Are you using http://www.creationkit.com/OnItemRemoved_-_ObjectReference?
I think you'd need to check for the akBaseItem instead of the akObjectReference.
Or what DocClox said. It sounds like a sound plan.
Checking akObjectReference is safe as long you as you make your object persistent. Assuming you know the object before dropping it you can make it persistent. Eg: if you have it in a quest alias it won't be enough to have it persistent i believe, but if you have it you can put an registedForUpdate on it anytime then unregisterForUpdate from onItemRemoved where you also do your stuff.
Bottom line if akObjectReference is not None, and won't be if persistent, you can safely use it.