Differentiating Lupus Anticoagulant from an Acquired Factor Inhibitor Using Special Mixing Study.
Ming Jin, Kurt Leuenberger, Spero Cataland, Carol Orr, Haifeng Wu. Ohio State University, Columbus
Background: Differentiation between lupus anticoagulant (LA) and an acquired coagulation factor inhibitor can sometimes be difficult since LA can interfere with in vitro phospholipid dependent clotting tests. Correct diagnosis is crucial since the management is completely different, and inappropriate treatment can potentially cause devastating consequences.
Design: We report a novel laboratory approach, a modified dilutional study, to differentiate interfering LA from factor inhibitor in a patient with high LA titer causing extremely false low Factor IX activity.
Results: A 78-year-old man with a two year history of myelodysplastic syndrome was admitted for worsening pancytopenia and concern for progression to acute leukemia. Several coagulation lab workups were performed.
Initial laboratory coagulation test results
|FIX||3%||PTT (24-35 sec)||68|
|FII||103%||PT (12.8-14.9 sec)||18|
|FX||114%||LA (DRVVT & Staclot)||Positive|
|anti-FIX titer||28 BU||ACA IgM (0-12.5 MPL units)||>150 MPL|
To further evaluate low FIX level, standard dilutional studies ranging from 1:2 to 1:8 were performed. However, the dilutional effect could not be satisfactorily assessed because the clotting times obtained from all diluted specimens were off the standard curve on several repeated attempts. We postulate that diluting patient plasma with a significant amount of pooled normal plasma (PNP) would effectively decrease LA titer while not changing the factor inhibitor level. At a dilution where the factor level reaches approximately 20% in a standard factor assay, further dilutional effect will be evident if the patient indeed has an interfering LA. Therefore, we serially diluted the patient plasma with PNP until we obtained a 25% Factor IX activity, which occurred at a 1:64 dilution (patient: PNP). Standard dilution studies were then performed on this PNP dilute. These studies demonstrated 40% activity at a 1:2 dilution, 68% activity at 1:4 dilution, and 96% activity at 1:8 dilution. These results convincingly demonstrate the presence of an interfering LA that results in a falsely low Factor IX activity.
Conclusions: Several approaches including chromogenic factor assay, ELISA based techniques, and phospholipid modified factor assay have been developed to help differentiate between LA and factor inhibitor. However, our novel approach of a modified dilution study is simpler, more rapid, and cost effective. Currently, we are validating this approach on other patients with high titer LA.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 177, Tuesday Afternoon