If you have already defragged the external drive without any problems, then that's great, but I would not recommend that you defrag it if you havent already done so.
I've heard of too many issues with external drives being corrupted due to bad defrag software (a lot of the 'free' defraggers are at fault). Atleast stick to the safe, well known defraggers if you insist on defragging the USB drive.
As for using the laptop when you are defragging, yes, it should be safe to do so. Infact, currently, with automatic defraggers popular, defragmentation has become something of a background task that occurs only when the system has enough free resources. It's really convenient compared to scheduled defrags because the CPU/disk is not hogged by the defragger and you can continue to work as you normally would, accessing any file on any disk, without any performance slowdown from the background defrag process.