Page 560 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

544 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis

screening o resistance to APC in as a ro in ivi ua s Like antigenic rotein C, antigenic rotein S can be ea-

with the actor V (Lei en) e ect. sure by ELISA or Laure techno ogies. More recent y, a

An APC-R ratio o <2.3 suggests abnor a resistance to ra i techno ogy has been eve o e invo ving agg utina-

APC o here itary origin. T e re ortab e range is 1.0–10.0. tion o antibo y-coate icro atex artic es. T is agg utina-

DNA-base testing or the actor V Lei en utation ay be tion is rea s ectro hoto etrica y.

use u in con r ing or exc u ing here itary APC-resistance, Both tota an ree rotein S antigens can be assesse by

a er initia screening with the APC-resistance test. these techniques. T e easure ent o ree (versus tota ) or s

o rotein S is one on 25% o yethy ene g yco –treate as a.
Protein S T e association o C4b-bin ing rotein an rotein S

Protein S is another vita in K– e en ent as a rotein necessitates C4b-bin ing rotein eva uation to exc u e

that is an essentia co actor or APC to ex ress an anticoagu- acquire ree rotein S e ciency. C4b-bin ing rotein

ant e ect. Protein S oes not require roteo ytic o i ca- can be easure by the Laure technique or icro atex

tion to unction but it can be regu ate by roteo ysis. agg utination.

Protein S circu ates to C4b-bin ing rotein (C4b-BP)

in two or s, ree an boun , in a ratio o 40% ree to 60% Cellular Regulators

boun . On y the ree rotein o ecu e su orts the unc-

tiona activity. E evation o C4b-bin ing rotein (which is an Ce u ar activities re ate to thro bosis are beco ing rec-

acute- hase reactant rotein) resu ts in an acquire ecrease ognize as essentia to the aintenance o he ostasis an

o ree rotein S. thro bosis.

Re evant ro erties an unctions o rotein S are su -

arize in ab e 27.5. Basic science research stu ies suggest Cellular Proteases

that ree, unctiona rotein S or s a one-to-one co ex P as a contains, in a ition to as in, another ower u

with APC on synthetic e brane sur aces, which increases echanis to i it the or ation or s rea o c otting an

the a nity o APC or e brane sur aces a roxi ate y the re ique action o c ots. T is echanis consists o the

10- o . cellular proteases erive ro the lysosomes o granu ocytes

Protein S increases the rate o inactivation o actor Va that ay be tra e within a thro bus. T ese roteases

by APC by enhancing the bin ing o APC to hos ho i i s, b ock the activation or action o as in. A ce u ar rotease

thereby sti u ating the inactivation o actor Va. Protein S o articu ar interest is a ha-2 as in inhibitor, which ra -

has been oun within ate ets, suggesting that these ce s i y neutra izes the brino ytic ro erties o as in.

ay a so be res onsib e or i iting coagu ation by the ro-

tein S–enhance inactivation o actors Va an VIIIa by Cells that Regulate Coagulation

APC. Si i ar interactions occurring in vivo ay be oca - Synthesis o b oo coagu ation roteins was once thought to

ize on the sur ace o ate ets, eri hera b oo ce s, an be the o ain o the he atic ce s; however, it is now known

en othe ia ce s. An increase in APC e iate by thro bin that other ce s are ca ab e o synthesizing so e o the coag-

necessitates an increase in rotein S eve s to attain axi- u ation actors an co actors. Monocytes an acro hages

u rotein C activity. have been e onstrate to synthesize actor VII. P ate ets

an en othe ia ce s are now known to be the rinci a
Protein S Testing co onents in the initiation, ro agation, an su ression

T e rinci e o a rotein S unctiona assay is base on the o he ostasis an thro bosis.

co actor activity o rotein S, which enhances the anticoagu- P ate ets store an re ease HMWK, vWF, an actor V, a

ation action o APC. T is enhance ent is ref ecte by the o which are invo ve in c ot or ation. En othe ia ce s are

ro ongation o the c otting ti e o a syste enriche with known to synthesize vWF, actor VIII, actor V, HMWK, an

actor Va, which is a hysio ogica substrate o APC. rotein S.

TABLE 27.5 Protein S Structure, Function, and Regulation

Protein S structure Single chain, Mr = 69,000

Accelerates factor Va and factor VIIIa inactivation by APC (functions as a cofactor)

Vitamin K dependent Yes

Binds to membranes Yes: forms a 1:1 complex with APC on membrane surfaces

Forms in plasma Free and in reversible complex with C4b-binding protein

Regulation Inactivated by thrombin; not active when complexed to C4b-binding protein

From Esmon CT. The Protein C Anticoagulant Pathway, Miami, FL: Baxter Healthcare, 1990.