There are a shit-ton to beware of, not the least of which being the weather. I have not run it but have a few buddies that have.
One of the guys I know who has done it said that his biggest challenge was fueling during the run. He was doing it completely self-supported, and just didn't bring enough of nor the correct fuel. I believe he used this to dial in his nutrition, as he has since won a 3-day ultra stage race.
One thing that he always does when he makes runs like this, is he will run with his avalanche beacon. Overkill? Maybe - but keep in mind that there is essentially no cell coverage up there, so it's something to think about.
Fitness is an obvious here - pushing 30 miles (depending on which route you're looking at - there are some slight variations) with a lot of it being above 4500' is certainly no joke.
But you also mention your ankle: do you have weak ankles or coming off an injury? Are you from the east, or have a lot of experience running/hiking out here? Lots of loose rocks/shale that can turn an ankle quickly. Actually, just lots of rock, period: loose rocks, ledge, drainage basins, etc. Not someplace you wanna risk getting stuck on a hobbled ankle.
If you do go, just make sure you completely understand all the risks, and be overly prepared.
Watch the weather carefully, plan the route well - and know your drop-outs in case something unforeseen happens (storm comes in, injury, slower than you anticipated, etc), try to either get someone who is familiar with it sherpa you and/or have someone meet you along the way at different intervals to resupply you.
The best thing you can do is buy your NH Hike Safe Card:
https://wildlife.state.nh.us/safe/ For $25 per person/$35 per family, it's cheap insurance in case of trouble.
'm sure there are plenty of people here that can give you more and better info than I can, but these are just a few things that I can think of. Good luck and hve fun!
- Jeff