{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:16:24Z","timestamp":1792664184844,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T00:00:00Z","timestamp":1403740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2007\/07433-9"],"award-info":[{"award-number":["2007\/07433-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["559158\/2008-4"],"award-info":[{"award-number":["559158\/2008-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["01\/10707-7"],"award-info":[{"award-number":["01\/10707-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    The tail bleeding model using haemophilic mice has been used as one of the standard assays for efficacy evaluation of novel antihaemophilic therapies at the preclinical level. A number of different configurations and endpoints have been proposed in the literature for this model, hindering interlaboratory comparisons. A particular configuration, known as the tail bleeding survival assay (TBS), adopted by several groups, involves measuring the ability of conscious haemophilic mice to survive exsanguination following tail transection. Major limitations to this configuration include ethical constraints and impaired quantitative determinations. The aim of this study was to standardize and validate a quantitative haemostatic assay for evaluation of antihaemophilic therapies employing an alternative to TBS, which involves a more humane endpoint associated with stable clot formation. Haemophilic mice were treated with vehicle or different doses of two antihaemophilic reference products licensed in Brazil. The haemostatic response was evaluated by our quantitative tail bleeding haemostatic assay (\n                    <jats:styled-content style=\"fixed-case\">qTBA<\/jats:styled-content>\n                    ) over a period of 120\u00a0min and then quantified by dose\u2013response modelling. We demonstrate that our\n                    <jats:styled-content style=\"fixed-case\">qTBA<\/jats:styled-content>\n                    method allows a direct relationship between the number of animals which achieved full haemostatic response and the dosage of both antihaemophilic factors evaluated over 120\u00a0min. In addition, the method sensitivity is suitable to demonstrate the conversion from a severe to a moderate haemophilia phenotype. Our proposed\n                    <jats:styled-content style=\"fixed-case\">qTBA<\/jats:styled-content>\n                    is easy to implement and constitutes an alternative and more ethical endpoint, which could be effectively used as a surrogate to the commonly employed survival endpoint, allowing quantitative haemostatic response evaluation associated with stable clot formation.\n                  <\/jats:p>","DOI":"10.1111\/hae.12484","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T22:19:11Z","timestamp":1403821151000},"source":"Crossref","is-referenced-by-count":10,"title":["A quantitative and humane tail bleeding assay for efficacy evaluation of antihaemophilic factors in haemophilia A mice"],"prefix":"10.1111","volume":"20","author":[{"given":"E. S.","family":"Molina","sequence":"first","affiliation":[{"name":"Department of Biochemistry Chemistry Institute NUCEL\u2010NETCEM School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Fujita","sequence":"additional","affiliation":[{"name":"Institute of Mathematics and Statistics University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Sogayar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Chemistry Institute NUCEL\u2010NETCEM School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Demasi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Chemistry Institute NUCEL\u2010NETCEM School of Medicine University of S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-353672"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(79)90064-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300308"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28416"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613377"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1519"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02780.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-152959"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1258\/la.2010.009113"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02133.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04084.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01636.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02828.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-212423"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01508.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.41.2.87"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-119"},{"key":"e_1_2_9_19_1","unstructured":"HosmerD LemeshowS.Applied Logistic Regression.New York:Wiley 1989. Available athttp:\/\/books.google.com.br\/books\/about\/Applied_Logistic_Regression.html?id=Po0RLQ7USIMC&redir_esc=y.Accessed March 16 2013."},{"key":"e_1_2_9_20_1","unstructured":"R Core Team.R: A language and environment for statistical computing.2012."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4541-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000130465.23430.74"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2700.82225"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.t01-1-00033.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199509000-00013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1055\/s-0038-1657230","article-title":"Bleeding time in rats: a comparison of different experimental conditions","volume":"48","author":"Dejana E","year":"1982","journal-title":"Thromb Haemost"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1351-8216.2001.00133.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00191.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1160\/TH04-08-0485","article-title":"Factor VIII efficient and specific non\u2010covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy","volume":"93","author":"Baru M","year":"2005","journal-title":"Thromb Haemost"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02045.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199012273232604"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12484","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T10:54:04Z","timestamp":1695466444000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,26]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/hae.12484"],"URL":"https:\/\/doi.org\/10.1111\/hae.12484","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,26]]}}}