Page 591 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 575

Heparin Le iru in, a reco binant ro uct, has the sa e antico-

He arin anticoagu ation is the ainstay o i e iate agu ant activity as hiru in, which is ro uce by e ici-

thera y or con itions such as acute u onary e bo is . na eech. T ese rugs act as irect thro bin inhibitors by

He arin has no anticoagu ant activity o its own but acts as b ocking both the active site an the substrate-bin ing site

an anticoagu ant by acce erating the bin ing o antithro bin on the thro bin o ecu e. Le iru in eve s can be oni-

to target enzy es (e.g., thro bin an actor Xa). He arin tore by the AP , ECARIN c otting ti e, or a chro o-

is ter e an antithro bin because it he s to revent new genic assay base on the inhibition o thro bin. T e AP

thro bus or ation an buys ti e or en ogenous brino- is the ost wi e y use etho o onitoring atients. T e

ytic echanis s to yse the c ot. target range or anticoagu ation is 1.5 to 2.5 ti es the base-

He arin can cause b ee ing, thro bocyto enia, an ine AP . A ong the isa vantages o this e ication is

osteo enia. Be ore initiating he arin, atients shou be the nee to onitor atients with a aboratory assay.

screene or c inica evi ence o active b ee ing. T e base ine Argatroban bin s to thro bin irect y an acts as an

aboratory eva uation shou inc u e co ete b oo count anticoagu ant by b ocking the active site on the thro bin

(CBC), ate ets, activate artia thro bo astin ti e, ro- o ecu e. T is rug is onitore by the activate artia

thro bin ti e, stoo ana ysis or occu t b oo , an urine thro bo astin ti e (AP ). T e thera eutic eve is 1.5

i stick or he aturia. to 3.0 greater than the base ine AP . Disa vantages o this

He arin anticoagu ation is use uring ercutaneous e ication inc u e no known inhibitor to reverse the anti-

trans u ina coronary angio asty (P CA) an car io u - coagu ant e ect, the nee or a inistration by continuous

onary by ass (CPB) to revent c ot or ation. intravenous in usion, an the nee or onitoring by abora-

T e activate c otting ti e (AC ) has been use or ore tory assay.

than 25 years to assess the egree o anticoagu ation in he a-

rinize atients. y ica y, AC s are onitore to estab ish Fondaparinux (Arixtra)

a ini u target AC to ensure a equate anticoagu ation. Fon a arinux is a synthetic entasacchari e that acce er-

T e AC was one o the rst coagu ation tests to be o ere ates the bin ing o antithro bin (A ) to activate actor Xa.

at the oint care, or exa e, o erating roo , car iac cath- It has no A activity. A though this rug usua y oes not

eterization, or he o ia ysis, an other interventiona roce- require onitoring, it is reco en e that it be assaye by

ures that require arge oses o he arin. y ica y, the AC a syste base on the inhibition o actor Xa, i onitoring

is easure rior to an i e iate y a er he arinization. is nee e .

Subsequent testing is er or e to ensure that a equate anti-

coagu ation continues or a itiona he arin is a inistere . New Oral Anticoagulants

Low Molecular Weight Heparin In recent years, the new ora anticoagu ants (NOAs) ac-

Low o ecu ar weight he arin (LMWH), a new a i y o tor Xa inhibitors a ixaban (E iquis, P izer an Bristo -

co oun s ro uce by the contro e rag entation o Myers Squibb), thro bin inhibitor abigatran (Pra axa,

he arin, is avai ab e or c inica use. T ese LMWHs (e.g., Boehringer Inge hei ), an actor Xa inhibitor rivaroxa-

tinza arin [Innohe ], a te arin [Frag in], an enoxa arin ban (Xare to, Bayer Hea thcare AG an Janssen Research

[Lovenox]) react with the regu atory rotein A to inhibit & Deve o ent LLC, a Johnson & Johnson Co any),

activate actor X ( actor Xa) but not thro bin ( actor IIa). an actor Xa inhibitor e oxaban have revo utionize

Un ractionate he arin, by contrast, is active against both anticoagu ation thera y. A though the NOAs have i ita-

rocoagu ants. LMWH is ess ca ab e than stan ar he a- tions in ter s o atients who can bene it or the , they

rin to activate resting ate ets so that they re ease ate et have been shown to be e ective or the treat ent an ro-

actor 4, an it bin s ess we to ate et actor 4. T e on y hy axis o V E an or the revention o stroke in atria

acce te etho o onitoring LMWH is by a chro ogenic ibri ation.

assay base on the inhibition o actor Xa. T is etho has Te search to re ace war arin, the anticoagu ant “go

been auto ate in coagu ation instru entation ca ab e o stan ar ,” was triggere because o the i cu ty o stabi iz-

con ucting chro ogenic assays. ing atients in the thera eutic internationa nor a ize ratio

LMWH eaks at about 4 hours a er subcutaneous injec- (INR) range o 2.0 to 3.0. Regu ar onitoring o war arin is

tion. At eak thera eutic eve s, aboratory assay va ues shou require to avoi the risks o both b ee ing ro excee -

be 0.5 to 1.1 IU/ L or atients who receive the rug twice a ing the thera eutic range an un ertreat ent that ay not

ay an 1.0 to 2.0 IU/ L or those receiving one ose a ay. a ow the reso ution o a b oo c otting rob e or ay a ow

c ots to or .
Targeted Anticoagulants In contrast to the uncertainty o war arin, NOAs

ay not require a regu ar aboratory assay to onitor.
Severa rugs are irect thro bin inhibitors. T ese rugs are
Phar aceutica co anies e hasize that it is not neces-

1. Hiru in an e iru in sary to onitor anticoagu ant e ects. However, in stu ies

2. Argatroban with i erent oses o NOAs, the inci ence o c inica y

3. Fon a arinux signi cant b ee ing co ications has been irect y re ate