Page 589 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 28 ■ Disorders of Hemostasis and Thrombosis: Blood Coagulation Factors, Hypercoagulable State, and Anticoagulant Therapy 573

PS a ong with a nor a C4b-BP. However, a ecrease in ree/ ro e ective rotein synthesis rather than ro a qua itative

unctiona PS cause by increase synthesis o C4b-BP can abnor a ity. He arin co actor II e ciency can a so be e -

occur transient y uring acute- hase reactions. onstrate in atients with DIC. In these situations, both A

A PS unctiona assay shou be use to screen or a an he arin co actor II eve s are i inishe in ara e .

ty es o PS e ciencies. Antigenic eve s o both ree an

tota or s o rotein, as we as C4b-BP, wi then be eter- Venous Thromboembolism

ine to i erentiate ty es I, II, an III.
Venous thro boe bo is (V E) has an inci ence o

Antithrom bin De ciency 300,000 e iso es er year in the Unite States, an the co -
ication o u onary e bo is causes 5% to 10% o a
Here itary e ects o antithro bin (A ) ay be cause by eaths in the hos ita . Venous thro bosis can resu t ro

quantitative or qua itative e ects. Quantitative e ciency o here itary or acquire actors or both ( ab e 28.15).

A is trans itte as an autoso a o inant isor er. y e Patients with venous thro boe bo is (V E) can be

I (quantitative) e ciencies re resent the ajority o cases. ivi e into two grou s. T e rst grou inc u es atients

Fa i ia stu ies revea that severe thro boe bo ic rob- with a isease such as cancer, a re is osing actor such as

e s usua y begin to be ani este in ate a o escence or recent surgery, or an acquire abnor a ity such as the u us

ear y a u thoo . Mani estations o A e ciency are rare anticoagu ant that is known to increase the risk o thro bo-

in in ancy. Wo en with the e ciency have a uch higher sis. T e atho hysio ogy is oor y un erstoo .

inci ence o thro bosis because regnancy, e ivery, an A secon category consists o atients without the usua

ora contrace tives are causative actors. risk actors that re is ose eo e to venous thro bosis. In

De ects o a qua itative nature (ty e II e ciency) are so e o these atients, it is ossib e to i enti y a e ciency o

o en characterize by ecrease he arin co actor activity. antithro bin, rotein C or rotein S an a i y stu ies show

T is unctiona ani estation o e ective A is not associ-

ate with a re uction in o ecu ar concentration. More than

ha o atients with ty e II e ciency eve o recurrent

ee venous thro bosis. Hypercoagulable States

TABLE 28.15 Associated w ith Venous
Decreased Antithrom bin Levels: Congenital Thrombosis

T e re ative inci ence o congenita antithro bin (A ) e -

ciency is between 1:2,000 an 1:5,000. A e ciency is inher- Hypercoagulable State Comments

ite as an autoso a o inant isor er. Ho ozygotes have Mutation in factor V gene Replaces arginine 506 with

not been re orte in A e ciency. Patients ani est signs glutamine, rendering factor

an sy to s o between 10 an 30 years o age, their rst V resistant to inactivation by

thro botic event. An initia event is s ontaneous in a roxi- activated protein

ate y ha o atients. Wo en requent y ex erience ani- Mutation in protein C gene Associated with protein C

estations uring regnancy or because o ora contrace tive de ciency

use. Decrease eve s o A usua y corre ate with the sever-

ity o venous thro bosis. Arteria thro bosis is a ess co - Protein S de ciency Protein S is a cofactor for

on n ing in A e ciency. protein C.

Antithrombin de ciency Autosomal dominant
Decreased Antithrom bin Levels: Acquired inheritance

Acquire antithro bin (A ) e ciency can be cause by Antiphospholipid Encompasses ACAs and LA;

ecrease synthesis, increase consu tion, or other isor- antibodies associated with venous and

ers; it can a so be rug in uce . T e A e ciency associate arterial thrombosis

isor ers are ecrease synthesis (arteriosc erosis, car io- Elevated concentration Relative risk of venous throm-

vascu ar isease, chronic he atitis, cirrhosis, ty e II iabe- of factor VIII bosis is vefold higher among

tes e itus); increase consu tion (DIC, ho ocystinuria, patients with factor V concen-

ne hrotic syn ro e, osto erative, ost artu , rotein- os- trations greater than 1,500 IU/L.

ing entero athy, u onary e bo is , stroke, thro bo h e-

bitis); rug in uce ( brino ysin, he arin, l -as araginase, ora Frequency in venous

contrace tives); an other isor ers (burns, a ignancies). thrombosis

Protein C, 2%–4%
Heparin Cofactor De ciency
Protein S, 2%–5%
A though e ciency o antithro bin (A ) is the ost co - Antithrombin, 1%–3%

on, recurrent thro botic co ications have been associate

with a e ciency o he arin co actor II. T e atter e ect is Plasminogen, 0.5%–2%

inherite in an autoso a o inant anner. Sy athetic Source: Goldhaber SZ. Deep vein thrombosis and pulmonary embolism. In:

heterozygous atients exhibit about ha the nor a as a Intensive Review of Internal Medicine, Boston, MA: Harvard University,

eve s o he arin co actor II activity. T is e ciency resu ts 1995:75.