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| Case Studies |
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| Case Study #2: DVT and Argatroban |
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| To view Powerpoint presentation click
here. |
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| A 77-year-old woman was admitted to the hospital with deep
vein thrombosis (DVT). The patient had recently been diagnosed
with heparin-induced thrombocytopenia (HIT) and as a result
was now treated with argatroban anticoagulation instead of heparin.
In order to ascertain the cause of the patient’s thrombophilia,
the following laboratory tests were performed. Before concluding
that the cause of this patient’s thrombophilia is a lupus anticoagulant
(prolonging PT, APTT and mixing studies, and likewise interfering
with Factor VIII, functional Protein S, and Activated Protein
C Resistance assays) what other consideration could explain
these findings? |
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| Argatroban acts as an anticoagulant by inhibiting thrombin
(Factor IIa), therefore it can affect virtually any clot-based
assay, including the PT, APTT, Activated Clotting Time (ACT),
and thrombin time. Because argatroban is a direct thrombin inhibitor,
it acts like an inhibitor in clotting-time assays. For example,
the PT and APTT remain prolonged in mixing studies. With PT-
or APTT-based factor assays, argatroban produces falsely low
values at lower dilutions, and values increase toward normal
in the higher dilutions (ie. an inhibitor pattern). Protein
C and Protein S PT- or APTT-based assays can be profoundly affected.
Chromogenic assays (chromogenic Protein C) that do not involve
Factor IIa are not affected. In Antithrombin III chromogenic
assays that are Factor IIa-based, the Antithrombin III level
is overestimated in the presence of argatroban. In the present
case study, the observed Antithrombin III level is likely to
be an overestimate of the true value by about 10-20%. Lupus
anticoagulant assays can be false-positive in the presence of
argatroban. In the present case, the screening assay (Dilute
Phospholipid APTT [PTT-LA]) is false-positive, because argatroban
prolongs the clotting time and acts like an inhibitor in the
PTT-LA mixing study. The confirmatory assay (Hexagonal Phospholipid
[Staclot-LA]) is false-positive because argatroban prolonged
the clotting time so substantially that after addition of phospholipid,
the resulting APTT shortened by 10.9 seconds presumably due
to increased variability of the assay in this high range. In
contrast to the above noted effects on clot-based assays, argatroban
does not affect the reptilase time (clot-based) or DNA-based
assays. Presumably it would not affect immunoassays or homocysteine
assays. |
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| A laboratory test that may help confirm your suspicion that
a specimen contains argatroban is the Thrombin Time, which is
typically substantially prolonged when therapeutic argatroban
levels are present. This is particularly useful if the presence
of heparin has been excluded, for example, with the use of heparinase
(removes heparin if present). |
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| The points raised in this Case Study also apply to specimens
containing hirudin, another thrombin inhibitor that is used
as an anticoagulant in HIT-positive patients. In summary, it
is important to keep in mind that these two new anticoagulants
can interfere with clot-based assays, potentially leading to
misdiagnoses from misinterpretation of coagulation test results. |
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| Submitted by Elizabeth Van Cott, MD, Director, Coagulation
Laboratory, Massachusetts General Hospital |
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| E-mail: evancott@partners.org
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