{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:38:15Z","timestamp":1765820295627,"version":"3.48.0"},"reference-count":51,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Foundation of Health and Family planning Commission of Shanghai","award":["ZY(2018-2020)-FWTX-6023"],"award-info":[{"award-number":["ZY(2018-2020)-FWTX-6023"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,6,26]]},"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This clinical trial is designed to evaluate the effect of multiple-dose tranexamic acid (TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A randomised, single-blinded, parallel-controlled study will be designed. Patients with RA (age 50\u201375 years) undergoing unilateral primary end-stage total knee arthroplasty will be randomly divided into group A or group B. Group A will be treated with one dose of TXA (1\u2009g; intravenous injection 3\u2009hours postsurgery) and group B with three doses (1\u2009g; intravenous injection at 3, 6 and 12\u2009hours postsurgery) after surgery. The primary outcomes will be evaluated with blood loss, maximum haemoglobin drop and transfusion rate. The secondary outcomes will be evaluated with knee function and complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The Shanghai Guanghua Hospital of Integrated Traditional Chinese Medicine and Western Medicine Ethics Committee approved in this study in July 2019. Informed consent will be obtained from all participants. Results of the trial will be published in the Dryad and repository in a peer-reviewed journal. Additionally, deidentified data collected and analysed for this study will be available for review from the corresponding author on reasonable request.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR1900025013.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-034431","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T12:55:48Z","timestamp":1597928148000},"page":"e034431","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Multiple-dose tranexamic acid for perioperative blood loss in total knee arthroplasty in patients with rheumatoid arthritis\uff1aa single-blinded, randomised, parallel-controlled study protocol in China"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8829-3853","authenticated-orcid":false,"given":"Bing-Xin","family":"Kang","sequence":"first","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-6243","authenticated-orcid":false,"given":"Sheng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song-Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Hui","family":"Ma","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Tao","family":"Zhai","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian-Bo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Orthopaedics, ShangHai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"2025121509334843000_10.8.e034431.1","first-page":"26","article-title":"Anaemia in newly diagnosed patients of rheumatoid arthritis and its correlation with disease activity","volume":"66","author":"Goyal","year":"2018","journal-title":"J Assoc Physicians India"},{"key":"2025121509334843000_10.8.e034431.2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jbspin.2016.07.007","article-title":"Time trends in the incidence, prevalence, and severity of rheumatoid arthritis: a systematic literature review","volume":"83","author":"Minichiello","year":"2016","journal-title":"Joint Bone Spine"},{"key":"2025121509334843000_10.8.e034431.3","doi-asserted-by":"publisher","DOI":"10.1136\/ard.58.12.751"},{"key":"2025121509334843000_10.8.e034431.4","doi-asserted-by":"crossref","DOI":"10.1186\/1749-799X-8-41","article-title":"Total knee arthroplasty treatment of rheumatoid arthritis with severe versus moderate flexion contracture","volume":"8","author":"Yan","year":"2013","journal-title":"J Orthop Surg Res"},{"key":"2025121509334843000_10.8.e034431.5","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.112474"},{"key":"2025121509334843000_10.8.e034431.6","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g4934"},{"key":"2025121509334843000_10.8.e034431.7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1537-2995.2007.01515.x","article-title":"Experience of a network of transfusion coordinators for blood conservation (Ontario Transfusion Coordinators [ONTraC])","volume":"48","author":"Freedman","year":"2008","journal-title":"Transfusion"},{"key":"2025121509334843000_10.8.e034431.8","doi-asserted-by":"publisher","DOI":"10.2165\/11209070-000000000-00000"},{"key":"2025121509334843000_10.8.e034431.9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.semarthrit.2017.03.001","article-title":"Clinical meaning and implications of serum hemoglobin levels in patients with rheumatoid arthritis","volume":"47","author":"Padjen","year":"2017","journal-title":"Semin Arthritis Rheum"},{"key":"2025121509334843000_10.8.e034431.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0160(00)00047-8"},{"key":"2025121509334843000_10.8.e034431.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-010-1205-3"},{"key":"2025121509334843000_10.8.e034431.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2010.11.013"},{"key":"2025121509334843000_10.8.e034431.13","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-013-3124-2"},{"key":"2025121509334843000_10.8.e034431.14","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1055\/s-0039-1681035","article-title":"Tourniquet use in total knee arthroplasty","volume":"32","author":"Arthur","year":"2019","journal-title":"J Knee Surg"},{"key":"2025121509334843000_10.8.e034431.15","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.2106\/JBJS.16.00750","article-title":"Use of a tourniquet in total knee arthroplasty causes a paradoxical increase in total blood loss","volume":"99","author":"Schnettler","year":"2017","journal-title":"J Bone Joint Surg Am"},{"key":"2025121509334843000_10.8.e034431.16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/00003086-200002000-00021","article-title":"Effect of tourniquet use on activation of coagulation in total knee replacement","volume":"85","author":"Aglietti","year":"2000","journal-title":"Clin Orthop Relat Res"},{"key":"2025121509334843000_10.8.e034431.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(97)00004-2"},{"key":"2025121509334843000_10.8.e034431.18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ocl.2015.08.014","article-title":"Application of tranexamic acid in trauma and orthopedic surgery","volume":"47","author":"Jennings","year":"2016","journal-title":"Orthop Clin North Am"},{"key":"2025121509334843000_10.8.e034431.19","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318292cc54"},{"key":"2025121509334843000_10.8.e034431.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60835-5"},{"key":"2025121509334843000_10.8.e034431.21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.artd.2017.08.004","article-title":"A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement","volume":"4","author":"Adravanti","year":"2018","journal-title":"Arthroplast Today"},{"key":"2025121509334843000_10.8.e034431.22","doi-asserted-by":"crossref","first-page":"230949901769352","DOI":"10.1177\/2309499017693529","article-title":"A randomized control trial to evaluate the effectiveness of intravenous, intra-articular and topical wash regimes of tranexamic acid in primary total knee arthroplasty","volume":"25","author":"Prakash","year":"2017","journal-title":"J Orthop Surg"},{"key":"2025121509334843000_10.8.e034431.23","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-016-0999-6"},{"key":"2025121509334843000_10.8.e034431.24","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.knee.2017.07.004","article-title":"Combined intravenous, topical and oral tranexamic acid administration in total knee replacement: evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate","volume":"24","author":"Jansen","year":"2017","journal-title":"Knee"},{"key":"2025121509334843000_10.8.e034431.25","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s00264-017-3519-x","article-title":"The efficacy and safety of multiple-dose intravenous tranexamic acid on blood loss following total knee arthroplasty: a randomized controlled trial","volume":"41","author":"Lei","year":"2017","journal-title":"Int Orthop"},{"key":"2025121509334843000_10.8.e034431.26","first-page":"281","article-title":"Chinese hip and total knee arthroplasty surgery perioperative Anti-fibrinolytic drug sequential anticoagulant application programme expert consensus","volume":"8","author":"Zhen","year":"2015","journal-title":"Chin J Bone Joint Surg"},{"key":"2025121509334843000_10.8.e034431.27","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.thromres.2018.11.025","article-title":"Comparison of three routes of administration of tranexamic acid in primary unilateral total knee arthroplasty: analysis of a national database","volume":"173","author":"Xie","year":"2019","journal-title":"Thromb Res"},{"key":"2025121509334843000_10.8.e034431.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2014.03.032"},{"key":"2025121509334843000_10.8.e034431.29","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/s-0037-1602248","article-title":"Tranexamic acid reduces occult blood loss, blood transfusion, and improves recovery of knee function after total knee arthroplasty: a comparative study","volume":"31","author":"Liu","year":"2018","journal-title":"J Knee Surg"},{"key":"2025121509334843000_10.8.e034431.30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00590-014-1461-9","article-title":"The reduction in blood loss with intra-articular injection of tranexamic acid in unilateral total knee arthroplasty without operative drains: a randomized controlled trial","volume":"25","author":"Yang","year":"2015","journal-title":"Eur J Orthop Surg Traumatol"},{"key":"2025121509334843000_10.8.e034431.31","doi-asserted-by":"crossref","first-page":"204253331351694","DOI":"10.1177\/2042533313516949","article-title":"A questionnaire-based survey investigating the current use of tranexamic acid in traumatic haemorrhage and elective hip and knee arthroplasty","volume":"5","author":"Young","year":"2014","journal-title":"JRSM Open"},{"key":"2025121509334843000_10.8.e034431.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2005.00204.x"},{"key":"2025121509334843000_10.8.e034431.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.11.006"},{"key":"2025121509334843000_10.8.e034431.34","doi-asserted-by":"publisher","DOI":"10.1111\/anae.12910"},{"key":"2025121509334843000_10.8.e034431.35","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.arth.2017.02.068","article-title":"Process improvement project using tranexamic acid is cost-effective in reducing blood loss and transfusions after total hip and total knee arthroplasty","volume":"32","author":"Demos","year":"2017","journal-title":"J Arthroplasty"},{"key":"2025121509334843000_10.8.e034431.36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijsu.2019.03.011","article-title":"The efficacy and safety of multiple doses of oral tranexamic acid on blood loss, inflammatory and fibrinolysis response following total knee arthroplasty: a randomized controlled trial","volume":"65","author":"Tang","year":"2019","journal-title":"Int J Surg"},{"key":"2025121509334843000_10.8.e034431.37","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/27.5.341"},{"key":"2025121509334843000_10.8.e034431.38","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148619"},{"key":"2025121509334843000_10.8.e034431.39","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1007\/s11999-016-4732-4","article-title":"Classifications in brief: Kellgren-Lawrence classification of osteoarthritis","volume":"474","author":"Kohn","year":"2016","journal-title":"Clin Orthop Relat Res"},{"key":"2025121509334843000_10.8.e034431.40","doi-asserted-by":"crossref","first-page":"283","DOI":"10.5312\/wjo.v5.i3.283","article-title":"Perioperative management of the patient with rheumatoid arthritis","volume":"5","author":"Krause","year":"2014","journal-title":"World J Orthop"},{"key":"2025121509334843000_10.8.e034431.41","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1016\/j.jhsa.2012.04.015","article-title":"Perioperative management of rheumatoid medications","volume":"37","author":"Thorsness","year":"2012","journal-title":"J Hand Surg Am"},{"key":"2025121509334843000_10.8.e034431.42","doi-asserted-by":"crossref","DOI":"10.1016\/S0196-6553(99)70094-5","article-title":"Commentary on the \u201cguideline for prevention of surgical site infection, 1999\u201d","volume":"27","author":"Lee","year":"1999","journal-title":"Am J Infect Control"},{"key":"2025121509334843000_10.8.e034431.43","doi-asserted-by":"publisher","DOI":"10.5555\/uri:pii:0039606062901666"},{"key":"2025121509334843000_10.8.e034431.44","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198303000-00016"},{"key":"2025121509334843000_10.8.e034431.45","doi-asserted-by":"crossref","first-page":"230949901773162","DOI":"10.1177\/2309499017731626","article-title":"The optimal protocol to reduce blood loss and blood transfusion after unilateral total knee replacement: low-dose IA-TXA plus 30-min drain clamping versus drainage clamping for the first 3 H without IA-TXA","volume":"25","author":"Park","year":"2017","journal-title":"J Orthop Surg"},{"key":"2025121509334843000_10.8.e034431.46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13012-017-0601-0","article-title":"The effectiveness of a de-implementation strategy to reduce low-value blood management techniques in primary hip and knee arthroplasty: a pragmatic cluster-randomized controlled trial","volume":"12","author":"Voorn","year":"2017","journal-title":"Implement Sci"},{"key":"2025121509334843000_10.8.e034431.47","doi-asserted-by":"crossref","DOI":"10.1186\/s13018-017-0559-2","article-title":"Is combined use of intravenous and intraarticular tranexamic acid superior to intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A meta-analysis of randomized controlled trials","volume":"12","author":"Mi","year":"2017","journal-title":"J Orthop Surg Res"},{"key":"2025121509334843000_10.8.e034431.48","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1007\/s00590-018-2210-2","article-title":"Intravenous tranexamic acid only versus combined intravenous and intra-articular tranexamic acid for perioperative blood loss in patients undergoing total knee arthroplasty","volume":"28","author":"Iseki","year":"2018","journal-title":"Eur J Orthop Surg Traumatol"},{"key":"2025121509334843000_10.8.e034431.49","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0002-9440(10)62299-7","article-title":"The plasminogen activator\/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis","volume":"166","author":"Li","year":"2005","journal-title":"Am J Pathol"},{"key":"2025121509334843000_10.8.e034431.50","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.arth.2016.07.043","article-title":"Patient-reported outcomes, quality of life, and satisfaction rates in young patients aged 50 years or younger after total knee arthroplasty","volume":"32","author":"Goh","year":"2017","journal-title":"J Arthroplasty"},{"key":"2025121509334843000_10.8.e034431.51","doi-asserted-by":"crossref","first-page":"e1041","DOI":"10.3928\/01477447-20160719-01","article-title":"Total knee arthroplasty after knee arthroscopy in patients older than 50 years","volume":"39","author":"Boyd","year":"2016","journal-title":"Orthopedics"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2019-034431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:33:55Z","timestamp":1765820035000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2019-034431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8,20]]},"published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1136\/bmjopen-2019-034431"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2019-034431","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2020,8]]}}}