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False Positive Phospholipid Neutralization

G Pihan from Beth Israel Deaconess asks, “What is the incidence of false positive hexagonal phospholipid neutralization tests in the presence of a strong (400-800 BU) factor VIII inhibitor?”

Great question! Hexagonal-phase phosphatidyl ethanolamine is the chemical formulation for the phospholipid neutralization reagent used in Diagnostica Stago’s Staclot-LA lupus anticoagulant (LA) confirmatory assay. Their hex-phase phospholipid is widely regarded as the most specific platelet membrane surrogate for identifying lupus anticoagulants when testing in a partial thromboplastin time (PTT) system. I’ve checked with three experts who confirm there are no data published on the incidence of false positives, although all concede it is possible that a high-titer anti-factor VIII antibody (factor VIII inhibitor) could cross-react in the Staclot-LA system.

The ISTH requires that we use at least two parallel testing systems to confirm LA, and in the US most of us use a PTT-based kit such as Staclot-LA and a dilute Russell viper venom (DRVVT)-based kit such as Precision BioLogic’s Cryocheck LA-Sure. In the Quick Guide to Coagulation Testing, 2nd edition, which I published with Dr. Marisa Marques in 2009, we recommend that in instances when the DRVVT result is negative but the PTT-based hex-phase phospholipid result is positive for LA, the lab should follow up with a factor VIII assay to rule out factor VIII deficiency or to rule out the possibility of a factor VIII inhibitor.

I am guessing that this question arose from some results you generated at Beth Israel Deaconess, and I am wondering what your experience has been with high-titer factor VIII inhibitors? Do you have some data to share? Geo.

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