Lack of evidence for the transmission of hepatitis E virus by coagulation factor concentrates based on seroprevalence data.

BACKGROUND: Whether hepatitis E virus (HEV) infection can be transmitted by coagulation factor concentrates remains unclear. OBJECTIVES: The HEV seroprevalence in blood donors and recipients of coagulation factor concentrates was compared to obtain evidence of whether a transmission of HEV by coagulation factor concentrates could occur. METHODS: Archived samples from whole blood donors and patients who had received coagulation factor concentrates were investigated for the presence of anti-HEV IgG by ELISA. Western blotting was used to confirm the positive samples that showed reactivity in the ELISA. RESULTS: Of 357 blood donors, 68 (19%) presented IgG antibodies against HEV. Two of 92 patients who had received coagulation factor concentrates (2·2%) and 1 of the 69 patients who had received plasma-derived products (1·5%) tested positive for anti-HEV IgG. The seroprevalence of HEV in the patient group was significantly lower (P = 0·038) than that in the donor group. The two positive patients were a 72-year-old man treated with plasma-derived products and a 5-year-old girl treated with a recombinant coagulation factor concentrate. CONCLUSION: HEV seroprevalence was significantly higher in the blood donors than in the patients with a history of coagulation factor concentrate administration. In one of two patients with detectable anti-HEV IgG antibodies, the coagulation factor concentrate was not the probable source of infection. Our data suggest that HEV is efficiently inactivated during the manufacturing process of coagulation factor concentrates. Thus, testing for the presence of HEV RNA in plasma donated for the preparation of coagulation factor concentrates may not be necessary.

Look-back study on recipients of Parvovirus B19 (B19V) DNA-positive blood components.

BACKGROUND AND OBJECTIVES: To assess the relevance of Parvovirus B19 (B19V) DNA at low to intermediate concentrations in blood donors for the recipients of their blood components. MATERIAL AND METHODS: We studied recipients of B19V DNA-positive blood components [red blood cell concentrates (RBCs), pooled platelet concentrates and fresh frozen plasma]. This included archived pretransfusion samples as well as follow-up samples investigated by ELISA or NAT and genome sequence analysis. RESULTS: In 132 out of 424 recipients, we could detect no anti-B19V IgG before transfusion. In 67 out of 132 sero-negative recipients, a follow-up sample was available. Sixty-five of these received blood components from donors with <10(4) IU B19V DNA/ml plasma and had no evidence of transfusion-transmitted (TT)-B19V infection. Homology in genome sequences in donor and recipient provided evidence for a TT-B19V infection in two recipients. Both patients received RBC containing 3.4 × 10(6) and 1.8 × 10(4) IU B19V DNA/ml plasma, respectively. The anti-B19V IgG titres in the donors were 2 and 76 IU/ml plasma, respectively. The antibodies in the second donor were directed against capsid proteins and are thus considered as potential neutralizing antibodies. CONCLUSIONS: TT-B19V infections through blood components with low (<10(4) IU/ml plasma) B19V DNA concentrations did not occur in our study. One of the TT-B19V infections occurred from RBC with intermediate B19V DNA concentration despite the presence of potential neutralizing antibodies in the donor, but its clinical significance was low.

Persistence of Parvovirus B19 (B19V) DNA and humoral immune response in B19V-infected blood donors.

BACKGROUND AND OBJECTIVES: Parvovirus B19 (B19V) DNA seems to persist in the plasma of B19V-infected blood donors. The relevance of this for recipients of single-donor blood components is yet unclear. MATERIAL AND METHODS: We studied serial archive and follow-up samples from 75 B19V-infected blood donors to obtain more data about the duration and degree of viraemia and the presence of IgG and IgM anti-B19V. IgG antibodies were further characterized by Western blot analysis in 29 donors. RESULTS: In 411 B19V DNA-positive samples collected, we found high concentrations (>10(6) IU B19V DNA/ml plasma) in five. B19V DNA persisted for a mean of 21·5 months (range: 2·3-52·4; 95% confidence interval, 19·1-23·9 months) in all donors. Only 15 such samples had either no or low-titre IgG anti-B19V. IgG antibodies were predominantly directed against epitopes on the minor capsid protein VP1, thus probably of neutralizing type with high avidity. IgM anti-B19V was detectable in 9/13 samples with high DNA concentrations. CONCLUSIONS: The vast majority of single-donor blood components with detectable B19V DNA are probably not infectious for their recipients because DNA is at only low levels and the donors also have potentially neutralizing antibodies with high avidity. Anti-B19V IgM testing does not identify every donation with high B19V DNA concentrations, but, in addition to B19V NAT testing, donors with persistent IgG anti-B19V might be considered 'B19V-safe' for single-donor blood components.

Comparison of the two fully automated anti-HCMV IgG assays: Abbott Architect CMV IgG assay and Biotest anti-HCMV recombinant IgG ELISA.

OBJECTIVE AND BACKGROUND: To assess the performance characteristics of two fully automated human cytomegalovirus (HCMV) antibody tests. MATERIALS AND METHODS: Samples from negatively or not pre-screened blood donors were tested by the Biotest anti-HCMV recombinant IgG enzyme-linked immunosorbent assay (ELISA) in comparison to the Abbott Architect CMV IgG assay [chemiluminescent microparticle immunoassay (CMIA)]. For clarification, samples with discordant results between both assays were subjected to supplemental testing for anti-HCMV IgG, IgM and HCMV DNA in plasma. RESULTS: From 4938 samples tested, 362 delivered positive results in both assays (7.3%). 91 (1.8%) samples were discordant. Of 43 (two not further tested) samples positive only by ELISA, 41 were false positive, one true positive and one indeterminate. Of 45 (one not further tested) samples positive only by CMIA, 20 were false positive, 9 indeterminate and 16 true positive. Anti-HCMV IgM and HCMV DNA testing from the plasma were negative in indeterminate samples. Considering the results of supplemental testing, the CMIA achieved altogether better results concerning resolved sensitivity, resolved specificity as well as negative predictive value. Both assays had an inferior positive predictive value, with a better result for CMIA. CONCLUSION: Overall, the performance characteristics of the CMIA were better than those of the ELISA. Owing to the inferior positive predictive value, positive test results require confirmation if blood products from donors with remote HCMV infection should be administered.

Can advanced edge enhancement software improve image quality to visualise tubes, catheters and wires in digital chest radiographs?

INTRODUCTION: This study aimed to test whether Advanced Edge Enhancement (AEE) software could improve the localisation of tubes, catheters or wires, while also affecting the overall image quality in chest x-rays (CXR). METHODS: In total, 50 retrospective CXRs were included. All images were obtained utilising the Canon X-ray system (CANON/Arcoma Precision T3 DR System, Canon Europe, Amsterdam, NL) with a CXDI-810C wireless detector. A clinical image, plus three additional AEE algorithms were applied using post processing (two intensity variations 1 and 4) on all CXRs totalling 350 different images. Three radiologists evaluated the images using a subjective Absolute Visual Grading Analysis (VGA). The clinical images used in post processing were not applied as reference in the analysis. Each radiologist graded the images separately in a randomized order, with a score of three indicating suitability for diagnostic assessment. RESULTS: The three AEE algorithms contributed to an overall improvement (average 16-49%) in visualisation of tube, catheter or wire on CXR images. The Mann-Whitney U tests showed a statistically significant (p < 0.05) improvement in contrast resolution and sharpness, indicating an increased ability to differentiate tubes, wires or catheters tips from surrounding tissues. For the noise criterion, not applying any AEE algorithm showed a significantly higher homogeneity in soft tissue (p < 0.001), reducing the ability to visualise soft tissue. The high-intensity catheter algorithm was the only algorithm to achieve a statistically significant (p = 0.017) increase in the ability to differentiate pulmonary tissues of similar density. CONCLUSION: An overall improvement in the visualisation of tube, catheter and wire placement was obtained using the three AEE-algorithms. The bone and catheter algorithms showed the highest consistency, with the small structure algorithm underperforming in resolution and low contrast resolution. In general, image noise increased regardless of algorithm type or applied intensity. The AEE-algorithms should therefore be seen as a supplementary tool to the clinical image protocol, while having the potential to improve image quality to specific clinical situations. IMPLICATIONS FOR PRACTICE: AEE filtered images appear to be a supplement to the current practice of using CXRs in the diagnosis in placement of catheters, tubes and wires in the chest region. The use of AEE-algorithms has the potential to improve the daily work in clinical practice, which serves the basis for further investigation of its effect on radiographic practices.

The influence of a novel edge enhancement software on image quality of DR hand images of patients with rheumatoid arthritis.

INTRODUCTION: This study aimed to evaluate the effects of a newly developed Advanced Edge Enhancement software (AEE) (Canon Europe, Amsterdam, NL) on image quality (IQ) of Digital Radiography (DR) hand images focusing on rheumatoid arthritis (RA). METHODS AND MATERIALS: Fifty posterior-anterior hand images with or suspected for RA were collected. For each of the 50 images, six copies were made with each their AEE algorithm settings. A total of 330 images (30 images iterated) were evaluated using relative Visual Grading Analysis (VGA) by three observers and combined into a VGA Score (VGAS). Second, 50 images of a technical Contrast Detail Radiography Phantom (CDRAD) was produced with three different AEE software settings, each at level 1,5 and without the AEE software yielding 350 CDRAD images. All images was analysed by the CDRAD Analyser and included for an objective analysis of the AEE software. RESULTS: The VGA study showed a significant difference in image quality between a standard image and images with AEE software applied. The average VGA score of the AEE software was better than the standard images (interval between 0.2 and 0.9). The AEE algorithms at level 5 scored significantly lower for noise but significantly higher for spatial resolution, sharpness and contrast in the VGA. The CDRAD images showed that all AEE algorithms had a statistically significant improvement for level 1 and deterioration for level 5 compared to the standard image. CONCLUSION: Overall the AEE algorithm: small structure level 1 showed an improvement of all IQ criteria in the VGA and a better technical IQ. IMPLICATIONS FOR PRACTICE: The AEE software ought to be considered as a useful addition to the current software, possibly enabling visualisation of structures currently visible.

The natural course of primary cytomegalovirus infection in blood donors.

BACKGROUND AND OBJECTIVES: As cytomegalovirus (CMV) DNA is frequently detectable in the plasma of recently infected sero-positive blood donors, information concerning primary CMV infection is important for the identification of possibly infectious donors. MATERIALS AND METHODS: Monitoring of 17 982 donors for CMV antibodies and DNA in plasma identified 14 subjects with ongoing primary CMV infection. Thirteen donors were interrogated for possible sources of infection and CMV-related symptoms, and monitored for CMV antigens, CMV DNA in plasma, leucocytes and urine, course of IgG and IgM antibodies as well as markers of systemic infection and parameters of organ function. RESULTS: CMV antigens and DNA were detectable in peripheral blood for up to 54 and 269 days respectively. Clearance of CMV DNA from blood correlated with clearance of IgM antibodies, development of IgG antibodies against the membrane glycoprotein gB and development of high avidity IgG antibodies. Eighty-five percent of subjects with primary CMV infection, but even 69% of matched controls reported possibly CMV-related symptoms. Sixty-two and 23%, respectively, had contact with possible sources of infection. One donor developed a febrile illness accompanied by increased levels of CMV DNA in peripheral blood 2 to 3 weeks after seroconversion. In other donors, neither markers of systemic infection nor parameters of organ function correlated with the course of CMV DNA and antigens. CONCLUSION: Potentially infectious donors can be identified by measuring CMV DNA, IgM antibodies or avidity of IgG antibodies. Alternatively, blood products donated during the first year after seroconversion should not be used for immunocompromised patients.

Detection of herpes simplex virus DNA in plasma of patients with primary but not with recurrent infection: implications for transfusion medicine?

Among the family of herpes viruses, only cytomegalovirus (CMV) and, to a lesser extent, human herpes virus 8 (HHV-8) are of relevance in transfusion medicine. Due to neutropism, herpes simplex viruses (HSV) types 1 and 2 are considered to be of minor relevance. However, several reports gave evidence that a HSV DNAemia might occur and HSV could therefore be transmissible by blood products. The aim of our study was to collect data about prevalence of HSV antibodies among blood donors and to clarify whether HSV DNAemia is possible. HSV antibody states of 653 blood donors were investigated. Blood specimens of 46 patients with primary and recurrent HSV infection were tested for HSV-1 and HSV-2 DNA using TaqMan polymerase chain reaction. In 505 of the 653 blood donors HSV antibodies were detectable, most of which were HSV-1 antibodies. HSV DNA was detected in plasma, but not in peripheral blood mononuclear cells (PBMCs) of seven rather seriously ill patients with primary herpes genitalis. No HSV viraemia was detectable in otherwise healthy patients with recurrent herpes labialis. Thus, HSV DNAemia is possible, but seems to be limited to primary infections and could not be detected in the recurrent infection. Therefore, blood donors with primary herpes infection should be deferred from donation. Blood donors with recurrent HSV infection are probably not at risk of transmitting HSV, but further studies are necessary to prove this hypothesis. Detection of HSV DNA in PBMCs as described formerly could not be confirmed by this study.

Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes.

INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.

Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction caused by heparin. As thrombocytopenia is common in hospitalized patients receiving heparin, it would be useful to have a clinical scoring system that could differentiate patients with HIT from those with other reasons for thrombocytopenia. AIM: To compare prospectively the diagnostic utility of a clinical score for HIT in two different clinical settings. METHODS: The pretest clinical scoring system, the '4 T's', was used to classify 100 consecutive patients referred for possible HIT in one hospital (Hamilton General Hospital, HGH) into high, intermediate, and low probability groups. This system was also used to classify likewise 236 patients by clinicians in Germany referring blood for diagnostic testing for HIT in Greifswald (GW). The clinical scores were correlated with the results of laboratory testing for HIT antibodies using the serologic criteria for HIT with high diagnostic specificity. RESULTS: In both centers, patients with low scores were unlikely to test positive for HIT antibodies [HGH: 1/64 (1.6%), GW: 0/55 (0%)]. Patients with intermediate [HGH: 8/28 (28.6%), GW: 11/139 (7.9%)] or high scores [HGH: 8/8 (100%), GW: 9/42 (21.4%)] were more likely to test positive for clinically significant HIT antibodies. The positive predictive value of an intermediate or high clinical score for clinically significant HIT antibodies was higher at one center (HGH). CONCLUSIONS: A low pretest clinical score for HIT seems to be suitable for ruling out HIT in most situations (high-negative predictive value). The implications of an intermediate or high score vary in different clinical settings.