Taken together, these
findings might indicate
that some patients are
being unnecessarily
overtreated. The other
important implication
is that patients do not
have to have extremely
low levels of leukaemia
on very sensitive tests to
safely try reducing their
dose of tyrosine kinase
inhibitor.
>19
Large percentage
of patients who
reached target second-
maintenance-dose
antithrombin-III
level achieved complete
response. Additional
treatment strategies may
be needed, however, for
patients who do not
reach the target second-
maintenance-dose
antithrombin-III level
with their current
antithrombin-III dosage.
>20
The findings will
help inform the first
guidelines on how to
use and select central
venous lines in children
and when anticoagulants
might be recommended
to prevent blood clots.
>21
Handheld device offers rapid,
comprehensive assessment of blood clotting
W
ith less than a drop of blood, a
prototype for ClotChip, a port-
able, disposable sensor provides
a complete report on a patient’s coagula-
tion status in less than 15 minutes, finds
a comparative study of ClotChip versus
conventional coagulation evaluations.
Evi X. Stavrou, MD, of Case Western Re-
serve School of Medicine, Cleveland, Ohio,
explained that the miniaturised microfluidic
dielectric sensor provides for point-of-care
assessment of blood coagulation. Such
results are now obtainable only with spe-
cialised laboratory testing.
Accurate information about coagulation
status is associated with better survival.
Early identification of coagulopathy carries
crucial clinical implications in the man-
agement of patients who are critically ill,
severely injured, or taking anticoagulation
therapy. Conventional laboratory-based
coagulation tests are time-consuming,
labour-intensive, and costly. Available
point-of-care devices are intended for use
in specific patient populations (those taking
warfarin). Measurements are insensitive
due to interference from the device surface.
A low-cost, easy-to-use, portable platform
is needed for point-of-care assessment of
the complete haemostatic process outside
of the laboratory setting.
The device has the potential for use in
health-care settings that lack easy access
to specialised laboratory testing. Unlike
standard blood coagulation and platelet
testing procedures that use specially trained
personnel, large machines, and collected
blood samples, ClotChip uses dielectric
spectroscopy to detect markers of coagu-
lation activity in real time.
Dr Stavrou and colleagues measured
coagulation in whole blood from healthy
volunteers (n=10) collected in 3.2% sodium
citrate. Coagulation was induced with cal-
cium chloride. ClotChip curves exhibited
a reproducible rise to peak within 4.5 to
6 minutes. Conventional coagulation tests
were also performed in each of the healthy
samples in duplicate and confirmed normal
activated partial thromboplastin time and
partial thromboplastin values.
ClotChip measurements were then per-
formed in seven clinical samples obtained
from patients with coagulopathy. These
patients were referred to a specialised
haematology clinic for workup of coagu-
lopathy. Four patients suffered from intrin-
sic pathway defects (two, haemophilia A;
three, haemophilia B); one, acquired von
Willebrand factor defect; and one, mild
congenital hypodysfibrinogenemia.
Compared to the normal curve, all samples
from patients with coagulopathy exhibited
an abnormal curve with an extended rise to
peak [range 7 to 15 minutes (P = 0.0004)].
A receiver operating characteristic curve
was generated, and the true positive rate
plotted against the false–positive rate.
The area under the curve for ClotChip
(1.00) was higher than those of both acti-
vated partial thromboplastin time (0.7813)
and partial thromboplastin time (0.5859),
illustrating that the ClotChip rise-to-peak
parameter exhibits superior sensitivity than
conventional screening coagulation tests.
Next, ClotChip measurements were per-
formed with whole blood from four healthy
donors after the samples were treated with
1 µM prostaglandin E2 to inhibit platelet
aggregation.
Dr Stavrou determined that prostaglandin
E2-treated samples exhibited a statistically
significant (P = 0.03) lower peak height than
that of untreated samples while rise-to-peak
values remained unchanged between treat-
ed and untreated samples. This showed that
the lower peak height parameter was sen-
sitive in response to platelet function and
that ClotChip was able to detect platelet
function defects.
Dr Stavrou said that ClotChip showed a
higher degree of sensitivity than convention-
al diagnostic tests for coagulation defects.
Compared to conventional tests, ClotChip
reduced the rate of false-negative results.
ClotChip is sensitive to multiple coagu-
lation factors and platelet activity, there-
by allowing whole blood assessment of
hemostasis in a single disposable sensor.
The ClotChip will bring blood coagulation
testing closer to the patient for time-sensi-
tive applications such as diagnosis of the
bleeding patient and in trauma-induced
coagulopathy.
“Our device gives you different informa-
tion – and more information – than other
devices out there,” Dr Stavrou said. “The
sensitivity and discriminatory ability of the
device compared to standard coagulation
tests is what excites me.”
Dr Stavrou and coinvestigators are recruit-
ing volunteers to participate in an expanded
round of testing. The team is also working
to optimise the device’s construction to
enhance its sensitivity.
PracticeUpdate Editorial Team
ASH 2016
11
VOL. 2 • NO. 1 • 2017