Mentor: Tracy Stokol
Contact Information: Email: email@example.com; Phone: 607-253-3255
Sponsor: American Society for Veterinary Clinical Patotholgy
Grant Number: N/A
Title: Procoagulant Activity in Horses: Measurement of Platelet-derived Microparticles and Endogenous Thrombin Potential
Annual Direct Cost: $2,435
Project Period: 11/01/10-10/31/11
DESCRIPTION (provided by applicant): Thrombosis is a common, potentially fatal, sequela of systemic inflammatory diseases in the horse. Unfortunately, identification of patients at risk for thrombosis is difficult because current laboratory assays are not configured to detect an activated or hypercoagulable hemostatic system. Identification of "at risk" (hypercoagulable or pre-thrombotic) patients prior to the emergence of clinical signs is essential to guide therapy and minimize the morbidity and mortality associated with systemic inflammation in horses. Microparticles (MPs) are small, membrane-derived vesicles shed from activated platelets. They are highly procoagulant and increased numbers have been associated with several thrombotic diseases in human patients. We hypothesize that platelet-derived MPs contribute to hypercoagulability and the subsequent development of thrombosis in horses with inflammatory disorders. Assays to measure platelet-derived MPs and determine their effect on coagulation have not been performed in horses. The aims of this project are: 1) To develop a bead-based flow cytometric assay for the semi-quantification of platelet-derived MPs in equine blood and plasma, and 2) To determine how MPs influence thrombin generation in equine plasma using an endogenous thrombin potential (ETP) assay. We will determine the effects of sample storage on MP formation and thrombin generation and how coagulation factors, specifically factor XII and tissue factor, and exogenous phospholipids affect thrombin generation in horses. We will also establish equine-specific reference intervals for these assays. Platelet-derived MP quantification and ETP represent new laboratory assays of procoagulant activity that have the potential to be useful for the detection or prediction of thrombosis in horses with systemic inflammation. We are planning future studies to determine their diagnostic utility for this purpose.