External Quality Assurance of Fibrinogen Assays Using Normal Plasma: Results of the 2008 College of American Pathologists Proficiency Testing Program in Coagulation

Abstract

N 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 620% 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.

Comparison of the prothrombin time‐derived and Clauss assays for the measurement of plasma fibrinogen in hospitalized dogs

“…This could reflect inter‐laboratory variation alone, but it seems likely that by including animals with out‐of‐reference range fibrinogen concentrations, the current study provides a more accurate estimate of proportional bias across the analytical range. Based on our regression equation, at a Clauss fibrinogen concentration of 50 mg/dL, the difference between the Clauss assay and PT‐derived fibrinogen assay would exceed the 20% error considered acceptable in humans 10 . At Clauss assay fibrinogen concentrations of 50, 364, or 500 mg/dL, the predicted differences between the Clauss and PT‐derived assays also exceeded the maximum acceptable bias of 7.7% calculated in a canine biologic variation study performed using the ACL Top 9000 PT‐derived fibrinogen assay.…”

“…Early recognition of hypofibrinogenemia could also prompt viscoelastic testing to identify hyperfibrinolysis, and the need for antifibrinolytic therapy 3 . Secondly, published proficiency testing data from human laboratories report lower biases and coefficients of variation for the Clauss assay compared with the PT‐derived assay 10 . Thirdly, the Clauss assay is reported to be more reliable than the PT‐derived assay in human patients receiving anticoagulants 12,17 or with abnormal fibrinogen concentrations 17 …”

Testing for dabigatran and rivaroxaban by clinical laboratories

“…Inter‐laboratory precision of dabigatran assays could be improved. A previously published study defined inter‐laboratory CV quality in coagulation as follows: >20% = low (poor) precision, 11 − 20% = intermediate precision, 6 − 10% = good precision, and <5% = very good precision . Using that definition, the two most commonly used dabigatran assays have intermediate precision, and the 3 least commonly used methods have poor precision (Table ).…”

Thrombophilia with an onset symptom of intracranial venous thrombosis: A case report and review of the literature

“…However, a number of specific indications are recommended for screening initiated by the Anticoagulation Forum (9), these include i) idiopathic or recurrent venous thromboembolism, ii) a family history of venous thromboembolism, specifically first-degree relatives with an early onset of venous thromboembolism, iii) recurrent miscarriage (>3), iv) thrombosis during perinatal period or following the use of oral contraceptives or estrogen replacement therapy (9), v) neonates with visceral thrombosis, fulminant purpura and hemorrhagic skin necrosis, vi) venous thromboembolism in uncommon sites such as the brain, liver, mesentery or renal vein, vii) younger patients (<40 years) with early onset venous thromboembolisms and viii) thrombosis or skin necrosis during warfarin therapy. However, for patients with malignant cancer, screening for thrombophilia is generally not recommended, because such patients receive long-term anticoagulation therapy (18).…”