Page 590 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

574 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis

here itary e ects. Activate rotein C- resistance occurs in 3. Anti hos ho i i antibo ies—anticyto as ic antibo ies

about one thir o atients. Preci itating actors or thro - an u us anticoagu ant.

bosis, such as regnancy an the use o ora contrace tives, 4. Hy erho ocysteine ia

are i enti e in 60% o these atients. Activate rotein C-

resistance a ears to be 5 to 10 ti es ore co on than a

e ciency o antithro bin, rotein C or rotein S in atients AN ICOAGULAN HERAPY

with venous thro bosis.
Most c inica aboratories are accusto e to onitoring

Congenital Plasm inogen De ciency atients who are receiving war arin (Cou a in) or he arin

Congenita as inogen e ciency is a rare autoso a reces- anticoagu ant thera y. In a ition to these tra itiona thera-

sive isor er characterize c inica y by chronic ucosa ies, new anticoagu ants are joining the ist o rugs in use.

seu o e branous esions consisting o sube ithe ia brin

e osition an inf a ation. y e I as inogen e ciency Multitargeted Anticoagulants: Traditional

is characterize by ecrease seru as inogen activity, Anticoagulants

ecrease as inogen antigen eve s, an c inica sy to s,

whereas ty e II as inogen e ciency, a so known as “ ys- Vitam in K Antagonist

as inogene ia,” is characterize by ecrease as inogen T e tra itiona ora anticoagu ant use ost co on y

activity with nor a or s ight y re uce antigen eve s. Patients wor wi e is war arin (Cou a in). An a vantage o war a-

with ty e II e ciency are usua y asy to atic. Presu ab y, rin is ow cost.

nor a a ounts o as inogen antigen with ecrease activ- War arin rugs are vita in K antagonists that inter ere

ity, as seen in ty e II, are su cient or nor a woun hea ing. with the nor a synthesis o actors II, VII, IX, an X as we

Te PLG gene irects the creation o the a ount an as Protein C an Protein S. T ese rugs cause inco ete

unction o as inogen. Enzy es ca e as inogen coagu ation because they ack ca ciu -bin ing sites, cannot

activators convert as inogen into as in, which breaks or enzy e substrate co exes, an are unab e to unc-

own brin. Fibrin is the ain rotein invo ve in a b oo tion as rocoagu ants or anticoagu ants.

c ot, thro bus, an is i ortant or woun hea ing. War arin is a natura ro uct an a inistere as a ix-

Congenita as inogen e ciency, cause by uta- ture o the R an S stereoiso ers o the rug. S-war arin is

tions in the PLG gene, is a isor er that resu ts in inf a e three to ve ti es ore otent an inhibitor o the vita in

growths on the ucous e branes, such as the eye i s an K e oxi e re uctase co ex, the target o action, than

the insi e o the outh. R-war arin. T e action o war arin can be inf uence by

rugs an consu tion o vegetab es containing vita in K,
Hyperhom ocysteinem ia such as s inach an ka e an avoca o. T e ost y he atic

Hy erho ocysteine ia re ers to above-nor a concentra- etabo ization via the cytochro e P450 athway see s

tions o as a/seru ho ocysteine. P as a/seru ho o- res onsib e or the irect egree o interaction with oo
cysteine is the su o ho ocysteine an the ho ocysteiny an other e ications o a vita in K antagonist. T is ty e

oiety o the isu es ho ocystine an cysteine-ho ocys- o an un re ictab e res onse requires a syste atic onitor-
teine, whether ree or boun to roteins. ing o the strength o anticoagu ant an a requent change in

Ho ocysteine ia is a so a eature o severa inherite osing.
etabo ic isor ers, inc u ing ho ocystinuria, because o Bio ogica activity is signi cant y ecrease , as revea e

utation in the CBS gene an N- ethy ene tetrahy ro o ate by the rothro bin (P ). T e onset o action o ost war-
re uctase e ciency cause by utation in the M HFR gene. arin erivatives is between 8 an 12 hours. T e axi u

Hy erho ocysteine ia ay be associate with an e ect occurs in a roxi ate y 36 hours, an the uration o
increase risk o atherosc erosis an recurrent arteria an action is a roxi ate y 72 hours.

venous thro bosis usua y in the thir or ourth eca e o T e rothro bin ti e (P ), use to a just the ose o
i e. Ho ocysteine ia/ho ocystinuria an ega ob astic ora anticoagu ants, shou be re orte accor ing to the

ane ia can resu t ro e ects in vita in B12. INR, not the P ratio or the P ex resse in secon s. T e

Laboratory Assessment of Hypercoagulable INR is essentia y a correcte P that a justs or the severa

States ozen assays use in North A erica an Euro e.
Ora anticoagu ant thera y onitoring in atients with

Four ajor areas o c inica testing are avai ab e to eva uate a u us inhibitors has resente rob e s or so e aborato-

atient or hy ercoagu abi ity. T ese categories are ries. T e rothro bin ti e (P ) can be ro onge in atients

with anti hos ho i i antibo y syn ro e or a variety o
1. Natura —Protein C e ciency, Protein S e ciency, actor reasons:
V (Leiden), antithro bin e ciency, an he arin co actor

II e ciency 1. Antibo ies ro uce in this syn ro e are irecte towar
2. Fibrino ysis— as inogen e ciency, oor tissue as- hos ho i i -bin ing roteins inc u ing rothro bin.

inogen activator re ease, excessive as inogen activa- 2. LA or inhibitor inter eres with the hos ho i i in the in
tor inhibitor, an ys brinogene ia vitro assays o P an AP .