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| Case Studies |
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| Case Study #1: Acquired FVIII Inhibitor |
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| To view Powerpoint presentation click
here. |
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| A 61-year-old man with emphysema and cancer of the head and
neck was admitted to the hospital with ecchymoses and hematomas
on the arms, legs, and back. While no overt GI bleeding was
observed, the patient’s hemoglobin was 6.1 gm/dL. Coagulation
studies were performed to ascertain the cause for bleeding. |
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| This case clinically presented as an acquired Factor VIII
inhibitor but the laboratory studies appeared paradoxical. Initial
studies suggested the presence of a Lupus Anticoagulant since
all APTT factor assays demonstrated non-parallelism of their
curves (that is required multiple dilutions to dilute the “inhibitor”
and obtain factor activity). Hexagonal Phospholipid (Staclot-LA)
test was negative once and positive on each of two other occasions. |
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| Time and temperature APTT mixing studies appeared to argue
against a Factor VIII inhibitor since there was no significant
prolongation of the patient’s APTT mixing study after incubation
at 37oC for 2 hours relative to a mix control. The mix control
(50% normal pooled plasma and 50% patient plasma individually
incubated for two hours at 37oC and then mixed just prior to
testing) serves to control for the loss of Factor V and Factor
VIII activity. Both factors are labile and activities will be
reduced following incubation at 37oC for two hours. Should a
patient’s incubated APTT sample time be prolonged by more than
15 seconds relative to the mix control plasma argues for the
presence of a time/temperature inhibitor of which Factor VIII
inhibitors are the most common. In this case the patient’s incubated
APTT clotting time was prolonged by slightly more than one second
suggesting that a Factor VIII inhibitor was not present. |
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| Following discussions with Dr Dorothea Scandella from the
American Red Cross in Virginia it was concluded that the incubated
APTT mixing studies failed to show prolongation after 2 hours
because the antibody to Factor VIII was of such high titer (870
Bethesda Units) and affinity that it bound immediately. Therefore
it did not require the customary two hours with which to interact
with Factor VIII and was unable to further prolong the APTT
mix when incubated. The potency of the antibody affected all
APTT factor assays and caused false positive Lupus Anticoagulant
test results. |
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| Thank you to Drs David Dennis, Larry Hirschfield, Dorothea
Scandella, and Elizabeth Van Cott. |
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| Submitted by Marlies Ledford, MT(ASCP)SH, Special Coagulation
Laboratory, University of Miami |
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| E-mail: marlies@CLOT-ED.com |
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