Thrombosis Update (May 2023)
Heterogeneity in the reported values and methodologies for detecting plasma D-Dimer in rat models: A systematic review
Abstract
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.