Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series Kira J. Tone a , Tyler E. James b , Dean A. Fergusson c, e , Alan Tinmouth b, d, e , Jason Tay e , Marc T. Avey b, e , Shaun Kilty e, f , Manoj M. Lalu a, g, ⁎ a Department of Anesthesiology, The Ottawa Hospital, Ottawa, Ontario, Canada b Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada c School of Epidemiology, Public Heath and Preventative Medicine, The University of Ottawa, Ottawa, Ontario, Canada d Department of Hematology, University of Ottawa, Ottawa, Ontario, Canada e Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada f Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, Ontario, Canada g Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada abstract article info Available online xxxx Keywords: Factor XIII Acquired inhibitor Case report Case series Systematic review Reporting Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII de- ficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagula- tion test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcuta- neous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in pa- tients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobu- lin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvi- ous lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients (27%) hav- ing partial resolution; 9 of these patients (14%) had a relapse. Thirteen patients (20%) died (7 from internal hem- orrhage). Completeness of reporting varied for specific CAse Report items. Patient demographics, clinician- assessed outcomes, and laboratory test results were reported in all case reports. Least reported items included informed consent (6%), patient perspective (3%), and a title containing the words case report (9%). Our systematic review provides the most complete overview of published reports of FXIII acquired inhibitor to date. There is a paucity of data available on FXIII acquired inhibitor, and the available data may be limited by variable reporting. Despite multimodal therapy, a significant proportion of patients with FXIII acquired inhibitor have a large burden of morbidity and mortality. © 2016 Elsevier Inc. All rights reserved. Contents Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 . Data Sources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 . Eligibility Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Transfusion Medicine Reviews xxx (2016) xxx–xxx ⁎ Corresponding author at: Manoj Lalu, MD, PhD, FRCPC, Department of Anesthesiology, The Ottawa Hospital Research Institute, Room B307, 1053 Carling Ave, Mail Stop 249, Ottawa, Ontario, Canada, K1Y 4E9. E-mail addresses: manojlalu@gmail.com, mlalu@toh.on.ca (M.M. Lalu). http://dx.doi.org/10.1016/j.tmrv.2016.04.001 0887-7963/© 2016 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Transfusion Medicine Reviews journal homepage: www.tmreviews.com Please cite this article as: Tone KJ, et al, Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series, Transfus Med Rev (2016), http://dx.doi.org/10.1016/j.tmrv.2016.04.001