Page 567 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 551

Disor ers o b oo coagu ation actors can be grou e into brin or ation. For actor VIII e ciency (hemophilia A)

three categories: an actor IX e ciency (he o hi ia B), between 91% an

99% o the causative utations can be etecte by current
1. De ective ro uction iagnostic etho s. T e abi ity to con uct genetic testing

2. Excessive estruction is i ortant to eter ine carrier status, renata iagnosis,
3. Patho ogica inhibition
an the ike ihoo o inhibitor eve o ent or ana hy axis

to in use coagu ation actor concentrates.

DEFEC IVE PRODUC ION
Hem ophilia A

Vitam in K De ciency Etiology

A con ition o e ective ro uction ay be re ate to a e - He o hi ia has been use as a ara ig or un erstan ing

ciency o vita in K. T e synthesis o vita in K an e en ent the o ecu ar atho ogica rocesses that un er ie here i-

actors can be isru te because o isease or rug thera y tary isease. T e genetic a o he o hi ia A begins with

(e.g., ce ha os orin antibiotics). Vita in K e ciencies are Queen Victoria in Eng an . Fro a stu y o a genetic a

a so encountere in neonates, a absor tion syn ro e, bi iary (Fig. 28.1), it is obvious that genetica y a icte a es su er

obstruction, an atients taking ora anticoagu ants. Vita in ro he o hi ia an e a es unction as carriers.

K e etion eve o s within 2 weeks i both intake an en og- T e c oning o actor VIII aci itate the i enti cation

enous ro uction are e i inate . Factors II, VII, IX, an X are o utations that ea to he o hi ia A, an inherite e -

vita in K e en ent. Factor VII has the shortest ha - i e an ciency o actor VIII coagu ant activity that causes severe

usua y ec ines in the ear y stages o vita in K e etion. A he orrhage. wo ty es o utations o inate the e ects

i e ciency o vita in K ay resent as an asy to atic i enti e so ar: gene e etions an oint utations. Gene

ro ongation o a atient’s rothro bin ti e assay. e etions are associate with severe he o hi ia A in which

no actor VIII circu ates in the b oo . o ate, a roxi ate y
Severe Liver Disease
50 e etion utations in the gene or actor VIII have been
Because the iver is the ri ary site o synthesis o ost characterize at the o ecu ar eve , an 34 in e en ent

coagu ation actors, severe iver isease can cause e ective e etion utations in the actor IX gene have been oun to

ro uction o coagu ation actors. T e iver oes not synthe- be the cause o he o hi ia B. Point utations, in which a

size von Wi ebran ’s actor (VWF), natura anticoagu ants, sing e base in DNA is utate to another base, re resent a

an severa brino ytic roteins. secon ty e o utation that causes he o hi ia.

Liver isease i acts ri ary he ostasis, coagu ation,

an brinolysis. In atients with iver isease, the rothro - Epidemiology

bin ti e is noticeab y ro onge , whereas the activate ar- In ivi ua s with here itary c otting e ects ay be either

tia thro bo astin ti es are variab e. genetica y ho ozygous or heterozygous carriers o the trait.

Conventiona coagu ation tests o not u y ref ect the Te eve o actor activity ranges ro 0% to 25% in ersons

erange ent in he ostasis an o not accurate y re ict the ho ozygous or the trait an ro 15% to 100% in ersons

risk o b ee ing. G oba coagu ation assays (thro bin genera- heterozygous or the trait. De ects o this origin ay resu t

tion, thro boe astogra hy) are nee e to ref ect the interaction. ro the ecrease ro uction o a c otting actor, actor

VIII, or the ro uction o unctiona y inactive o ecu es o
Renal Disease
the c otting actor. He o hi ia A, a sex- inke ho ozygous
Chronic rena ai ure is associate with ate et ys unction isor er ex resse in a es, occurs in 1 in 10,000 a es.

that resu ts in b ee ing. When inactive coagu ation actors

are activate , brin or s an inter eres with rena unction, Signs and Symptoms

such as in disseminated intravascular coagulation (DIC). Severe b ee ing into the joints, he arthrosis, an cerebra

In ne hrotic syn ro e, a con ition o increase rena g o- b ee ing an in arcts are sy to s o actor VIII e ciency.

eru ar er eabi ity, associate with various con itions such as Chronic he arthrosis causes inf a ation that can ea to

syste ic u us erythe atosus (SLE), so e ow o ecu ar weight er anent oss o obi ity. B ee ing into usc es can cause

roteins ass through the e ective g o eru us. Coagu ation nerve co ression injury. Cerebra invo ve ent can ro-

actors II, VII, IX, X, an XII are excrete in the urine. In a i- uce ara ysis, seizures, an co a that can be ra i y ata .

tion, regu atory roteins, protein C an antithro bi, are excrete .

Te oss o regu atory roteins creates a risk o thro bosis. Pathophysiology

C assic he o hi iacs have an intact high– o ecu ar weight
X-Linked Disorders of Secondary Hem ostasis oiety an a e cient ow– o ecu ar weight rocoagu ant

Factor VIII an actor IX e ciencies have an X- inke reces- ortion. T is isor er o rocoagu ant synthesis ex resses
sive attern o inheritance. T ese ost co on X- inke itse by ecrease actor VIII c otting activity in aboratory

isor ers are associate with utations in the genes or ac- assay an a nor a b ee ing ti e. Converse y, severe von
tor VIII an actor IX on the X chro oso e. T ese roteins Wi ebran ’s isease has both a ecrease high– o ecu ar

artici ate as a co actor ( actor VIII) or serine rotease weight ortion an a ecrease ow– o ecu ar weight
( actor IX) in the intrinsic coagu ation athway resu ting in ortion.