In 1994, the Irish Blood Transfusion Service Board (BTSB) informed the Minister for Health that a blood product they had distributed in 1977 for the treatment of pregnant mothers had been contaminated with the hepatitis C virus. Following a report by an expert group, it was discovered that the BTSB had produced and distributed a second infected batch in 1991. The Government established a Tribunal of Inquiry to establish the facts of the case and also agreed to establish a tribunal for the compensation of victims but seemed to frustrate and delay the applications of these, in some cases terminally, ill women.
This controversy also sparked an examination of the BTSB's lax procedures for screening blood products for the treatment of haemophilia and exposed the infection of many haemophiliacs with HIV, hepatitis B and hepatitis C.
Background The Blood Transfusion Service Board (BTSB) has responsibility for the production and supply of human blood products used for the treatment of various blood-related conditions. In 1970, it began production of anti-D human immunoglobulin for the treatment of rhesus negative (blood type) mothers who, having previously given birth to rhesus positive babies, could have anti-bodies that would cause haemolytic disease (HDFN) in the foetus of future pregnancies. If, following a neo-natal blood test, the rhesus (Rh) factor of the infant is found to be incompatible with that of the mother, an anti-D injection can be given to the mother to protect her future pregnancies. If the mother were to develop her own rhesus anti-bodies, she would be required to undergo a course of plasma exchange transfusion throughout her pregnancy to reduce the level of rhesus antibodies in her blood.
In 1970 the BTSB began manufacturing anti-D human immunoglobulin for intravenous application at its Dublin laboratory using a process developed in 1967 by Professor Hans-Hermann Hoppe of Hamburg's Central Institute for Transfusionmedicine, one of the founders of the German transfusion service, StKB. The process involved the use of ion-exchange chromatography together with an ethanol precipitation, which was thought at the time to inactivate viruses that might be present in donated blood, thereby removing them from the plasma eventually fractionated in the process. In 1972 Professor Hoppe notified the BTSB that he had refined his process to include a plasma quarantine period and ultrafiltration (instead of ethanol precipitation) but the BTSB continued to use his 1967 process. By 1975 it was known that hepatitis was a blood-born disease and that multiple types of hepatitis virus were in circulation. Tests were available to identify the hepatitis A and hepatitis B viruses and although it was suspected that another strain of the virus was responsible for Jaundice in patients whose blood did not test positive for either type, there was no diagnostic test for hepatitis C until 1990.
The 1977 contamination In 1976 a pregnant woman (referred to as "Patient X" in the report of the Finlay Tribunal) was a patient of Dr. McGuinness, assistant master of the Coombe Maternity Hospital. Having had several pregnancies severely affected by haemolytic disease, Patient X was prescribed a therapeutic course of plasma exchange over a 25-week period, to reduce the antibodies that would damage her foetus. The obstetric consultant suggested to one of the BTSB staff that they could off-set the cost of Patient X's treatment by using the plasma extracted from her (which had high concentrations of anti-D) to manufacture anti-D immunoglobulin. Patient X was never asked to consent to her plasma being used in this way.
Her treatment began in September 1976 and plasma from her first two treatments was mixed with that from other donors in 5 batches of anti-D produced by the BTSB and distributed between January and April 1977. On 4 November 1976, Patient X had a reaction to her plasma exchange and her treatment was suspended temporarily. On 17 November the Coombe Hospital notified the BTSB that Patient X had become jaundiced and was diagnosed as having hepatitis.
Dr. McGuinness requested that a sample of her blood be tested for hepatitis B and sent a second sample to the Middlesex Hospital in London. These tests reported negative for hepatitis B (hepatitis C was not recognized not to mention testable at this time.) As Patient X's plasma exchange treatments continued, regular blood samples were sent to the BTSB to monitor the level of rhesus anti-bodies in her blood, each sample labelled "infective hepatitis". Despite all senior medical staff at the BTSB being aware of this infection, they continued to take plasma donations from Patient X throughout January 1977 and include these in the pools used to make 16 batches of anti-D which were distributed to maternity hospitals for administration. The number of doses in each batch could vary from 250 to 400 injections.
In July 1977, the BTSB received a report from the Rotunda Hospital that 3 mothers who had received injections from anti-D batch 238 had subsequently developed hepatitis. On 25 July, the chief biochemist of the BTSB laboratory was instructed to exclude Patient X's plasma from all pools used to manufacture anti-D. She did precisely this but did not, however, consider disposal or recall of existing batches in which Patient X's plasma had already been used and continued to distribute these to hospitals.
Samples from the 16 batches of anti-D that included Patient X's plasma and samples from the 3 Rotunda patients were sent to the Middlesex Hospital for testing, which again were inconclusive as no test for hepatitis C existed. The Scientific Committee of the BTSB began to compile a list of the destinations to which doses from anti-D batch 238 had been sent. It is unclear however, if this was completed or used in any recall operation. Between August and December 1977, the BTSB received notifications of similar cases from the maternity hospitals at the Coombe and Holles Street in Dublin indicating contamination amongst two other batches of anti-D. Despite continued notifications of hepatitis cases in 1977 and 1978, the BTSB issued no national recall of its anti-D product.
Subsequent testing of 1977 samples By 1990 scientists had developed multiple diagnostic test mechanisms for hepatitis C: ELISA: HCV antibody enzyme immunoassay detects specific antibodies the body creates against HCV RIBA: Recombinant ImmunoBlot Assay (aka Western blot test) detects specific proteins associated with HCV PCR: HCV Polymerase Chain Reaction detects RNA of the specific virus HCV RNA can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and be detected. Screening a population usually relies on a combination of all three test types.
With the development of a diagnostic test for hepatitis C in 1990, Dr Jeremy Garson of the Middlesex Hospital conducted retrospective testing on the many non-A, non-B hepatitis (NANBH) samples it had retained over many years. On 16 December 1991, the Middlesex Hospital FAXed a letter to the BTSB in Dublin to inform them that retained samples from Patient X and the 1977 batches of anti-D had tested positive for hepatitis C. Attached to his letter, Dr. Garson provided a list of questions that would need to be answered to determine the causes and extent of infection caused in 1977. The BTSB replied to this letter suggesting the questions be discussed at a meeting in London. The meeting never happened and the BTSB seems to have taken no further action in respect of this letter.
When check-back of the Patient X's case commenced in 1992, 8 of the 16 batches made from the BTSB's plasma pools in from January to July 1977 were shown to be contaminated with hepatitis C. These included batch 250 from which Brigid McCole received her anti-D injection on 5 November 1977.
The 1989 contamination In August 1989 a pregnant woman (referred to as "Donor Y" in the report of the Finlay Tribunal) began a course of plasma exchange transfusions at St. James's Hospital in Dublin. In the first month of her treatment 10 donations of plasma were taken from her, all of which were clear of hepatitis C when subsequently tested in 1992.
On 13 September 1989 "Donor Y" received a unit of plasma from the BTSB which was almost certainly contaminated with hepatitis C. (Check back tests of her plasma donations after this date tested positive for hepatitis C, a sub-type different from the one that infected Patient X.) With the emergence of HIV in the 1980s and the BTSB's previous difficulties with hepatitis contamination, the BTSB now had a precautionary protocol surrounding plasma donations by mothers undergoing exchange transfusions: Plasma donations from such women could not be included in the production of blood products until they had given birth and had a blood test showing they were clear of HIV, hepatitis B and hepatitis C.
All of the plasma donated by Donor Y, therefore was frozen and stored subject to clearance for anti-D production. In September and 12 October more donations of plasma were taken from Donor Y and placed in storage. Throughout 1990, the laboratory staff of the BTSB requested the blood test clearance of Donor Y from the BTSB medical staff responsible for her case.
Despite receiving no test results, in January 1991 the BTSB lab began to include Donor Y's plasma in the plasma pools used to manufacture 46 batches of anti-D.
In November 1991, Donor Y was tested for HIV, hepatitis B and hepatitis C (for which a new test was available) and was found negative for all three. (It is assumed that by this point she had "sero converted" for hepatitis C, having produced sufficient antibodies to eliminate it from her blood stream.) The 4 batches of anti-D suspected of infecting women at the various Dublin maternity hospitals (and which included plasma taken from Donor Y in 1989) tested positive for hepatitis C.
It was not clearly established whether or not the BTSB laboratory chief was notified of these tests but she continued to manufacture and distribute 21 batches using Donor Y's plasma. Upon subsequent check-back of all 46 anti-D batches produced from the pools containing Donor Y's plasma, 20 batches were found to be positive for Hep-C, 3 were negative and in the remaining 23 "infectivity could not be ruled out".
1994 discovery of HCV contamination After the hepatitis C virus (HCV) was identified in 1988 and a diagnostic test developed in 1990, in 1991 the BTSB added this test to its screening of all blood donors (along with HIV and hepatitis B). The BTSB's regional director for Munster set up a survey of all donors in the region who tested positive for HCV, with a view to tracing the source of infection.
She began to notice very soon that almost all positive cases were females and fell across a relatively narrow age range. As a result of this survey, by 1994 she had identified a possible link between infected donors and the anti-D injections they had received many years previously. She made an interim report in this survey at a meeting of the BTSB Medical Consultants Group on 19 January 1994. It was decided to perform a similar study of HCV infection outside the Munster region.
Samples from the Munster donors who had tested positive for HCV were sent to the Middlesex Hospital and compared with samples from Patient X. The results suggested "a strong causative relationship" between them and the 1977 hepatitis infections. It was decided to send samples of the BTSB's current stocks of anti-D to Middlesex for testing. These still contained some batches in which Donor Y's plasma had been used. The results indicated some contamination with HCV but of a different sub-type from that found in 1977 samples.