Richard C. Friedberg

Q-tracks: A College of American Pathologists program of continuous laboratory monitoring and longitudinal performance tracking

CONTEXT Continuous monitoring of key laboratory indicators of quality by hundreds of laboratories in a standardized measurement program affords an opportunity to document the influence of longitudinal tracking on performance improvement by participants focused on that outcome. OBJECTIVE To describe the results of the first 2 years of participation in a unique continuous performance assessment program for pathology and laboratory medicine. DESIGN Participants in any of 6 modules in the 1999 and 2000 College of American Pathologists (CAP) Q-Tracks program collected data according to defined methods and sampling intervals on standardized input forms. Data were submitted quarterly to CAP for statistical analysis. Interinstitutional comparison reports returned in 6 weeks provided each laboratory with its performance profile of key indicators and its percentile ranking compared with all participants in that quarter. This also included longitudinal comparisons of performance during previous cumulative quarters. Control charts graphically displayed data with flags identifying performance points that were out of statistical control. SETTING Hospital-based laboratories in the United States (98%), Canada, and Australia. PARTICIPANTS Voluntary subscriber laboratories in the CAP Q-Tracks performance measurement program: roughly 70% from hospitals of 300 occupied beds or fewer, 65% from private, nonprofit institutions, slightly more than half located in cities, one third from teaching hospitals, and 20% with pathology residency training programs. MAIN OUTCOME MEASURES Each module measured several major and additional minor quality indicators and unbenchmarked individualized data for internal use. RESULTS Participants in 4 of 6 Q-Tracks continuous monitors demonstrated statistically significant performance improvement trends in 1999 and 2000, which were most marked for laboratories that continued participation throughout both years. These monitors were wristband patient identification, laboratory specimen acceptability, blood product wastage, and intraoperative frozen section consultation. CONCLUSIONS Key continuous indicators chosen on the basis of a decades experience in the CAP Q-Probes quality improvement program are useful measurement and benchmarking tools for laboratories to improve performance. In general, measures in which there is a broad range of demonstrable performance initially are most optimal for subsequent improvement using continuous monitoring. These studies have shown that quality is not static, but rather is a moving benchmark of performance as seen in the redefinition of benchmarks over time by participants in the first 2 years of the CAP Q-Tracks program.

Critical values comparison: a College of American Pathologists Q-Probes survey of 163 clinical laboratories.

CONTEXT Critical laboratory values are values that may be indicative of life-threatening conditions requiring rapid clinical intervention. Designation of critical values by clinical laboratories is required by the Clinical Laboratory Improvement Amendments and regulatory agencies. The development of critical values often involves consultation with clinical services. Also, questions are frequently asked about how critical values compare between institutions. OBJECTIVE To examine and compare critical value ranges for selected common critical value analytes. Additional specific questions addressed the source of these values, the inclusion of specific items on a critical values list, and the procedures for establishing such lists. DESIGN A total of 163 clinical laboratories provided critical values for potassium, calcium, magnesium, thyroid-stimulating hormone, hemoglobin, platelet count, and activated partial thromboplastin time. Collected data were subjected to analysis for statistical variation. A questionnaire regarding demographic characteristics, institutional practices, and critical values management was also completed by participants. RESULTS There was slight variation in pediatric and adult critical values used by the central 80% of study laboratories. Three areas of interest were noted: (1) 27% of laboratories allowed nonpractitioners to accept inpatient critical value reports, (2) there was nonconsensus regarding the handling of outpatient critical values during weekday versus evening/weekend hours, and (3) only 56% of respondents had a written critical values policy or procedure. CONCLUSIONS Pediatric and adult critical values for the selected analytes were consistent in a comparison between the 163 clinical laboratories. Several weaknesses in current critical values management were identified. A consensus critical values list that may be of value to other institutions was assembled.

The origin of reference intervals: A college of American pathologists Q-probes study of normal ranges used in 163 clinical laboratories

Abstract Context.—Standards have been developed for establishing reference intervals, but little is known about how intervals are determined in practice, interlaboratory variation in intervals, or errors that occur while setting reference intervals. Objectives.—To determine (1) methods used by clinical laboratories to establish reference intervals for 7 common analytes, (2) variation in intervals, and (3) factors that contribute to establishment of “outlier” intervals. Design.—One hundred sixty-three clinical laboratories provided information about their reference intervals for potassium, calcium, magnesium, thyroid-stimulating hormone, hemoglobin, platelet count, and activated partial thromboplastin time. Results.—Approximately half the laboratories reported conducting an internal study of healthy individuals to validate reference intervals for adults. Most laboratories relied on external sources to establish reference intervals for pediatric patients. There was slight variation in intervals used by the ...

Proteinase expression during differentiation of human osteoclasts in vitro.

Osteoclasts are macrophage‐derived polykaryons that degrade bone in an acidic extracellular space. This differentiation includes expression of proteinases and acid transport proteins, cell fusion, and bone attachment, but the sequence of events is unclear. We studied two proteins expressed at high levels only in the osteoclast, cathepsin K, a thiol proteinase, and tartrate‐resistant acid phosphatase (TRAP), and compared this expression with acid transport and bone degradation. Osteoclastic differentiation was studied using human apheresis macrophages cocultured with MG63 osteosarcoma cells, which produce cytokines including RANKL and CSF‐1 that mediate efficient osteoclast formation. Immunoreactive cathepsin K appeared at 3–5 days. Cathepsin K activity was seen on bone substrate but not within cells, and cathepsin K increased severalfold during further differentiation and multinucleation from 7 to 14 days. TRAP also appeared at 3–5 d, independently of cell fusion or bone attachment, and TRAP activity reached much higher levels in osteoclasts attached to bone fragments. Two proteinases that occur in the precursor macrophages, cathepsin B, a thiol proteinase related to cathepsin K, and an unrelated lysosomal aspartate proteinase, cathepsin D, were also studied to determine the specificity of the differentiation events. Cathepsin B occurred at all times, but increased two‐ to threefold in parallel with cathepsin K. Cathepsin D activity did not change with differentiation, and secreted activity was not significant. In situ acid transport measurements showed increased acid accumulation after 7 days either in cells on osteosarcoma matrix or attached to bone, but bone pit activity and maximal acid uptake required 10–14 days. We conclude that TRAP and thiol proteinase expression begin at essentially the same time, and precede cell fusion and bone attachment. However, major increases in acid secretion and proteinases expression continue during cell fusion and bone attachment from 7 to 14 days. J. Cell. Biochem. 78:627–637, 2000.

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.

Independent roles for platelet crossmatching and HLA in the selection of platelets for alloimmunized patients.

Background: Although HLA‐matched platelets are frequently requested for alloimmunized patients, recent evidence has indicated that 1‐hour posttransfusion platelet increments in these patients are specifically sensitive to crossmatch compatibility.

Type and screen completion for scheduled surgical procedures. A College of American Pathologists Q-Probes study of 8941 type and screen tests in 108 institutions.

CONTEXT Market-driven changes in the timing of elective surgeries and admissions have introduced barriers to completing pretransfusion testing in a timely manner. Consequently, blood bank personnel may not have adequate time to identify appropriate blood products for scheduled surgeries. Incomplete pretransfusion testing can delay surgery and significantly compromise patient safety. OBJECTIVES To identify the incidence of avoidable problems associated with obtaining timely samples for adequate pretransfusion type and screen (T&S) testing, to identify the practices and characteristics associated with improved rates of pretransfusion testing completed prior to surgery, and to determine the likelihood of antibody identification problems that affect the availability of blood. DESIGN Participants in the College of American Pathologists (CAP) Q-Probes laboratory quality improvement program were asked to collect data on when a T&S was collected in anticipation of elective scheduled surgery, when the T&S was completed, when the surgery started, and the results of those T&S tests. Participants also completed questionnaires describing their facilities, procedures, and practices. SETTING AND PARTICIPANTS One hundred eight public and private institutions participated in this Q-Probes Study, 97% of which were located in the United States. MAIN OUTCOMES MEASURES Type and screen collection and completion relative to the start of surgery, and the results of those tests. RESULTS Of the 8941 T&Ss, 64.6% were collected prior to the day of surgery. The median laboratory completed approximately 69% of their T&S testing for scheduled surgeries at least 1 day prior to the surgery. Of those T&S tests that were collected on the day of surgery, the median laboratory completed almost 23% after the start of surgery. For 10% of participants, more than 75% of all T&Ss collected on the same day as surgery were not complete until after the start of surgery. When red blood cell-directed antibodies were identified, 78.7% were considered clinically significant, and 95.2% were alloantibodies. Positive antibody screens were significantly associated with delayed surgery and special efforts needed to obtain blood. Of those institutions with a specific protocol in place to collect T&S samples prior to hospital admission, the median laboratory completed the T&S at least 1 day prior to surgery 74% of the time. When the institution coupled the T&S collection protocol with T&S collection earlier than 3 days prior to surgery, the median laboratory completed the T&S at least 1 day prior to surgery almost 87% of the time. Type and screen collection less than 3 days prior to surgery resulted in special efforts needed to obtain blood more than 1% of the time. Type and screen collected on the same day as surgery directly resulted in a surgery delay 0.8% of the time. CONCLUSIONS Patients are unnecessarily being placed at risk by inadequate mechanisms to ensure available blood for surgery. All T&Ss were collected for scheduled surgeries with adequate opportunity for a T&S to be completed in advance of the surgery. Specific protocols helped improve the performance in terms of completing the T&S prior to surgery, as did mechanisms that permitted T&S collections in advance of the admission. Type and screen collection time relative to surgery was significantly associated with the incidence of surgery delay due to unavailable blood; the less time between collection and surgery, the less likely blood was available.

Removal of Vancomycin during Plasmapheresis

OBJECTIVE: To examine the removal of vancomycin during plasmapheresis, determine whether drug administration should be withheld prior to or a supplemental dose given after the procedure, and determine whether a redistribution phenomenon in vancomycin serum concentrations occurs after plasmapheresis. DESIGN: Prospective, cohort study. SETTING: An 800-bed, tertiary-care, teaching hospital. PATIENTS: Twelve patients receiving vancomycin as prescribed who were also undergoing therapeutic plasmapheresis. METHODS: Blood samples for determination of vancomycin concentrations were obtained from each patient immediately before, during, immediately after, and 2 hours after plasmapheresis. Vancomycin concentration in plasma removed by plasmapheresis and volume of plasma removed were measured. Patient-specific pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model. Percent of drug removed by plasmapheresis and percent increase in vancomycin total clearance secondary to plasmapheresis were calculated. RESULTS: A mean of 6.3% of the total body store of vancomycin was removed by plasmapheresis. Vancomycin clearance during plasmapheresis averaged 1.6 L/h, which was an average increase of 285% in the total clearance of vancomycin from the body. Nine of 10 patients had a higher observed vancomycin concentration 2 hours after plasmapheresis than that predicted by degrading the concentration observed immediately after the procedure, suggesting that redistribution in serum concentrations occurs after the procedure. CONCLUSIONS: A single one-volume plasmapheresis does not remove a clinically important amount of vancomycin; therefore, supplemental dosing after the procedure is not necessary. A redistribution phenomenon in vancomycin concentrations appears to exist after plasmapheresis. Further study is needed to determine how long the redistribution phase lasts and when vancomycin concentrations should be measured after plasmapheresis.

COMPLICATIONS OF BLOOD TRANSFUSION : HOW TO RECOGNIZE AND RESPOND TO NONINFECTIOUS REACTIONS

Preview Severe, life-threatening reactions to blood transfusion are rare but may be clinically similar to minor reactions, which are fairly common. The authors describe the manifestations of various noninfectious reactions and the laboratory workup necessary to discriminate among them. They also discuss the mechanisms of these transfusion reactions and tell how to treat and prevent them.

Clinical and laboratory factors underlying refractoriness to platelet transfusions

Of the spectrum of clinical and laboratory factors responsible for refractoriness to platelet transfusions, some are amenable to intervention, some to circumvention, and others only to acceptance and support for complications. Identification of the likely reason for refractoriness in a given individual patient is critical to determine the optimum management strategy. The blood bank or transfusion service can and perhaps should play a direct role in that strategy through the provision of single donor platelets collected by apheresis. Single donor platelets offer a number of real and theoretical advantages over random donor platelets, including the potential for crossmatching, reduction in net donor exposures, maintenance of ABO‐compatibility, improved inventory management, and perhaps diminished rate of alloimmunization. The sole perceived benefits of random donor platelets are cost and availability. The cost differential, however, needs to take into account a variety of factors beyond the immediate concern of platelet collection and distribution, including many highly dependent upon local factors. The optimum management of the platelet refractory patient requires more appropriate use of single donor apheresis platelets coupled with platelet crossmatching when necessary. Data from outcomes studies presented indicates that increased reliance upon single donor apheresis platelets at the expense of pooled random donor units can improve the overall quality of transfusion practice by decreasing platelet utilization, resource consumption, donor exposures, and platelet wastage.