Factor VIII Aurora: a naturally occurring gain-of-function FVIII variant with enhanced FIXa affinity.

FVIII-R571S (Factor VIII Aurora) shows a sixfold higher 1-stage assay activity than FVIII-WT, linked to a 10- to 20-fold increased FVIIIa–FIXa affinity.

• Why it matters: A naturally occurring FVIII variant in a patient with recurrent thrombosis and early mortality needs a mechanistic explanation for its gain-of-function procoagulant behavior.
• What they did: The authors generated recombinant FVIII-R571S and tested it in vitro and in vivo, finding comparable chromogenic activity to FVIII-WT and attributing the difference to FVIIIa–FIXa binding.
• The result: In hemophilia A mice, FVIII-R571S increased tail-clip potency by four- to fivefold and enhanced platelet and fibrin accumulation in a thrombosis model at matched antigen levels.

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