How is the presence of factor VIII (FVIII) inhibitor confirmed in hemophilia A?

Updated: Jun 05, 2020
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Laboratory confirmation of a FVIII inhibitor is clinically important when a bleeding episode is not controlled despite infusion of adequate amounts of factor concentrate. For the assay, the aPTT measurement is repeated after incubating the patient's plasma with normal plasma at 37°C for 1-2 hours. If the prolonged aPTT is not corrected, the inhibitor concentration is titrated using the Bethesda method. Ideally, the Nijmegen modification of the Bethesda inhibitor assay should be used to detect an inhibitor if the mixing test result is positive. [14]

By convention, more than 0.6 Bethesda units (BU) is considered a positive result for an inhibitor. Less than 5 BU is considered a low titer of inhibitor, and more than that is a high titer. The distinction is clinically significant, as patients with low-titer inhibitors may respond to higher doses of FVIII concentrate while those with high-titer inhibitors require treatment with agents that bypass FVIII and consideration for induction of immune tolerance.

Caution is warranted when obtaining blood samples for coagulation assays from heparinized central lines because of the effect of heparin contamination on all coagulation test results. The excess heparin causes false-positive results and/or higher inhibitor titer values than are actually present in the patient, because heparin is also an inhibitor of coagulation.

One study found significant heparin contamination in 45% of all specimens obtained through implanted venous access devices. These researchers suggested that all blood samples obtained from such devices, which are usually flushed with heparin, should be treated with heparinase before performing an inhibitor assay. [29]

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