Di Maria is the latest player who looks set to leave Old Trafford as a move to French champions Paris Saint-Germain nears completion.
The Red Devils have already lost strikers van Persie and Falcao to Fenerbahce and Chelsea respectively and the exit of another attacking player will only make life more difficult for Louis van Gaal according to Cascarino.
"But if you think they will have lost Di Maria, Falcao and van Persie, that's a huge loss to Man United.
"They must find replacements. If they lose Wayne Rooney (to injury), they've got a problem."