents re c p ble o pro ucing in vitro pl te-

A P, n serotonin. let ggreg tion, n energy- epen ent process. T ese gents

T e r chi onic ci pl telet ggreg tion ss y is the only inclu e p rticul te teri l such s coll gen, proteolytic

pr ctic l w y to onitor the e ects o spirin ther py, now enzy es such s thro bin, n biologic l ines such s

wi ely use to prevent stroke n he rt tt cks. epinephrine n serotonin.

Pl telet ggreg tion is the gol st n r test to eter ine It is believe th t bri ges or e by f brinogen in the

pl telet unction. Pl telet ggreg tion in vivo is uch ore presence o c lciu pro uce sticky sur ce on pl telets.

co plex n yn ic process th n previously thought. Over T is results in ggreg tion. I these ggreg tes re rein orce

the l st ec e, it h s beco e cle r th t pl telet ggreg tion by f brin, they re re erre to s thro bus.

represents ultistep hesion process involving istinct Aggreg tion o pl telets by t le st one p thw y c n

receptors n hesive lig n s, with the contribution o in i- be blocke by subst nces such s prost gl n in E (PGE),

vi u l receptor-lig n inter ctions to the ggreg tion process enosine, n nonsteroi l nti-in tory gents

epen ent on the prev iling bloo ow con itions. Pl telet (e.g., spirin). Aspirin, inclu ing spirin-cont ining pro -

ggreg tion occurs with the en pro uction o thro box ne ucts such s Alk -Seltzer, in uces long-l sting unction l

A . It is now believe th t three istinct ech nis s c n ini- e ect in pl telets. It is clinic lly etect ble s prolong tion
2
ti te pl telet ggreg tion. o blee ing ti e. T e ech nis o spirin ppe rs to be