{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:51:07Z","timestamp":1787014267445,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In patients with haemophilia A undergoing surgery, factor VIII (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative to bolus infusion (BI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To compare the perioperative haemostatic efficacy and safety of antihaemophilic factor (recombinant) (ADVATE\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ; Baxalta US Inc., a Takeda company, Lexington, MA, USA) CI or BI administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicentre, phase III\/IV, controlled study (NCT00357656), 60 previously treated adult patients with severe or moderately severe disease undergoing elective unilateral major orthopaedic surgery (knee replacement,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a048; hip surgery,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04; other,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08) requiring drain placement were randomized to receive antihaemophilic factor (recombinant) CI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a029) or BI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a031) through postoperative day 7. Primary outcome measure was cumulative packed red blood cell (PRBC)\/blood volume in the drainage fluid within 24\u00a0h after surgery, used to establish non\u2010inferiority of CI to BI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CI:BI ratio of cumulative PRBC volume in the 24\u2010h drainage fluid was 0.92 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value &lt;.001 for non\u2010inferiority; 95% confidence interval, 0.82\u20131.05). Total antihaemophilic factor (recombinant) dose per kg body weight received in the combined trans\u2010 and postoperative periods was similar with CI and BI to maintain targeted FVIII levels during\/after surgery. Treatment\u2010related adverse events (AEs) were reported in five patients treated by CI (eight events) and five treated by BI (six events), including two serious AEs in each arm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CI administration of antihaemophilic factor (recombinant) is a viable alternative to BI in patients with haemophilia A undergoing major orthopaedic surgery, providing comparable efficacy and safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.14219","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T16:19:11Z","timestamp":1616861951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Results of a randomized phase III\/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-9896","authenticated-orcid":false,"given":"Ingrid","family":"Pabinger","sequence":"first","affiliation":[{"name":"Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily","family":"Mamonov","sequence":"additional","affiliation":[{"name":"National Research Center for Hematology Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7877-4784","authenticated-orcid":false,"given":"Jerzy","family":"Windyga","sequence":"additional","affiliation":[{"name":"Department of Disorders of Hemostasis and Internal Medicine Institute of Hematology and Transfusion Medicine Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Engl","sequence":"additional","affiliation":[{"name":"Baxalta Innovations GmbH, a Takeda company Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Doralt","sequence":"additional","affiliation":[{"name":"Baxalta Innovations GmbH, a Takeda company Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilatha","family":"Tangada","sequence":"additional","affiliation":[{"name":"Baxalta US Inc., a Takeda company Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Spotts","sequence":"additional","affiliation":[{"name":"Baxalta US Inc., a Takeda company Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Ewenstein","sequence":"additional","affiliation":[{"name":"Baxalta US Inc., a Takeda company Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"ADVATE (antihemophilic factor [recombinant]) [summary of product characteristics];2013.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_\u2010_Product_Information\/human\/000520\/WC500022467.pdf. 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