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538 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis
3. Factor VIII antibo ies in he o hi iacs. An ELISA tech- assays, i uno ogica assays, an the o i e thro bin
nique that uses the bin ing o antibo ies in the as a to ti e. . T e nor a va ue o 200 to 400 g/ L ay be
so i - hase antigen, which is subsequent y etecte by a ecrease in iver isease or the consu tion o brinogen
hu an o yc ona IgG abe e with the a ka ine hos ha- owing to acce erate intravascu ar c otting. Fibrinogen titers
tase- -nitro heny hos hate substrate syste . ay be use u . T e nor a titer o brinogen is 1:128 to
1:256; a titer ess than 1:64 is abnor a .
NOTE: This is a good time to complete Review Questions Throm bin Tim e
related to the preceding content.
T e thro bin ti e shou be easure in s eci ens
with a ro onge AP . I the is ro onge , a he arin
New Thromboplastins assay (anti-Xa inhibition assay; by a chro ogenic assay,
that can istinguish a he arin e ect ro a irect thro bin
T e new ty es o thro bo astins or easuring the ro- inhibitor can be use .
thro bin (P ) are ixtures o hos ho i i s an reco bi- T e test eter ines the rate o thro bin-in uce
nant y erive hu an tissue actor. ( F). Because the new c eavage o brinogen to brin ono ers an the subse-
thro bo astins are ore sensitive (ty ica ISI, 1.0) than quent o y erization o hy rogen-bon e brin o y ers
the tra itiona North A erican ones (ISIs, 1.8 to 3.0), the to or an inso ub e brin c ot. T e nor a va ue is ess than
P s or atients with inherite or acquire e ciencies o 20 secon s. Pro onge resu ts wi be seen i the brinogen
coagu ation actors wi be uch ore ro onge with use o concentration is ess than 100 g/ L. Abnor a resu ts wi
the new reagents, a though nor a va ues ay change ini- a so be encountere in the resence o thro bin inhibitors
a y. However, the thera eutic range (in secon s) o the or substances that inter ere with brin or ation (e.g., he a-
P s in atients receiving ora y a inistere anticoagu ant rin, brin egra ation ro ucts), or high concentrations
agents is wi er with the sensitive thro bo astins than with o i unog obu ins that inter ere with brin ono er
the tra itiona ones. T e INR, however, wi be the sa e, o y erization such as in cases o u ti e ye o a.
as wi the reco en e ranges o the INR or intensity o
anticoagu ation. Reptilase Tim e
Reco binant thro bo astin has the o owing T is assay is si i ar to the thro bin ti e . T e i er-
a vantages: ence is that the c otting sequence is initiate with the snake
1. It is a e ro a hu an rotein, not ro the rotein o veno enzy e, re ti ase, which is thro bin- ike in nature
a i erent s ecies. an hy ro yzes brino e ti e A ro the intact brino-
2. T e ateria is ure, an the concentration can be rea i y gen o ecu e. In contrast to thro bin, which hy ro yzes
a juste , un ike current y avai ab e rabbit brain thro bo- brino e ti e A an B ro brinogen, re ti ase is not
astins. A just ent wi ini ize variation between i - inhibite by he arin. T is assay is use to screen or ys-
erent ots o the reagent; thus, the nor a an thera eutic brinogene ia, a coagu ation isor er cause by a vari-
ranges o the P wi re ain the sa e. ety o acquire or inherite structura abnor a ities in the
3. T e reagent is ree o conta ination with noxious viruses brinogen o ecu e. In the inherite or , a i y e bers
because it is a reco binant ro uct. wi exhibit assay abnor a ities. In co arison, atients
4. When the ISI is a roxi ate y 1.0, the P s wi be the with the acquire or o ys brinogene ia wi not have
sa e as those obtaine with use o the Wor Hea th a ecte a i y e bers an wi exhibit abnor a iver
Organization re erence thro bo astin. T ere ore, the P unction tests.
ratio (P o atient/ ean nor a P ) wi be the sa e as
the INR. D-Dim er Testing
5. T e new reagents are ore sensitive to i e ciencies Te D-dimer (Fig. 27.6) is a s eci c rag ent generate ro
o coagu ation actors than are the tra itiona thro bo- two cross- inke brin o ecu es a er a c ot has or e . For
astins. Patients with he ostatica y a equate eve s o d- i ers to be or e , three ajor he ostatic stages ust
coagu ation actors II, V, VII, or X (30% to 40% o ean be unctioning:
nor a activity) wi have INRs o 1.4 or ess. 1. Coagu ation to or the c ot
2. Cova ent cross- inking o brin by activate actor XIII
Assays for Fibrin Formation 3. Fibrino ysis to isso ve the ibrin c ot into s a er
Fibrinogen Levels rag ent
Fibrinogen assays are use u in etecting e ciencies o A three o these stages require a equate or ation o
brinogen an a terations in the conversion o brinogen thro bin. Fo owing the or ation o a c ot, the brino ytic
to brin. Fibrinogen can be quantitate by various eth- syste is activate to regu ate as in or ation. P as in
o s inc u ing reci itation or enaturation etho s, tur- egra es the brin c ot into s a er s eci c brin rag-
bi i etric or brin c ot ensity etho , coagu ab e rotein ents o which so e or a contain the d- i er e ito e. On

