Suicide bombers rammed into a bus in Karachi yesterday then hit a hospital where casualties were rushed for treatment, killing 25 people in the second assault on Shiites in the Pakistani city in weeks.

The attacks in a city largely isolated from Islamist violence highlighted the instability in Pakistan, which is on the frontline of the US war on Al-Qaeda and where militants have killed more than 3,000 people since 2007.

Women and children were among the 12 people killed when a suicide attacker rammed a motorbike bomb into a bus carrying Shiites on one of Karachi's busiest roads, gutting the bus and sending glass flying, officials and witnesses said.

A second bomber killed 13 people, damaging ambulances and the entrance to the casualty department at Jinnah Hospital, where the victims of the first attack were being treated and anxious relatives were gathering.

Sectarian violence periodically flares between Sunni and Shiite Muslims, who account for about 20 per cent of Pakistan's 167-million-strong population. Such violence has killed more than 4,000 people since the late 1980s.

Police said they defused a third bomb rigged inside a television and left in the hospital car park.

Witnesses and officials said the bus was packed with Shiite Muslims heading to a religious procession to mark the last day of the holy month of Muharram in Karachi, a southern port city of 16 million people on the Arabian sea.

"I heard a deafening explosion. I saw stretchers flying in the air. Two men fell just in front of me. I think they died," said Azam Ali, 26, who went to the hospital to inquire about a cousin wounded in the bus attack.

"Those killed and injured were mostly Shiites. They were relatives of those hurt in the first blast."

Ambulances were heavily damaged outside the hospital, blood stained the bus and wreckage strewed the ground after both attacks, witnesses said.

Twelve people died in the first blast and 13 in the second, with more than 100 people wounded, said Sagheer Ahmed, Health Minister for the southern province of Sindh.

"The dead included two women and two children," he told AFP.

The US embassy in Islamabad condemned the "terrorist attacks" and Pakistan's Prime Minister Yousuf Raza Gilani appealed for calm in the politically volatile city, where violence has killed up to 85 party activists so far this year.

Police said they were investigating who was responsible for an apparently sophisticated and well-organised attack designed to inflict maximum casualties.

"The perpetrators knew Jinnah Hospital was the nearest to the site of the first attack and ensured a follow-up attack when they saw significant numbers of people gathered there," said senior police official Mazhar Mishwani.

Doctor Seemi Jamali, head of Jinnah Hospital, urged the government to provide security assistance and training for a war-like situation, saying that staff, patients and relatives were terrified after the attack.

"The hospital is at standstill. Patients are scared, relatives are scared, all hospital employees are scared.

"We are trained as doctors, paramedics and nurses... If it goes on like this, working in a war, then we should have training," she told reporters.

It was the deadliest bombing in Pakistan since 101 people were killed at a volleyball match in the northwestern district of Lakki Marwat on New Year's Day, and follows a recent decline in militant activity.

On December 28, a bombing killed 43 people and reduced to a bloodbath a parade marking the holiest Shiite day of Ashura, earlier in Muharram.

Pakistan's feared Taliban network claimed responsibility for that attack, sparking riots that caused huge financial losses.

US officials believe Pakistani Taliban chief Hakimullah Mehsud, who oversaw a major increase in bomb attacks and plotted with Al-Qaeda to kill five CIA agents in Afghanistan, was probably killed in a US drone attack last month.

Security had been stepped up in Karachi as a wave of political violence killed at least 37 activists from rival parties in the local government in the last five days, following 48 similar killings last month.

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