Page 592 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

576 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis

TABLE 28.16 Comparative Properties of Warfarin, Dabigatran, Rivaroxaban, and Apixaban

Warfarin Dabigatran Rivaroxaban Apixaban

Target Vitamin K Factor Iia (free and Factor Xa Factor Xa

Epoxide reductase clot-bound thrombin)

Half-life (hours) 40 14–17 5–9 10–14

Peak effect (hours) 72–96 2 2–4 3–4

Antidote Vitamin K None None None

Source: Modi ed from Mayo Clinic Proceedings, 88(5):495–511, May 2013.

to the ose o NOA. T era eutic excesses can increase the i act the b oo coagu ation casca e at two i erent eve s.

risk o b ee ing an thera eutic i itations can increase Rivaroxaban an a ixaban inhibit activate actor Xa an

thro botic risk, es ecia y when short-acting NOAs abigatran is a irect thro bin inhibitor. In ose- n ing

are use . stu ies with gra e oses o NOAs active by this route, the

inci ence o c inica y signi cant b ee ing co ications was
Advantages and Lim itations of Warfarin Versus irect y re ate to the ose.

NOAs Dabigatran etexi ate is the ro uct o abigatran that

War arin has been the on y ora anticoagu ants or the treat- reversib y inhibits the thro bin active sites o both ree

ent o V E or eca es. T e ajor i itations o treat ent thro bin an thro bin boun to brin. About 80% is

with war arin are a narrow thera eutic win ow, that is, INR, excrete unchange by the ki ney so its a inistration is

an the s ow onset o e ects an o set o action. contrain icate in atients with rena ai ure. In contrast,

Te Unite States Fe era Drug A inistration (FDA) has rivaroxaban is a s a o ecu e with irect inhibitory activ-

a rove a ixaban, abigatran, an rivaroxaban, an these ity on activate actor X. It is ra i y absorbe an has a

are a inistere as a xe ora ai y ose to a atients an high bioavai abi ity, is a inistere once ai y, an has

see to share so e a vantages. T e attractiveness o NOAs a very short ha - i e o 5 to 9 hours in hea thy vo unteers

is a re ictabe e ect without the nee or onitoring, ewer ( ab e 28.16) but is signi cant y higher in the e er y at 9 to

oo an rug interactions, shorter as a ha - i e, an an 13 hours. E i ination by u ti e routes is via the he atic

i rove e cacy-sa ety ratio. etabo is by cytochro e P450 3A4.

NOAs are ab e to overco e so e o the shortco ings o

war arin, such as s ow onset o action, variab e har aco- Laboratory Assays

ogic e ects, oo - rug interactions, an the nee or c ose NOAs o not easure the concentration o the rug

onitoring. NOAs co are avorab y with war arin or irect y, but ana yze their i act on the coagu ation cas-

stroke revention in atients with atria bri ation. NOAs ca e. NOAs can be re orte as coagu ation ti e or as the

signi cant y re uce stroke or syste ic e bo ic events by coagu ation ti e ex resse as a concentration o the cir-

19% co are with war arin ain y riven by a re uction cu ating NOA concentration. T e re erre re orting o

in he orrhagic stroke. Low- ose NOA regi ens show si i- resu ts is the concentration o the rug. T e coagu ation

ar overa re uctions in stroke or syste ic e bo ic event to assays that are use to onitor he arin erivatives or vita-

war arin an a ore avorab e b ee ing ro e but signi - in K antagonists ay not a ways accurate y ref ect the

cant y ore ische ic strokes. anticoagu ant activity o the NOAs, an s ecia ize assays

T e i itations o NOAs inc u e high cost; a ack o s e- ay be nee e ( ab e 28.17).

ci c anti otes, i nee e in an e ergency; an the ack o With rivaroxaban, the P is a ecte in a concentration-

ong-ter sa ety ata. NOA shou be avoi e in regnancy, e en ent anner. T ro bin generation as easure by the

atients with echanica heart va ves, an atients with en ogenous thro bin otentia ecreases with rivaroxaban.

severe rena insu ciency. A ajor isa vantage o NOAs For abigatran, the activate artia thro bo astin ti e

is the absence o an anti ote in case o serious b ee ing or (AP ) is chosen, a though the ose-res onse curve is not

when e ergency intervention nee s i e iate correction inear an resu ts vary er reagent. T e E P ag ti e was a so

o coagu ation. use because it is the ara eter o the en ogenous thro bin

otentia that is inf uence ost by abigatran. A uch ore
Characteristics of NOAs recise onitoring etho or abigatran than the AP is

In contrast to vita in K antagonists that re uce the unc- the thro bin c otting ti e ( ), but the assay can be too

tiona eve s o severa coagu ation actors, the NOAs sensitive. A though the is ays a inear ose-res onse