Blood transfusions and clotting factors are among medicine’s most iconic interventions. In addition to replacing blood shed during surgery, childbirth or accidents, transfusions treat, for instance, thalassemia, sickle cell disease and leukaemia.1,2 Until cryoprecipitate’s introduction, people with haemophilia (PwH) could die from blood loss during routine dental work, such as removing wisdom teeth.3
But even iconic interventions carry risks. Transfusions can cause non-infectious adverse events, such as allergic reactions. Sometimes these non-infectious adverse events are asymptomatic. But some reactions can be lethal.4
Today, the likelihood of contracting a ‘classic transfusion-transmitted infectious agent’ – human immunodeficiency virus (HIV) hepatis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic virus types I and II – is less than 1 in 1 million in high-income countries. But blood can transmit other infections including West Nile virus, zika virus and malaria, although the risk is less than 1 in 3 million.5
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However, transfusions and clotting factors were not as safe as they should have been in the 1970s and 1980s. About 1250 of the 4000–6000 people with bleeding disorders at this time contracted HIV.1 Blood transfusions infected between 80 and 100 people with HIV and approximately 26,800 with HCV.1 Children accounted for about a third of those infected with HIV from contaminated blood in the 1970s and 1980s.6
In addition, almost everyone who received factor VIII (FVIII) during the 1970s and 1980s contracted HCV. Many were infected with both viruses.3 One haemophiliac contracted HBV, HCV, HIV, cytomegalovirus and the human herpes virus from contaminated FVIII.6 A more effective and rapid response from the political and medical establishment might have avoided much, although not all, of this suffering.1
‘The scale of what happened is horrifying’, said Sir Brian Langstaff who chaired the Infected Blood Inquiry. ‘The most accurate estimate is that more than 3,000 deaths are attributable to infected blood, blood products and tissue.’1 The Inquiry identified a ‘catalogue’ of largely preventable failures. But the writing was on the wall decades before Langstaff started collecting evidence. And the Inquiry’s findings have implications not just for haematological services, but also for every clinical interaction.
The blood factor
Thrombin ‘plugs the gap’ in damaged tissue, stimulates production of a strong fibrin clot and instigates wound healing.7 Essentially, PwH do not produce enough thrombin, which leaves them vulnerable to heavy bleeding after minor trauma. They can also spontaneously bleed, usually into joints, muscles or intracranially.7
A complex cascade of ‘factors’ controls clotting. Haemophilia A and B, which occur once every 5000 and 25,000 male births respectively, arise from deficiencies in FVIII and factor IX respectively.7,8 Depending on the levels of clotting factor, haemophilia can be severe (<1% of normal factor activity), moderate (1–5%) or mild (5–50%).8
In 1937, researchers showed that a ‘fraction’ separated from plasma could correct the coagulation problems in PwH.9 In the early 1960s, researchers discovered that freezing and thawing plasma produced a layer rich in blood clotting factors. For example, this ‘cryoprecipitate’ contained 10 times the amount of FVIII as untreated plasma. PwH received infusions of cryoprecipitate to stop bleeding. But cryoprecipitate was in short supply.6 So, researchers developed a freeze-dried powder from plasma, called concentrates. PWH could now treat bleeds at home or work.6
These were life-saving, transformative treatments. During the 1940s, most people with severe haemophilia died during their teens. Fresh frozen plasma and cryoprecipitate increased life expectancy to about 20 and 57 years respectively. Widespread use of FVIII extended life-expectancy among PwH to a median of about 60 years in the 1970s.3 However, with hindsight what happened next seems inevitable.
Dirty blood
Unlike the UK’s voluntary system, companies in the USA pay donors for blood. In 1964, some companies started collecting blood from prison inmates, many of whom were drug addicts and so harboured blood-borne infections, with little if any screening.6 In 1975, the TV documentary series World in Action revealed that the NHS bought blood collected for money from drug addicts, alcoholics and the homeless in US cities.6
At the time, John Cash, from the Royal Infirmary Edinburgh, commented that ‘There is no doubt that the import into the United Kingdom of factor VIII concentrates derived from external sources, however well screened for hepatitis viruses, represents an unequivocal pathway by which the level of a potentially lethal virus into the whole community is being deliberately increased.’10
Critically, manufacturers pooled blood donations. So, a FVIII batch could contain blood from 25,000 donors. Only one donor needed to harbour a blood-borne infection to contaminate the entire batch.3 Langstaff noted the UK increased the size of the pools used to manufacture FVIII and IX concentrates ‘although it was well known that this would markedly increase the risks of viral transmission’.1
In 1973, an Expert Group recommended that the UK should become self-sufficient in blood and blood products, and the Department of Health and Social Security accepted the recommendation.1,6,11 Yet by the early 1980s, FVIII imported from the USA accounted for half the UK’s supply.3 In his wide-ranging report, Langstaff highlighted the failure to ensure a sufficient supply of FVIII concentrates from UK donors ‘to meet reasonable foreseeable demand’ as a key failing.1,6,11
Then in July 1982, the US Centers for Disease Control and Prevention (CDC) reported that three PwH had been diagnosed with pneumocystis pneumonia (PCP), a potentially deadly fungal infection.3 The cases seemed reminiscent of a severe immunodeficiency disease then spreading rapidly among men who had sex with men (MSM): gay-related immune deficiency (GRID), today known as AIDS.3 Researchers in France and the USA identified human T-lymphocytic virus type III as the cause of AIDS in 1984. Virologists renamed the retrovirus HIV in 1986.3
In January 1983, the New England Journal of Medicine warned that healthcare professionals ‘must now be alert’ to the risk posed by HIV in blood products. ‘Preventing the complications of the present treatment [FVIII contaminated with HIV] may have to take precedence over preventing the complications of hemophilia itself,’ the journal remarked.9 In March 1983, the CDC listed the four groups at highest risk of AIDS: MSM with multiple sexual partners; people from Haiti; those who inject street drugs; and PwH.3
Meanwhile, journalists raised concerns about contaminated blood on this side of the Atlantic. The story really hit the headlines in May 1983 when the Mail on Sunday published an exposé: ‘Hospitals Using Killer Blood’.3
In July 1983, the UK’s Committee on the Safety of Medicines concluded that FVIII could transmit AIDS. But argued that the risk was small and withdrawing imported FVIII from the NHS was impractical.3 Yet the Government failed to keep the decision under review.1
In November 1983, the Lancet reported that a 58-year-old heterosexual man was the first person outside the gay community to die from AIDS in the UK.3,12 He had received large amounts of FVIII that originated in North America.12 Despite the deaths and the warnings, the Department of Health (DoH) did not publicly state that blood could definitely transmit AIDS until December 1984.3 Britain started screening blood donors for HIV in October 1985.3
By then, researchers had reported that heating FVIII concentrates to 68°C for several hours inactivated ‘substantial quantities’ of HIV.13 The DoH recommended that doctors should use only heat-treated factor VIII at the start of 1985. Britain began producing heat-treated factor VIII in March that year.3 Nevertheless, Langstaff highlighted the failure to encourage and finance research into methods of viral inactivation of factor VIII and IX concentrates’ as another key failing.1 Introducing viral inactivation more rapidly ‘could have prevented many infections … and deaths’.1
Another tragedy
Meanwhile, another tragedy was unfolding. Haematologists recognised that acute hepatitis in people who received blood products was ‘not … uncommon’.14 In 1967, researchers identified two types of hepatitis (now called hepatitis A and B), which differ in routes of transmission and incubation period.15 Limited data meant that the Infected Blood Inquiry could not estimate the number of people infected with chronic HBV from blood transfusions and blood products.1
But haematologists realised that another cause (non-A, non-B hepatitis) lurked in blood. In 1981, Bamber et al reported 10 cases of non-A, non-B hepatitis after treating coagulation disorders with various FVIII preparations. But these hepatitis cases had a short incubation period of one to four weeks, five patients were symptomatic and serum transaminases (which indicate liver function) remained raised during follow up of 6-45 months. Bamber et al presciently noted that the slow recovery ‘suggests that this viral agent is an important cause of chronic liver disease in patients with coagulation disorders and possibly also in the general population’.14 HCV was identified in 1989.16
Again the UK authorities did not act in time. Despite the risks, the UK relaxed the rules regarding blood donors with a history of jaundice or hepatitis in 1977 and collected blood from prisoners until 1986.17 Moreover, in 1983, UK researchers noted ‘There is a higher incidence of hepatitis in patients receiving transfusions of blood obtained from paid donors compared with patients whose transfusions were obtained from volunteer donors’.18 Yet 23 countries introduced HCV screening before the UK in 1991.17
A very British response
Some of those involved in the French infected blood scandal ended up in prison.3 Doctors and officials in Japan, Portugal and Iran faced criminal charges.3 The UK’s response was typically British: hold an inquiry.
The Haemophilia Society started calling for an inquiry in 1988.3 In 2007, Lord Peter Archer opened an inquiry into contaminated blood. Because a minister did not establish the inquiry, Archer could not compel people to testify. The DoH and Health Secretary declined to participate. But after two-years deliberation, Archer called the HIV and HCV infections ‘a horrific human tragedy’. He noted that quicker action from the UK authorities may have ‘significantly reduced’ the ‘scale of the catastrophe’ and called for compensation.3
The Scottish government also held an inquiry starting in 2008. But again the inquiry could not compel people to give evidence.3,11 In July 2017, then Prime Minister Theresa May announced, at last, a full public inquiry into contaminated blood.3 Langstaff’s Infected Blood Inquiry started hearing evidence in April 2019.3
Meanwhile, the death toll rose. By the time the Langstaff Inquiry started hearing evidence, at least 1170 people with bleeding disorders had died from HCV and HIV contracted from plasma products and 1675 from infections transmitted by blood transfusions.3 Between July 2017 and January 2024, 680 people died from contaminated blood.6 Even today, many people with viral hepatitis probably do not realise that have been infected. As one of the Inquiry’s recommendations, Langstaff suggested that primary care staff should ask newly registered patients if they have received a transfusion. This could help identify and support people who are currently undiagnosed.2
Follow the money
A plethora of ‘wrongs … on individual, collective and systemic levels’ contributed to the infected blood scandal.1 For instance, the ‘establishment’ had ‘an attitude of denial towards the risks of treatment with factor concentrates’.1 Thatcher’s government did not want to discuss promiscuity. So, they did not explicitly identify MSM as being at greater risk. Thatcher also questioned a comment about ‘risky sex’ concerned that the mention would encourages experimentation.3
Langstaff noted that ‘fear of financial exposure’ mainly drove the response to the infected blood scandal.2 Officials of successive governments expressed concern about the scandal’s cost and the consequences for the NHS more widely.6 Nevertheless, on May 21 2024, the Government announced a compensation scheme. A person infected with HIV could receive about £2.5 million. A person living with viral hepatitis may receive £35,500 and £1.5 million, depending on chronicity.17 The cost of compensation could reach £10 billion.2
Throughout the chain of events that lead to the deaths, the NHS tended to focus on cost rather than quality. During the 1970s, for example, Immuno made two versions of FVIII. One derived from plasma from European volunteers. The other used plasma imported from the USA. As long ago as 1976, an Immuno internal memo noted that ‘The British market will accept a higher risk of hepatitis for a lower-priced product’.3
Ironically, tranexamic acid, an inexpensive generic, significantly reduces life-threatening bleeding, major bleeding or bleeding into a critical organ within the 30 days after treatment. There is no difference in the risk of unwanted thrombosis. Yet Langstaff’s Inquiry highlighted the NHS’s on-going under-use of alternatives to transfusion.19
The inquiry and the history of the scandal underscores the importance of the duty of candour, good communication and informed consent.2 It’s a lesson not just for every transfusion service, but also for every practice, every healthcare professional and every nurse. Langstaff noted that healthcare professionals inadequately discussed the risks of transfusion with patients.19 In general, healthcare professionals failed ‘to tell people of the risks of treatment and of available alternative treatments, thus treating them without their informed consent’.1
Statistics and forensic investigations do not tell the whole scandalous saga. Langstaff added that a ‘level of suffering which it is difficult to comprehend, still less understand, has been caused to so many, and that this harm has, for those who survived long enough to face it and for those who, infected and affected, are now able to read [the Inquiry’s report], been compounded by the reaction of the government, NHS bodies, other public bodies, the medical professions and others’.1
A brace of books eloquently explore the often heart-wrenching human tragedies behind the figures and go some way to sharing the suffering.3,6 The books left me in turn angry, sad and shocked. McGoogan and Wheeler also detail the machinations among the pharmaceutical companies and the political and medical establishments, including arguably unethical experiments on adults and children, which there is not space to cover.3,6
However, the scandal’s victims may never hear the whole story. ‘It will be astonishing to anyone who reads this Report that these events could have happened in the UK,’ Langstaff wrote. ‘It may also be surprising that the questions why so many deaths and infections occurred have not had answers before now. Those answers cannot be as complete as they might have been 30 years ago, and I acknowledge that despite the vast number of pages of documents which the Inquiry has examined, some questions must remain unanswered.’1
Mark Greener is a freelance Medical writer
References
1. Infected Blood Inquiry. Volume One Available at https://www.infectedbloodinquiry.org.uk/reports/inquiry-report.
2. Thornton J. 2024. Infected blood report release marks a day of shame for the UK. Lancet. 403 (10441):2276-7. https://doi.org.10.1016/s0140-6736(24)01072-9.
3. McGoogan C. 2024. The Poison Line: Life and Death in the Infected Blood Scandal. London: Penguin Books.
4. Goel R, Tobian AAR and Shaz BH. 2019. Noninfectious transfusion-associated adverse events and their mitigation strategies. Blood. 133 (17):1831-9. https://doi.org.10.1182/blood-2018-10-833988.
5. Busch MP, Bloch EM and Kleinman S. 2019. Prevention of transfusion-transmitted infections. Blood. 133 (17):1854-64. https://doi.org.10.1182/blood-2018-11-833996.
6. Wheeler C. 2024. Death in the Blood. London: Headline.
7. Berntorp E, Fischer K, Hart DPet al. 2021. Haemophilia. Nat Rev Dis Primers. 7 (1):45. https://doi.org.10.1038/s41572-021-00278-x.
8. Peters R and Harris T. 2018. Advances and innovations in haemophilia treatment. Nature Reviews Drug Discovery. 17 (7):493-508. https://doi.org.10.1038/nrd.2018.70.
9. Desforges JF. 1983. AIDS and preventive treatment in hemophilia. N Engl J Med. 308 (2):94-5. https://doi.org.10.1056/nejm198301133080209.
10. Cash JD. 1976. Commercial and NHS factor VIII concentrates. Br Med J. 1 (6003):221. https://doi.org.10.1136/bmj.1.6003.221-b.
11. Penrose Inquiry. Self-sufficiency and the supply of blood products in scotland (with particular reference to the treatment of haemophilia A. Available at https://www.penroseinquiry.org.uk/index.html.
12. Daly HM and Scott GL. 1984. Fatal AIDS in a UK haemophiliac. Lancet. 1 (8367):44. https://doi.org.10.1016/s0140-6736(84)90203-4.
13. Levy JA, Mitra G and Mozen MM. 1984. Recovery and inactivation of infectious retroviruses from factor VIII concentration. Lancet. 2 (8405):722-3. https://doi.org.10.1016/s0140-6736(84)92627-8.
14. Bamber M, Murray A, Arborgh BAet al. 1981. Short incubation non-A, non-B hepatitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders. Gut. 22 (10):854-9. https://doi.org.10.1136/gut.22.10.854.
15. Yuen M-F, Chen D-S, Dusheiko GMet al. 2018. Hepatitis B virus infection. Nature Reviews Disease Primers. 4 (1):18035. https://doi.org.10.1038/nrdp.2018.35.
16. Manns MP and Maasoumy B. 2022. Breakthroughs in hepatitis C research: from discovery to cure. Nature Reviews Gastroenterology & Hepatology. 19 (8):533-50. https://doi.org.10.1038/s41575-022-00608-8.
17. Anonymous. 2024. No accident: the UK infected blood scandal. Lancet Gastroenterol Hepatol. 9 (8):677. https://doi.org.10.1016/s2468-1253(24)00195-x.
18. Fletcher ML, Trowell JM, Craske Jet al. 1983. Non-A non-B hepatitis after transfusion of factor VIII in infrequently treated patients. Br Med J. 287 (6407):1754-7. https://doi.org.10.1136/bmj.287.6407.1754.
19. Burki T. 2024. Underuse of tranexamic acid in the UK. Lancet. 403 (10446):2772. https://doi.org.10.1016/s0140-6736(24)01343-6.