Op is correct. This has been the case on the Mac for some time when using usb. I have the same behavior on multiple macs, OS X versions, and axe iiis with multiple firmware versions, a variety of usb hubs (happens direct to the Mac with a single axefx as well), and a variety of aggregate audio devices. I primarily have this issue when upgrading the firmware of the axefxs bc of the reboot.
It is not a word clock issue because you can’t simply change the word clock source to something else and back to fix it like you normally could with typical word clock issues.
Like the op said, core audio stops working. As I’ve said before, while this could be Apple’s responsibility, it is quite repeatable with the Axefx so Fractal stands a chance in helping diagnose the issue to help fix it. I haven’t experienced this with other gear but it doesn’t mean it doesn’t happen.
With the frequency of fw updates, it would be nice to finally figure this out. I have my startup sequence timed so that it doesn’t occur unless I restart an axe after the fw update.