Transfusion-associated circulatory overload in Ireland: a review of cases reported to the National Haemovigilance Office 2000 to 2010.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is an increasingly reported condition but symptoms and signs are still unrecognized. We present a review of the incidence and clinical features of TACO reported to the National Haemovigilance Office at the Irish Blood Transfusion Service. STUDY DESIGN AND METHODS: Between 2000 and 2010, a total of 1071 cases of serious transfusion-related reactions were reported, of which 221 (21%) cases were TACO. RESULTS: A total of 2,000,684 blood components were issued, with a TACO incidence of one in 9177. The TACO incidence per red blood cells, plasma, and platelet components issued was one in 8000, one in 16,000, and one in 57,884, respectively. The majority of cases (68%, n = 151) were elderly patients, while no sex difference was seen. Twenty-eight (13%) patients experienced severe morbidity; 31 (14%) deaths were reported, of which five (2%) were considered due to TACO and the other deaths considered due to and underlying conditions, which in most cases were cardiovascular (76%). An increased risk of mortality was found in patients on diuretics either before transfusion as part of their routine therapy or given as pretransfusion medication (odds ratio, 2.49; 95% confidence interval, 1.06-6.01). In 19 (21%) cases, TACO reaction was due to human error. CONCLUSIONS: The strong association between TACO and human errors supports the role of hemovigilance and of adequate transfusion medicine teaching for preventing morbidity and mortality associated with TACO.

Chronic hepatitis C infection and sicca syndrome: a clear association with HLA DQB1*02.

BACKGROUND: Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection. AIM: The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients. METHODS: Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured. RESULTS: DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02. CONCLUSION: The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.

The value of autofluorescence as a diagnostic feature of acute promyelocytic leukemia.

Autofluorescence is an immunophenotypic characteristic of leukemic blasts in acute promyelocytic leukemia (APL). We examined the fluorescent intensity of isotype controls in 25 cases of APML and 25 controls with acute myeloid leukemia. The fluorescence of the FITC- and PE-conjugated controls was consistently higher in APML. Autofluorescence may therefore represent a helpful diagnostic marker in APML.

Modelling infectious disease transmission with complex exposure pattern and sparse outcome data.

We present a regression modelling framework to analyse infectious disease transmission during a time period where extensive exposure data are available, but where the outcome data are sparse. A latent variable model is used for each exposure time, allowing a straight-forward accumulation of risk for a collection of exposures for which outcome data are available. We describe an analysis of HIV infection from blood products among a cohort of haemophiliacs in Ireland between 1980 and 1985. The analysis provides estimates of the time pattern and batch effects; we show how analytical complexity such as smoothly varying coefficients or random coefficient models can be accommodated by the model. Finally, we discuss other problems where the model is applicable.

Outcome of an optional HCV screening program for blood transfusion recipients in Ireland.

BACKGROUND: An optional (general) HCV testing program for blood and blood component recipients before the introduction of routine donor anti-HCV screening (October 1991) was launched in Ireland in 1995 to complement the targeted lookback program in progress at that time and to identify transfusion-transmitted hepatitis C. STUDY DESIGN AND METHODS: The public were informed of the opportunity to avail of screening by widespread media coverage. Screening was by an initial ELISA (Abbott 3.0, Abbott Laboratories) at the transfusion center laboratories. Reactive samples were referred to a virus reference laboratory where two additional ELISAs (Ortho 3.0, Ortho Clinical Diagnostics; and Murex 3.0, Murex) were performed. Confirmation of ELISA-positive samples was by a RIBA (RIBA 3.0, Chiron Corp.). All patients found to be anti-HCV- seropositive were tested for HCV RNA by PCR and were referred to a hepatologist. RESULTS: A total of 14,917 persons have been tested for hepatitis C in this program to date (85% women). Sixty-one people were confirmed positive for HCV by RIBA 3.0 (0.4%). Excluding persons with other risk factors (n = 15), the HCV positivity rate for blood component transfusion recipients (n = 46) was 0.3 percent. Of the 46 confirmed hepatitis C-positive blood component transfusion recipients, 32 were women (70%), 24 of whom received transfusion for obstetric or gynecologic indications (75%). Thirty-eight of 46 (83%) anti-HCV seropositive transfusion recipients tested had detectable HCV RNA by PCR. CONCLUSION: This program identified 46 transfusion recipients and 10 coagulation factor concentrate recipients, all of whom were previously unaware of their infection. The majority of HCV-positive transfusion recipients identified were women. This may reflect that women are longer living survivors of transfusion therapy or alternatively, in our experience, that Irish women perceive themselves at greater risk of hepatitis C because of the well-publicized association of this virus with recipients (women) of Irish RhIG.

Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source.

The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included chi(2) testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < or = .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with only 37% of those with chronic infection (P <.0001). The haplotypes A*03-B*07-DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501 are associated with viral clearance (P =.004 and.01, respectively). By multiple logistic regression analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99). The haplotype A*01-B*08-Cw*07-DRB1*03011-DQB1*0201 is associated with chronic infection (P =.002), being independent for DQB1*0201 (OR 0.27). In conclusion, certain class I alleles are associated with outcome in this homogeneous cohort. More significantly, either HLA-A*03, -DRB1*0101, or -*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV.