The Diagnostic Utility of the in-vitro Provoked D dimer test in patients with suspected pulmonary embolism

Project Summary The D-Dimer assay is the current diagnostic standard to exclude patients of VTE due to its high sensitivity1. However, D-Dimer levels are commonly elevated in patients without thromboembolism, leading to poor specificity and poor positive predictive value (PPV). Due to the lack of a robust diagnostic tool for VTE, we propose a novel advancement upon current D- Dimer testing which improves specificity through the addition of thrombolytics in vitro to increase the degradation of fibrin multimers present from the incomplete digestion of the in vivo fibrin rich clot. This increases the D-Dimer signal in instances of a true clot. The elevation in the ?provoked? D-Dimer (PDD) signal in comparison to the baseline, or Standard D-Dimer (SDD), can be used to improve the specificity and PPV of the D-Dimer assay. Our patented D-Dimer test appears to move the field towards these goals but requires further study aimed at understanding the characteristic and efficacy of commercially available thrombolytics. The PDD assay is a simple, rapid, and economical detection method for thromboembolism which improves specificity and PPV while maintaining high SDD sensitivity. Our PDD assay has U.S. and Europe patents which cover 80% of the $1.5 billion worldwide market and we are currently seeking to commercialize our discovery. Our discussions with hemostasis diagnosis companies has lead us to two top priorities 1) Determine optimal incubation time and concentration needed for commercially available thrombolytics to establish their role in performing the provoked D-dimer methodology. 2) To evaluate the test characteristics of all commercially available thrombolytic agents in effecting the new provoked D-dimer methodology so that the most durable and effective agent can be utilized. To accomplish this, we are applying for the Small Business Technology Transfer (STTR) Phase 1 award to stimulate clinical application of our patented technological innovation. Dr. Robinson is from an underrepresented minority (African-American) where the STTR mission is to foster and encourage participation in innovation and entrepreneurship in this group. Clinically, we anticipate with our PDD a true screening test will now be developed for patients with potential thromboembolism. The potential areas which will be impacted in the future are cryptogenic stroke, atrial fibrillation risk stratification, screening of immobile individuals, and defining thromboembolic risk in cardiomyopathic patients. 6