The Measurement of Haemostatic Factors in 16 European Laboratories: Quality Assessment for the Multicentre ECAT Angina Pectoris Study

Abstract

SummaryAs part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first Qa exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre’s performance in comparison to that of others was adopted, which preserved the confidentiality of each centre’s results. The factor VIII clotting activity assay (VIII: C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest betweenduplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWFR:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.

High plasma levels of factor VIII and risk of recurrence of venous thromboembolism

“…Providing that the amount of thrombin added to maximize the FVIII activation is appropriate, this test might be more specific than the clotting assay. However, although it has been previously reported that chromogenic FVIII methods had a better reproducibility than clotting assays (Rosen et al, 1985;Tripodi & Mannucci, 1986;van Dieijen et al, 1987;Thompson et al, 1989), we did not find any significant differences in the intra-assay and run-to-run coefficients of variation between the two methods.…”

“…Therefore, it cannot be excluded that these tests can give falsely high results due to the activation of coagulation system during blood collection and/or storage conditions. The use of a clotting method to determine FVIII levels may lead to considerable variations, as the reproducibility of these assays has been shown to be very poor, especially at high FVIII concentrations (Rosen et al , 1985; Tripodi & Mannucci, 1986; van Dieijen et al , 1987; Thompson et al , 1989). Moreover, the different reagents and equipments used for clotting assays make them hard to standardize and the comparison of inter‐laboratory results difficult.…”

Elevated Factor VIII Levels and the Risk of Thrombosis

“…First, the assay of factor VIII itself may lead to considerable variation. 119 Together with vWF:Ag, factor VIII:C showed the highest between-duplicate (5.6%) and betweenday (15%) coefficients of variation. Most often, factor VIII is measured as factor VIII:C by using modifications of the activated partial thromboplastin time (1-stage assay).…”

The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model

“…This is of particular importance when considering the generalisability of findings to symptomatic patients awaiting CABG. Very few studies (with the possible exception of the European Concerted Action on Thrombosis and Disabilities study) 209 were designed with the purpose of assessing the incremental prognostic value of biomarkers. No studies were identified that reported the incremental prognostic value of biomarkers in relation to a clearly defined clinical decision.…”