Incidence and associations of acute renal failure complicating high-dose intravenous immunoglobulin therapy.

In a formal study, we have identified increasing age, pretreatment renal impairment and diabetes mellitus as risk factors for the development of intravenous immunoglobulin-induced renal failure. Identification of these characteristics in potential recipients should alert clinicians to the associated increased risk of this serious complication.

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 x 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.

A one-centre prospective audit of peri- and postoperative blood loss and transfusion practice in patients undergoing hip or knee replacement surgery.

We prospectively audited peri-operative blood loss and blood transfusion practice in 42 elderly patients (mean age, 71.8 years, 68% female) undergoing hip or knee surgery in an orthopaedic unit. Only in 57% of all operations was blood loss recorded. Compliance with the Maximum Surgical Blood Ordering Schedule (MSBOS) was variable, and Cross-matching to Transfusion (C/T) ratios were low. In 86% of operations, blood had been issued pre-operatively (average three units, range = 1-61 units). Of these patients, 75% subsequently received a transfusion. In 26% of all the operations, the transfusion, although confirmed by the blood transfusion laboratory records, had not been recorded in the medical or nursing notes. The average pre-operative Hb in the transfusion group was 123 g/l (range, 80-144 g/l) and 112 g/l postoperatively and after a transfusion (range, 75-133 g/l). This compared to the non-transfusion group's value of 124 g/l (range, 86-186 g/l) and 113 g/l (range, 77-147 g/l) postoperatively. The high blood issuing and transfusion rates raise the concern that transfusions are being given in response to habit or blood availability, and not medical indications. This would imply that some patients are exposed to unnecessary risks. Furthermore, inadequate documentation of the transfusion process opens the medical profession to criticism and medical, legal and ethical complications regarding patient care. Positive improvements suggested by regular medical audit may help address these problems.

Transfusion associated graft versus host disease in an immunocompetent individual following coronary artery bypass grafting.

Transfusion associated graft versus host disease (TA-GVHD) is a rare but commonly fatal complication of transfusion of cellular blood products, which usually occurs in immunosuppressed individuals following transfusion and subsequent engraftment of viable T lymphocytes. Very rarely it may arise in apparently immuno-competent individuals. A case is reported of TA-GVHD in a non-immunocompromised 60 year old white man, resulting from red cell transfusion after coronary artery bypass grafting. HLA typing confirmed homozygosity of the donor for an HLA type shared by the recipient--the classic scenario for the development of TA-GVHD in immunocompetent individuals. The patient died 21 days after transfusion. There is a perceived increased risk of TA-GVHD following bypass grafting and other surgical procedures where cardiopulmonary bypass is required. TA-GVHD is probably underreported and the incidence in the UK is felt to be too low to warrant routine irradiation of cellular products for this group of patients. Clinicians, pathologists, and transfusion centres should be aware of this rare but devastating complication of blood transfusion after cardiac surgery.

Anti-HBs detection: a modified passive haemagglutination assay.

Modification of a commercial haemagglutination assay for the detection of anti-HBs has reduced the test time from over one hour to approximately 25 min. increased sensitivity ten-fold without any prozoning, maintained specificity and reduced costs by 90%. The modification consists of diluting the reagent cells ten-fold; these are then added to dilutions of test serum in a V-well microplate. After incubation, plates are centrifuged and then inclined at 70 degrees. Positive and negative reactions can be clearly distinguished within approximately 10 minutes.

Is there a wastage of resources due to non-specificity of anti-HIV ELISAs?

A library of anti-HIV ELISA 'grey-area' and repeatably reactive samples sent for confirmatory testing, were retested using a second technique, the modified (Fujirebio Gelatin Particle) agglutination test (MAT). On testing 224 grey-area reactive samples, only four were found to be reactive with this second test. On retesting a further 259 ELISA repeatably reactive samples, of which only 33 were confirmed to be anti-HIV-1, only 45 were reactive by MAT; these included the 33 confirmed as positive samples, thereby reducing the false-positive from 226 to 12. The introduction of this second technique supported our decision to cease the referral of grey-area samples. It also demonstrated the high prevalence of non-specificity of repeatable reactivity associated with some of the most specific ELISA kits currently available.

Anti-HIV-1: extended validation of a modified gelatin particle agglutination assay, and its use with an image analyser.

Modification of a commercial gelatin particle agglutination assay for anti-HIV-1 (MAT) has increased sensitivity, reduced reaction time and lowered the cost by 90%. We tested over 10,000 blood donations in parallel with the ELISA currently in use, and found the modified test to be highly sensitive and to enhance cost-effectiveness as it substantially reduces false-positive rates. The patterns of agglutination are clearly reproducible and readable by the naked eye and/or Image Analyzer, which provides objectivity and hard-copy documentation of results.