Page 551 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 27 ■ Principles of Hemostasis and Thrombosis: Blood Coagulation Factors and Natural Coagulant Systems 535

atients e onstrate increase rothro bin activity. T ere 3.0 or the uration o anticoagu ation. Perio s o treat ent

is no screening test or this utation, but it can be investi- have a so engthene : rst-ti e DV atients are treate or

gate using o ecu ar techniques i c inica signs an sy - 3 to 6 onths an rst-ti e PE atients are treate or 6 to

to s are suggestive o a e ect. 12 onths with war arin. Anticoagu ation is ca e treat-

ent, but it rea y constitutes secon ary revention o recur-
International Norm alized Ratio rent PE.

Because thro bo astins are ro uce using i erent eth- T ree regi ens are current y use or ora anticoagu ant

o s an ro i erent sources, the sensitivity o an in ivi - thera y: ow-intensity, xe - ose thera y (usua y 1.0 to 2.0

ua thro bo astin to another can vary great y between an g/ ); o erate-intensity thera y (P ratio, a roxi ate y

within ots. Variance can even occur within a sing e batch 1.3 to 1.5; INR, 2.0 to 3.0); an high-intensity thera y (P

e en ing on she ti e o the reagent. T e ore sensitive ratio, a roxi ate y 1.5 to 1.8; INR, 2.5 to 3.5). INR is use

the thro bo astin reagent, the onger the resu ting ro- on y or atients receiving stab e, ora y a inistere anti-

thro bin (P ); the ess sensitive the reagent, the shorter the coagu ant thera y. It oes not substantia y contribute to the

resu ting P . iagnosis or the treat ent o atients whose P is ro onge

o he stan ar ize the i erence in sensitivity in in i- or other reasons.

vi ua thro bo astin reagents an the e ect on P assays, So e atients o not res on to war arin. As a resu t,

two a roaches have been eve o e to stan ar ize resu ts. their INR oes not change as the osage is increase . A

T e rst was the Internationa Sensitivity In ex (ISI) an the he atic cytochro e P450 is centra to etabo is o rug

secon was the Internationa Nor a ize Ratio INR. T e o ecu es resu ting in c inica i ications.

INR was eve o e to incor orate the ISI va ues an atte t

to ake rothro bin resu ts uni or y useab e. The Activated Partial Throm boplastin Tim e (APTT)

T e ISI is a ca ibration ara eter that e nes the Te activated partial thromboplastin time (APTT) is one o the

res onsiveness o the reagent re ative to a Wor Hea th ost co on y use screening tests to investigate b ee ing

Organization (WHO) Internationa Re erence Pre aration, atients, onitor anticoagu ant thera y, an as a reo era-

which by e nition has an ISI o 1.0. A anu acturer assigns tive screening. A ro onge AP can be cause by a coagu-

an ISI to each co ercia batch o reagent a er co aring ation actor e ciency or the resence o an inhibitor.

each batch to a “working re erence” reagent re aration. T is T e AP easures the integrity o the intrinsic an co -

working re erence has been ca ibrate against internationa y on athways o the coagu ation casca e. T e AP roce-

acce te stan ar re erence re arations that have an ISI ure easures the ti e require to generate thro bin an

va ue o 1.0. T eoretica y, the ore sensitive thro bo astin brin o y ers via the intrinsic an co on athways. In

has ISI ess than 1.0, an ess sensitive reagents have an in ex the AP assay, ca ciu ions an hos ho i i s that substi-

that is greater than 1.0. T e ISI va ue is critica or ca cu ation tute or ate et hos ho i i s are a e to b oo as a. In

o the INR, because the ISI va ue is the ex onent in the or- vitro, the activation o actor XII to XIIa, reka ikrein to ka -

u a. S a errors in the ISI va ue ay a ect the ca cu ate ikrein, an actor XI to XIa occurs on the negative y charge

INR substantia y. g ass sur ace. T e generation o brin is the en oint.

INR use has been reco en e or onitoring ora anti- Te AP assay ref ects the activity o reka ikrein,

coagu ant thera y. It is i ortant to e hasize that the INR HMWK, an actors XII, XI, IX, VIII, X, V, II, an I. AP

is not a new aboratory test. It is si y a athe atica ca - ay be ro onge because o a actor ecrease, such as brin-

cu ation that corrects or the variabi ity in P resu ts cause ogen ( actor I), or the resence o circu ating anticoagu ants.

by variab e sensitivities (ISI) o the thro bo astin agents T e re erence range or AP is ess than 35 secon s

use by aboratories. ( e en ing on the activator use ). I an AP is ro onge ,

a ixing stu y is use to investigate the cause o the ro-
ISI
P atient onge AP resu t. T e ixing stu y shou inc u e an
INR
ean nor a P AP i e iate Mix an AP incubate Mix. In a i-

tion, a thro bin ti e an he arin anti-Xa assay shou be

P R ( rothro bin ti e ratio) is the atient’s observe P consi ere in o ow-u .

(in secon s) ivi e by each aboratory’s ca cu ate ean Other s ecia ize or c assic roce ures inc u e activate

nor a P (in secon s). A target INR range o 2.0 to 3.0 is c otting ti e, Escarin c otting ti e, c ot wave or ana y-

reco en e or ost in ications (e.g., treat ent or ro- sis, brin s it ro ucts test, mixing study, s eci c actor

hy axis o ee venous thro bosis [DV ], or revention assays, an the various tests or inhibitors an circu ating

o urther c otting in atients who have ha a yocar ia anticoagu ants.

in arction). An INR o 2.5 to 3.5 is reco en e or atients

with rosthetic heart va ves. When the INR is use to gui e Mixing Study

anticoagu ant thera y, there are ewer b ee ing events. T ere A ixing stu y can be use in the case o a ro onge AP .

is a so a tren towar ewer thro boe bo ic co ications. A ixing stu y is a co on coagu ation test use to istin-

T e target INR or u onary e bo is (PE) treat ent is guish between a coagu ation actor e ciency, such as actor