{"id":"https://openalex.org/W2060452011","doi":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","title":"Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C","display_name":"Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C","publication_year":2004,"publication_date":"2004-04-28","ids":{"openalex":"https://openalex.org/W2060452011","doi":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","mag":"2060452011","pmid":"https://pubmed.ncbi.nlm.nih.gov/15118525"},"language":"en","primary_location":{"id":"doi:10.1097/01.ccm.0000126122.34119.d1","doi":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","pdf_url":null,"source":{"id":"https://openalex.org/S108732581","display_name":"Critical Care Medicine","issn_l":"0090-3493","issn":["0090-3493","1530-0293"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Critical Care Medicine","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111669144","display_name":"Sau-Chi Betty Yan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"S. Betty Yan","raw_affiliation_strings":["Lilly Research Laboratories, Indianapolis, IN, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lilly Research Laboratories, Indianapolis, IN, USA","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5015873957","display_name":"David R. Nelson","orcid":"https://orcid.org/0000-0002-3240-0725","observed_orcids":["https://orcid.org/0000-0002-3240-0725"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"David R. Nelson","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":3.2,"has_fulltext":false,"cited_by_count":56,"citation_normalized_percentile":{"value":0.91671796,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"32","issue":"Supplement","first_page":"S239","last_page":"S246"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.76419997215271,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.76419997215271,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10218","display_name":"Sepsis Diagnosis and Treatment","score":0.2151000052690506,"subfield":{"id":"https://openalex.org/subfields/2706","display_name":"Critical Care and Intensive Care Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10993","display_name":"Complement system in diseases","score":0.0071000000461936,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/factor-v-leiden","display_name":"factor V Leiden","score":0.9760000109672546},{"id":"https://openalex.org/keywords/severe-sepsis","display_name":"severe sepsis","score":0.9940000176429749},{"id":"https://openalex.org/keywords/recombinant-activated-protein-c","display_name":"recombinant activated protein C","score":0.8550000190734863},{"id":"https://openalex.org/keywords/drotrecogin-alfa","display_name":"drotrecogin alfa","score":0.984000027179718},{"id":"https://openalex.org/keywords/coagulation-activation","display_name":"coagulation activation","score":0.8629999756813049},{"id":"https://openalex.org/keywords/treatment-benefit","display_name":"treatment benefit","score":0.3970000147819519},{"id":"https://openalex.org/keywords/prowess","display_name":"PROWESS","score":0.7360000014305115},{"id":"https://openalex.org/keywords/heterozygous-carriers","display_name":"heterozygous carriers","score":0.7379999756813049},{"id":"https://openalex.org/keywords/organ-dysfunction","display_name":"organ dysfunction","score":0.6190000176429749},{"id":"https://openalex.org/keywords/sepsis-mortality","display_name":"sepsis mortality","score":0.5059999823570251}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.93522047996521},{"id":"https://openalex.org/C40767141","wikidata":"https://www.wikidata.org/wiki/Q285697","display_name":"Recombinant DNA","level":3,"score":0.6475914716720581},{"id":"https://openalex.org/C2777175894","wikidata":"https://www.wikidata.org/wiki/Q185986","display_name":"Factor V Leiden","level":4,"score":0.5735048651695251},{"id":"https://openalex.org/C2778384902","wikidata":"https://www.wikidata.org/wiki/Q183134","display_name":"Sepsis","level":2,"score":0.5258184671401978},{"id":"https://openalex.org/C2781287897","wikidata":"https://www.wikidata.org/wiki/Q412810","display_name":"Protein C","level":2,"score":0.48724332451820374},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.35470259189605713},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.34055590629577637},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.33315205574035645},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.14078807830810547},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.12544584274291992},{"id":"https://openalex.org/C2780868729","wikidata":"https://www.wikidata.org/wiki/Q261327","display_name":"Thrombosis","level":2,"score":0.11572834849357605},{"id":"https://openalex.org/C2780011451","wikidata":"https://www.wikidata.org/wiki/Q2751330","display_name":"Venous thrombosis","level":3,"score":0.0},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D000890","descriptor_name":"Anti-Infective Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D002986","descriptor_name":"Clinical Trials as Topic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005165","descriptor_name":"Factor V","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011110","descriptor_name":"Polymorphism, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D011446","descriptor_name":"Prospective Studies","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011486","descriptor_name":"Protein C","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D011994","descriptor_name":"Recombinant Proteins","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D012720","descriptor_name":"Severity of Illness Index","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018805","descriptor_name":"Sepsis","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D018805","descriptor_name":"Sepsis","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1097/01.ccm.0000126122.34119.d1","doi":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.ccm.0000126122.34119.d1","pdf_url":null,"source":{"id":"https://openalex.org/S108732581","display_name":"Critical Care Medicine","issn_l":"0090-3493","issn":["0090-3493","1530-0293"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Critical Care Medicine","raw_type":"journal-article"},{"id":"pmid:15118525","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15118525","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Critical care medicine","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":1.0,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":32,"referenced_works":["https://openalex.org/W172709144","https://openalex.org/W1605065455","https://openalex.org/W1623803297","https://openalex.org/W1884922248","https://openalex.org/W1896959165","https://openalex.org/W1923666981","https://openalex.org/W1976250839","https://openalex.org/W1988958782","https://openalex.org/W2003024037","https://openalex.org/W2003140148","https://openalex.org/W2013155340","https://openalex.org/W2049979007","https://openalex.org/W2052494211","https://openalex.org/W2053367545","https://openalex.org/W2058144497","https://openalex.org/W2065435420","https://openalex.org/W2073806998","https://openalex.org/W2082578906","https://openalex.org/W2087595514","https://openalex.org/W2099283936","https://openalex.org/W2112348962","https://openalex.org/W2117196810","https://openalex.org/W2142076534","https://openalex.org/W2143249342","https://openalex.org/W2147581820","https://openalex.org/W2162235775","https://openalex.org/W2165077166","https://openalex.org/W2218246823","https://openalex.org/W2322121630","https://openalex.org/W2338765002","https://openalex.org/W2419321379","https://openalex.org/W2470002211"],"related_works":["https://openalex.org/W2165077166","https://openalex.org/W4206083109","https://openalex.org/W2436707969","https://openalex.org/W2156157701","https://openalex.org/W2024494263","https://openalex.org/W2085941287","https://openalex.org/W2072913659","https://openalex.org/W2184425568","https://openalex.org/W2040732894","https://openalex.org/W7169678741"],"abstract_inverted_index":{"OBJECTIVE:":[0],"Coagulation":[1],"activation":[2,29],"is":[3],"part":[4],"of":[5,49,90,113,126,157,166,176,186,229,271,283,303,320,352,428],"the":[6,47,68,219,230,240,263,323,327],"acute":[7],"innate":[8],"host":[9],"response":[10],"to":[11,18,59,109,218,437],"infection":[12],"that,":[13],"when":[14],"uncontrolled,":[15],"may":[16,96,422],"contribute":[17],"organ":[19,353],"dysfunction":[20],"and":[21,34,75,130,170,265,344,358,381,391,401,444,448],"death.":[22],"Activated":[23],"protein":[24,63,144],"C":[25,145],"limits":[26],"excessive":[27],"coagulation":[28],"by":[30,53,61,322],"inactivating":[31],"factors":[32],"Va":[33,56],"VIIIa.":[35],"The":[36,227,247,301,384],"factor":[37,55,70,83,116,158,231,251,295,304,417,457],"V":[38,71,84,117,151,159,232,252,296,305,418,458],"Leiden":[39,72,85,118,152,160,233,253,297,306,419,459],"mutation":[40,119],"(R506Q),":[41],"a":[42,87,91,98,424],"prothrombotic":[43,115],"gene":[44,93],"polymorphism,":[45],"disrupts":[46],"activity":[48],"this":[50,114,466],"natural":[51],"anticoagulant":[52],"rendering":[54],"partially":[57],"resistant":[58],"inactivation":[60],"activated":[62,143],"C.":[64],"Previous":[65],"findings":[66],"in":[67,76,236,239,308,338,366,441],"mouse":[69],"endotoxemia":[73],"model":[74],"patients":[77,189,258,284,309],"with":[78,104,133,190,259,287,310,373,394,414],"severe":[79,105,128,134,167,191,237,260,288,311,430,442],"sepsis":[80,129,135,168,238,261,289,312,431,468],"suggest":[81],"that":[82,95,111,131,316],"constitutes":[86],"rare":[88],"example":[89],"balanced":[92],"polymorphism":[94],"provide":[97],"survival":[99],"advantage":[100],"for":[101,212,326,388],"heterozygous":[102,291,356,379,389,420],"carriers":[103,112,132,298,307,357,380,390,393,421,460],"sepsis.":[106,192],"We":[107],"sought":[108],"confirm":[110],"do":[120,434],"not":[121,435,462],"have":[122,423,438],"an":[123],"increased":[124,439],"risk":[125,427,449],"developing":[127,429],"derive":[136,445],"similar":[137,446],"treatment":[138,377,398],"benefit":[139,447],"from":[140,162,255,262,315,432,451,465],"recombinant":[141],"human":[142],"(drotrecogin":[146],"alfa":[147,202,273,375,396,453],"[activated])":[148,274],"as":[149],"non-factor":[150],"carriers.":[153,292,360,383],"DESIGN:":[154],"Prospective":[155],"collection":[156],"status":[161,235,254],"two":[163],"clinical":[164,178],"studies":[165,275],"(PROWESS":[169],"ENHANCE).":[171],"SETTING:":[172],":":[173,412],"A":[174,184],"total":[175,185],"447":[177],"sites":[179],"across":[180],"25":[181],"countries.":[182],"PATIENTS:":[183],"3894":[187,256],"adult":[188,257],"INTERVENTION:":[193],"Either":[194],"24":[195],"microg":[196],"x":[197,199],"kg":[198],"hr":[200],"drotrecogin":[201,272,374,395,452],"(activated)":[203,376,397,454],"(n":[204,209,222],"=":[205,210,223],"3063)":[206],"or":[207,215,350,369],"placebo":[208],"800)":[211],"96":[213],"hrs":[214],"no":[216,335,363],"exposure":[217],"study":[220,242,270,280],"drug":[221],"31).":[224],"MAIN":[225],"RESULTS:":[226],"effect":[228],"carrier":[234],"PROWESS":[241,264],"has":[243],"been":[244],"previously":[245],"reported.":[246],"combined":[248],"data":[249],"on":[250],"ENHANCE":[266],"(a":[267],"single-arm,":[268],"open-label":[269],"are":[276],"reported":[277],"here.":[278],"At":[279],"entry,":[281],"3.9%":[282],"(150/3894)":[285],"presenting":[286],"were":[290,299,399],"No":[293],"homozygous":[294],"identified.":[300],"proportion":[302],"differs":[313],"slightly":[314,425],"predicted":[317],"(allelic":[318],"frequency":[319],"2.5%)":[321],"Hardy-Weinberg":[324],"equation":[325],"general":[328],"white":[329],"population":[330],"(p":[331],"=.05).":[332],"There":[333,361],"was":[334,362],"significant":[336,364],"difference":[337,365],"baseline":[339],"disease":[340],"severity":[341],"(Acute":[342],"Physiology":[343],"Chronic":[345],"Health":[346],"Evaluation":[347],"II":[348],"score":[349],"number":[351],"dysfunctions)":[354],"between":[355,378],"non-Leiden":[359,382,392,415],"serious":[367],"bleeding":[368],"thrombotic":[370],"event":[371],"rates":[372,387],"28-day":[385],"mortality":[386,440],"20.3%":[400],"24.9%,":[402],"respectively":[403],"(risk":[404],"ratio,":[405],"0.82;":[406],"95%":[407],"confidence":[408],"interval,":[409],"0.57-1.17).":[410],"CONCLUSIONS:":[411],"Compared":[413],"carriers,":[416],"decreased":[426],"infection,":[433],"seem":[436],"sepsis,":[443],"profiles":[450],"treatment.":[455],"Therefore,":[456],"should":[461],"be":[463],"excluded":[464],"new":[467],"therapy.":[469]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":2}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}