{"doi":"10.1101/2021.09.01.21262974","title":"Long-term Stored Platelets Coupled to Thrombospondin-1 Detection for Rapid and Accurate Identification of Pathogenic HIT Antibodies","abstract":"Abstract Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening disorder characterized by antibodies to Platelet Factor 4 (PF4)-polyanion complexes which cause thrombocytopenia and thrombosis. Currently used technically-simple frontline assays such as the PF4-polyanion enzyme-linked immunosorbent assays (ELISAs) lack specificity, and more accurate functional assays such as the serotonin release assay (SRA) and PF4-dependent P-selectin expression assay (PEA) have long turnaround times due to technical complexity and availability only in the reference laboratory setting. There is a critical need for accurate near-patient functional testing to guide patient management, but a key barrier to attaining this goal is the short-term viability of platelets. Here, we detail a process of platelet cryopreservation that renders them viable for at least one year and show that PF4-treated cryopreserved platelets, when coupled with ELISA-based measurement of thrombospondin-1 release (a platelet α -granule protein), detects pathogenic HIT antibodies with high accuracy. Furthermore, testing of a cohort of non-pathogenic HIT antibodies that were strongly reactive in PF4/polyanion ELISA but negative in functional assays demonstrated negative results in the thrombospondin-1 release assay, confirming high specificity of this technique. These findings have the potential to transform the diagnostic testing paradigm in HIT by making in-hospital functional testing available for rapid and accurate diagnosis.","journal":"medRxiv","year":2021,"id":226431,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":829821,"name":"Curtis G. Jones","orcid":null,"position":1,"is_corresponding":false},{"id":766079,"name":"Bandana Singh","orcid":null,"position":2,"is_corresponding":false},{"id":829822,"name":"Rachel Leger","orcid":null,"position":3,"is_corresponding":false},{"id":829823,"name":"NM Heikal","orcid":null,"position":4,"is_corresponding":false},{"id":262018,"name":"Dong Chen","orcid":"0000-0001-7627-9560","position":5,"is_corresponding":false},{"id":829824,"name":"RK Pruthi","orcid":null,"position":6,"is_corresponding":false},{"id":409240,"name":"Anand Padmanabhan","orcid":"0000-0003-2519-4377","position":7,"is_corresponding":false},{"id":806800,"name":"Adam J. Kanack","orcid":"0000-0002-6077-0475","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}