It's actually easy to compute classes of characters that have the same derivative (it's done in the linked "Regular-expression derivative re-examined" paper, although their particular implementation favors simplicity over efficiency), and it's not even necessary when using Antimirov's partial derivatives.
Actually, the complexity of the derivation is independent of the size of the alphabet. You could even define derivation on an arbitrary semi-lattice, not necessarily a set of characters. (Or a boolean algebra if you care about negation/complementation).
The difficulty in handling unicode has more to do with the efficiency of the automaton representation and manipulation rather than in turning the RE in an NFA or DFA.