{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:22:02Z","timestamp":1783012922447,"version":"3.54.6"},"reference-count":69,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anti\u2010IL\u20106 directed therapy, especially tocilizumab (TCZ), is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis, giant cell arteritis and systemic juvenile idiopathic arthritis. Next to being a master regulator of inflammation, IL\u20106 also is an important regulator of haemostasis. Although generally well tolerated, increasing clinical experience has associated TCZ treatment with rare, yet clinically significant, bleeding complications. These complications reflect disruption of IL\u20106\u2010regulated hepatic fibrinogen synthesis, thrombopoiesis and possibly FXIII expression and local wound healing, although the precise mechanisms remain incompletely defined. The purpose of this narrative review is to detail the current knowledge of haemostatic effects and bleeding complications associated with anti\u2010IL\u20106 therapeutics in autoimmune diseases. This review encompasses delineating the incidence, clinical characteristics and severity of haemostatic disruptions, discussing the proposed underlying mechanisms and providing a summary of possible management strategies. Bleeding can present across a spectrum, from subtle bruising or gingival bleeding to severe haematomas, and possibly diffuse intravascular coagulation. Routine coagulation parameters such as prothrombin time and activated partial thromboplastin time are frequently normal, masking significant hypofibrinogenaemia or FXIII deficiency. Recent cohort studies demonstrate that hypofibrinogenaemia is common, occurring in more than half of treated patients in some series, although often without overt bleeding. By contrast, acquired FXIII deficiency is rare. In light of the expanding use of anti\u2010IL\u20106 therapeutics, this review underscores the importance of early recognition of bleeding complications, targeted laboratory monitoring and individualised perioperative and haemostatic management.<\/jats:p>","DOI":"10.1111\/bph.70514","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:17:47Z","timestamp":1779956267000},"page":"4111-4125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Haemostatic changes and bleeding with anti\u2010IL\u20106 directed therapy in autoimmune diseases"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-3107","authenticated-orcid":false,"given":"Charlotte D. C. C.","family":"van der Heijden","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6436-8094","authenticated-orcid":false,"given":"Loes C.","family":"Oskam","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9060-4241","authenticated-orcid":false,"given":"Lenny","family":"van Bon","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-6262","authenticated-orcid":false,"given":"Chantal P.","family":"Rovers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf284"},{"issue":"2","key":"e_1_2_16_3_1","first-page":"S1","article-title":"The concise guide to PHARMACOLOGY 2023\/24: Introduction and other protein targets","volume":"180","author":"Alexander S. P. H.","year":"2023","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-024-06937-0"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2023.08.011"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/CH-2008-1127"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207628"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-019-04268-x"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03043-1"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112802"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02529-4"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000126265.08175.BE"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2024-004838"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2022.10.027"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031459"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez265"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60250-0"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12291"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12408"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24893"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01118-x"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36246-6"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3632"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key208"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1997.0330"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2018.1428041"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.4.1241.1241"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.4078\/jrd.2019.26.3.186"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/107602969900500108"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00649-0"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.9.2720"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.03061.x"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-016-0043-1"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-149628"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1656076"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-024-00827-6"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0802397"},{"issue":"3","key":"e_1_2_16_38_1","first-page":"S44","article-title":"Tocilizumab in patients with Takayasu arteritis: A retrospective study and literature review","volume":"34","author":"Loricera J.","year":"2016","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvscit.2025.101936"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2016.04.008"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-012-1191-x"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204345"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069944"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30639"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211878"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez630"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03150"},{"issue":"2","key":"e_1_2_16_48_1","first-page":"203","article-title":"Involvement of IL\u20106 and IL\u20106 receptor in fibrinogen synthesis in the liver of triton WR\u20101339\u2010induced hyperlipidemic rats","volume":"18","author":"Ohta S.","year":"2004","journal-title":"In Vivo"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-015-3379-x"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(02)00202-X"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-6-13"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1470488"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00520-1"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319077"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(93)90035-4"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3455"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.03.014"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.02.026"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614223"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00038-2"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613849"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000171805.24799.fa"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S470107"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54175-1"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1665293"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14110766"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-025-01867-6"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-024-05714-1"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.11.2740.2740"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.11.33"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70514","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70514","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:50:04Z","timestamp":1783011004000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":69,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/bph.70514"],"URL":"https:\/\/doi.org\/10.1111\/bph.70514","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"assertion":[{"value":"2026-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}