Christopher M. Lehman

Blood bank safety practices: mislabeled samples and wrong blood in tube--a Q-Probes analysis of 122 clinical laboratories.

CONTEXT Although a rare occurrence, ABO incompatible transfusions can cause patient morbidity and mortality. Up to 20% of all mistransfusions are traced to patient misidentification and/or sample mislabeling errors that occur before a sample arrives in the laboratory. Laboratories play a significant role in preventing mistransfusion by identifying wrong blood in tube and rejecting mislabeled samples. OBJECTIVES To determine the rates of mislabeled samples and wrong blood in tube for samples submitted for ABO typing and to survey patient identification and sample labeling practices and sample acceptance policies for ABO typing samples across a variety of US institutions. DESIGN One hundred twenty-two institutions prospectively reviewed inpatient and outpatient samples submitted for ABO typing for 30 days. Labeling error rates were calculated for each participant and tested for associations with institutional demographic and practice variable information. Wrong-blood-in-tube rates were calculated for the 30-day period and for a retrospective 12-month period. A concurrent survey collected institution-specific sample labeling requirements and institutional policies regarding the fate of mislabeled samples. RESULTS For all institutions combined, the aggregate mislabeled sample rate was 1.12%. The annual and 30-day wrong-blood-in-tube aggregate rates were both 0.04%. Patient first name, last name, and unique identification number were required on the sample by more than 90% of participating institutions; however, other requirements varied more widely. CONCLUSIONS The rates of mislabeled samples and wrong blood in tube for US participants in this study were comparable to those reported for most European countries. The survey of patient identification and sample labeling practices and sample acceptance policies for ABO typing samples revealed both practice uniformity and variability as well as significant opportunity for improvement.

Laboratory Monitoring of Heparin Therapy: Partial Thromboplastin Time or Anti-Xa Assay?

The activated partial thromboplastin time (PTT) is the principal method by which laboratories monitor unfractionated heparin therapy. A review of the experimental basis for heparin monitoring by the PTT reveals significant shortcomings of the assay. The availability of anti-Xa heparin assays on automated coagulation analyzers presents a seemingly logical alternative because the PTT therapeutic range is derived from anti-Xa measurements of plasma from heparinized patients. The anti-Xa assay is not susceptible to many of the preanalytical interferences affecting the PTT, and adoption of anti-Xa monitoring would eliminate the need for validating a PTT therapeutic range. However, anti-Xa heparin monitoring has not been rigorously validated by clinical outcomes studies, and decreasing clinical use of unfractionated heparin makes it unlikely that such data is forthcoming. Nonetheless, many laboratories may find themselves in the position of being unable to continue to validate their PTT therapeutic ranges according to current recommendations and accreditation requirements.

Comparative Performance of Three Anti-Factor Xa Heparin Assays in Patients in a Medical Intensive Care Unit Receiving Intravenous, Unfractionated Heparin

The availability of automated anti-Xa heparin assays provides the opportunity to manage patient unfractionated heparin levels directly, rather than by the activated partial thromboplastin time. Because critically ill patients can acquire an antithrombin deficiency, we compared the performance of 3 anti-Xa heparin assays, 1 with and 2 without antithrombin supplementation, by analyzing in vitro aliquots of plasma with defined antithrombin levels and specimens from intensive care patients receiving intravenous heparin therapy. Heparin concentration recovery, in vitro, was dependent on the plasma antithrombin concentration for all 3 assays. The antithrombin-supplemented assay demonstrated improved heparin recovery in direct correlation to the heparin concentration in the plasma. The greatest effect of antithrombin supplementation occurred when the antithrombin level dropped below 40%, a level present in only 5% of the patient specimens. Analysis of patient specimens demonstrated significant correlation among the 3 assays. Classification of the clinical adequacy of patient heparin levels showed agreement of 80% or more between the antithrombin-supplemented and nonsupplemented assays. The antithrombin-supplemented assay did not significantly improve clinical usefulness.

False-Positive AxSYM Cardiac Troponin I Results in a 53-Year-Old Woman

A number of classes of endogenous antibodies, including heterophile, rheumatoid factor, and autoantibodies, can interfere with immunoassay measurements of many different analytes. Heterophile and rheumatoid factor antibody interferences have been described previously for the AxSYM cardiac troponin I assay. Several commercial products have been developed to neutralize heterophile antibody interferences. We describe a patient with multiple apparently falsely elevated cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac troponin I results diluted linearly. When treated with 2 different heterophile-blocking reagents, the magnitudes of the falsely elevated results increased 17- and 26-fold, and these results also demonstrated dilution linearity. This interfering substance could be removed by passage through an immobilized protein A column and by polyethylene glycol precipitation. It does not appear to be a classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain constantly vigilant for immunoassay interferences that lead to clinically significant inaccurate results and must recognize that accepted methods for detecting and neutralizing the interference may be ineffective.

Change in the in vivo hyperthermic response resulting from the metabolic effects of temporary vascular occlusion

Previous workers have reported that clamping of animal tumors in vivo enhanced the effect of hyperthermia; the enhancement has been attributed to pH and nutritional effects of vascular occlusion. It has not been clear, however, the degree to which improved heating patterns or effects on the tumor cells and vasculature from the clamping procedure itself might have contributed to the observed effect. In the experiments herein reported, care was taken to insure comparable heating of C3H mouse mammary tumors transplanted on the flank whether clamped or unclamped. Clamping for one hour with hyperthermia during the final 30 minutes caused a marked thermosensitization as measured by tumor control. The temperature at 30 minutes heating to control 50% of the tumors for 120 days (TCT 50-120) was reduced from 46.8 degrees C in controls to 43.5 degrees C in clamped tumors, a difference of 3.3 +/- 0.09 degrees C. No cytotoxicity from the clamping alone was evident by assessment of subsequent tumor growth and no lasting vascular effects could be detected by 133Xe washout and tumor growth. Since the techniques used produced essentially identical heating patterns, we conclude that the striking enhancement in hyperthermic response in clamped tumors can be attributed to the metabolic consequences of temporary vascular occlusion.

Utility of Repeat Testing of Critical Values: A Q-Probes Analysis of 86 Clinical Laboratories

CONTEXT A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. OBJECTIVES To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. DESIGN Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. RESULTS Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. CONCLUSION Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

Discard tubes are not necessary when drawing samples for specialized coagulation testing.

Discard tubes have traditionally been obtained when drawing samples for coagulation testing to avoid potential tissue factor activation of coagulation in the first tube that may lead to inaccurate results. Although discard tubes are no longer required for prothrombin time and partial thromboplastin time, the practice is still recommended for other coagulation studies due to lack of sufficient evidence that discard tubes are not needed. The objective of the present study was to determine whether the first citrate tube drawn can be used for special coagulation testing. We performed testing for fibrinogen, D-dimer, factors VIII, IX, XI, proteins C and S, and antithrombin on 30 healthy individuals and factors II, VII, IX, X, and proteins C and S on a second group of 30 healthy individuals and 30 individuals receiving warfarin. Testing was performed on two consecutive samples to evaluate the level of agreement between the two tubes. Paired t-testing showed no statistically significant differences between tube 1 and tube 2 for any of the tests performed. Most data pairs (tube 1, tube 2) agreed within 10% difference or less, and no positive or negative biases were observed. To our knowledge, this study is the first to evaluate the need for discard tubes in a variety of coagulation tests using both normal and abnormal samples. Our data suggest that discard tubes are not necessary when drawing samples for specialized coagulation testing.

Overestimation of Hemoglobin in a Patient With an IgA-κ Monoclonal Gammopathy

Abstract A patient with multiple myeloma had an automated blood count performed on a Coulter STK-S counter that repeatedly failed internal limits for both mean corpuscular hemoglobin and mean corpu...

A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population

Background The Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method. Methods Method comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk. Results We obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit. Conclusion The Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.

In Vivo Cytotoxicity of Misonidazole and Hyperthermia in a Transplanted Mouse Mammary Tumor

The cytotoxicity of misonidazole (miso) in vivo in unclamped tumors at hyperthermic temperatures, and in clamped tumors at hypothermic, euthermic, and hyperthermic temperatures has been examined. No cytotoxicity, measured as increased tumor control, was observed in unclamped tumors heated 30 min after systemic miso administration. This may reflect the short serum half-time of miso in the mouse and a small hypoxic fraction in this tumor system. There was, however, significant miso cytotoxicity in clamped tumors at euthermic and hyperthermic temperatures when the clamp was applied 30 min after systemic miso. The degree of cytotoxicity observed was dependent upon the temperature of incubation, the length of clamping, and the dose of miso.