Profile RANDOM corruption/missing/lost/XYZ?!

Hey,

I have some serious issues with FF, TB and several other Apps over PortableApps!

I own three different PC (Windows 10 64bit as User/AntiVirGear-N10, Windows 7 64bit as AntiVirGaming/AntiVirGamingT7 and Windows 7 64bit as User/AntiVirGear-N7) and all my data and apps are on a 1TB HDD without any errors (weekly SMART check, file defragmentation and chkdsk) and here is the point: It happens randomly!

Let me show you some scenarios and define N10 as A, T7 as B and N7 as C!

1. A using TB for emailing and downloads some attachments.
2. B uses TB for emaling.
3. A uses TB again emailing.
4. C uses TB for xyz.
5. B uses TB...
6. A get a corrupted profile, settings are lost or not detected (for example and last example, IMAPMAIL contained everything, pref.js still contained my emails like xyz@yandex.com and 5-6 other email accounts but thunderbird only showed xyz@live.de and nothing more! All just gone... luckily I switched to IMAP but I can't set everything back again over and over...)

Sounds like B cause the corruption, right? NO! It also happen if I use C, it mostly happens, if I use FF on another PC and then it just need a bit of luck whether I can use FF without any problem or have to restore/rebuild a profile AGAIN!
But here is the point, PortableApps is MADE for using apps on any kind of PC so why does it happen to me all the time?

AV doesn't affect anything since I refuse them to access the portableapps folder!
I always safely remove the HDD and only plug it in after windows have been loaded!
I don't start FF or else as admin since I don't think I need to.

So yes... I'm now making a backup with toucan every time before unplugging but this shouldn't be a solution for that.
Tell me what's wrong with my configuration and thank you therefore so much.

Best regards
AntiVirGear