Page 571 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 555

Characteristics of Various Types of von Willebrand’s
TABLE 28.4
Disease

Feature Type I Type IIA Type IIB Platelet Type IIC Type III

Platelet count N N N or ↓ Low N or ↓ N N

Bleeding time ↑ or N ↑ ↑ ↑ ↑ ↑

Factor VIII:C N or ↓ N or ↓ N or ↓ N or ↓ N N

vWF:Ag ↓ N or ↓ N or ↓ N or ↓ N

vWF:RCoF ↓ ↓ N or ↓ N or ↓

RIPA N or ↓ ↓ or absent ↑ ↑ ↓ Absent

vWF, von Willebrand’s factor; vWF:RCoF, ristocetin cofactor; RIPA, ristocetin-induced platelet aggregation;
N, normal.

vWF circu ates in the b oo in two istinct co art- Qua itative or quantitative abnor a ities o vWF resu t in

ents, with two ty es o ce s being res onsib e or vWF ro- ecrease a hesion an are res onsib e or the b ee ing

uction. Vascu ar en othe iu is the ri ary source o the associate with von Wi ebran ’s isease.

synthesis an re ease o as a vWF; the other ty e o ce T e signi cance o vWF in the regu ation o VIII:C

that synthesizes vWF is the egakaryocyte. A roxi ate y re ains unc ear. T e increase in VIII:C o owing in usion o

15% o circu ating vWF is ro uce in the egakaryocyte. uri e vWF suggests a ossib e ro e o vWF in the synthe-

vWF circu ates in ate ets, being store ri ari y in the sis, re ease, or stabi ization o VIII:Ag. T ere ore, ecrease

a ha granu es, in association with actor VIII rocoagu ant eve s o vWF ay ro ong the rate o b oo c otting.

rotein (VIII:Ag). P ate et vWF is re ease ro the a ha

granu es by various agonists an subsequent y rebin s to the Clinical Signs and Sym ptom s

GP IIb/IIIa co ex. T e site synthesis o VIII:Ag re ains Te severity o sy to s a ong atients with von Wi ebran ’s

unknown, a though the iver is thought to ay an i ortant isease varies great y. Severe cases are not easi y istinguish-

ro e. ab e c inica y ro severe he o hi ia A, in which b ee ing

vWF is a arge, a hesive, u ti eric GP resent in occurs into the joints an ascia anes. Characteristica y, in

as a, ate ets, an suben othe iu . It is synthesize as atients with von Wi ebran ’s isease, the b ee ing is uco-

a arge recursor that consists o a signa e ti e, a ro e - sa in origin, with e istaxis, enorrhagia, an gastrointestina

ti e (von Wi ebran ’s antigen II), an the vWF subunit. It b ee ing being the ost co on. B ee ing associate with

has the two ain unctions o regu ating coagu ant activity surgica roce ures an ora surgery is a articu ar rob e .

(VIII:C) an ai ing in a hesion o ate ets to suben othe- Ho ozygous atients ay ex erience severe b ee ing, inc u -

ia ce wa s o owing vesse a age. In circu ating b oo , ing he arthrosis, or otentia y etha gastrointestina tract or

vWF is art o a noncova ent bi o ecu ar co ex with the centra nervous syste he orrhage.

actor VIII rocoagu ant rotein. T is co ex stabi izes

actor VIII an rotects it ro ra i re ova ro the cir- Inherited Classi cation of von Willebrand’s Disease

cu ation. T e vWF ortion re resents ore than 95% o the y e I is the ost co on variant o von Wi ebran ’s is-

ass o the co ex an there ore contro s the o ecu ar ease an a ears to be base on a quantitative e ciency o

stereoche istry. T e vWF consists o re eating u ti ers, vWF. It is ex resse as an autoso a o inant trait an is re-

with the s a est circu ating u ti er thought to be a i er su e to be cause by an inheritance o one nor a an one

or tetra er. e cient a e e. Patients with severe ty e III isease ay have

Circu ating vWF un ergoes roteo ytic c eavage un er ho ozygous ty e I (or co oun heterozygous) isease. T e

hysio ogica con itions; thus, it can be istinguishe ro o ecu ar basis or ty e I an ty e III isease is unc ear but is

ate et vWF, which is not roteo yze . T e athogenesis o characterize by ecrease circu ating eve s o vWF. Factor

von Wi ebran ’s isease is base on quantitative or qua ita- VIII:C is ecrease ro ortiona y with res ect to vWF.

tive abnor a ities, or both, o vWF. When an abnor a ity Most atients with von Wi ebran ’s isease (50% or

is resent, the ecrease actor VIII rocoagu ant activity is ore) have quantitative abnor a ities an no evi ence

attributab e to the re uce concentration o vWF. o a unctiona abnor a ity o vWF, which corres on s to

vWF is essentia in rovi ing the basis or or ation o a ty e I von Wi ebran ’s isease an its subty es. T e genetic

nor a ate et thro bus. vWF bin s to s eci c sites on the trans ission o the isease is o inant, exce t ossib y or

ate et, na e y, GP Ib an GP IIb/IIIa, whi e concurrent y subty e I-3. Most atients have ow as a eve s o vWF

bin ing to the suben othe iu o a age vesse wa s, antigen (usua y between 5% an 30% o nor a ) an corre-

or ing a bri ge. Patients with ecrease eve s o vWF, s on ing y ow eve s o ristocetin co actor activity (the assay

es ecia y the arger u ti eric or s, wi ack a equate ref ects the ro erty o vWF to bin to GP Ib an e iate

bri ging action that ro uces ro onge b ee ing ti es. ate et agg utination). T e actor VIII rocoagu ant rotein