Clinical Utility of the Signal-to-Cutoff Ratio of Reactive HIV Antigen/Antibody Screening Tests in Guiding Emergency Physician Management.

BACKGROUND: The signal-to-cutoff (S/CO) ratio of the HIV antigen/antibody test may help immediately to differentiate true-positive results from false-positive results, which may be particularly useful in time-sensitive circumstances, such as when providing emergency department (ED) care. SETTING: Seven US EDs with HIV screening programs using HIV antigen/antibody assays. METHODS: This cross-sectional study of existing data correlated S/CO ratios with confirmed HIV status. Test characteristics at predetermined S/CO ratios and the S/CO ratio with the best performance by receiver operator characteristic (ROC) curve were calculated. RESULTS: Of 1035 patients with a reactive HIV antigen/antibody test, 232 (22.4%) were confirmed HIV-negative and 803 (77.6%) were confirmed HIV-positive. Of the 803 patients, 713 (88.8%) experienced chronic infections and 90 (11.2%) experienced acute infections. S/CO ratios were greater for HIV-positive (median 539.2) than for HIV-negative patients (median 1.93) (P < 0.001) and lower for acute infection (median 22.8) than for chronic infection (median 605.7) (P < 0.001). All patients with an S/CO ratio < 1.58 (n = 93) were HIV-negative (NPV 100%), and nearly all with an S/CO ≥ 20.7 (n = 760) (optimal level by ROC analysis) were HIV-positive (PPV 98.6%). Of patients with S/CO values between 1.58 and 20.7 (n = 182), 29.7% were HIV-positive. CONCLUSIONS: The S/CO ratio may be used in real time to classify most ED patients as almost certain to be either HIV-positive or HIV-negative long before nucleic acid confirmatory testing is available. When combined with clinical judgment, this could guide preliminary result disclosure and management.

Clinician-ordered peripheral blood smears have low reimbursement and variable clinical value: a three-institution study, with suggestions for operational efficiency.

BACKGROUND: Peripheral blood smears are performed to evaluate a variety of hematologic and non-hematologic disorders. At the authors' institutions, clinician requests for pathologist-performed blood smear reviews have increased in recent years. Blood smears may contribute significantly to pathologists' workloads, yet their clinical value is variable, and professional reimbursement rates are low. This study aimed to identify clinical scenarios in which smear review is likely to provide value beyond automated laboratory testing. METHODS: Blood smear review practices at three institutions were examined, and the indications for and interpretations of clinician-initiated smears were reviewed to determine the percentage of smears with potential added clinical value. A smear review was classified as having added clinical value if the pathologist's interpretation included a morphologic abnormality that had the potential to impact patient management, and that could not be diagnosed by automated complete blood count with white blood cell differential or automated iron studies alone. RESULTS: Among 515 consecutive clinician-requested smears performed during the study timeframes, 23% yielded interpretations with potential added clinical value. When sorted by indication, 25, 19, and 13% of smear reviews requested for white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities, respectively, had findings with potential added clinical value. The proportion of smears with potential clinical value differed significantly across these three categories (p = 0.0375). CONCLUSIONS: Smear review ordering practices across three institutions resulted in a minority of smears with potential added clinical value. The likelihood of value varied according to the indication for which the smear was requested. Given this, efforts to improve the utilization and efficiency of smear review are worthwhile. Solutions are discussed, including engaging laboratory staff, educating clinicians, and modifying technology systems.

Liquid plasma: A solution to optimizing early and balanced plasma resuscitation in massive transfusion.

BACKGROUND: Early and balanced resuscitation for traumatic hemorrhagic shock is associated with decreased mortality, making timely plasma administration imperative. However, fresh frozen plasma (FFP) thaw time can delay administration, and the shelf life of thawed FFP limits supply and may incur wastage. Liquid plasma (LP) offers an attractive alternative given immediate transfusion potential and extended shelf life. As such, we hypothesized that the use of LP in the massive transfusion protocol (MTP) would improve optimal plasma/red blood cell (RBC) ratios, initial plasma transfusion times, and clinical outcomes in the severely injured patient. METHODS: Using Trauma Quality Improvement Program data from our level 1 trauma center, we evaluated MTP activations from 2016 to 2018. Type A LP use was instated April 2017. Before this, thawed FFP was solely used. Plasma/RBC ratios and initial plasma transfusion times were compared in MTP patients before and after LP implementation. Patient and injury characteristics were accounted for using linear regression analysis. Secondary outcomes of mortality, 28-day recovery, and complications were evaluated using Cox proportional hazards regression. RESULTS: A total of 95 patients were included (pre-LP, 39; post-LP, 56). Time to initial plasma transfusion and plasma/RBC ratios at 4 and 24 hours were improved post-LP implementation with a coinciding reduction in RBC units transfused (p < 0.05). In a 28-day Cox proportional hazards regression LP implementation was associated with favorable recovery (hazard ratio, 3.16; 95% confidence interval, 1.60-6.24; p < 0.001) and reduction in acute kidney injury (hazard ratio, 0.092; 95% confidence interval, 0.011-0.77; p = 0.027). No post-LP patients with blood group type B or AB (n = 9) demonstrated evidence of hemolysis within 24 hours of type A LP transfusion. CONCLUSION: Initial resuscitation with LP optimizes early plasma administration and improves adherence to transfusion ratio guidelines. Furthermore, LP offers a solution to inherent delays with FFP and is associated with improved clinical outcomes, particularly 28-day recovery and odds of acute kidney injury. Liquid plasma should be considered as an alternative to FFP in MTPs. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Draft Genome Sequences of Four NDM-1-Producing Klebsiella pneumoniae Strains from a Health Care Facility in Northern California.

We report the draft genome sequences of Klebsiella pneumoniae strains from four patients at a northern California health care facility. All strains contained the New Delhi metallo-ß-lactamase (NDM1) carbapenemase with extended antibiotic resistance, including resistance to expanded-spectrum cephalosporins, imipenem, ertapenem, and meropenem. NDM gene alignments revealed that the resistance was plasmid encoded.

Utilization management in the core laboratory.

The need for appropriate utilization management of diagnostic testing is increasingly important. The majority of laboratory tests are performed in highly automated core laboratories that combine chemistry, immunoassays, hematology, coagulation and esoteric assays. These core laboratories are designed for high throughput leveraging economies of scale to produce large numbers of test results relatively inexpensively. Most core laboratory tests can be categorized based on whether they should or should not be ordered at all and, if so, by the frequency with which test ordering is reasonably appropriate (e.g. unrestricted, daily, weekly, monthly, yearly or once in a lifetime). Classifying tests by this approach facilitates electronic rule-based logic to detect which tests are appropriate for a given clinical indication.

Liver disease, coagulation testing, and hemostasis.

This article reviews the variety of coagulation testing abnormalities identified and the evidence demonstrating their lack of correlation with hemostasis and inability to predict bleeding for patients with liver disease. The article discusses the historical and incorrect evolution of the commonly used "1.5x" prothrombin time/international normalized ratio "threshold" for fresh frozen plasma/frozen plasma (FFP/FP) administration. Finally, this article reviews why FFP/FP cannot correct minimally prolonged clotting times in patients with liver disease, nor provide adequate prophylaxis against bleeding from percutaneous liver biopsy.

Prothrombin time and partial thromboplastin time assay considerations.

Prothrombin times and activated partial thromboplastin times have long been used as tests of overall ("global") clotting function. Laboratory coagulation testing issues should be at the forefront of the reader's consciousness whenever critically evaluating and extrapolating published study conclusions reliant on the results of these tests. Thus, this article reviews laboratory issues and known variables influencing prothrombin time and partial thromboplastin time results and international normalized ratio determinations.

Anticoagulation monitoring.

This article reviews the commonly used anticoagulants (warfarin and heparin) and associated recommended laboratory testing. Emphasis is on the various modes of International Normalized Ratio testing and associated variability (clinical laboratory, point of care, patient self-testing). Unfractionated heparin and well-recognized coagulation testing issues are reviewed. The newer anticoagulants (heparin analogs, direct factor Xa inhibitors, and direct thrombin inhibitors) and various applied coagulation laboratory testing and related issues are also discussed.

Contemporary standards for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT).

BACKGROUND: Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs). CONCLUSIONS: Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.

Reducing unnecessary inpatient laboratory testing in a teaching hospital.

After an inpatient phlebotomy-laboratory test request audit for 2 general inpatient wards identified 5 tests commonly ordered on a recurring basis, a multidisciplinary committee developed a proposal to minimize unnecessary phlebotomies and laboratory tests by reconfiguring the electronic order function to limit phlebotomy-laboratory test requests to occur singly or to recur within one 24-hour window. The proposal was implemented in June 2003. Comparison of fiscal year volume data from before (2002-2003) and after (2003-2004) implementation revealed 72,639 (12.0%) fewer inpatient tests, of which 41,765 (57.5%) were related directly to decreases in the 5 tests frequently ordered on a recurring basis. Because the electronic order function changes did not completely eliminate unnecessary testing, we concluded that the decrease in inpatient testing represented a minimum amount of unnecessary inpatient laboratory tests. We also observed 17,207 (21.4%) fewer inpatient phlebotomies, a decrease sustained in fiscal year 20042005. Labor savings allowed us to redirect phlebotomists to our understaffed outpatient phlebotomy service.

Evaluation of the VACUTAINER PPT Plasma Preparation Tube for use with the Bayer VERSANT assay for quantification of human immunodeficiency virus type 1 RNA.

Separation and storage of plasma within 2 h of phlebotomy is required for the VACUTAINER PPT Plasma Preparation Tube (PPT) versus 4 h for the predecessor VACUTAINER EDTA tube for human immunodeficiency virus type 1 (HIV-1) viral load (HIVL) testing by the VERSANT HIV-1 RNA 3.0 assay (branched DNA). The 2-h limit for PPT imposes time constraints for handling and transporting to the testing laboratory. This study compares HIVL reproducibility from matched blood in EDTA tubes and PPTs and between PPT pairs following processing within 4 h of phlebotomy, stability of plasma HIV-1 RNA at 24- and 72-h room temperature storage in the tube, and comparative labor and supply requirements. Blood from 159 patients was collected in paired tubes (EDTA/PPT or PPT/PPT): 86 paired EDTA tubes and PPTs were processed 4 h following phlebotomy and their HIVLs were compared, 42 paired PPT/PPT pairs were analyzed for intertube HIVL reproducibility, and 31 PPT/PPT pairs were analyzed for HIV-1 RNA stability by HIVL. Labor and supply requirements were compared between PPT and EDTA tubes. PPTs produce results equivalent to standard EDTA tube results when processed 4 h after phlebotomy. PPT intertube analyte results are reproducible. An average decrease of 13% and 37% in HIVL was observed in PPT plasma after 24 and 72 h of room temperature storage, respectively; thus, plasma can be stored at room temperature up to 24 h in the original tube. PPTs offer labor and supply savings over EDTA tubes.

Clinically relevant differences in prothrombin time and INR values related to blood sample collection in plastic vs glass tubes.

We compared prothrombin times (PTs) and international normalized ratios (INRs) for blood samples drawn into plastic vs glass collection tubes. We collected 60 venous blood samples into 4.5-mL glass and 2 plastic tubes (2.7 and 3.5 mL). An additional 153 samples, including 63 from warfarin-anticoagulated patients, were collected only in glass and 2.7-mL plastic tubes. The PTs and INRs were determined following routine laboratory procedures. A subset of 35 frozen aliquot samples was analyzed with a different instrument-reagent combination. The PTs and INRs for samples in plastic tubes were significantly lower than for samples in glass tubes. The mean INR differences increased with INR magnitude from approximately -0.1 (INR, 1.5) to -0.7 (INR, 4.5). Of the plastic tube INRs, 50% were more than 10% lower than INRs from samples collected in glass tubes. Therapeutic monitoring based on plastic-tube INRs could result in higher doses of warfarin.

Origins of community strains of methicillin-resistant Staphylococcus aureus.

To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community, we identified predictors of isolating community MRSA and genotyped a sample of MRSA collected from a community-based, high-risk population. Computerized databases of the Community Health Network of San Francisco and the Clinical Microbiology Laboratory were searched electronically for the years 1992-1999 to identify community-onset infections caused by MRSA. Sequential analyses were performed to identify predictors of MRSA strains. The majority (58%) of infections were caused by strains traceable to the hospital or to long-term care facilities. Injection drug use was associated with infections that were not associated with health care settings. Genotypes for 20 of 35 MRSA isolates recovered from injection drug users did not match any of >600 genotypes of clinical isolates. In a nonoutbreak setting, the hospital was the main source of community MRSA; however, the presence of genetically distinct and diverse MRSA strains indicates MRSA strains now also originate from the community.

Classifying laboratory incident reports to identify problems that jeopardize patient safety.

We developed a laboratory incident report classification system that can guide reduction of actual and potential adverse events. The system was applied retrospectively to 129 incident reports occurring during a 16-month period. Incidents were classified by type of adverse event (actual or potential), specific and potential patient impact, nature of laboratory involvement, testing phase, and preventability. Of 129 incidents, 95% were potential adverse events. The most common specific impact was delay in receiving test results (85%). The average potential impact was 2.9 (SD, 1.0; median, 3; scale, 1-5). The laboratory alone was responsible for 60% of the incidents; 21% were due solely to problems outside the laboratory's authority. The laboratory function most frequently implicated in incidents was specimen processing (31%). The preanalytic testing phase was involved in 71% of incidents, the analytic in 18%, and the postanalytic in 11%. The most common preanalytic problem was specimen transportation (16%). The average preventability score was 4.0 (range, 1-5; median, 4; scale, 1-5), and 94 incidents (73%) were preventable (score, 3 or more). Of the 94 preventable incidents, 30% involved cognitive errors, defined as incorrect choices caused by insufficient knowledge, and 73% involved noncognitive errors, defined as inadvertent or unconscious lapses in expected automatic behavior.

Comparative analysis of HIV-1 viral load assays on subtype quantification: Bayer Versant HIV-1 RNA 3.0 versus Roche Amplicor HIV-1 Monitor version 1.5.

Quantification of HIV-1 subtypes is essential for appropriate clinical management. Whereas viral load assays were initially developed to accurately quantify subtype B, the recent worldwide spread of non-B subtypes and the introduction of treatment programs in regions with non-B subtypes have prompted adaptations of these assays. The Bayer Versant HIV-1 RNA 3.0 Assay (branched DNA [bDNA] 3.0) and the Roche Amplicor HIV-1 Monitor version 1.5 (Amplicor 1.5) assays are reported to quantify all subtypes in group M; however, evaluation of performance characteristics remains limited. In this study, we evaluated the accuracy and reliability of bDNA 3.0 and Amplicor 1.5 on multiple serially diluted viral isolates from HIV-1 group M, subtypes A through F. Testing was conducted on both assay systems in two independent laboratories. Comparative pansubtype quantification from regression analysis showed that quantification by bDNA 3.0 was approximately 0.3 log-fold lower than that by Amplicor 1.5. Comparative pansubtype accuracy analysis showed data points more closely distributed about their respective regression lines and thus showing greater reliability by bDNA 3.0 than by Amplicor 1.5.