SECTION 36.12
Case Studies
871
responsible for the throm bosis and the test results? M ea-
surem ents o f antithrombin in the presence and absence o f
heparin are normal. W hat w ould you consider candidate
factors to explain the throm bosis? If both protein C and
protein S were normal, what w ould you suspect? If assays
for the inactivation o f factor V by activated protein C were
norm al, to w hich o f the know n factors in the anticoagulant
subsystem w ould you ascribe his throm bosis?
•
T h e c o m p o n e n ts a re a ll m e n tio n e d in th e ca se.
B e c a u s e o f th e c u r r e n t a tte n tio n o n A P C re sista n c e , it
is a lm o s t c e r ta in ly th a t th is te s t w o u ld b e p e r fo r m e d
fir s t. A n tith r o m b in is in d ic a te d a s b e in g m e a s u r e d fir s t
b e c a u s e o f its s im p lic ity c o m p a r e d to p ro te in C a n d
p r o te in S m e a su re m e n ts. I f th e re is n o A P C re sista n c e ,
th r o m b o m o d u lin d e fe c ts m ig h t b e c o n sid e re d .
Antibiotic-Induced Vitamin K Deficiency
A 4-year-old girl w as brought to the “urgent care”
department o f your hospital after a m inor autom obile ac-
cident in w hich glass shards had caused som e cuts. C on-
tinued bleeding from the cuts w as noted from a pile o f
blood-spotted tissues collected during her 3-h w ait in
the em ergency room ! W hat questions w ould you ask her
and/or her parents about the bleeding? If the parents indi-
cated that she had been receiving high d oses o f antibiotics
for an infection during the last few w eeks, what coagula-
tion test w ould you expect to be abnormal?
•
A h is to r y o f b le e d in g b y th e g irl, p a re n ts, o r o th e r
r e la tiv e s s h o u ld b e e x p lo re d . I f th e re w a s n o b le e d in g ,
g iv e n th e p a ti e n t’s a g e a n d a n y in fo rm a tio n a b o u t
in fe c tio u s d is e a s e s in th e c o m m u n ity , u se o f a n tib io tic s
m ig h t b e in d ic a te d . T h e P T c o u ld b e p r o lo n g e d i f th e
g ir l h a d u s e d a n tib io tic s . T h is is th e re su lt o f th e
a n tib io tic s k illin g th e in te s tin a l b a c te r ia th a t p r o d u c e
v ita m in K fr o m d ie ta r y so u r c e s o f p h y llo q u in o n e s .
Hemophilia
A
young A frican-A m erican m ale patient is brought to
you because o f a hem arthrosis sustained after he tw isted
his knee w hile running. H is PT is norm al, but his A PTT
is 51 s (normal 2 0 -3 2 s). M ixing equal volum es o f the
patient’s plasm a and norm al plasm a shortens the A PTT
to 25 s. Specific factor assays show a norm al factor IX
activity, but a factor VIII activity o f ~ 25 % o f that in pooled
norm al plasm a. W hy w as his PT norm al? W hat else, prior
to the factor IX and VIII assay results, m ight have been
responsible for the prolonged A PTT? •
•
F a c to r V III is n o t in v o lv e d in th e PT, i.e., “e x tr in s ic ,”
p a th w a y . B e fo re th e n o r m a l fa c t o r I X re s u lt w a s
o b ta in e d , fa c t o r X I I d e fic ie n c y m ig h t h a v e c a u s e s a
p r o lo n g e d A P T T . B e c a u s e th e p a tie n t w a s n o t u n d e r
tr e a tm e n t f o r a n y th in g , h e p a r in w o u ld b e u n likely.
Von Willebrand Disease
A 7-year-old boy is brought to you because o f recurrent
nose b leeds and b leeding after m inor injuries associated
with ordinary “horse play.” There is no history o f any type
o f bleeding disorder in the four brothers in the m other’s
fam ily; she is the only girl. T he PT and the A PTT tests
were perform ed and both w ere at the low end (shorter
clotting tim es) o f the normal range. A platelet count w as
done and found to be norm al. W hat hem ostatic system
com ponents m ight be responsible for the bleeding but not
be detectable in the tw o tests for w hich results had been
obtained? W hat test w ould you suggest to com plete the
diagnosis?
•
v o n W ille b ra n d fa c t o r a n d fa c t o r X I I I s h o u ld b e
te ste d . B e c a u s e te s tin g o f fa c t o r X I I I is easier, it m ig h t
b e d o n e first.
Laboratory-Created Artifacts
A plasm a sam ple w as obtained from a fem ale patient
for routine coagulation testing, i.e., there w as no history
o f bleeding. T he PT w as 11.9 s (norm al 1 0 .5 -1 2 .2 s). The
A PTT w as 80 s (normal 2 0 -3 2 s). Sam ple w as sent to
a reference laboratory sp ecializin g in coagulation factor
testing. A t the reference laboratory, the PT w as 1 1 .6 s and
the A PTT w as 43 s. B ecau se o f this discrepancy, blood
w as drawn at the reference laboratory and a new plasm a
sam ple prepared. In a second set o f tests perform ed at the
reference laboratory, the PT w as 10.9 s and the A PTT w as
94 s. W hat m ight account for the discrepancy betw een the
results obtained on the original plasm a sam ple in the tw o
laboratories?
•
I f th e in itia l s a m p le w a s n o t c e n tr ifu g e d a p p r o p r ia te ly
to re m o v e th e p la te le ts , p la te le t fr a g m e n ta tio n a n d
m ic r o p a r tic le fo r m a tio n c o u ld h a v e o c c u r r e d d u r in g
tr a n s p o r t to th e re fe re n c e la b o ra to ry . T h e m e m b r a n e
fr a g m e n ts c o u ld a r tifa c tu a lly s h o r te n th e A P T T .
Acknowledgments
The im ages show n in this chapter are created using
R asM ol 2.6, M olecular G raphics V isualisation Tool by
R oger Sayle, B ioM olecular Structures Group, G laxo
R esearch
&
D evelopm ent,
G reenford,
M iddlesex,
U K . R asM ol can be obtained at http://w w w .um ass.edu/
m icrobio/rasm ol/. T he coordinates w ere obtained from
the Protein Data Bank at Brookhaven N ational Laboratory
