ABSTRACT
Background: D-dimer assessment has an established role in the exclusion of venous thromboembolism (VTE) in symptomatic outpatients. It is also used in diagnosing disseminated intravascular coagulation (DIC), and more recently in the risk stratification of illness severity in COVID-19. D-dimer assays are neither standardized nor harmonized, use varying methodologies, and different reporting units, resulting in a potential lack of interchangeability between assay results.Objectives: Using large multi-year datasets from an international laboratory quality assurance program, we assessed: (1) common D-Dimer assays in use worldwide (2) differences in analytical performance between different methods and (3) inter-laboratory variability between positive samples.Methods: External proficiency testing results from laboratories participating in the External quality Control for Assays and Tests (ECAT) Foundation were analyzed from 2017 to 2020.Results: Annually, between 578 and 640 laboratories participated in the D-dimer sample surveys. The three commonest assays in use in the last survey of 2020 were the Siemens Innovance D-dimer (42%), the IL HemosIL D-dimer HS 500 (16%), and the Stago Liatest D-dimer Plus (11%) - all automated, quantitative, latex immunoassays expressed in Fibrinogen Equivalent Units (FEU). The highest inter-laboratory variability on the same samples was observed around the typical VTE exclusion threshold of 0.5 mg/L FEU. Lower inter-laboratory variability was observed at values above 0.7 mg/L FEU.Conclusions: Our study provides recent, international performance data on currently used D-Dimer assays and describes the significant variability between assays and across concentrations. We demonstrate that assays are not interchangeable, and using them interchangeably has the potential to result in clinically important errors. There is an urgent need to educate users about this issue and to work towards harmonization of D-dimer results and reporting units.