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536 PART 7 ■ Principles and Disorders of Hemostasis and Thrombosis
VIII e ciency, an a actor inhibitor, such as a s eci c ac- a visua i age. T e gra h is co uterize , an the rst an
tor VIII inhibitor or u us anticoagu ant. . secon erivatives are a e to the na ot. T e tracing
T e rinci e o the ixing stu y re ies on a 1:1 ixing o against the ti e shou ref ect the who e rocess o c ot or-
oo e nor a as a an atient’s test as a. T is ix- ation an c ot ysis.
ing is one as an i e iate ix an an incubate ix. T e In each o three gra hs, three hases are istinguishe : a
basic rinci e is that the nor a as a contributes a su - recoagu ation hase, a coagu ation hase, an a ostcoagu-
cient concentration o c otting actors to “correct” or a actor ation hase with a set o ara eters.
e ciency. Possib e c inica a ications inc u e
A ixing stu y that corrects the AP is characteristic
o actor e ciency, an a ixing stu y that oes not correct ■ onitoring the course o isse inate intravascu ar coag-
u ation (DIC)
the AP in icates a actor inhibitor. T ere are two ty es o sensitivity to i actor e ciencies (Factors XII, X, IX,
ixing stu ies: the i e iate ix an the incubate ix. ■ VII, V, an II)
In the i e iate ix, the AP is er or e i e iate y otentia y re icting the severity an the rognosis o
a er ixing the atient as a an nor a as a, with- ■ se sis because
out urther incubation. S eci ens with ast-reacting actor
inhibitors wi not correct the i e iate ix. CWA resu ts are ore accurate than stan ar inf a a-
tion assays such as C-reactive rotein an roca citonin.
Specialized Coagulation Testing A though the CWA is inex ensive an easy to er or ,
there are so e isa vantages i e ing its wi e use. Current y
Activated Clotting Tim e there are on y two syste s, which are ab e to assess the ight
Te activated clotting time (AC ) was eve o e in 1966 as trans ittance or absorbance tracings. Disa vantages inc u e
a o i cation o the c assic Lee-White who e b oo c ot- the ossibi ity o a rob e in cases o co ore as a such
ting ti e to onitor coagu ation status an he arinization as in hy erbi irubine ia, hy er i i e ia, or he o ysis. In
in i e iate nee situations. T e AC is a oint-o -care a ition, ata on c inica va i ation are scarce.
who e-b oo c otting test use to onitor high- ose he arin
thera y or treat ent with biva iru in. T e ose o he arin Factor De ciency
or biva iru in require in these settings is beyon the range I a ro onge AP screen is ue to a actor e ciency,
that can be easure with the AP . i e iate ixing with an equa vo u e o nor a as a
y ica y, who e b oo is co ecte into a tube or cartri ge with a roxi ate y 100% o coagu ation actors resent wi
containing a negative y charge articu ate coagu ation acti- re ace the atient’s e cient actor. T e resu t in the AP
vator (e.g., ce ite, kao in, or g ass artic es) an a agnetic stir i e iate ix is shortene or correcte into the re erence
bar, an the ti e taken or the b oo to c ot is then easure . range.
Te re erence va ue or the AC ranges between 70 an 180 Correction o the AP in the ixing stu y suggests a
secon s. During car io u onary by ass surgery, the esire coagu ation actor e ciency either in the intrinsic athway
AC range with he arin ay excee 400 to 500 secon s. T e ( actors VIII, IX, XI, an XII; high- o ecu ar weight kinin-
AC oes not corre ate we with other coagu ation tests.
ogen [HMWK]; or reka ikrein [PK]), or in the co on
athway (a so with a ro onge rothro bin ti e [P ])
Ecarin Clotting Tim e
such as actor II, V, an X.
For the ecarin c otting ti e (EC ), veno ro the De ciency o actors VIII, IX, an XI wi resent with
Echis carinatus snake is use to convert rothro bin to b ee ing. A e ciency o actor XII, or reka ikrein, wi
eizothro bin, a rothro bin inter e iate that is sensi- not increase b ee ing risk but it ight increase the atient’s
tive to inhibition by irect thro bin inhibitors. Ecarin a so thro botic risk. A itiona testing, such as c otting actor
activates the noncarboxy ate rothro bin oun in as a assays, is necessary to iagnose a s eci c actor e ciency.
o war arin-treate atients. T is assay is insensitive to he - I the rothro bin ti e P is nor a , this suggests an
arin. T ere ore, eve s o irect thro bin inhibitors can be intrinsic athway e ciency (VIII, IX, XI, XII, PK, HMWK).
assaye even when a atient is receiving conco itant war- I the P is ro onge , this suggests a co on athway e -
arin treat ent. ciency ( brinogen, II, V, X).
A chro ogenic variant o this assay has a so been eve -
o e in which ecarin is a e to a as a s eci en an Inhibitors
eizothro bin generation is easure with a chro ogenic
substrate. A though the EC has been use in research, the T ere are three i erent ty es o inhibitors:
assay has yet to be stan ar ize an is not wi e y avai ab e. 1. S eci c actor inhibitors irect y against s eci c actors
such as actor VIII or actor V inhibitors
Clot Waveform Analysis 2. Nons eci c inhibitors such as u us anticoagu ant (LA). s
Princi a y c ot wave or ana ysis (CWA) is base on the tra- 3. Anticoagu ants such as he arins, on a arinux, abiga-
itiona AP assay. T is gra h otte over ti e ro uces tran, an other irect thro bin inhibitors

