National Blood Transfusion Service Research Articles

Fetomaternal alloimmune thrombocytopenia

Thrombocytopenia is the second commonest haematological abnormality in the neonatal period after anaemia due to iatrogenic blood letting. One to four percent of all newborn babies have a platelet count <150×10 9/l at birth and approximately 20–40% of neonates in intensive care units are affected by neonatal thrombocytopenia. The most common cause of severe neonatal thrombocytopenia is fetomaternal platelet incompatibility and subsequent alloimmunisation. During the last decade recent advances in molecular techniques have led to rapid and efficient methods for diagnosis. Progress in fetal medicine has enabled accurate determination of fetal status, allowing improvements in fetal diagnosis and therapy. Human platelet antigen (HPA)-1a is by far the most frequently involved platelet antigen system in Caucasians accounting for 90% of cases, followed at a much lower frequency by HPA-5b (5–15%) and HPA-3a. The incidence is estimated to be 1 per 2000 to 1 per 5000 live births, but this is low in comparison to the incidence of fetomaternal platelet antigen incompatibility especially for the HPA-1 alloantigen system in the Caucasian population in whom the estimated frequency of HPA-1b1b individuals is 2%. Retrospective and prospective studies have reported that the immunogenetic background is important, and the chance of HPA-1a alloimmunisation is strongly associated with maternal HLA class II DRB3 ∗ 0101 (DR52a) type. A significant association ( p=0.004) between severe thrombocytopenia and a third trimester antiHPA titre >1:32 has been observed. It is now possible to genotype the fetus or neonate and the parents, which provides confirmation as to which HPA systems are incompatible between the mother and father. Simultaneous genotyping of HPA-1, 2, 3 and 5 can be carried out using the polymerase chain reaction–sequence specific primers (PCR–SSP) protocol, which has been widely used for HLA class II determination. The platelet count may continue to fall during the first 48 h after birth and the risk of intracranial bleeding is highest during this period. The best option is transfusion of specially selected antigen negative compatible donor platelets or if unavailable, maternal washed platelets. Antenatal screening for the most common form of fetomaternal alloimmune thrombocytopenia (FMAIT), due to antiHPA-1a is under consideration, but there is no established method at present. The Scottish National Blood Transfusion Service started a study in August 1999 on 25,000 pregnancies to carry out a cost benefit analysis of routine antenatal screening. The aims of the study are to determine the frequency of HPA-1b homozygosity; monitor antibody titres during pregnancy and confirm correlation of antibody emergence with HLA-DRB3 ∗ 0101, and finally to access cost effectiveness of routine screening across Scotland. Of 26,509 women screened in three Scottish regions 501 (1.9%) are HPA-1b homozygous and about 9% of the consented women are antibody positive.

Audit of anti-D immunoglobulin administration to pregnant Rhesus D negative women following sensitising events

We performed a retrospective audit of 99 Rhesus D (RhD) negative women to discover if anti-D immunoglobulin (anti-D) prophylaxis was given in accordance with guidelines from the National Blood Transfusion Service Immunoglobulin Working Party (1991). It was found that all patients received appropriate management postpartum. However, more than half of the antepartum sensitising events beyond 20 weeks' gestation were not managed according to the guidelines. Only one patient was sensitised during the studied pregnancy and no sensitising events were recorded in her case. This supports the introduction of a policy of routine anti-D prophylaxis in the third trimester.

Super model behaviour.

EVA HERZICOVA (pictured) was one of five models praised by the National Blood Transfusion Service (NBTS) for giving blood in a photo shoot for the August edition of the style magazine.

The estimation of fetomaternal haemorrhage

Prepared by a working party of the BCSH Blood Transfusion (Chairman P. Kelsey) and General Haematology (Chairman J. T. Reilly) Task Forces Working party: J. F. Chapman, B. J. Bain, S. C. Bates, S. M. Knowles, K. H. Shwe, J. Parker-Williams, L. Robson and S. C. Robson Blood Transfusion Task Force: M. Bruce, J. F. Chapman, J. Duguid, S. M. Knowles, M. F. Murphy, L. Williamson, I. Cavill and J. K. Wood Haematology Task Force: R. J. Amos, B. J. Bain, C. Chapman, K. Hyde, E. Matutes, J. Parker-Williams, I. Cavill and J. K. Wood

Supply and demand of bone allograft for revision hip surgery in Scotland

The Scottish National Blood Transfusion Service is the main provider of bone for grafting in Scotland. Bone is procured only from live donors, following very strict selection criteria, and we have investigated whether the amount being collected was adequate. Our current harvest of approximately 1700 femoral heads per year is shown not to be enough to meet the future demand for revision surgery of the hip. Many more of these operations are being undertaken, and impaction grafting is being used increasingly. We have calculated the predicted rates of collection and usage for the next four to five years so that we can expand our service in a controlled fashion.

Supply and demand of bone allograft for revision hip surgery in Scotland.

The Scottish National Blood Transfusion Service is the main provider of bone for grafting in Scotland. Bone is procured only from live donors, following very strict selection criteria, and we have investigated whether the amount being collected was adequate. Our current harvest of approximately 1700 femoral heads per year is shown not to be enough to meet the future demand for revision surgery of the hip. Many more of these operations are being undertaken, and impaction grafting is being used increasingly. We have calculated the predicted rates of collection and usage for the next four to five years so that we can expand our service in a controlled fashion.

Organizational changes in Estonia.

The situation of the blood transfusion service in Estonia is analyzed since 1991. Considerable changes towards the establishment of a cost-effective on a cost-efficient system providing self-sufficiency of good quality blood products in future have been made. National blood transfusion service based on voluntary nonremunerated donations is under development.

Screening asymptomatic people at high risk for hepatitis C. The case against.

The hepatitis C virus is usually transmitted parenterally through blood products or shared needles. Most infected people develop mild chronic hepatitis, which tends to pursue an asymptomatic course over years or decades.1 It is not known how many of those affected will eventually develop clinical sequelae from liver disease. Screening blood donations for antibodies to the hepatitis C virus has led to a considerable reduction in the incidence of transfusion associated hepatitis.2 The United Kingdom's National Blood Transfusion Service has introduced a hepatitis C “lookback” programme to identify and screen those known to have received infected blood before testing of donations began in 1991. Other individuals at risk include injecting drug users, people with haemophilia, and health care workers. According to one estimate there may be 200 000 people with chronic hepatitis C in the United Kingdom.3 Should asymptomatic individuals belonging to these groups be offered screening for hepatitis C? This question raises both medical and ethical issues which share an analogy with screening for infection with HIV. A positive test result for hepatitis C comes as a devastating blow to a healthy person. Concerns are raised about the mode of viral acquisition, risk of transmission to close contacts, marriage, employment and life insurance prospects, and the future risk of cirrhosis and hepatoma. …

Management of blood donors whose donations are repeatedly falsely positive by the HIV antibody screening test.

Since 1985, over 1,800,000 donations have been screened by the West Midlands Regional Blood Transfusion Service for antibody to HIV. Twelve regular donors gave three or more donations that were alternatingly positive and negative in the screening test, but not confirmed to be HIV positive by supplementary testing. Extensive investigation of six of these donors, including the polymerase chain reaction (PCR), failed to confirm HIV infection. The donors were reassured but, nevertheless, retired to comply with the guidelines of the National Blood Transfusion Service. These findings indicate that, for UK donors, ambiguous serological findings are unlikely to reflect HIV infection. On the rare occasions where serological results are particularly ambiguous, PCR testing of donors' blood may be helpful.

Seroprevalence of total antibodies to hepatitis A virus in haemophiliacs in the West of Scotland.

Serum samples taken from 73 patients with haemophilia A were tested for the presence of total antibody against hepatitis A (antiHAV) by radiommunoassay. 29 (39.7%) were antiHAV positive and 44 (60.3%) were antiHAV negative. These figures are comparable with local prevalence figures for immunity (40.3%) and susceptibility (59.7%) to HAV in adults. 30 patients were subsequently exposed to Scottish National Blood Transfusion Service High-Purity Factor VIII (SNBTS HPVIII). They were re-tested for the presence of antiHAV at a median of 5 months after exposure. Of these, 25 (83.3%) were antiHAV negative and five (16.7%) were antiHAV positive. All five of these antiHAV-positive patients were positive on samples taken prior to exposure. No cases of seroconversion to hepatitis A occurred.

Functional assessment of therapeutic anti-D immunoglobulin using Fc-mediated assays.

Therapeutic anti-D immunoglobulin preparations issued by the Scottish National Blood Transfusion Service, between 1980 and 1986, were evaluated using in-vitro Fc-mediated functional tests that reflect potential in-vivo mechanisms of specific red cell destruction and clearance. All batches tested were found to: (a) contain anti-D of mainly IgG1 subclass and lesser amounts of IgG3; (b) mediate lymphocyte and monocyte rosetting; and (c) produce lytic activity in both K cell and monocyte ADCC. The functional activity of the therapeutic immunoglobulin preparations over this period of production had not altered despite increased plasma contributions latterly to the pool from deliberately immunized male donors. This is the first in-vitro study of the Fc-mediated function of therapeutic polyclonal anti-D preparations. As these preparations were clinically effective in the prophylactic anti-D programme, such bioassays of FcRI/II and FcRIII activity are justified for the future evaluation of immune plasma before blending for fractionation and production of therapeutic anti-D immunoglobulin.

Absence of hepatitis A virus transmission by high‐purity solvent detergent treated coagulation factor concentrates in Scottish haemophiliacs

Recent reports of hepatitis A virus (HAV) infection in haemophiliacs receiving high-purity solvent detergent (HP.SD) treated factor VIII concentrates have brought into question the efficacy of this virucidal method for inactivating HAV. To assess whether HAV may have been transmitted by HP.SD concentrates, we compared seroprevalence in haemophiliacs with different disease severity, sought evidence of seroconversion to HAV since introduction of HP.SD products, and directly examined concentrates for HAV RNA by PCR. Our data suggest that Scottish haemophiliacs are not being infected with HAV by HP.SD concentrates produced initially by CRTS Lille and presently by PFC Edinburgh and supplied by the Scottish National Blood Transfusion Service (SNBTS).

Distribution of Hepatitis A Antibody over a Process for the Preparation of a High‐Purity Factor VIII Concentrate

The levels of hepatitis A antibody were studied in factor VIII products manufactured by the Scottish National Blood Transfusion Service. It was found that the current high-purity factor VIII product has no detectable hepatitis A antibody, whereas the superseded intermediate-purity product had significant antibody levels (6,700 mIU/ml). Although the finished high-potency factor VIII product has no detectable hepatitis A antibody, significant levels of antibody are found in the early stages of product manufacture. This antibody may offer some protection against hepatitis A contamination present in very occasional plasma donations. Antibody to parvovirus B19 is also present at intermediate stages in the manufacture of high-potency factor VIII, but its significance is not known. Hepatitis A antibody levels were also measured in normal immunoglobulin. These data indicate that antibody levels in the plasma pools used to manufacture factor VIII are falling.

Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK)

The introduction of screening for hepatitis C virus (HCV) by the National Blood Transfusion Service identified donors who had acquired HCV infection. We undertook a case-control study amongst blood donors in the Trent Region to determine risks for HCV infection. A total of 74 blood donors confirmed positive for hepatitis C infection and 150 age, sex and donor venue matched controls were included in the study. Fifty-three percent of hepatitis C infected blood donors reported previous use of injected drugs compared to no controls; relative risk (RR) not estimatable (lower limit 95% CI = 20). Other risk factors were a history of: receipt of a blood transfusion or blood products RR = 3.6 (95% CI 1.5-8.3), having been a 'health care worker' RR = 2.8 (95% CI 1.1-7.6), tattooing RR = 3.3 (95% CI 1.2-8.7), and an association with having been born abroad RR = 3.2 (95% CI 1.1-9.5). No risk was shown for a history of multiple sexual partners, ear piercing or acupuncture. Injecting drug use explains more than 50% of hepatitis C infections in blood donors, a group who are less likely to have injected drugs than the general population.

Report demands greater safety with blood transfusions.

A national system for reporting critical blood transfusion incidents should be set up, the Scottish National Blood Transfusion Service hits demanded.

Follow up of blood donors positive for antibodies to hepatitis C virus

The hepatitis C virus has been identified as the main cause of post- transfusion hepatitis.1 Mandatory screening of blood donations for antibodies to hepatitis C virus was introduced by the National Blood Transfusion Service on 1 September 1991. Donors confirmed to be positive for antibodies to hepatitis C virus at the North London Blood Transfusion Centre are offered counselling by medical staff at the centre, who explain the relevance of the test results. They are then referred to their general practitioner. Current evidence suggests that many of the asymptomatic donors positive for antibodies to hepatitis C virus are chronic carriers, in whom the virus replicates.2 Probably some asymptomatic donors will progress to clinically significant, and possibly severe, liver disease in the future. Follow up of the donor by the general practitioner or hospital clinic, or both, will be influenced by information and advice given as a result of the initial counselling. To date there has been no information on the …

Prophylaxis with anti-D immunoglobulin

EDITOR, - D Lee, writing on behalf of the National Blood Transfusion Service's Immunoglobulin Working Party,1 advocates the continued use of a standard dose of 500 IU anti-D immunoglobulin for postnatal prophylaxis in Rh D negative women …

Distribution of Hepatitis A Antibody over a Process for the Preparation of a High-Purity Factor VIII Concentrate

The levels of hepatitis A antibody were studied in factor VIII products manufactured by the Scottish National Blood Transfusion Service. It was found that the current high-purity factor VIII product has no detectable hepatitis A antibody, whereas the superseded intermediate-purity product had significant antibody levels (6,700 mIU/ml). Although the finished high-potency factor VIII product has no detectable hepatitis A antibody, significant levels of antibody are found in the early stages of product manufacture. This antibody may offer some protection against hepatitis A contamination present in very occasional plasma donations. Antibody to parvovirus B19 is also present at intermediate stages in the manufacture of high-potency factor VIII, but its significance is not known. Hepatitis A antibody levels were also measured in normal immunoglobulin. These data indicate that antibody levels in the plasma pools used to manufacture factor VIII are falling.

Chairman??s Introduction

Mr David McIntosh is with the Scottish National Blood Transfusion Service, 21 Ellen's Glen Road, Edinburgh, EH17 7QT, UK.

Study of viral safety of Scottish National Blood Transfusion Service factor VIII/IX concentrate

Summary. To assess the viral safety of the Scottish National Blood Transfusion Service (SNBTS) intermediate purity factor VIII and IX concentrates, the liver function and viral status were assessed prospectively in 13 recipients. None developed hepatitis or seroconverted to HIV or HCV. This study provides additional evidence for the efficacy of dry heat treatment at 80°C for 72 h in preventing virus transmission by coagulation factor concentrates.