Meet the donors, patients, doctors and scientists involved in the complex global network of rare – and very rare – blood. By Penny Bailey.
His doctor drove him over the border. It was quicker that way: if the man donated in Switzerland, his blood would be delayed while paperwork was filled out and authorisations sought.
The nurse in Annemasse, France, could tell from the label on the blood bag destined for Paris that this blood was pretty unusual. But when she read the details closely, her eyes widened. Surely it was impossible for this man seated beside her to be alive, let alone apparently healthy?
Thomas smiled to himself. Very few people in the world knew his blood type did – could – exist. And even fewer shared it. In 50 years, researchers have turned up only 40 or so other people on the planet with the same precious, life-saving blood in their veins.
Red blood cells carry oxygen to all the cells and tissues in our body. If we lose a lot of blood in surgery or an accident, we need more of it – fast. Hence the hundreds of millions of people flowing through blood donation centres across the world, and the thousands of vehicles transporting bags of blood to processing centres and hospitals.
It would be straightforward if we all had the same blood. But we don’t. On the surface of every one of our red blood cells, we have up to 342 antigens – molecules capable of triggering the production of specialised proteins called antibodies. It is the presence or absence of particular antigens that determines someone’s blood type.
Some 160 of the 342 blood group antigens are ‘high-prevalence’, which means that they are found on the red blood cells of most people. If you lack an antigen that 99 per cent of people in the world are positive for, then your blood is considered rare. If you lack one that 99.99 per cent of people are positive for, then you have very rare blood.
If a particular high-prevalence antigen is missing from your red blood cells, then you are ‘negative’ for that blood group. If you receive blood from a ‘positive’ donor, then your own antibodies may react with the incompatible donor blood cells, triggering a further response from the immune system. These transfusion reactions can be lethal.
Because so few people have it, by definition, rare blood is hardly ever needed. But when it is, finding a donor and getting the blood to a patient in crisis can become a desperate race against the clock. It will almost certainly involve a convoluted international network of people working invisibly behind the bustle of ‘ordinary’ blood donation to track down a donor in one country and fly a bag of their blood to another.
© Greg White
Forty years ago, when ten-year-old Thomas went into the University Hospital of Geneva with a routine childhood infection, his blood test revealed something very curious: he appeared to be missing an entire blood group system.
There are 35 blood group systems, organised according to the genes that carry the information to produce the antigens within each system. The majority of the 342 blood group antigens belong to one of these systems. The Rh system (formerly known as ‘Rhesus’) is the largest, containing 61 antigens.
The most important of these Rh antigens, the D antigen, is quite often missing in Caucasians, of whom around 15 per cent are Rh D negative (more commonly, though inaccurately, known as Rh-negative blood). But Thomas seemed to be lacking all the Rh antigens. If this suspicion proved correct, it would make his blood type Rhnull – one of the rarest in the world, and a phenomenal discovery for the hospital haematologists.
Rhnull blood was first described in 1961, in an Aboriginal Australian woman. Until then, doctors had assumed that an embryo missing all Rh blood cell antigens would not survive, let alone grow into a normal, thriving adult. By 2010, nearly five decades later, some 43 people with Rhnull blood had been reported worldwide.
Hardly able to believe what she was seeing, Dr Marie-José Stelling, then head of the haematology and immunohaematology laboratory at the University Hospital of Geneva, sent Thomas’ blood for analysis in Amsterdam and then in Paris. The results confirmed her findings: Thomas had Rhnull blood. And with that, he had instantly become infinitely precious to medicine and science.
Researchers seeking to unravel the mysteries of the physiological role of the intriguingly complex Rh system are keen to get hold of Rhnull blood, as it offers the perfect ‘knockout’ system. Rare negative blood is so sought after for research that even though all samples stored in blood banks are anonymised, there have been cases where scientists have tried to track down and approach individual donors directly to ask for blood.
And because Rhnull blood can be considered ‘universal’ blood for anyone with rare blood types within the Rh system, its life-saving capability is enormous. As such, it’s also highly prized by doctors – although it will be given to patients only in extreme circumstances, and after very careful consideration, because it may be nigh on impossible to replace. “It’s the golden blood,” says Dr Thierry Peyrard, the current Director of the National Immunohematology Reference Laboratory in Paris.
Blood groups are inherited, and Rhnull is known to run in families. So the next step for the haematologists in Geneva was to test Thomas’ family in the hope of finding another source, particularly as Thomas wouldn’t be able to donate until he turned 18. Things looked even more hopeful when it turned out Thomas’ grandfathers were third-degree cousins. But the tests showed Thomas’ Rhnull blood was due to two completely different random mutations on both sides. Pure chance, twice over, in the face of vanishingly small odds.
© Greg White
In 2013, Walter Udoeyop received a letter from an old friend back in Nigeria. Father Gerald Anietie Akata’s 70-year-old mother had a tumour in her heart, but no hospital in Nigeria could perform the surgery she needed. Akata enclosed his mother’s medical records, asking for Walter’s help.
Walter, a consultant at Johnson City Medical Center, Tennessee, knew from the start this wasn’t going to be easy. Francisca Akata’s operation would cost a daunting $150,000 minimum if she had it in the USA. Father Akata had been a pastor in Johnson City for several years, and Walter initially hoped to enlist the help of the church and hospitals his friend had served in. But neither could raise such a large amount of money.
He recalled that another friend had recently had open-heart surgery in the United Arab Emirates (UAE) for only $20,000. He phoned the hospital there, and the staff agreed to operate on Francisca. Father Akata’s parishioners in the USA and Nigeria raised the money, and three months later, Francisca Akata was flying eastwards towards the UAE.
But a few days after her admission, the doctors told Francisca that blood tests had revealed that she had a rare blood type, shared by 0.2 per cent of the white population: Lutheran b negative. To complicate the matter, she was also O negative – the uncommon, but not officially rare blood type that many of us have heard of, shared by around 5 per cent of people. The combination made Francisca’s blood so rare it would be difficult, if not impossible, to find a match for her.
Since there was no compatible blood in the UAE or any of the other Gulf States, Mrs Akata had to fly back home and wait until matching blood was found. The hospital searched for blood but couldn’t find any in the two weeks that followed.
Walter requested Francisca’s blood tests from the hospital and then began the search for compatible blood in the USA. He tried blood centre after blood centre across the country before he was referred to the American Rare Donor Program in Philadelphia, a database of all rare blood donors in America. Finally, he had located some suitable donors.
His relief was short lived because, as Thomas or Peyrard could have told him, it’s a lot harder for blood to cross borders than it is for people. “You would not imagine how difficult it is when you have to import or export rare blood,” Peyrard says. “Your patient is dying, and you have people in an office asking for this paper and that form. It’s just crazy. It’s not a TV set, it’s not a car. It’s blood.”
Sometimes sending blood from one country to another is more than a bureaucratic nightmare. As Walter now discovered, the hospital in the UAE had a policy not to accept blood donations from outside the Gulf States, which meant that Francisca wouldn’t be able to use the blood he had found in America.
The situation looked bleak. But then, after a chance meeting with a colleague, Father Akata found out about a small general hospital in Cameroon, Nigeria’s neighbour to the east, that had set up a heart surgery programme with funding from the Catholic Church. Walter got in touch with the surgeons there, who confirmed that they could do the surgery if he could supply compatible blood.
The American Rare Donor Program contacted the South African National Blood Service, which had four suitable donors listed; however, one of these was unreachable, one wasn’t able to donate until later in the year, and two had been medically retired from donating. These are all common problems with rare donors. There are limits placed on how often people can donate. What’s more, keeping track of donors can also be a challenge – some get ill or die, and others move home without updating the blood services.
There were two units of compatible blood in South Africa’s frozen rare blood bank, but frozen blood has a 48-hour lifespan, compared to four weeks for fresh blood. If it got held up at customs, or delayed for any other reason, it would be unusable by the time it reached the hospital in Cameroon. To use the frozen South African blood, Francisca would have to have her operation in South Africa. Walter was running out of options.
© Greg White
When he turned 18, Thomas was encouraged to donate blood for himself. There is now no frozen blood bank in Switzerland, so his blood is stored in the rare blood banks in Paris and Amsterdam. He travels to France to donate, avoiding the bureaucratic machinery that would grind into action if his blood had to be sent over the Swiss border to Paris.
The first urgent request came a few years after Thomas began donating, when he got a phone call asking if he would mind taking, and paying for, a taxi to the blood centre in Geneva to donate for a newborn baby. That moment brought it starkly home to him how valuable his blood was. It was perhaps also the first intimation that the costs of donating would ultimately be his. Some countries do pay donors (and some pay more for rare blood) to encourage donations. But the majority of national blood services don’t pay, to deter donors with infections such as HIV.
The altruistic ethos of the blood services in western Europe means that they also don’t cover donors’ travel costs or time off work, both of which would constitute payment for blood. They can’t even send a taxi to take a rare donor to a blood centre, although the blood itself can travel by taxi from the centre to a patient.
It’s something that can become a frustrating and potentially fatal problem. Thierry Peyrard told me that he was recently contacted by a doctor in Zurich asking for blood with another rare combination of negatives, for a patient about to undergo surgery. There were only four compatible donors in France, and Peyrard could only contact two by phone. One of them was a 64-year-old lady living in a village near Toulouse. Although she was more than willing to go to the blood centre in the city and donate, since she can’t drive she simply couldn’t get there.
So unless his doctor drives him over the border again – a courtesy going far beyond the call of duty between a doctor and patient – Thomas will take a day’s holiday from work, twice a year, and travel to Annemasse in France to donate, paying his own travel costs there and back.
© Greg White
Walter had one last chance to find the blood Francisca Akata so desperately needed: a small laboratory on the other side of the Atlantic. The modest size of the International Blood Group Reference Laboratory (IBGRL) in Filton, near Bristol in England, is misleading; the expertise at the IBGRL means it’s one of the world’s leading laboratories in rare blood identification.
If the donor and recipient are in different countries, the blood services of both countries will negotiate costs. The requesting country usually covers the cost of flying the blood in at 4°C, the temperature at which fresh red blood cells have to be preserved to keep them intact before transfusion.
“It’s generally a reciprocal agreement between countries so that no one who ever needs blood is penalised for being where they are,” Nicole Thornton, Head of Red Cell Reference at the IBGRL, told me. “Some countries charge a bit more per unit of blood, but there’s no hard and fast rule. Most don’t charge too much because they might be in the same situation at some point.” In the UK the charge is £125.23 per bag of blood.
Walter contacted Thornton, who searched the International Rare Donor Panel and identified 550 active O negative/Lutheran b negative donors worldwide. Because they are inherited, blood types tend to pool in specific populations, and 400 of those donors turned out to be in the UK – most of them in or around London. A flight from the UK to Cameroon would be much shorter than a flight from the USA. And the blood would be fresh.
As the blood was available, and because it wouldn’t make logistical sense to fly a second consignment if Francisca needed more than four units, the UK blood services agreed to send six bags of blood. All six UK donors who received a phone call and were able to donate did so within days.
In Rochester, Kent, England, it was James'* 104th donation. He first donated as an 18-year-old in the army in 1957, when he was told his O negative blood was “good for blue babies”. In 1985 he got a letter explaining his blood was rare (although not how rare) and asking if anyone in his family would donate so their blood could be tested. The family members he asked were reluctant, however, believing they “needed their blood for themselves”.
A few years later, in the early 1990s, James got his first phone call from the blood services, asking whether he would mind “popping down to the local hospital to donate blood for someone in Holland”. There, he was told that a taxi was waiting for his blood. He didn’t think this particularly unusual, saying that it was all in a day’s donation.
He wasn’t surprised to be called up again, but he didn’t know that his blood was going to Cameroon. And previously he hadn’t known he was Lutheran b negative, as well as O negative. He was surprised and mildly intrigued to learn that there were only 550 known people with the same blood in the world.
The bag of James’ blood joined the five bags from the other donors, and all six were couriered to Tooting in south London to start their 7000-km journey.
This was when Walter discovered how remote the hospital really was. Kumbo, in the mountains of north-west Cameroon, is more than 400 km north of both Douala and Yaoundé, the sites of the country’s major international airports. The blood would have to travel for several hours to get there, bumping over a dirt road in the March heat. Even packed in ice, it would be hard to keep it at the cell-preserving 4°C.
Francisca Akata’s blood landed at the international airport in Douala and was cleared through customs by noon on Friday 21 March 2014. A helicopter, supplied at the last minute by the hospital to avoid the lengthy road journey, was waiting outside. Her blood flew the rest of the way to Kumbo and arrived at 14.00, just after Francisca had been wheeled into the operating theatre.
The operation was a success, and the Catholic Diocese of Kumbo found her somewhere to recuperate before flying home. Walter still marvels at the efforts of so many people – on three separate continents – to save one life, “just like the shepherd who left 99 sheep and went after the one that was lost.”
© Greg White
Since his blood can be given to anyone with a negative Rh blood type, Thomas could save countless lives. But if he ever needs blood himself, he can receive only Rhnull blood. If he donates a unit for himself, he has to permit it to be used by anyone else who might need it.
This leaves Thomas dependent on other Rhnull donors. But of the other 40-odd people known worldwide with Rhnull blood, only six or so besides Thomas are thought to donate. And they’re all a long way away: their locations include Brazil, Japan, China, the USA and Ireland. The reluctance to donate is perhaps understandable, but it places an added burden on the people who do give their blood. It’s also probably why Thomas, when Peyrard and I met him in Lausanne, greeted us with mild amusement. “Is it interesting to put a face to the bag of blood?”
Over tea, he described the impact of his blood on his life. As a child he couldn’t go to summer camp because his parents feared he might have an accident. As an adult he takes reasonable precautions: he drives carefully and doesn’t travel to countries without modern hospitals. He keeps a card from the French National Immunohematology Reference Laboratory in Paris, confirming his Rhnull blood type, in his wallet in case he is ever hospitalised. But one thing that is in his blood – and that of almost everyone growing up in the shadow of the Alps – is skiing. Abstaining seems to have been an option he never even considered.
The only apparent health effect he experiences is mild anaemia, which is why he was advised to donate twice a year instead of four times. Intriguingly, one doctor once asked whether he has a quick temper. In fact, the opposite is the case: “I am very calm. If it’s just my personality or if my blood has an impact or not, I don’t know.”
On the whole, Thomas is laid back about his ‘condition’. “I don’t have a problem like haemophilia that has an impact on daily life. In that sense, I’m lucky. I’m glad also that when I was told I had this special blood, they told me it’s okay to have children. I was allowed to have a family, so I’m happy.”
Donors like James and Thomas never learn what has happened to their blood – and haematologists don’t fly across borders to express their appreciation. But on this day, as we sat in a room full of spring sunlight looking out at the hazy white-flecked peaks, Peyrard told Thomas that his blood had saved lives. Just recently, a unit was sent back from France to Switzerland for a young child who would otherwise have died.
On one level, Thomas’ blood does divide him from the rest of us. On another, as the French philosopher Simone Weil observed, every separation is a link.
And Thomas’ different blood has given him the odd unexpected perk. When he was due for conscription, the doctor who first told him about his blood – Dr Marie-José Stelling – wrote to the army saying it was too dangerous for him to do military service, so he was exempted. Over the course of the past 40-odd years, Thomas and Stelling have developed a particularly close relationship. Last year, she joined him and his family and friends to celebrate his 50th birthday party on a boat on Lake Geneva. “She was very kind,” Thomas says. “She saw the human aspect of being Rhnull – not just a bag of blood.”
*Name has been changed.