Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients

Background: Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes. Objectives: We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis. Methods: With ethics approval, we retrospectively reviewed FXIII...

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Main Authors: Mohammed Abdullah Al Sharif, Natalie Mathews, Subia Tasneem, Karen A. Moffat, Stephen A. Carlino, Siraj Mithoowani, Catherine P.M. Hayward
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925000135
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author Mohammed Abdullah Al Sharif
Natalie Mathews
Subia Tasneem
Karen A. Moffat
Stephen A. Carlino
Siraj Mithoowani
Catherine P.M. Hayward
author_facet Mohammed Abdullah Al Sharif
Natalie Mathews
Subia Tasneem
Karen A. Moffat
Stephen A. Carlino
Siraj Mithoowani
Catherine P.M. Hayward
author_sort Mohammed Abdullah Al Sharif
collection DOAJ
description Background: Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes. Objectives: We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis. Methods: With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency. Results: Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (n = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (R2 = 0.84, P < .001) and weak correlation with plasma fibrinogen (R2 = .005, P < .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (P < .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes. Conclusion: Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.
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spelling doaj-art-d5e7aee2e6ef4e2a8e1a9be188bdf5712025-08-20T02:13:52ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-019110268910.1016/j.rpth.2025.102689Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patientsMohammed Abdullah Al Sharif0Natalie Mathews1Subia Tasneem2Karen A. Moffat3Stephen A. Carlino4Siraj Mithoowani5Catherine P.M. Hayward6Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Laboratory Medicine, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah University, Riyadh, Saudi ArabiaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Division of Hematology-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Special Coagulation, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, CanadaSpecial Coagulation, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, CanadaDepartment of Medicine, McMaster University, Hamilton, Ontario, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Special Coagulation, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada; Correspondence Catherine P. M. Hayward, Departments of Pathology and Molecular Medicine, and Medicine, McMaster University and the Hamilton Regional Laboratory Medicine Program, Room 2N29A, McMaster University Medical Centre, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada.Background: Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes. Objectives: We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis. Methods: With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency. Results: Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (n = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (R2 = 0.84, P < .001) and weak correlation with plasma fibrinogen (R2 = .005, P < .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (P < .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes. Conclusion: Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.http://www.sciencedirect.com/science/article/pii/S2475037925000135blood coagulation disordersblood coagulation factor inhibitorsblood coagulation testsfactor XIII deficiencyfactor XIIIhemostatic disorders, inherited coagulation disorders
spellingShingle Mohammed Abdullah Al Sharif
Natalie Mathews
Subia Tasneem
Karen A. Moffat
Stephen A. Carlino
Siraj Mithoowani
Catherine P.M. Hayward
Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
Research and Practice in Thrombosis and Haemostasis
blood coagulation disorders
blood coagulation factor inhibitors
blood coagulation tests
factor XIII deficiency
factor XIII
hemostatic disorders, inherited coagulation disorders
title Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
title_full Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
title_fullStr Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
title_full_unstemmed Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
title_short Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients
title_sort measurement of factor xiii for the diagnosis and management of deficiencies insights from a retrospective review of 10 years of data on consecutive samples and patients
topic blood coagulation disorders
blood coagulation factor inhibitors
blood coagulation tests
factor XIII deficiency
factor XIII
hemostatic disorders, inherited coagulation disorders
url http://www.sciencedirect.com/science/article/pii/S2475037925000135
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