SBIR-STTR Award

A functional assay system for monitoring antithrombin drugs, such as recombinant hirudin and hirudin analogs, in patients will be developed. This assay system will be based on a novel dry reagent paramagnetic particle-based assay technology that has recently been applied successfully to whole blood, bedside monitoring of prothrombin time and activated partial thromboplastin time testing. The dry reagent assay consists of paramagnetic iron oxide particles whose oscillations in an imposed magnetic field will be dampened by the formation of a fibrin clot around the particles. The clotting time in turn is related to the concentration of thrombin inhibitor present in the blood sample. Specific aims include: (1) compare the aPPT-based assay with a thror bin-based test system; (2) refine the prototype aPPT-based hirudin assay or thrombin time-based assay by test card optimization and testing; (3) develop algorithms for rapid calibration and standardization to a reference method; and (4) study the effects of potential influencing factors on the assay and determine performance characteristics. Introduction of a rapid, convenient assay system for antithrombin drugs at the patient point-of-care could provide results earlier than existing and newly-emerging laboratory methods and could serve as an important diagnostic guide during therapy.Awardee's statement of the potential commercial applications of the research:This research has the potential to provide new diagnostic products for monitoring antithrombin drugs at the point-of-care to optimize and individualize therapy. More specifically, this work could provide products for monitoring in disseminated intravascular coagulation (DIC), adjunctive administration during thrombolytic therapy, anticoaguration in hemodialysis and extracorporeal circulation, and prophylaxis in surgery.National Heart, Lung, and Blood Institute (NHLBI)

A functional assay system for monitoring antithrombin drugs, such as r- hirudins and hirudin analogs, in patients will be developed. This system will be based on a novel dry reagent assay technology which has recently been applied successfully to whole blood, bedside monitoring of PT and activated PTT testing. Introduction of a rapid, convenient assay system for antithrombin agents at the patient point-of-care could provide results sooner than existing and newly emerging laboratory methods and could serve as an important diagnostic guide during therapy. We propose to continue development of this assay system and to assess its potential using a combination of laboratory studies of influencing factors and clinical sample studies. Application to early determination of functional drug levels in patients will be explored. This work will be performed in conjunction with Loyola University Medical Center. Phase Il support would fund pilot production of developed assays, pharmacokinetic studies, and comparison with reference methods in on- going clinical trials of antithrombin drugs at three hospital sites. PROPOSED COMMERCIAL APPLICATION: This research has the potential to provide new diagnostic products for monitoring antithrombin drugs at the point-of-care to optimize and individualize therapy. More specifically, this work could provide products for monitoring in disseminated intravascular coagulation (DIC), adjunctive administration during thrombolytic therapy, anticoagulation in hemodialysis and extracorporeal circulation, and prophylaxis in invasive cardiology procedures and in surgery.