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And to address your second paragraph: obviously the 2v1 situations will only be fruitful if you're ahead. This goes without question.
I prefer EQ+aa and QE+aa; both are fine and do the exact same thing, just giving the illusion of losing less health. The desync in cooldowns is less noticeable with QE when you have cooldowns maxed -- again, why its a focus in the build.
Lastly, Spell vamp quints/masteries help to mitigate the health cost of your E. Sometimes in rough lanes you cant keep them stacked, and need to Transfusion a few times before stacking damage again; This guide is geared towards playing adaptively in lane, one of the most useful skills in League. Sometimes you have to adjust playstyle to deal with certain matchups, from build order to skill order. There are games on vlad where I build a completely differently than my guide (but the rarity of those matchups is extreme).
In fact, while you do mention how CDR can be effective in 2v1 situations, how do you have such confidence fighting 2v1 in the first place? Vladimir has 0 mobility other than his Sanguine Pool, which is nice, but doesn't change the fact that the enemy doesn't need CC to reach and kill you. They can just straight walk up and smash your face, especially since Vladimir's movement speed is only 335- and you don't even seem to have MS quints either. Do you simply have confidence that you'll be so far ahead that you can outdamage them as long as they cannot apply hard CC?
Second, why do you prefer QE+aa as your combo? EQ/EQ+aa seems to be the general consensus in this matter. This method would desync your cooldowns in most cases ( Tides of Blood having a longer cooldown than max Transfusion), which would lead to an unnecessary drop in DPS.
Third, you recommend maintaining full stacks of Tides of Blood during the early levels 1~6 phase. How do you deal with the constant health costs of maintaining said stacks, and the fact that this will lead you to constantly the lane?