Coming to Grey's Anatomy: New Hookup, Devastating Breakup

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Brace yourself, Grey's Anatomy fans.

According to inside sources, there's a major shakeup coming by the end of this season - one that will result in a Seattle Grace couple calling it quits. But this is heavier than usual.

Apparently, it's "one of the longer-term, most-loved couples" that splits up, and it's "going to leave both of them pretty devastated." Doesn't sound good, does it? There's more still.

The backdrop of the breakup involves "a very serious issue "that it certainly seems like the two cannot get past - and does not arise because either of them have met someone new.

Any guesses?

Gather 'Round

Everybody's going to be glued to Grey's Anatomy message boards after this.

Meanwhile, there's also going to be a new fling in the hospital we love, and it involves one of the newcomers this season, and someone who's been around for a good long while. 

One clue to the hookup: It stinks (and only die-hard fans of a certain other show will get that reference)! If you have any theories on this, we'd welcome them in the comments.

Finally, we hear that the Grey's Anatomy sixth season finale will be "a serious game changer for every single character." Okay, Shonda Rhimes said that, but it's worth repeating.

Sound off below with who you think the breakup - and hookup - involves, and what you think the upcoming season-ending Grey's Anatomy bonanza will entail ...

Steve Marsi is the Managing Editor of TV Fanatic. Follow him on Google+ or email him here.

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Grey's Anatomy Quotes

Did you say it? 'I love you. I don't ever want to live without you. You changed my life.' Did you say it? Make a plan. Set a goal. Work toward it, but every now and then, look around; Drink it in 'cause this is it. It might all be gone tomorrow."

Meredith (closing voiceover)

There's a reason I said I'd be happy alone. It wasn't 'cause I thought I'd be happy alone. It was because I thought if I loved someone and then it fell apart, I might not make it. It's easier to be alone, because what if you learn that you need love and you don't have it? What if you like it and lean on it? What if you shape your life around it and then it falls apart? Can you even survive that kind of pain? Losing love is like organ damage. It's like dying. The only difference is death ends. This? It could go on forever.