Heterogeneity in the reported values and methodologies for detecting plasma D-Dimer in rat models: A systematic review

Background Plasma D-Dimer (DD) is a degradation product of cross-linked fibrin and represents the activation of the fibrinolytic and coagulation system. Clinically, DD tests have a high negative prediction value for thrombotic events and can be used to rule-out venous thromboembolism (VTE). The DD cut-off value for VTE in humans is 500 ng/mL; however, the baseline and cut-off values for rats are unknown. Aims To systematically evaluate the reported results and methodology of DD tests on rat models. Methods A systematic literature search was conducted using MEDLINE, EMBASE and Web of Science to include relevant full-length publications, published abstracts and conference proceedings from Jan-01-2000 to Dec-20-2019 that reported rat DD values. The search strategy used categorical search terms: “rat” AND “D-dimer” OR “fibrin degradation product”. Eligible articles were independently reviewed for strain, age, sex, baseline DD and measurement methodology. Results Of the 520 identified records 60 studies were included for qualitative analysis. The three primary rat strains used had a body mass ranging from 160 to 410 g and of both sexes were included in the analysis. There was a significant difference in reported baseline DD that was seen both, within and between rat strains and detection methodologies. Conclusion Large discrepancies in reported rat plasma DD values suggest that factors such as species and detection methods can lead to the variation of results and should be considered when designing a rat model that measures DD. We recommend using related negative control models as a baseline DD reference range for each study aiming to measure DD level in rats. Further research is required to establish a standardized reference range for baseline DD levels to help scientists better interpret rat DD test results.