Development of a multiplex point-of-care assay to identify patients with Venous Thromboembolism

SUMMARY ABSTRACT Venous thromboembolismVTEis the third leading cause of death from cardiovascular disease behind heart attack and strokeAnnuallyVTE affects approximatelyAmericans with as many asof VTE patients dying withindaysVTE begins as a deep vein thrombosisDVTor blood clot in a deep veinLeft untreatedDVT can break free from the vein walltravel to the lungs and block some or all of the blood supply as a pulmonary embolismPEMuch of the morbidity and mortality associated with VTE could be prevented with the earlyrapid and accurate diagnosis of DVTallowing for early intervention and decreasing the risk of fatal PEHoweverdiagnosing DVT VTE is challengingresulting in both underdiagnosis and overtreatment with anticoagulantsDVT patients present with variable and non specific symptomsandpeople with DVT are asymptomaticSudden death is actually the first symptom inof people with PEUpon clinical assessmentpatients suspected of having DVT VTE are subjected to Wells criteria scoring and D dimer blood testingwhich are only valuable as rule out testsDespite availability of recommended pretestsonlyof patients evaluated for DVT andevaluated for PE via diagnostic imaging actually have the diseaseFurtherof patients screened for VTE are unnecessarily treated with anticoagulantswhich is associated with a high mortality risk due to bleedingWhile advanced imaging can diagnose DVT VTEit is expensivetime consumingharmful to some patientsnot always accurateand is often not available in the outpatient setting whereof VTEs occurThusthere is an urgent unmet need for a rapid DVT VTE diagnostic that can be performed at the point of careThe pathobiology of DVT VTE has been characterized and several plasma biomarkers have shown promise in their ability to confirm DVTthough individuallythese biomarkers lack the required sensitivity and selectivity for reliable DVT detection in patient studiesIdentification of a novel panel of peptides that recognize multiple serological markersi eseromarkersof DVT simultaneously has the potential to overcome these limitations and yield a robust diagnostic for DVT VTEWe propose to identify a sensitive and selective peptide signature for DVTwhich we will develop into a reliablecost effectivenon invasivediagnostic assay that can be performed at the point of care to improve DVT VTE patient outcomes and reduce unnecessary medical costsIn this Phaseapplicationwe will identify peptides that bind seromarkers uniquely associated with acute DVT patientsWe will then validate a subset of these peptides thatcollectivelycan accurately and reproducibly detect DVT from patient plasmaIn Phasewe will develop this peptide signature into a novel assay capable of objectively diagnosing DVT VTE rapidly at the point of careand scale up assay production PROJECT NARRATIVE Venous thromboembolismcomprised of a deep vein thrombosis that can travel to the lung and cause a pulmonary embolismis the third leading cause of cardiovascular related death in the United StatesVenous thromboembolism associated mortality could be prevented with the early diagnosis and immediate treatment of deep vein thrombosisfor which there is no diagnostic lab testAffinergy plans to identify a panel of peptides that bind serological markers of deep vein thrombosis for incorporation into a multiplexed peptide based assay capable of objectively and rapidly diagnosing deep vein thrombosis venous thromboembolism at the point of care