In bloodborne, is the level 10 weapon upgrade mat the only mat obtainable only once in a single playthrough?

On a straight playthrough, yes. There's only one per NG cycle located in the Nightmare of Mensis. One of the later patches also allows you to purchase Blood Rocks through the Insight shop after beating Mergo's Wet Nurse for 60 Insight.

You can also find them in chalice dungeons, one per each type of Depth 5 dungeon, from sarcophagus chests, but the drop rate is fairly low.

There's also one more in the Old Hunters area, near the Fishing Hamlet.

Short answer, yes, there’s only one in the main game. Longer answer, you're rewarded with one rock when you complete one of the four types of chalice dungeons (Pthumeru, Loran, Isz, Hintertomb... so that’s a total of 4 more rocks). There’s also one rock in the DLC. That’s a total of 6 blood rocks (1 in the main game, 1 in the DLC, and 4 from the dungeons).