Page 514 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

498 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis

pri rily, i not exclusively, the per nent in ctiv tion o Antiplatelet Agents

prost gl n in G/H synth se, which c t lyzes the f rst step in

the synthesis o the prost gl n ins, the conversion o r chi- Pl telets re critic l in the process o he ost sis. D ge

on te to prost gl n in H . Re uce or tion o v rious en otheliu ctiv tes pl telets th t respon by hering n
2
eicos noi s (thro box ne A , prost gl n in E , n prost - ggreg ting. Rele se o thro box ne A2 n ADP pli-
2
2
cyclin) in v rious tissues prob bly ccounts or the v riety o f es n prop g tes the process by sti ul ting surroun ing

ph r cologic l e ects o spirin th t or the b sis o its pl telets. T e pro uction o thro bin vi the co gul tion

ther peutic use n its toxicity. c sc e is lso cceler te , st bilizing the thro bus by the

Bec use pl telets l ck the biosynthetic ech nis s conversion o f brinogen to f brin.

nee e to synthesize new protein, the e ect in uce by T e ter , ntipl telet rug, is generic ter , escribing

spirin c nnot be rep ire uring their li e sp n ( pproxi- gents th t ecre se pl telet ggreg tion n inhibit thro -

tely 8 to 10 ys). T ere ore, er tre t ent with spirin bus or tion. Antipl telet rugs re ost e ective or rte-

is stoppe , cyclooxygen se ctivity recovers slowly, s unc- ri l clots th t re co pose l rgely o pl telets. Di erent

tion o pl telet turnover. T is expl ins the pp rent p r ox cl sses o ntipl telet rugs ct t i erent junctures in this

o how rug with 20- inute h l -li e in the syste ic cir- process. T ese rugs re:

cul tion c n be ully e ective s n ntipl telet gent when ■ Aspirin

inistere once ily. ■ Clopi ogrel

Bec use o the per nent n ture o spirin-in uce in c- ■ Pr sugrel

tiv tion o pl telet prost gl n in G/H synth se, the inhibitory ■ Dipyri ole

e ect o repe te ily oses less th n 100 g is cu ul tive. ■ GP IIb/III nt gonists

D ily inistr tion o 30 to 50 g o spirin results in virtu-

lly co plete suppression o pl telet thro box ne biosynthe- Aspirin

sis er 7 to 10 ys. T ese ch nges in pl telet bioche istry re

ssoci te with xi l inhibition o thro box ne- epen- A typic l ex ple o rug-in uce ys unction is the inges-

ent pl telet ggreg tion, n prolong tion o the blee ing tion o spirin. One or two spirin t blets re su cient to

ti e ccounts or the ntithro botic e ects o spirin. exten the blee ing ti e to twice the nor l v lue. T e nti-

Qu lit tive pl telet isor ers c n be ttribute to he- pl telet e ects o spirin re ue to the inhibition o pl telet

sion, ggreg tion, or secretion e ects. Rele se e ects re the unction. T is inhibition is c use by ction s nonselective,

l rgest group o pl telet unction isor ers. T is con ition is irreversible cetyl tion o pl telet cyclooxygen se 1 (COX-1)

c use by bnor lities o sign l tr ns uct se ro e - which c t lyses the pro uction o thro box ne n pros-

br nes, bnor l intern l et bolic p thw ys, or bnor l t gl n ins. T e result is inhibition o thro box ne A
2
rele se ech nis s. synthesis, potent e i tor o pl telet ggreg tion n v so-
constriction. Aspirin-tre te pl telets will here nor lly to

Platelet Plug Consolidation and enu e rteri l seg ents o coll gen-co te sur ces but will

Stabilization il to or thro bi bec use o the inhibition o ggreg tion.

T e per nently nchore pl telet plug requires ition l Clopidogrel

consoli tion n st biliz tion. Fibrinogen, un er the in u- Clopi ogrel is n ADP receptor nt gonist th t co petitively

ence o s ll ounts o thro bin, provi es the b sis or inhibits ADP ro bin ing to pl telet receptors, preventing

this consoli tion n st biliz tion. T is process involves ADP- e i te upregul tion o GP IIb/III receptor, n blocks

the precipit tion o poly erize f brin roun e ch pl telet. plif c tion o pl telet ggreg tion (Fig. 25.9). Clopi ogrel is

T e result is f brin clot th t pro uces n irreversible pl telet the ost co only use P2Y12 pl telet receptor inhibitor.

plug (Box 25.1).

Prasugrel

Pr sugrel is in the s e ily o rugs s clopi ogrel.
BOX 25.1 However, it exhibits ore e cient pl telet inhibition.

Dipyridam ole
Platelet Plug Consolidation and Stabilization
T e ech nis o ction o ipyri ole is not ully un er-

■ V scul r injury exposes suben otheliu n stoo , but it is thought to ct by inhibiting enosine upt ke
v soconstriction into pl telets n re ucing ADP-in uce ggreg tion.

■ pl telet hesion

■ pl telet ggreg tion Glycoprotein IIb/ IIIa Antagonists

■ pl telet plug or tion GP IIb/III nt gonist shoul inhibit pl telet ggreg te

■ consoli tion o pl telets or tion. he rug, bcixi b, w s the origin l GP

■ f brin st biliz tion. IIb/III nt gonist n is onoclon l ntibo y. It h s
ore prolonge ur tion o i p ct co p re to newer