The drug that could save tens of thousands of lives - if only doctors could be told about it

The clotting drug tranexamic acid has already been included in the White House Medical Unit treatment protocols for President Obama. But until more people know about it, thousands of trauma victims all over the world will die needlessly without it.

Nothing could have saved President Lincoln. Kennedy might have survived the bullet in his back but not the one in his head. Garfield and McKinley, shot in the abdomen, died from massive internal bleeding. With four out of forty-four incumbents assassinated, and many more failed attempts, the job of US President is among the world’s more hazardous occupations.

However, the recent inclusion of the drug tranexamic acid into White House Medical Unit treatment protocols will increase the chance that Obama and future presidents will survive their terms. Being Commander in Chief means that presidential medical care is a military matter. The White House Medical Unit is in the White House Military Unit. Obama’s doctor is a Navy Captain.

In March 2010, results from the largest clinical trial ever conducted in trauma patients were reported in medical journal the Lancet. The CRASH-2 trial had randomly allocated over 20,200 bleeding victims of accidents or violence to receive either an injection of a drug called tranexamic acid or a matching placebo.1,2 Tranexamic acid had been used for decades to treat heavy monthly bleeding in women, but could it help in life threatening bleeding say from a knife in the ribs or bullet in the groin?

The results were spectacular. There were 160 fewer deaths in the tranexamic acid treated group. If given soon after injury, tranexamic acid reduced the risk of bleeding to death by about one third and without any side effects. Two weeks later, the British Army were using tranexamic acid to treat combat casualties in Afghanistan.

US military medics were not convinced. They had only recently burned their fingers on a new blood clotting drug called activated Factor VII. Seduced by industry hype and dubious expert advice, they had started using activated Factor VII to treat bleeding American soldiers even before results from randomised controlled trials were available. When the trials eventually reported they showed no evidence of benefit but significant side effects from unwanted clotting, with more heart attacks, strokes and gangrene.3 Lawyers smelled blood. And so even though there was a truckload of controlled trial evidence for tranexamic acid, they still wanted more data. The Taliban were more than happy to provide it.

Between January 2009 and December 2010, around 900 seriously wounded soldiers were treated by military medics at Camp Bastion in the Helmand province of Afghanistan. Improvised explosive devices had wreaked bloody havoc and double, triple, even quadruple amputees were not uncommon. One military surgeon described how he had worked on three soldiers wounded in the same explosion who had only two remaining testicles between them.

Of the 900 wounded, one third had been treated with tranexamic acid. Although the treated third were more severely injured than the untreated group, they were significantly less likely to die (17 per cent dead with tranexamic acid versus 25 per cent dead without). After statistical adjustment, the treatment benefit was even more dramatic.4 Although results from a randomised controlled trial with more than 20,000 participants should pack much greater scientific clout than the Helmand data, the experience of seeing a treatment effect in their own data was a powerful one and on 11 August 2011 US Tactical Combat Casualty Care Guidelines (pdf) were revised to include tranexamic acid.

A flag draped over a military coffin is politically inflammable. In large numbers, they can even smoke a president out of the White House. It takes the precise choreography of an Arlington funeral to get the corpse safely underground. Much less pomp and political risk surrounds the routine urban slaughter of young black Americans even though the number of deaths is considerably higher. A recent study estimated that the use of tranexamic acid to treat bleeding trauma patients in US hospitals could prevent more than 3,500 premature deaths each year.5 It was with these deaths in mind that the CRASH-2 investigators sent the entire clinical trial dataset to the US Food and Drug Administration (FDA) in March 2011 in the hope that the FDA would scrutinise the data and consider amending the licensing indications for tranexamic acid so that it could be marketed for use in trauma. Until this happens, any pharmaceutical company that promotes the use of tranexamic acid in trauma risks large fines.

Sadly, saving lives is not as easy as that. According to Dr Susan Shurin acting Director of the US Department of Health and Human Services, the FDA does not approve drugs unless the marketing company requests it and the marketing company will only request it if there is a demand. So we have a drug that could save a lot of lives if doctors knew about it but no one can tell them about it until it is licensed and it cannot be licensed until doctors know about it.

In an attempt to break this vicious circle, the trial investigators have had to take over the role of a pharmaceutical marketing department. Art students have been are enlisted to create informational cartoons that might go viral but might not.6 Doctors and university professors have had to lobby drug companies, to persuade them to take more interest in one of their own drugs, which is now generic and so not particularly profitable. If we do manage to raise the profile of this lifesaving treatment, the drug company will pay the FDA the license application fee, the FDA might give them permission to tell US doctors about tranexamic acid, the company will make some money and a few thousand Americans will not die.

It is absolutely right that those who risk their lives in the service of the President deserve the same standard of emergency medical care as the president. But so do the many tens of thousands of victims of violence and accidents who die needlessly every year around the world.

Ian Roberts is Professor of Epidemiology & Public Heath and Director of the WHO Centre for Injury and Violence Prevention at the London School of Hygiene & Tropical Medicine

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1CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23-32.

2The CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet 2011;377:1096-101.

3Levi M, Levy J, Andersen H, Trulof D. Safety of recombinant factor VII in randomized clinical trials.  N Engl J Med 2010;363:1791–1800.

4Morrison J, Dubose J, Rasmussen T, Midwinter M. Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147:113-119.

5Ker K, Kiriya J, Perel P, Edwards P, Shakur H, Roberts I. Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial. BMC Emergency Medicine 2012, 12:3 doi:10.1186/1471-227X-12-3

6The Lancet. CRASH-2 goes viral. The Lancet 2011;378:1758

 

The inclusion of tranexamic acid in White House treatment protocols will increase the chance that Obama and future presidents will survive their terms. Photo: Getty

Ian Roberts is Professor of Epidemiology & Public Heath at the London School of Hygiene & Tropical Medicine

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“Journalists are too scared to come”: Refugees on the forgotten war in Yemen

Only the few who have managed to flee the war-torn country can reveal the suffering of those left behind.

Last weekend’s BBC Our World report on the humanitarian crisis caused by the Yemen civil war highlighted that not only is the conflict a forgotten war, it is also an unknown war. Since war broke out 18 months ago in March 2015, surprisingly little has been written about the conflict, despite its similarity to ongoing and widely-reported other conflicts in the region, such as the Syrian crisis.

The main conflict in Yemen is taking place between forces allied to the President, Abdrabbuh Mansour Hadi, and those loyal to Zaidi Shia rebels known as Houthis, who forced Hadi to flee the capital city Sana’a in February. The loyalties of Yemen’s security forces are split, with some units backing President Hadi and others his predecessor Ali Abdullah Saleh, who is seen as the leader of the Houthi forces.

While these two forces have been at war, separate terrorist groups have been gaining more and more influence on the ground. Opposed by both the Houthis and Hadi’s forces, al-Qaeda in the Arabian Peninsula (AQAP) have staged deadly attacks from strongholds in the south and south-east. They are also opposed by Islamic State, which has claimed responsibility for a number of suicide bombings in Sana’a.

After rebel forces closed in on the president's southern stronghold of Aden in late March, a coalition led by Saudi Arabia responded to a request by Hadi to intervene and launched air strikes on Houthi targets.

I have spent the last couple of months working in the “Jungle” refugee camp in Calais, home to refugees from Sudan, Afghanistan, Syria, Iraq, Eritrea, Somalia – to name just a few. Having heard very little about the civil war, I was surprised to meet a handful of Yemeni men living inside the camp.

Hussein*, 28, is a film producer and dancer from Yemen who fled the country two years ago and has travelled through 11 countries to reach the Calais camp, where he has been living for just over a month. In a mixture of English and French, he tells me how groups of Houthi militia forcibly try to confiscate cameras and notebooks from both local and international journalists. He knows local journalists, friends of his, who have been threatened, tortured and even killed by Houthi forces.

He pulls out his phone and shows me a picture of his friend, Mohammed, who worked as a photojournalist, documenting brutality as a result of the war. Mohammed’s friends and family have not heard from him since April; the best-case scenario is that he is being detained, but Hussein seems pretty certain that he is dead. As a result, many who otherwise would have reported on the conflict have fled from besieged cities such as Sana’a, Aden and Taiz to the relative safety of the countryside in the north of the country, or have left Yemen altogether.

His friend Jamil, with whom he shares a tent, adds: “from other countries journalists [they are] too scared to come”. He claims that there are only “five or seven” foreign journalists in the capital city, Sana’a and tells me about journalists from the UK, France and the US who, after spending days being held up by countless militarised checkpoints while trying to reach the main cities, are then interrogated and detained by Houthi forces. If they are let go, they are harassed throughout their visit by National Security officers.

After watching his mother die during an airstrike in the city of Hodaida in January, Jamil took the decision to flee Yemen and claim asylum in Europe. He is worried about his father and his friends who are still in Yemen, especially after hearing reports that random border closures and cancelled domestic flights have been preventing crucial aid convoys of food, medical supplies and trained aid workers from accessing the citizens who are desperately in need of humanitarian assistance. Jamil reminds me that Yemen was in economic crisis even before war broke out, with widespread famine and limited access to healthcare or clean water.

Movement within the country is restricted and dangerous, and in the last twelve months alone, four Médecins Sans Frontières (MSF) facilities have been attacked and destroyed by airstrikes. Writing on 15 September 15, MSF head of mission in Yemen, Hassan Bouceninem spoke of:

“Other health centers, schools, markets, bridges . . . [that] have been attacked and destroyed by airstrikes, shelling, or bombs. Such attacks create direct victims but the war (economic failure, access problems, closing of hospitals, no health staff etc.) also causes a lot of indirect victims within the population.”

Such widespread instability and the resultant lack of access for journalists and aid workers means that it is difficult for the world to know how much Yemen is suffering. Only by speaking to the few who have managed to flee can even begin to grasp the realities of daily life for those left behind.

*Names have been changed to protect the identities of our sources.

Neha Shah has been volunteering in the Calais camp.