Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem
Raschke R.A.,Banner Good Samaritan Medical Center |
Curry S.C.,Banner Good Samaritan Medical Center |
Curry S.C.,University of Arizona |
Warkentin T.E.,McMaster University |
And 2 more authors.
Chest | Year: 2013
Background: Heparin-induced thrombocytopenia (HIT) is diagnosed using clinical criteria and detection of platelet-activating anti-platelet factor 4/heparin (anti-PF4/H) antibodies, usually through a surrogate enzyme-linked immunosorbent assay (ELISA). The high false-positive rate (FPR) of this ELISA prompted us to reexamine its interpretation. Methods: We analyzed anti-PF4/H ELISA results from a previously published dataset of 1,958 patients, using clinical suspicion and serotonin-release assay (SRA) to diagnose HIT. We performed receiver operating characteristic (ROC) analysis using stratum-specific likelihood ratios (SSLRs) and used Bayes theorem to construct a clinical decision-support algorithm. Results: The most discriminant single cutoff by anti-PF4/H ELISA for the diagnosis of HIT was found to be 0.8 optical density (OD) units, not 0.4 OD (currently accepted practice). This change reduced the FPR from 31% to 6% (95% CI, 5%-8%). ELISA results were grouped into five strata, which yielded SSLRs ranging from 0.02 (strongly ruling HIT out) to 104.4 (strongly ruling HIT in). Comparison of ROC curves demonstrated that this five-strata approach is statistically more accurate than current accepted practice at discriminating whether patients have HIT or not (area under the ROC curve, 0.97 [95% CI, 0.93-1.00] vs 0.83 [95% CI, 0.80-0.89]). Our decision-support algorithm incorporated clinical assessment into this stratified model and clarified HIT diagnosis with a high degree of certainty and without the need for SRA testing in approximately 90% of patients. Conclusions: Diagnostic accuracy of the anti-PF4/H ELISA can be optimized by using a higher cutoff and a stratified interpretation of the results. Our algorithm should significantly reduce overdiagnosis of HIT and the need for SRA testing. © 2013 American College of Chest Physicians.
Chagla Z.,McMaster University |
Quirt J.,McMaster University |
Woodward K.,McMaster University |
Neary J.,McMaster University |
Rutherford C.,Hamilton Regional Laboratory Medicine Program
Journal of Clinical Virology | Year: 2013
Norovirus infection causes a significant burden of morbidity and (in the developing world) mortality. In immunocompromised hosts, norovirus infection can become chronic, with devastating consequences. Unfortunately, therapeutic options for chronic disease are unproven, and treatment is largely supportive. We report a case of norovirus infection causing debilitating chronic gastroenteritis in a transplant patient that responded to a short course of enterally administered human immune globulin. © 2013 Elsevier B.V.
Kassam Z.,McMaster University |
Lee C.H.,McMaster University |
Lee C.H.,Hamilton Regional Laboratory Medicine Program |
Yuan Y.,McMaster University |
And 3 more authors.
American Journal of Gastroenterology | Year: 2013
OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I 2 =33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI-0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated. © 2013 by the American College of Gastroenterology.
Ditomasso J.,Hamilton Regional Laboratory Medicine Program |
Liu Y.,McMaster University |
Heddle N.M.,McMaster University
Transfusion and Apheresis Science | Year: 2012
Hemovigilance systems are important programs for: monitoring trends of known risks; evaluating effectiveness of steps taken to reduce risks; providing data to support recommendations for change and guideline development; and contributing overall to the safety of transfusion. The Transfusion Transmitted Injury Surveillance System is the hemovigilance system implemented in Canada. It evolved in 1999 as a pilot program and expanded across Canada in 2005. Each province reports their adverse reactions to the transfusion of blood products and plasma proteins to the Public Health Agency of Canada (PHAC) at predetermined intervals. PHAC reconciles, summarizes the data and publishes a report approximately 2. years after the data are collected. This is considered a passive reporting system but in spite of the delays, the program provides useful information to address a variety of questions. Examples include: assessing the impact of a provincial patient transfusion history registry in Québec on reporting of hemolytic transfusion reactions; identifying trends of bacterial contamination of blood products and assessing the impact of interventions on these events; and the impact of male-only plasma on the incidence of Transfusion Related Acute Lung Injury. Although hemovigilance data has been successfully used to improve blood safety, we must continue to explore ways to utilize such data to improve and implement safe transfusion practices. © 2012 Elsevier Ltd.
Hayward C.M.,McMaster University |
Moffat K.,Hamilton Regional Laboratory Medicine Program |
Moffat K.,McMaster University |
Liu Y.,McMaster University
Seminars in Thrombosis and Hemostasis | Year: 2012
Bleeding disorder panels often include the prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen level, and thrombin time (TT). We explored the detection of abnormalities from bleeding disorders by these tests among subjects referred for bleeding disorder assessments, using data from a bleeding disorder study to determine sensitivities and specificities. Among subjects referred to hematologists for bleeding disorder assessment, coagulation defects were uncommon and the APTT and TT detected many nonsignificant abnormalities. While all test and panel specificities were acceptable (88 to 100%), coagulation screening tests were less sensitive to clinically significant abnormalities (1.0 to 2.1%) than von Willebrand disease (VWD) screens (6.7%), and light transmission platelet aggregometry (LTA) (26%). Accordingly, panels comprising PT/INR, APTT, fibrinogen, and TT had lower sensitivity to bleeding disorders (3.7%) than panels expanded to include VWD screens (8.5%), or VWD screens and LTA (30%). These findings have important implications for bleeding disorder diagnosis. Copyright © 2012 by Thieme Medical Publishers, Inc.