From Deborah Whetzel, Children’s Hospital of the King’s Daughters, Norfolk, VA: We’ve had a couple patients lately that demonstrated inhibition but their factor VIII results are within normal limits or even elevated. The result values differ 30–40% typically between dilutions but as they’re diluted more, the values go up to 300 or 400%. FVIII values that high seem really odd to me. We dilute to 1:160, as I’ve seen recommended, with results to that point continuing to get higher. Have you seen this occur and is there something that we should be doing? Thanks for your help.
Hi, Deborah, and thank you for your question. I turned for help to a local colleague who has a lot of experience with inhibitors. She responds, “George, are they getting a positive Bethesda titer? Or is it just an inhibitor pattern in the factor dilutions? Are any other factors affected or is it just VIII? It kind of makes me think more of a lupus anticoagulant or another specific factor inhibitor. This doesn’t seem like an VIII inhibitor to me. We’ve had patients who have had inhibitor patterns due to lupus anticoagulants that have FVIIIs that high. And I can think of one patient right off hand who had a FV inhibitor who had an VIII in the 600s that had evidence of inhibition in all her factors. I hope this helps. Talk to you soon!”
I also would add, were the patients you describe bleeding? This would indicate a factor VIII inhibitor.
A direct thrombin inhibitor (dabigitran, argatroban, bivalir
A direct thrombin inhibitor (dabigitran, argatroban, bivalirudin) could also produce this “interference” pattern. We prefer the term “interference” so as not to confuse clinicians that a specific factor inhibitor is present. I agree that a TCT would be helpful.
Hi Deborah and George. It seems to me that what you are exp
Hi Deborah and George. It seems to me that what you are experiencing is a specimen that is exceeding the linearity of your assay curve and as your dilutions come closer to the linearity of your curve, your are seeing the reportable result.
If this were a case of a lupus anticoagulant (LA), I would expect factor VIII results to be moderately suppressed. Typically we see patient results around half of normal and increasing on dilution on plasmas that show LA inhibitor patterns, but not all LA positive plasmas show inhibitor patterns in our test system.
Patients whose plasma contains heparin will show similar results and dilution patterns as a LA patient. Performing a thrombin time would help determine if the plasma was contaminated with heparin.
A factor VIII inhibitor is highly unlikely and a Bethesda assay can not be successfully performed on a plasma with elevated factor VIII levels (unless the plasma was heat treated to remove the excess factor VIII).
Regards,
Herb Crown
St. Louis University Hospital Coagulation Reference Laboratory