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| Case Studies |
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| Case Study #3: Lupus Anticoagulant
Testing and Heparin |
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| To view Powerpoint presentation click
here. |
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| A 67 year old female with a history of rheumatic heart disease
underwent a porcine mitral valve replacement in 1981. The valve
had to be revised to a mechanical prosthetic valve in 1991 after
which she was placed on chronic warfarin therapy. In 1996, she
was admitted to the Cardiology service for consideration of
tricuspid valve replacement due to progressive valvular regurgitation
resulting in right sided heart failure. |
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| While on warfarin, the APTT was noted to be disproportionately
prolonged for the degree of anticoagulation (Slide 1-data set
1). Warfarin was discontinued and intravenous unfractionated
heparin was initiated in anticipation of cardiac surgery. Four
days later, a plasma sample (Slide 1-data set 2) was submitted
for a work-up of the prolonged PT/APTT. |
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| Interpretation of data from Slide 2 showed that the prolonged
PT corrected with a 1:1 mixing study with normal pooled plasma,
consistent with the patient's known warfarin therapy. However,
a mixing study of the prolonged APTT demonstrated inhibition.
This inhibition could reflect the presence of a specific inhibitor
to a clotting factor such as factor VIII (FVIII) or a non-specific
inhibitor such as a lupus anticoagulant (LAC) or presence of
heparin. Once presence of heparin has been excluded, the next
step in evaluation of an inhibitor would be guided by the patient's
clinical history. If there is a history of a bleeding disorder,
the presence of a specific inhibitor is likely, however an isolated
prolongation in an asymptomatic patient or in a patient with
thrombosis makes a lupus anticoagulant more likely. |
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| Testing for LAC, which included the platelet neutralization
procedure (PNP) and dilute Russell Viper Venom time (DRVVT),
was performed. The PNP resulted in characteristic shortening
which is suggestive a LAC, and the DRVVT was also consistent
with presence of a LAC. However, this data should be interpreted
with caution. |
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| It is critical to exclude the presence of heparin since it
results in a prolonged and inhibited mixing study and a false
positive PNP assay (since APTT reagents do not contain a heparin
neutralizer). Although DRVVT reagents contain a heparin neutralizer,
which can neutralize up to 1 Unit/mL of heparin, false positive
test results are possible. To screen for the presence of heparin,
a thrombin time test was performed and it was prolonged, which
in combination with a normal reptilase time, indicates presence
of heparin. |
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| A second plasma sample was submitted after withholding heparin
infusion for 6 hours (Slide 2). The absence of heparin was confirmed
with the normal thrombin time. The APTT continued to be inhibited
and the results of the PNP and DRVVT were consistent with presence
of a LAC. |
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| The main issue this case raises is the accuracy of LAC test
interpretation in patients on heparin therapy. Although in this
case, the diagnosis of LAC was ultimately confirmed, the testing
of patients while receiving heparin therapy has the potential
to result in false positive LAC test results. In this patient,
confirmation of the LAC was critical given that she was to undergo
cardiopulmonary bypass (CPB) for her valve replacement. |
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| High-dose heparin therapy used for CPB is typically monitored
by activated clotting time (ACT). This is a whole blood clotting
time that uses a strong contact activator, either celite or
kaolin, of the intrinsic coagulation system. As a result, the
test is linearly responsive to the high concentrations of heparin
used during bypass (1-5 U/mL). Because the basic principles
of the APTT and the ACT are similar, there is potential for
the LAC to impact the ACT, thus necessitating use of alternative
assays such as the anti-Xa activity assay. |
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| Submitted by Rajiv K Pruthi, MD, Coagulation Laboratory, Mayo
Clinic-Rochester |
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| E-mail: pruthi.rajiv@mayo.edu |
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