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If you complete the Granny Rags missions, you will have a mini-boss fight (of sorts) later in the game. Knocking the mini-boss unconscious before the fight will count as a kill due to how it's scripted.
To the best of my knowledge, there's no bug with skipping the Granny Rags missions, and this is considered the safer way. You lose out on a few runes, but that's it. It also makes getting Ghost easier because you avoid the mini-boss fight.
I personally got Ghost and Clean Hands while still doing the Granny Rags missions, so it is possible. You simply can't knock out the mini-boss before you're supposed to.