External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation.

CONTEXT: Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays. OBJECTIVE: To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation. DESIGN: Two identical vials of normal plasma were sent to more than 3500 laboratories. Participants measured fibrinogen levels using local methods. RESULTS: Fifty different fibrinogen methods were evaluated. All-method bias was 8.3% (range of method-specific biases, 0.0%-27.0%) and all-method coefficient of variation was 7.7% (range of method-specific coefficients of variation, 0.7%-25.8%). After controlling for reagent/instrument type, mean fibrinogen levels were 11.6% higher for prothrombin time-based reagents compared to Clauss (P < .001), and coefficient of variation was 46% lower for mechanical endpoint instruments compared to photo-optical. Most testing events (97.4%) could be reliably graded as pass or fail using a target range of ±20% from the method mean (total pass rate, 98.8%). Total fail rate was 3.0-fold lower for mechanical instruments compared to photo-optical (0.5% versus 1.5%, P  =  .001). Nonetheless many photo-optical methods had very high precision and very low fail rates. CONCLUSIONS: Fibrinogen assays showed highly variable methodology and performance characteristics. Bias, precision, and grading were affected by the type of reagent or instrument used.

Understanding and recognizing the Pelger-Huët anomaly.

The Pelger-Huët anomaly (PHA) is a recognized morphologic variant affecting all granulocytes but is most evident in polymorphonuclear neutrophils (PMNs). PHA is caused by a decreased amount of the lamin B receptor (LBR). Recognition of PHA morphologic features serves as a marker for mutations in the LBR gene. This review summarizes the history of PHA and the current knowledge of the functions of the LBR. Guidance is given for distinguishing PHA from other hematologic disorders in which granulocytes may show similar changes. Recognition of PHA in the laboratory should prompt communication to the patient's physician about the possible clinical significance of this finding and the recommended screening for the anomaly in other family members by CBC and review of a peripheral blood smear.

External quality assurance of antithrombin, protein C, and protein s assays: results of the College of American Pathologists proficiency testing program in thrombophilia.

CONTEXT: Hereditary and acquired deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are risk factors for venous thromboembolism. Proper diagnosis requires high-quality assays for these proteins. OBJECTIVE: To determine the accuracy and interlaboratory precision of AT, PC, and PS assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in thrombophilia and to grade the performance of laboratories. DESIGN: Standardized normal plasma with assigned analyte values was sent in 2 separate challenges to participating laboratories. Participants measured AT, PC, and PS levels using local methods. RESULTS: When compared with the assigned values for the international standard, the order of assay accuracy from highest to lowest was AT activity, PC antigen, AT antigen, total PS antigen, PC activity, PS activity, and free PS antigen (range of assay bias, 2.6%-8.8%). The order of assay precision from highest to lowest was PC activity, AT activity, AT antigen, total PS antigen, PS activity, free PS antigen, and PC antigen (range of assay coefficient of variation, 6.1%-20.0%). Most testing events (87.8%) could be graded as pass or fail using a target range of ±3 standard deviations from the method-specific mean. The pass rate was 98.2% for all AT, PC, and PS testing events combined. CONCLUSIONS: Accuracy and precision were higher for AT assays and lower for PC and PS assays. It was feasible to grade individual laboratory performance.

Women with red hair report a slightly increased rate of bruising but have normal coagulation tests.

There is an anecdotal impression that redheads experience more perioperative bleeding complications than do people with other hair colors. We, therefore, tested the hypothesis that perceived problems with hemostasis could be detected with commonly used coagulation tests. We studied healthy female Caucasian volunteers, 18 to 40 yr of age, comparable in terms of height, weight, and age, with natural bright red (n = 25) or black or dark brown (n = 26) hair. Volunteers were questioned about their bleeding history and the following tests were performed: complete blood count, prothrombin time/international normalized ratio, activated partial thromboplastin time, platelet function analysis, and platelet aggregation using standard turbidimetric methodology. Agonists for aggregation were adenosine diphosphate, arachidonic acid, collagen, epinephrine, and two concentrations of ristocetin. The red-haired volunteers reported significantly more bruising, but there were no significant differences between the red-haired and dark-haired groups in hemoglobin concentration, platelet numbers, prothrombin time/international normalized ratio, or activated partial thromboplastin time. Furthermore, no significant differences in platelet function, as measured by platelet function analysis or platelet aggregometry, were observed. We conclude that if redheads have hemostasis abnormalities, they are subtle.

A simplified algorithm for the laboratory detection of lupus anticoagulants: utilization of two automated integrated tests.

Diagnosis of antiphospholipid antibody syndrome includes laboratory testing for lupus anticoagulants (LAs). Guidelines for testing have been published, but approaches vary, often incorporating multiple tests. We evaluated the performance of the activated partial thromboplastin time using 2 reagents, a dilute Russell viper venom time, and a hexagonal phospholipid assay for detecting LAs in 105 adults. Of the patients, 26 were taking anticoagulants at the time of testing. Based on findings, an algorithm was derived for optimal detection of LAs using 2 easily performed, automated, integrated test systems. Of 105 patient samples, 30 (28.6%) were positive for LAs, using the algorithm interpretive criteria. Of these 30 positive results, 10 were detected in the 26 patients taking anticoagulants. Analysis by chi2 showed no difference in performance of the integrated tests between samples from patients taking and not taking anticoagulants. The algorithm is offered as a means for standardization of laboratory testing for LAs.

Errors in pathology and laboratory medicine: consequences and prevention.

Reducing errors and improving quality are an integral part of Pathology and Laboratory Medicine. The rate of errors is reviewed for the pre-analytical, analytical, and post-analytical phases for a specimen. The quality systems in place in pathology today are identified and compared with benchmarks for quality. The types and frequency of errors and quality systems are reviewed for surgical pathology, cytopathology, clinical chemistry, hematology, microbiology, molecular biology, and transfusion medicine. Seven recommendations are made to reduce errors in future for Pathology and Laboratory Medicine.