{"doi":"10.15761/jts.1000391","title":"Protein Z-dependent protease inhibitor/protein Z complex, a new target for hemophilia treatment","abstract":"Protein Z-dependent protease inhibitor (ZPI), a serpin family protein, together with its tightly bound vitamin K-dependent protein cofactor, protein Z (PZ), function to rapidly and specifically inhibit membrane-bound FXa. Along with antithrombin, tissue factor pathway inhibitor (TFPI), and activated protein C (APC), the ZPI/PZ complex comprises one of the major endogenous anticoagulants in human plasma. Recent findings showing that ZPI/PZ regulates prothrombinase activity and that ZPI/PZ gene knockout partly restores hemostasis in a hemophilia mouse model have suggested that the neutralization of ZPI/PZ anticoagulant function could provide an alternative therapy for hemophilia treatment. Compared with other alternative therapies currently in development that target APC, TFPI, and antithrombin anticoagulants, anti-ZPI/PZ therapy is expected to be safer and similarly effective. Recent progress in the development of potent, specific ZPI/PZ antagonists should enable testing of this potentially safer therapy in a hemophilia mouse model.","journal":"Journal of Translational Science","year":2021,"id":223330,"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":0.96,"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":824775,"name":"Xin Huang","orcid":"0000-0003-0778-7611","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:54:11.061295Z","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":[]}