Take a situation where on the first half the player fights an enemy and after a cutscene, the player cuts off the hand of the enemy. How can I show him without his hand after this moment (when modeling it with the hands in Blender in a single skeletal mesh)? Do I have to make another skeletal mesh but without the hand? Similar to how in Assassin's Creed Origins where at the end of the snake quest after the cutscene Bayek losses his ring finger and remains without it all game. But in my case, the entire hand is removed.
There are a few approaches.
If the hand mesh can be separated from the rest of the body, you could make a unique animation where the hand is detached and out of view, such as behind the camera (if this is a first-person animation).
If the hand cannot be removed from the arm (in the case of a continuous mesh), perhaps you can animate the hand's scale down to 0, and maybe translate it up into the wrist if it looks funny. Some games have used effects like this for 'headshots' that blow off characters heads, scaling it down to a finite point such that only the neck is visible.
Then there is the solution you mentioned, where you swap it out with an entirely different model where the hand is missing.