Jim,
The handful of times I have encountered this, before realizing and ensuring all our pdf's were saved as a single layer, these were the most common situations.
1) the draftsman used a bracket, a border, or some other alignment tool while preparing the drawings and just turned off that layer. These are the ones that make it to the examiner and get objections. Typically easy to amend as a replacement sheet in response to the OA and I had no concerns about the amended drawing supporting the application.
2) the draftsman used a hand sketch or other image as a template while preparing the patent art and just turned off that layer. These drawings are usually caught by the technology center and we got a notice to file corrected papers. Although there have been instances where the messy drawings made it to examiner and were objected to. The convolution of the drawings varies on how clear the drawings are. Sometimes the template image is rotated 90 degrees and is right under the patent drawing making it almost impossible to tell what the drawing is.
There is an application which just received a NOA. Once it issues, if I remember, I will post the patent # and you can look at the PAIR images of the drawings which have an example of each type of the above noted errors.
For those severe #2 cases, I would worry about the replacement sheets being supported by the original drawings. However, my understanding is it this messy drawing are only the version the examiners see when the pdf is processed by the PTO into the image format used with the PAIR system. The way it was explained to me by the Tech Center was that the original pdf drawings submitted are saved on a different system as the .pdf, so if support ever became an issue hopefully the applicant can rely on the pdf version and filing date but I have not encountered that yet.