Page 583 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 567

rotein. T is utation ren ers actor V resistant to the activ- by other con itions (e.g., u us anticoagu ant, e evate ac-

ity o aPC an in uces a e ect in the natura anticoagu ation tor VIII an brinogen eve s, ora contrace tive use, or

syste . T e overa e ect o this utation is an a teration in regnancy).

the anticoagu ant ro erties o actor V. Another etho o testing or the utation is by a

Factor V, ike thro bin, ossesses both anticoagu ant an i ute Russe ’s vi er veno ti e (DRVV )-base test. T e

rocoagu ant ro erties. T e activate rotein C- e iate DRVV etho avoi s i itations inherent in the activate

c eavages, i er or e on actor V, trans or it into an acti- artia thro bo astin ti e (AP ) base etho , which

vate rotein C co actor (FVac). FVac acts in unison with requires a nor a base ine AP an ay be a ecte by

activate rotein C an rotein S to increase the rate o inac- high concentrations o actor VIII, u us anticoagu ant, an

tivation o actor VIII. anticoagu ant thera y. T e DRW a so e i inates the tech-

In contrast to other coagu o athies, actor V (Lei en) nica require ent o re i ute atient sa es with actor

oses a i e ong risk o ee venous thro bosis with a greater V– e cient as a.

requency o occurrence o thro bi in the ower i bs than

in the chest. Fortunate y, everyone who has the utation Genetic Testing

wi not su er a thro botic event. Heterozygotes have a ow Sing e nuc eoti e o y or his s (SNPs) are ajor contrib-

(a roxi ate y 10%) i eti e risk, but ho ozygotes can utors to genetic variation, co rising a roxi ate y 80%

ex erience a 50- to 100- o increase in risk. o a known o y or his s. T eir ensity in the hu an

geno e is esti ate to be on average 1 er 1,000 base airs.
Prothrom bin Gene Mutation
Activate rotein C-resistant atients ay be con r e or
Prothro bin gene utation (prothrombin 20210a) is the sec- actor V (Leiden) utation by DNA PCR a i cation o a

on ost co on cause o inherite thro bo hi ia in the seg ent o the otentia y a ecte gene. Genera o u ation

Unite States. It is resent in about 2% o Caucasians. About screening is not reco en e . At this oint, the reco en-

one ercent o atients with this rothro bin gene change ations or testing ocus ri ari y on in ivi ua s younger

are ho ozygous, which signi cant y increases u to 50 ti es than age 50 who have a rea y ha an i io athic thro botic

higher risk o thro bosis. event.

Rare y, the rothro bin gene change is inherite a ong Prothrombin 20210a utation ea s to an increase risk

with actor V Leiden. I a atient has a genetic rothro bin o cerebra vascu ar thro bosis. Methy ene tetrahy ro o ate

utation an actor V Leiden, the onset o thro bosis ay re uctase (M HFR) is a rotein that breaks own ho ocys-

be ear ier in i e or ore severe. teine. De ciency o M HFR can cause hy erho ocystein-

e ia. M HFR e ciency ea s to hy erho ocysteine ia
Laboratory Assessm ent
that ay injure the vascu ar en othe iu . It ay ay a ro e
A ane o assays is require to assess hy ercoagu abi ity. in V E.

T e activate rotein C- resistance test is a b oo test that can Tree assays can be er or e si u taneous y by ana yz-

be use to etect actor V Leiden. Functiona screening tests ing geno ic DNA in eri hera b oo ononuc ear ce s

inc u e the o owing: using o y erase chain reaction (PCR).

■ rothro bin ti e (P ) T e three ost co on assays or ere to investigate a

■ Activate an artia thro bo astin ti e (AP ) genetic re is osition to thro bosis are

■ Lu us anticoagu ation (LA) screening 1. Factor V (Leiden)

■ Factor VIII an brinogen ( actor I) assays 2. Prothrombin 20210a mutation

■ aPC assay 3. Methy ene tetrahy ro o ate re uctase enzy e (M HFR)

■ Protein C an Protein S assays

■ d- i er screening test Circulating Inhibitors

In a ition, acute- hase reactants (e.g., C-reactive ro- T ere are three i erent ty es o inhibitors:

tein [CRP]) ay be assaye . 1. Inhibitors irect y against s eci c actors such as actor

ra itiona y, the activate rotein C- resistance assay
VIII
i enti es atient insensitivity to activate rotein C. T e 2. Nons eci c inhibitors such as LAs

assay is base on the activate artia thro bo astin ti e 3. Anticoagu ants such as he arins, on a arinux, abiga-

(AP ) assay with an without reagent activate rotein C. tran, an other irect thro bin inhibitors ( iscusse ater

T e AP in the resence o aPC (CaC /aPC) is ivi e in this cha ter)
2
by the una tere (CaC ) AP to yie a unit ess ratio. A
2
ratio o greater than 2 (a onger c otting ti e) genera y Acquire inhibitors o c otting roteins, a so known as

in icates an una ecte con ition. A ratio o ess than 2 (a circu ating anticoagu ants, inactivate or inhibit the usua

shorter c otting ti e) in icates a otentia actor V (Leiden) rocoagu ant activity o coagu ation actors. Inhibitors are

utation an resistance to aPC. Factor V– e cient as a requent y characterize as s eci c, those irecte against a

ay be a e to the test syste to correct or any existing coagu ation actor, or nons eci c, those irecte against a

actor e ciencies. T e aPC resistance assay ay be a ecte co ex o actors, such as the LA.