The prothrombin gene G20210A variant: prevalence in a U.K. anticoagulant clinic population.

We have investigated the prevalence of a recently reported genetic variation in the prothrombin gene (G20210A) in patients with an objectively confirmed history of venous thrombosis, 12/219 patients (5.5%) were found to be heterozygous carriers of the 20210A allele. The incidence of the 20210A allele in a group of 164 healthy controls was 1.2% (allele frequency 0.61%, 95% CI 0.08-2.19). When patients with a known alternative hereditary risk factor for venous thrombosis (factor V Leiden mutation or deficiency of antithrombin, protein C or protein S) were excluded, the G20210A variant was found to increase the risk for venous thrombosis by approximately 5-fold (odds ratio 5.4, 95% CI 1.16-25.0). This prothrombin gene sequence variation adds further to the list of recognized genetic risk factors for thrombophilia.

Flow cytometry in diagnosis and management of large fetomaternal haemorrhage.

AIMS: To evaluate an indirect immunofluorescence flow cytometry technique in a series of patients with large fetomaternal haemorrhage (FMH). METHODS: Patient samples identified by Kleihauer testing in local laboratories as having FMH > 4 ml were sent for flow cytometric analysis. In a proportion of cases the mothers received anti-D immunoglobulin prophylaxis according to the flow cytometer estimate of FMH volume. RESULTS: Forty three cases of FMH were studied prospectively. The correlation between Kleihauer and flow cytometry results was poor. In 38 (88%) cases the size of FMH quantitated by flow cytometry was lower than that estimated using the Kleihauer technique. In 13 (30%) cases no Rh D immunoglobulin positive cells were detected by flow cytometry. Centralised review of the original Kleihauer films using a calibrated microscope resulted in improved, but still suboptimal correlation with flow cytometry results. In 15 cases anti-D immunoglobulin was given according to the flow cytometer estimation of FMH size, resulting in a 58% reduction in the amount of anti-D immunoglobulin given. None of the patients were immunised when tested six months later. CONCLUSIONS: Flow cytometry is helpful for the accurate quantitation and management of patients with large FMH and in cases where the presence of maternal haemoglobin F containing cells renders the Kleihauer technique inaccurate. Worthwhile reductions in the use of anti-D immunoglobulin can be achieved.

Quantification of anti-c in haemolytic disease of the newborn.

Anti-c is an important Rh antibody that causes haemolytic disease of the newborn (HDN). We have carried out a retrospective analysis of the clinical outcome of pregnancy in 120 mothers with anti-c. Of these, 100 gave birth to c-positive infants, of whom 14 had severe HDN requiring exchange transfusion. In all of these, the maternal level was 9.5 iu/ml or greater. Of the 29 women with anti-c levels of 9.5 iu/ml or above, in addition to the 14 with severely affected infants, 15 had infants requiring only phototherapy or no treatment. Our observations suggest that when the anti-c level is below 7.5 iu/ml, the fetus is unlikely to be seriously affected and invasive obstetric intervention is unnecessary. Of the 120 women studied, 50% had had a blood transfusion, in most cases for obstetric complications in a previous pregnancy. Although it was not possible to attribute alloimmunization to blood transfusion rather than previous pregnancy in any individual case, this observation points to the value of routine c typing as part of antenatal screening, so that c-negative blood can be selected.

U.K. multicentre study on blood donors for surrogate markers of non-A non-B hepatitis. Part I: Alanine transferase and anti-HBc testing.

Blood samples from 9,215 blood donors in three U.K. centres (North London, Bristol and Manchester) were tested for their alanine aminotransferase (ALT) level and the presence of anti-HBc and anti-HCV. This paper presents the results of the ALT and anti-HBc tests. The prevalence of ALT > 45 IU/l was 3.1% overall (North London 3.06%, Bristol 4.56% and Manchester 1.97%). Manchester results were skewed by the methodology used for ALT measurement, highlighting the need for standard test methods. Anti-HBc was detected using the Wellcome enzyme-immunosorbent assay (EIA) and confirmatory testing was performed using a radioimmunoassay (RIA) and the Corecell haemagglutination assay. Repeat reactive rates were 0.9, 0.79 and 0.94% for North London, Bristol and Manchester, respectively, with an overall rate of 0.9%. The confirmed positive rate was 0.73, 0.53 and 0.65% for the three centres with an overall rate of 0.63%. Donors with an ALT > 45 IU/l, or with confirmed anti-HBc, were interviewed with a medical questionnaire for risk factors. The major contributing factors in donors with a raised ALT were alcohol consumption and obesity.