If Isabel marries earlier (which is more than likely) than IOTL her chances for surviving offspring increase.
Given how D. Felipe kept her on-side as a spare OTL, I'm not sure that that would happen. She's not marrying until Felipe's wife no. 5 can't have kids anymore (either cause she's dead or menopausal), which if the girl's a strapping (my autocorrect wanted to change it to strap-on

) 16 in 1581, is likely not to be for another 15-20yrs (menopausal, not dead in childbed).
Also, as to a triple marriage, I'm not so sure. Even ICE's late periods didn't stop Felipe marrying his second daughter to the duke of Savoy, although he offered either to the duque of Bragança's heir, i.e. a non-Habsburg. So I'm not sure he'd waste all 3 on the Austrians TTL. And even if he does, he might spread it around:
Isabel to Ernst/Albrecht
Catalina to the duque de Bragança/duke of Savoy/second wife to Archduke Ferdinand II(if Felipe's swiping Ferdy's 2e wife)
Maria (girl-Felipe III) to OTL HRE Ferdinand II.
That way, no matter the outcome of these marriages, a Habsburg is left holding the Spanish baby and no fears of a reborn empire of Karl V's empire (which, come to think of it, he might marry ICE to Ferdinand II and Catalina to Ernst/Albrecht - but that might be too retroactive a look at things)