{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T11:58:51Z","timestamp":1780747131362,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Over the past decades, haemophilia management has continually evolved, with prophylaxis now considered the treatment of choice. Prophylaxis primarily seeks to prevent bleeding and haemarthrosis episodes from occurring and avert the otherwise inevitable haemophilic arthropathy. Yet, numerous unanswered issues remain. These concern dose levels, dosing intervals, ways of integrating variability in bleeding phenotype, patient age, joint status, lifestyle, physical activity, treatment adherence and individual responses to<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>concentrates. Individualized prophylaxis may thus be paramount. One crucial tool that may allow more accurate prophylaxis regimens to be implemented is the individual pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) study. Therefore, physicians in charge of managing those living with haemophilia must be comfortable with<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>profiling in order to be in a position to tailor patients\u2019 treatment, taking into account<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>data, while minimizing patients\u2019 inconvenience, discomfort, as well as, possibly, treatment costs. For optimization of prophylaxis, recent development of recombinant molecules with more attractive<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>properties, such as prolonged elimination half\u2010life, increases the choice of dosing regimens, enabling decreased frequency of dosing for some, if deemed appropriate. For each patient,<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>parameters can be determined, including trough levels,<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>, and time spent under a predefined threshold, with additional pharmacodynamic (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) parameters possibly established by means of a global coagulation test like the thrombin generation test. Most importantly, target<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>parameters will need to consider clinical variables like patient age, body weight, joint status, treatment adherence, number of bleeding episodes, activity index or lifestyle.<\/jats:p>","DOI":"10.1111\/hae.13397","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T15:05:33Z","timestamp":1521126333000},"page":"3-17","source":"Crossref","is-referenced-by-count":33,"title":["Individualized PK\u2010based prophylaxis in severe haemophilia"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4888-1463","authenticated-orcid":false,"given":"Y.","family":"Dargaud","sequence":"first","affiliation":[{"name":"Unit\u00e9 d'H\u00e9mostase Clinique H\u00f4pital Cardiologique Louis Pradel CRTH de Lyon CHU de Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-0713","authenticated-orcid":false,"given":"X.","family":"Delavenne","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1059 P\u00f4le Biologie\u2010Pathologie H\u00f4pital Nord CHU de Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.P.","family":"Hart","sequence":"additional","affiliation":[{"name":"The Royal London Haemophilia Centre Barts and The London School of Medicine Blizard Institute QMUL London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Meunier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d'H\u00e9mostase Clinique H\u00f4pital Cardiologique Louis Pradel CRTH de Lyon CHU de Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Mismetti","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1059 P\u00f4le Biologie\u2010Pathologie H\u00f4pital Nord CHU de Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1997.130135000.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2002.00581.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2002.00580.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04214.x"},{"key":"e_1_2_8_7_1","volume-title":"Guidelines for the Management of Hemophilia","author":"World Federation of Hemophilia"},{"key":"e_1_2_8_8_1","first-page":"111","article-title":"Our experience in Sweden with prophylaxis on hemophilia","volume":"34","author":"Nilsson IM","year":"1968","journal-title":"Br J Haematol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1998.440409.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1992.tb00546.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1999.01463.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01501.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000208615"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02580.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00815.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01953.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12113"},{"key":"e_1_2_8_18_1","first-page":"61","article-title":"Hemophilia: an amazing 35\u2010year journey from the depths of HIV to the threshold of cure","volume":"121","author":"White G","year":"2010","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02879.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13058"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12838"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03270.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1001\/archinte.1970.00310060082008","article-title":"Hemophilia A prophylaxis with factor VIII concentrate","volume":"125","author":"Kasper CK","year":"1970","journal-title":"Arch Intern Med"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1600-0609.1977.tb01528.x","article-title":"Hemophilia A prophylaxis with factor VIII concentrate in a home\u2010treatment program: a controlled study","volume":"30","author":"Schimpf K","year":"1977","journal-title":"Scand J Haematol"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1182\/blood.V116.21.544.544","article-title":"Inter\u2010 and intra\u2010individual variation of factor VIII half\u2010life in severe hemophilia A","volume":"116","author":"Anthony LM","year":"2010","journal-title":"Blood"},{"key":"e_1_2_8_26_1","first-page":"169","article-title":"Prophylaxis for adults with haemophilia: one size does not fit all","volume":"10","author":"Fischer K","year":"2012","journal-title":"Blood Transfus"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03703.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1971.tb92876.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01060053"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02191.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-360594"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12851"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1997.00091.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02823.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12672"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01876.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02539.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02383.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04611.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1182\/blood.V126.23.547.547","article-title":"Personalized prophylaxis with human\u2010Cl recombinant FVIII in hemophilia A patients","volume":"126","author":"Klamroth R","year":"2015","journal-title":"Blood"},{"key":"e_1_2_8_41_1","first-page":"111","article-title":"Our experience in Sweden with prophylaxis on haemophilia","volume":"34","author":"Nilsson IM","year":"1970","journal-title":"Bibl Haematol"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.63B4.7298694"},{"key":"e_1_2_8_43_1","first-page":"310","article-title":"Experimental haemophilic synovitis: rationale and development of a murine model of human factor VIII deficiency","volume":"18","author":"Valenti Valentino LA","year":"2012","journal-title":"Haemophilia"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20555"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1998.440502.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0390"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1616932"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03767.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12381"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH04-10-0706"},{"key":"e_1_2_8_51_1","unstructured":"Thrombin Generation Assay (TGA) and Prophylaxis in Haemophilia (HOPE). ClinicalTrials.gov. Identifier: NCT02781766."},{"key":"e_1_2_8_52_1","unstructured":"Individualizing Hemophilia Prophylaxis Using Thromboelastography. ClinicalTrials.gov. Identifier: NCT02582060"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH15-08-0664"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0676-x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12188"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.2196\/resprot.6558"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.2196\/resprot.6559"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.13397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.13397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T01:34:31Z","timestamp":1719884071000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.13397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":56,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/hae.13397"],"URL":"https:\/\/doi.org\/10.1111\/hae.13397","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]}}}