If you have updated App-V 4.6 SP1 to SP2 or SP3 using only the MSI, please be aware that you will need to also ensure that the Visual C++ 2005 and 2008 updates (containing the critical Redistributable Package MFC Security Update) are also installed.
If you deploy using and ESD such as Configuration Manager, you may have noticed some quirky behavior post-deployment - especially with FTA (file-type-association) behavior. Before you do anything else make sure these run-times are updated.
The specific updates can be downloaded here:
If you are upgrading by using the EXE, this should happen automatically.