{"doi":"10.1055/s-0038-1649598","title":"Evidence that the Protein C Activation Pathway Amplifies the lnhibition of Thrombin Generation by Recombinant Human Thrombomodulin in Plasma","abstract":"<jats:title>Summary</jats:title><jats:p>Thrombomodulin (TM) is a cofactor for the thrombin-catalyzed activation of anticoagulant protein C. However, we have no evidence that thrombomodulin actually activates protein C during blood coagulation processing, nor do we know whether this activated protein C acts as an anticoagulant. We studied the inhibitory action of recombinant human soluble TM (rhs-TM) on thrombin generation in whole plasma. Human plasma was activated with small amounts of tissue factor using phospholipid vesicles in place of activated platelets. Thrombin generation was observed. The addition of only 2 nM of rhs-TM prevented rapid generation of thrombin and reduced the total amount of thrombin generated. In order to study the influence of the protein C activation pathway on this inhibitory action of rhs-TM, protein C-depleted plasma was used. rhs-TM had little inhibitory effect on protein C-depleted plasma. However, the addition of protein C caused a delay in thrombin generation and a reduction of the maximum thrombin concentration. We concluded that the anticoagulant activity of rhs-TM was amplified by the protein C activation pathway.</jats:p>","journal":"Thrombosis and Haemostasis","year":1993,"id":622777,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1609289,"name":"Naoko watanabe","orcid":null,"position":1,"is_corresponding":false},{"id":1609290,"name":"Masaharu Aritomi","orcid":null,"position":2,"is_corresponding":false},{"id":1609291,"name":"Komakazu Gomi","orcid":null,"position":3,"is_corresponding":false},{"id":1609292,"name":"Takao Kiyota","orcid":null,"position":4,"is_corresponding":false},{"id":1609293,"name":"Shuji Yamamoto","orcid":null,"position":5,"is_corresponding":false},{"id":1609294,"name":"Torao lshida","orcid":null,"position":6,"is_corresponding":false},{"id":122803,"name":"Ikuro Maruyama","orcid":null,"position":7,"is_corresponding":false},{"id":1609288,"name":"Rika ohishi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Evidence that the Protein C Activation Pathway Amplifies the lnhibition of Thrombin Generation by Recombinant Human Thrombomodulin in Plasma","abstract":"<jats:title>Summary</jats:title><jats:p>Thrombomodulin (TM) is a cofactor for the thrombin-catalyzed activation of anticoagulant protein C. However, we have no evidence that thrombomodulin actually activates protein C during blood coagulation processing, nor do we know whether this activated protein C acts as an anticoagulant. We studied the inhibitory action of recombinant human soluble TM (rhs-TM) on thrombin generation in whole plasma. Human plasma was activated with small amounts of tissue factor using phospholipid vesicles in place of activated platelets. Thrombin generation was observed. The addition of only 2 nM of rhs-TM prevented rapid generation of thrombin and reduced the total amount of thrombin generated. In order to study the influence of the protein C activation pathway on this inhibitory action of rhs-TM, protein C-depleted plasma was used. rhs-TM had little inhibitory effect on protein C-depleted plasma. However, the addition of protein C caused a delay in thrombin generation and a reduction of the maximum thrombin concentration. We concluded that the anticoagulant activity of rhs-TM was amplified by the protein C activation pathway.</jats:p>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4302342687","authors":[],"funders":[],"total_grants":0,"fwci":0.3862,"citation_percentile":0.60606061,"influential_citations":0,"citation_trend":[{"year":2017,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0038-1649598.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1055/s-0038-1649598","host_type":"journal"}],"fields_of_study":["Blood Coagulation and Thrombosis Mechanisms","Venomous Animal Envenomation and Studies"],"mesh_terms":[],"keywords":["Thrombomodulin","Thrombin","Protein C","Recombinant DNA","Thrombin generation","Chemistry","Coagulation","Platelet activation","Protein S","Biochemistry","Platelet","Molecular biology","Biology","Medicine","Internal medicine","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T20:59:11.212743Z","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":[]}