Recombinant DNA technology has allowed large-scale production of the physiological, fibrin-specific, plasminogen activators tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA). The results of clinical trials with these agents, mainly for the treatment of acute myocardial infarction, have revealed a limited fibrin specificity at the large therapeutic doses required for efficient thrombolysis. Mutants and variants of t-PA and scu-PA have given important information on structure-function relationships in these proteins and have resulted in rt-PA variants with significantly prolonged half-lives in vivo. Construction of chimaeric plasminogen activators containing various portions of t-PA and scu-PA has produced functionally active enzymes, however with a lower fibrin-affinity than wild-type t-PA. The promise of antibody targeting and the use of synergistic combinations of thrombolytic agents remains to be further investigated. We anticipate that eventually these research lines will yield artificial plasminogen activators with improved efficacy, risk/benefit and cost/benefit ratios.
{"title":"New strategies in the development of thrombolytic agents.","authors":"H R Lijnen, D Collen","doi":"10.1159/000419340","DOIUrl":"https://doi.org/10.1159/000419340","url":null,"abstract":"Recombinant DNA technology has allowed large-scale production of the physiological, fibrin-specific, plasminogen activators tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA). The results of clinical trials with these agents, mainly for the treatment of acute myocardial infarction, have revealed a limited fibrin specificity at the large therapeutic doses required for efficient thrombolysis. Mutants and variants of t-PA and scu-PA have given important information on structure-function relationships in these proteins and have resulted in rt-PA variants with significantly prolonged half-lives in vivo. Construction of chimaeric plasminogen activators containing various portions of t-PA and scu-PA has produced functionally active enzymes, however with a lower fibrin-affinity than wild-type t-PA. The promise of antibody targeting and the use of synergistic combinations of thrombolytic agents remains to be further investigated. We anticipate that eventually these research lines will yield artificial plasminogen activators with improved efficacy, risk/benefit and cost/benefit ratios.","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 58","pages":"69-72"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000419340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13113122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The molecular basis of von Willebrand disease.","authors":"T Vink, J J Sixma","doi":"10.1159/000419342","DOIUrl":"https://doi.org/10.1159/000419342","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 58","pages":"78-83"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000419342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13113124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic hemapheresis in the 1990s.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"1-276"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Viscosity as the symptom leading to plasma exchange.","authors":"L Guillevin, A Bussel, F Schooneman, Z Amoura","doi":"10.1159/000418562","DOIUrl":"https://doi.org/10.1159/000418562","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"220-38"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The risk/benefit equation for therapeutic plasma exchange. Analysis of the rationale for and the safety aspects of therapeutic plasma exchange.","authors":"J P Isbister","doi":"10.1159/000418552","DOIUrl":"https://doi.org/10.1159/000418552","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"10-30"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experience with low-density lipoprotein apheresis by polyclonal and monoclonal anti-apolipoprotein B antibodies and by dextran sulfate cellulose.","authors":"W F Riesen","doi":"10.1159/000418561","DOIUrl":"https://doi.org/10.1159/000418561","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"208-19"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasma exchange in nephrological diseases.","authors":"P D Mason, C D Pusey","doi":"10.1159/000418557","DOIUrl":"https://doi.org/10.1159/000418557","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"152-66"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13302310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H Matsuo, T Nakamura, K Shibayama, M Motomura, K Nagasato, G Takeo, M Tsujihata, S Nagataki
{"title":"Plasmapheresis to treat human T lymphotropic virus type I-associated myelopathy.","authors":"H Matsuo, T Nakamura, K Shibayama, M Motomura, K Nagasato, G Takeo, M Tsujihata, S Nagataki","doi":"10.1159/000418560","DOIUrl":"https://doi.org/10.1159/000418560","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"198-207"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Apheresis in transition.","authors":"H G Klein","doi":"10.1159/000418550","DOIUrl":"https://doi.org/10.1159/000418550","url":null,"abstract":"","PeriodicalId":77091,"journal":{"name":"Current studies in hematology and blood transfusion","volume":" 57","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000418550","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13423594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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