An in vitro diagnostic assay for the early and accurate detection of platelet-activating antibodies associated with Heparin-inducedThrombocytopenia

PROJECT SUMMARY/ABSTRACT This Phase IIB SBIR proposal is aimed at performing clinical and analytical validation studies of a highly accurate functional in vitro diagnostic (IVD) assay for the detection of pathogenic antibodies in Heparin-induced thrombocytopenia (HIT), an adverse reaction to heparin treatment. This assay is based on findings that platelet factor 4 (PF4)-treated platelets can be used for the sensitive and specific detection of clinically significant HIT antibodies. HIT kills more than five patients every day in the US and is frequently suspected in heparin-treated hospitalized patients who may have several potential causes for thrombocytopenia. To assist with diagnosis and management, physicians rely on two families of HIT assays. The first, the PF4/Polyanion ELISA-based IVD assays are sensitive but are highly non-specific such that the positive predictive value of these assays is poor at only 30-50%. The second, more accurate platelet activation-based (functional) assays such as the Serotonin Release Assay (SRA) are technically complex and are performed only at a few reference laboratories which leads to long turnaround times. As a result, frontline ELISAs are used to manage most HIT-suspected patients while SRA results are pending and many patients with false-positive ELISAs are inappropriately treated with alternative anticoagulants which are expensive and have a significantly worse bleeding profile. Retham’s goal is to revolutionize HIT diagnosis by replacing the technically complex and slow reference lab assays with HITDx, a simple yet accurate functional IVD that can be performed in the hospital laboratory. HITDx is based on groundbreaking research that suggests that pathogenic platelet-activating HIT antibodies can be detected using cryopreserved platelet technology that Retham has developed. Retham will perform clinical and analytical validation studies on HITDx which will serve as the backbone of a planned regulatory submission to the FDA. The project will be led by Curtis Jones, lead inventor of this technology. He will be supported by Dr. Padmanabhan, a leading HIT expert, QA/RA and biostatistics consultants, manufacturing partners and expert Retham advisors. It is expected that this patient- impacting product will revolutionize HIT diagnosis by decentralizing functional testing and providing rapid, accurate results that will facilitate early and appropriate patient management.