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Veteran US diplomat Richard Holbrooke has died following a second round of surgery to treat a torn aorta.
He fell ill on Friday while meeting US Secretary of State Hillary Clinton.
He was President Barack Obama's special envoy to Afghanistan and Pakistan. The presidents of both nations had called to wish him well, prior to his death.
Mr Obama called the 69-year-old, who was known for bringing warring leaders to the negotiating table, a "true giant of American foreign policy".
Mr Holbrooke was meeting Ms Clinton at the US state department on Friday morning when he collapsed.
He was rushed to the US capital's George Washington University Hospital, where he underwent surgery to repair a tear in his aorta - the largest artery in the human body, which carries oxygenated blood from the heart.
Mr Holbrooke's death comes as the Obama administration prepares to make public its latest review of US policy in Afghanistan and Pakistan later this week.
'Foreign policy giant'
Following the news of his death, Mr Obama said: "Michelle and I are deeply saddened by the passing of Richard Holbrooke, a true giant of American foreign policy who has made America stronger, safer and more respected.
"He was a truly unique figure who will be remembered for his tireless diplomacy, love of country, and pursuit of peace."
Ms Clinton also paid tribute to Mr Holbrooke's service, saying the US had lost "one of its fiercest champions and most dedicated public servants".
"He was one of a kind - a true statesman - and that makes his passing all the more painful," she said in a statement.
Beginning with a foreign service posting in Vietnam in 1962, the veteran diplomat served under every Democratic president from John F Kennedy to Mr Obama.
But it was his role in Europe, helping bring to an end the war in Bosnia, that solidified his reputation as an important figure in foreign policy.
Nicknamed "the Bulldozer", the veteran diplomat once said he had no qualms about "negotiating with people who do immoral things", if it served efforts for peace.
"He's a bulldog for the globe," United Nations Foundation president Tim Wirth once said.
Mr Holbrooke was named by Mr Obama as his special representative to Afghanistan and Pakistan shortly after the president took office in January 2009.
Since moving into that position under the Obama administration, he had led the difficult task of pushing Kabul and Islamabad to work together against al-Qaeda and Taliban militants.
Mr Holbrooke, a New York City native, also served as the US ambassador to the United Nations and to Germany, as well as the assistant secretary of state.
BBC diplomatic correspondent Bridget Kendall says Mr Holbrooke was famous for his blunt speaking behind the scenes, despite his handshakes and careful courtesy in public.
Never afraid to bulldoze his way to a solution, our correspondent says, he got them all, Serb, Croat and Bosnian, to sign an accord in 1995.
"He was a remarkable man, a remarkable public servant and someone who contributed enormously to the cause of a more peaceful and just world," said former British Prime Minister Tony Blair.
Analysts had said the veteran diplomat could one day serve as a future secretary of state.
Mr Holbrooke's deputy, Frank Ruggiero, is expected to stand in for him in the interim.
Source: BBC
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