Interference of Heterophilic Antibody in D-dimer Determination in an Asymptomatic Elderly Woman

Background: D-Dimer is considered a pivotal biomarker in diagnosis of disseminated intravascular coagulation and in differential diagnosis of thrombosis and pulmonary embolism. Case Summary: BL, Caucasian woman, 81 years old, was admitted to hospital, in October 2023, for concussive head trauma after an accidental fall. The patient had a "non-assayable D-Dimer due to excess antigen" utilizing Sysmex Innovance D-dimer using a Sysmex CS 5100 analyser. This abnormal result was firstly observed in March 2022. A second Laboratory confirmed the raised D-dimer concentration. The patient had undergone periodic D-dimer checks which had always confirmed the results and had been treated with a direct FXa inhibitor. Methods:  Patient’s samples were tested for D-dimer using different assays and different analysers, moreover sample diluted in phosphate buffer and heterophilic antibodies blocking reagent have been tested. Results: The Sysmex Innovance D-dimer assay gave us, constantly “non-assayable D-dimer due to excess antigen" results; the HemosIL D-dimer HS assay gave us, constantly a raised D-dimer concentration (four to five higher than upper reference values); the Quidel Triage D-dimer gave us, constantly  D-dimer normal concentration. Results obtained from dilution curves confirmed the presence of high concentration high avidity  heterophilic antibodies. Conclusions: Reports regarding the influence of heterophilic antibodies on the measurement of D‐dimer are quite uncommon in literature however, they constitute a significant potential risk. Interference from heterophile antibodies often has a different impact using different instruments and methods in the measurement of D‐dimer. Using a combination of different assays and analysers, of dilution strategy with heterophilic antibody blockers, and combining laboratory results with clinical examinations and imaging data, we were able to identify the interference and exclude the presence of thrombosis.