Sure, and in many ways it may inform the overarching design of the game itself then moment to moment play. Like, we have the Stress -> Vice -> Trauma link not because it's pure game based attrition, but to see if you can deal with the costs of the Scoundrel's life or if you flame out. The game definitely expects you to dig into the cost of that life explicitly, and reinforces that with mechanics.
But I think you could take the
sandbox side of Blades and run it with a D&D ruleset and get a really solid game out of it (there's been some buzz in the 5e community over the last couple of years about wrapping a bunch of the core tech from Blades etc in to your play, including a book about uhh
"Proactive Roleplaying?" - Reddit thread reviewing said book). It just would lack the character thematic portions in mechanics and expectation.