Arkansas prison plasma donor the late Bud Tant a known drug user infected with hepatitis C who was allowed to sell his plasma which was put into US pools of up to 400,000 donors

(Image, thanks to Linda Miller)

In the early 1970s when US factor concentrates were first licensed for introduction into the UK, haemophiliacs that have an inherited bleeding disorder where the blood has difficulty clotting, went from receiving cryoprecipitate, a treatment made from a handful of unpaid British donors to imported factor concentrates manufactured from plasma pools in America that over the years could reach as high as hundreds of thousands of paid donors. Many of these US donors were considered “high risk” for transmitting viral infections such as hepatitis B and included prisoners, drug addicts, prostitutes, skid -row donors, gay men and plasma sourced from donors in Haiti and Central American mainland countries.

As well as being high-risk for viruses, US prisoners for example were also the subject of unethical experimentation put on chemical trials with new drugs tested out on them, applied with new topical treatments that could affect the body through the skin, and injected with viruses which were sometimes deliberately mutated. These prisoners were STILL allowed to sell their blood, despite such experimentation resulting in a poorer quality of plasma and often unsafe donations.

Stanford Children’s Health describes plasma as “the largest part of your blood. It, makes up more than half (about 55%) of its overall content. When separated from the rest of the blood, plasma is a light yellow liquid. Plasma carries water, salts and enzymes.” It also contains clotting factors (which were used to treat haemophiliacs) as well as other components such as antibodies and the proteins albumin and fibrinogen. Haemophiliacs could be classed as mild, moderate or severe depending on the ability of their blood to clot.

A Freedom of Information request response recently received by long term campaigner Carol Grayson (Haemophilia Action UK) highlighted that no risk assessment was ever officially carried out by the UK government PRIOR to importing the so called “miracle” factor concentrate” treatment in 1973 This was particularly disturbing as the risks of pooling plasma had been written about for decades in international medical journals. Factor concentrates were small bottles of dried plasma that had to be mixed with sterile water and then injected directly into a vein.

Grayson has long argued that factor concentrates should never have been put on the market in the 1960 without first finding a way to inactivate viruses within the blood, even if this meant delaying the new treatment by several years.

As Grayson highlighted in a previous article on blood safety, as soon as factor concentrates were released onto the US market place there were outbreaks of hepatitis in the American haemophilia population. Jessica H Lewis wrote in Vox Sanguinus in 1970,

“The widespread therapeutic use of fractions prepared from large pools of plasma has increased the risk of exposure to SH (serum hepatitis) and has produced an apparent sharp increase in the incidence of jaundice (table 1 shown) in a group of 300 haemophiliacs seen in this clinic….”

Grayson’s husband, Peter Longstaff, a haemophiliac with less than 1% clotting factor who was treated with cryoprecipitate during his childhood years did not become infected with hepatitis until given his first US factor concentrates.

The Infected Blood Inquiry set up in 2017 to examine how haemophiliacs came to be infected with blood borne viruses chaired by Sr Brian Langstaff has been asked by campaigners to investigate pool size, historic and current and the associated risk of viral infection. (Those infected by whole blood transfusions are also included in the Inquiry, but they were NOT exposed to high plasma pools, NOT given blood from paid donors and NOT treated with imported blood.)

Haemophiliacs, on the contrary, have long been referred to as the “canaries in the coal mine”. In 2006, an ABC, Nightline article looking at the historic infection of haemophiliacs with HIV and hepatitis viruses had this to say,

Think of them as “canaries in the coal mine.” Like the fragile birds sent down into the mines to detect the first whiffs of toxic gas, hemophiliacs represent a first line of defense against any infectious threat to the nation’s blood supply.

If groups of hemophiliacs suddenly become sick, their misfortune may very well alert the rest of us to the dangers of bad blood.

For hemophiliacs, regular infusions of a blood-clotting agent made from donated plasma have become essential to life. This agent, known as Factor VIII, reduces their blood-clotting time from hours to just minutes. It has been received by hemophiliacs and their families as a miracle drug that permits children to play without fear of uncontrolled bleeding from a simple scrape and allows adults to live twice as long as they might have a generation ago.

But Factor VIII, which was synthesized from the plasma of 20,000 to 100,000 donors, also carried a significant downside: If one of these donors is infected with a blood-born virus, the miraculous factor would also be contaminated. Many hemophiliacs were exposed to the hepatitis virus in the 1970s and to AIDS in the early 1980s — experiences that suggest how a miracle can become a nightmare.

https://abcnews.go.com/Nightline/story?id=128947&page=1

It wasn’t as if haemophiliacs were warned of the increased risks of going from cryoprecipitate to factor concentrates or the paid donors being used in imported treatment. Grayson’s late husband who attended Lord Mayor Treloar College in Hampshire as a child had his first US factor concentrates whilst on treatment trials. The boarding school catered for children with a range of disabilities including bleeding disorders. Peter’s parents received a letter from Newcastle Consultant Dr Peter Jones, who wrote to them on the 12th April 1973, stating,

You will have received a letter from Lord Mayor Treloar asking for your permission for Peter to participate in a special trial of regular factor VIII injections. The …… (referring to another child’s parents, name removed) have also been asked for their permission. I saw the …… last week and explained that I was in complete agreement with the trial and that it could do nothing but good for the boys and other patients.

It is important to note, that without knowing both the positives of taking treatment AND the risks, there is no “informed consent” which was deemed so important in the 1949 Nuremberg Code that produced key principles in terms of medical ethics.

Keeping in mind, some haemophiliacs were on prophylaxis treatment with factor concentrates three times a week to prevent bleeds and then extra treatment if they had breakthrough bleeds, you do the maths regarding how many hundreds of thousands of donors patients were exposed to potentially with each injection. This is why some doctors made efforts to ensure patients had treatment from the same manufacture with batch number in succession to avoid mixing factor concentrates and further increasing donor numbers but this was not always possible.

It is widely accepted that haemophiliacs were infected with hepatitis viruses B and C from their very first shot of imported commercial factor concentrates. Then they were often re-infected with different genotypes. It is also important to note that as haemophilia is an inherited condition there may be several family members born with haemophilia, receiving treatment and living with blood borne viruses.

Many years after the introduction of US factor concentrates to the UK, Corey Dubin, an haemophilia activist from the Committee of Ten Thousand (COTT) in the US highlighted the following regarding pool size that haemophiliacs were exposed to and in a video talk to university students, he said,

For years we were told that those pools were 30,000 donors per pool what we learned in internal industry documents was that those pools were anywhere from 30,000 donors to 300,000 donors which is a very different risk landscape, only the community never understood that.

UK haemophiliacs began to understand and question as they learned of the implications of their own infection with HIV and hepatitis viruses and watched their fellow haemophiliacs die. Acquiring knowledge was not made easy for the haemophilia community who were often tested for these viruses without their knowledge and permission using blood samples taken to check their clotting levels and then positive test results were sometimes withheld for years.

So what efforts were made to reduce pool sizes over the years and limit the spread of blood borne infections? It appears once heat treatment was introduced in the mid 1980s as a form of viral inactivation for factor concentrates, largely as a response to the emerging AIDS epidemic, little emphasis was put on limiting the number of donors per pool as a safety factor. This element was largely put on the back burner for another decade.

In 1996, a study in a September edition of Transfusion stated that, “risk of exposure increases with pool size and the prevalence of the agent in question and accumulates with repeated treatments with material manufactured from different pools.” The study also highlighted that, “reducing pool size would at best decrease this risk in proportion to the reduction in manufacturing scale. However, for individuals requiring repeated or continuous treatments, the risk of exposure to all but the rarest infectious agents would be only minimally affected, even by large reductions in manufacturing scale.”

Again this highlights why it was so important to put viral inactivation and safety first with factor concentrates not years later as a reaction to AIDS after the horse had already bolted.

Regarding receiving treatment from different pools… Longstaff’s records showed he had regular treatment from ALL the US plasma companies during the critical period of infection PRIOR to heat treatment and AFTER. It is no coincidence that the Newcastle Haemophilia Centre was noted to have the highest haemophilia death rates in the UK.

As previously mentioned, US pool sizes made with plasma from paid donors were considerably higher than those in the UK that used unpaid donors. Longstaff’s treatment was a mix of the 4 main US plasma company products with a much smaller amount of UK products. Depending on what was in the fridge at the haemophilia centre or at home, he could have different treatments with different products from different US pools even within the same day when on prophylaxis treatment or during an intense treatment period of several days if bleeding. A book written by Simon Garfield “The End of Innocence: Britain in the Time of AIDS” which included a chapter on UK haemophiliacs infected with HIV actually had a chapter titled, “the fridge that day” for that very reason.

Longstaff’s HIV infection was traced back to source with the help of lawyers and a documentary film maker Kelly Duda to an identified US Arkansas prison plasma donor via treatment batch numbers, a fact accepted by the US pharmaceutical companies involved in litigation. This prison plasma programme did not close down until 1991 which was years AFTER the UK stopped collecting blood from inmates, thus prolonging exposure to high-risk donors.

To reiterate, Longstaff had almost everything going in terms of different treatments manufactured from multiple high -risk, large donor number, plasma pools that included plasma collection that went against WHO guidelines with Longstaff receiving the aforementioned paid donations from Haiti, Central American mainland countries, US skid row donors, prisoners, prostitutes, drug users and gay men.

For those severe haemophiliacs that needed regular treatment and higher amounts over longer periods for bleeds it was especially important not to mix different treatments and different pools. Imported treatment from the US that relied on plasma from Central American countries also ran the risk of including viruses other than HIV and hepatitis viruses which were not generally present in UK donors or products. Donors were also over bled compared to the UK putting them at risk and sometimes to the point of collapse, this over bleeding depleted the blood of key elements and was again affecting the quality of the plasma.

Haemophiliacs who relied on only UK products were not exposed to the same level of mixing of different plasma pools as those who had predominately US products from numerous different companies and manufacturers with a far higher number of (remunerated) donors to the plasma pools.

On 31st July 1997, at at time when UK haemophiliacs were still being treated with American factor concentrates, a Congressional Hearing finally took place in the US titled, FDA Oversight: Blood Safety And The Implications Of Pool Sizes In The Manufacture Of Plasma Derivatives. The following is taken from that hearing with an introduction by Mr Christopher Shays, Chairman of the Sub Committee of Human Resources:-

Mr. Shays. I would like to call this hearing to order.

    Welcome to our witnesses and our guests. To minimize the

risk of injury or death in the event of an emergency, the fire

safety laws set a maximum on the number of people allowed in

this room.

    This was not a good way to open.

    Surprisingly, the blood safety laws don’t contain the same

type of common-sense safeguard. There are currently no limits

on the number of blood plasma donations combined into the pools

from which therapeutic proteins are extracted or fractionated.

In the event of an emergency such as the appearance of a new

blood-borne infectious agent, excessively large plasma pools

increase the risk of disease transmission to the users of

plasma-derived products, and make recalls more difficult.

    A user of a single dose of a fractionated product today may

be exposed to plasma from as many as 400,000 donors. Pool sizes

vary widely from company to company, product to product, lot to

lot, dose to dose. There is no standard.

    Patients are not routinely informed of the risks associated

with plasma pool sizes. Last year, in our oversight report on

blood safety, we recommended, among other steps, that plasma

fractionators should limit the size of plasma pools, with pool

sizes determined as much by public health risk factors as by

production economies of scale.

    Today, we ask Federal public health agencies, blood product

consumers, and the plasma industry what progress has been made

bringing safety considerations to bear and setting practical

upper limits on plasma pool sizes. For some products, pooling

is beneficial, even required, to capture a broad range of

antibodies, for example, or to extract a sufficient volume of a

scarce protein. For other products, however, there is an

undeniable and direct relationship between the number of donors

in the plasma pool and the risk of exposure to an undetected

infectious agent.

    Tragedy taught us that lesson. In the early 1980’s, new

hepatitis strains and the human immunodeficiency virus, HIV,

slipped into the blood supply. Thousands died. Hundreds of

thousands were exposed to Hepatitis C, many of whom have never

been told of their possible infection.

    Now other viral agents, and perhaps prion diseases, pose

similar threats to the safety of the blood supply. Yet the

risks presented by pool sizes have not been addressed.

A discussion on the issue of pool size included the following verbal exchange between Mr Shays, and a Ms Zoon, Ph.D, Director , Center for Biologics, Evaluation and Research, Food and Drug Administration

Mr. Shays. Is it fair to say the FDA was thinking that

these pool sizes were more like 10,000 and then learned it was

60,000? But wouldn’t it be pretty surprising for you all to

have learned that it was 400,000 in one instance? I mean, was

that a surprise?

    Ms. Zoon. I think the number of 400,000 was high. I think

at the Blood Products Advisory Committee earlier, I believe a

presentation was made by one of the blood associations, that it

was potentially as high as 100,000. But 400,000, I think was

higher than I would have predicted.

    Mr. Shays. Does that give the FDA a greater interest in

trying to take a look at this issue?

    Ms. Zoon. Well, we are committed to putting a limit on pool

size.

    Mr. Shays. OK.

    Ms. Zoon. And I think as we get additional information and

analyze it and verify that information, we will certainly view

limits on pool size as part of a–our recommendations.

    Mr. Shays. OK.

https://www.govinfo.gov/content/pkg/CHRG-105hhrg45902/html/CHRG-105hhrg45902.htm

In the mid 1990s, the emergence of v CJD in the blood supply in some countries (which is a prion that can’t be killed in the same way as HIV and hepatitis viruses) appears to have been a big motivator for finally looking at limiting pool size following decades of mostly inactivity.

In 2005, pool size and safety continued to appear on the agenda, The Atlantic quoted the following, again highlighting that US plasma pools were significantly higher than those in Europe.

Critics today still question the wisdom of cutting costs by maintaining massive plasma pools. Safer systems operate on a not-for-profit basis, and require only sufficient amounts of plasma to meet domestic needs. A 2005 report published by writers at Ghent University in Belgium says that in Belgium, “approximately 5,000 donations are mixed into such pools. In Germany, pools containing up to 60,000 donations are considered.” In the United States, “some donor pool sizes are in excess of several hundred thousand [donations].”

https://www.theatlantic.com/health/archive/2014/05/blood-money-the-twisted-business-of-donating-plasma/362012/

So far, the Infected Blood Inquiry has only discussed evidence where US pool sizes reached 60,000 and it is important that further research is carried out to include documents detailing the far higher pool sizes that we now know existed and may continue to exist. Fortunately in 2022, most UK haemophiliacs are now on a product called Recombinant, a synthetic clotting treatment to treat bleeds However, this may not be suitable for all, leaving some patients still relying on human plasma products which have continued to be imported due to the risk of variant CJD in the plasma of UK blood donors.

As mentioned at the beginning of this article, for decades the UK has only collected blood from volunteer donors compared to the US that largely relies on the higher risk paid donors. World Health Organization 1975 guidelines highlighted the importance of countries being self-sufficient in their own blood products and not relying on remunerated donors. The UK failed miserable on the self sufficiency aspect but remained committed to not paying donors for their blood. A recent look at the blood.co.uk website which provides information on donation and collection to the general public, states the following,

In some other countries, plasma derived medicinal products are made from plasma donated by donors who are paid. These medicines can be imported to the UK.

It’s illegal to pay blood donors in the UK.

Seeing the world “illegal” came as something as a surprise. Illegal is defined as, “contrary or forbidden by law, especially criminal law”. (What would be the implications and penalties for a company/organization if they were to use blood from paid donors in the UK?)

The Adam Smith Institute blog, titled “Paying The Blood Price Is The Way To End Donor Shortages” (22^nd August, 2013) also states,

The real issue is that it is illegal to pay for blood directly from the source but it’s not illegal to buy it from countries that have a surplus. Often this surplus is from paying their citizens to donate – like in the United States for example.

Over the years, the type of language used in publications regarding selling blood in the UK has tended to be along the lines of “against guidelines” “not permitted” “against the rules” “immoral” “high-risk” but not stated as “illegal” I have now written to both the website and the Department of Health and Social Care to ask them to clarify the following:-

Please can you advise,

1. What year was this ruling first introduced?
2. Under which part of UK legislation can I find this ruling?
3. Could you please provide a link.

It will be interesting to see how they respond. The point is however is that there is a great hypocrisy here as haemophiliacs were not allowed to be given blood products manufactured from UK paid donors but this safety point was ignored in terms of them receiving factor concentrates made from the plasma of remunerated US donors. So in essence, haemophiliacs received an inferior product, they were treated as second class citizens when it came to both protecting them from viral infection compared to the rest of the UK population receiving blood. These double standards were a key factor covered in documents within the 1991 HIV Haemophilia litigation but sadly the evidence was never heard in court.

Contaminated Blood victims need to know who was responsible for actions taken which affected the safety of patients, therefore, along with plasma pool size, it is important that the Inquiry looks at the implications of using paid donors as to date there has been no accountability for decisions made that led to harm in haemophiliacs and serious loss of life. In addition to haemophiliacs, some partners and children also became infected and many families were left bereaved and have spent years fighting for truth, justice and financial recompense, as, so far, not a penny in compensation has ever been paid.

Update

Today, 12th January 2022, I received the following response to my questions from Dr Rekha Anand, Consultant in Transfusion Medicine, NHSBT

Dear Carol,

Thank you for your enquiry to NHS Blood and Transplant regarding blood donation.

In 1946, the Ministry of Health set up the National Blood Transfusion Service.  It relied on the commitment and dedication of voluntary donors, as NHS Blood and Transplant does today.  Blood donation has been voluntary since the service was first established in 1946, so there has never been any requirement for us to refer to UK legislation.  The blood service in England has never paid donors to give blood or blood component donations.

If you have any further questions, then please do not hesitate to contact me.

Kind regards,

Rekha.

END

Carol Anne Grayson is an independent writer/researcher on global health/human rights/WOT and is Executive Producer of the Oscar nominated, Incident in New Baghdad.  She was a Registered Mental Nurse with a Masters in Gender Culture and Development. Carol was awarded the ESRC, Michael Young Prize for Research 2009, and the COTT ‘Action = Life’ Human Rights Award’ for “upholding truth and justice”. She is also a survivor of US “collateral damage”.