RARE DISEASE
Acquired factor XIII deficiency
Acquired factor XIII deficiency
Acquired factor XIII deficiency
Synonyms: aFXIII
Synonyms: aFXIII
Synonyms: aFXIII
Drug discovery
0
drugs
With orphan designations
Overview
Acquired Factor XIII Deficiency: Clinical Overview
Acquired factor XIII (FXIII) deficiency is a rare bleeding disorder caused by immune-mediated inhibitors (autoantibodies) or non-immune mechanisms (e.g., hyperconsumption in sepsis, liver disease, or malignancies). It manifests as spontaneous or trauma-related bleeding, including life-threatening intracranial or intramuscular hemorrhage. Diagnosis requires specialized FXIII activity assays, as routine coagulation tests (PT/aPTT) remain normal. Management involves FXIII replacement (e.g., plasma-derived concentrates), immunosuppression for inhibitors, and antifibrinolytics. Mortality is significant (up to 20%), particularly with delayed diagnosis or refractory inhibitors [1][5][10][14].
Categories: rare hematological diseases
Research Papers
141 drug discovery papers about Acquired factor XIII deficiency. Recent publications:
141 drug discovery papers about Acquired factor XIII deficiency. Recent publications:
categories:
Small molecules
small molecules
2025-11-01 | Postsurgical Hemorrhage in Senile Entropion Due to Factor XIII Deficiency
Background: When diagnosing postsurgical bleeding with normal coagulation tests, factor XIII (F XIII) deficiency must be ruled out. This circulates in plasma, mainly bound to fibrinogen, and has a half-life of 7 to 14 days. F XIII acts as a fibrin stabilizer and is involved in tissue repair and healing. In F XIII deficiency, coagulation tests are normal because it does not participate in thrombus formation but rather in its stabilization, both in congenital and acquired deficiency. Patients with FXIII levels below 1 U/dL are at high risk of early onset bleeding (with umbilical cord hemorrhage). With factor levels between 1 and 4 U/dL, the hemorrhagic phenotype is severe or moderate. With values above 5 U/dL, hemorrhagic symptoms are occasional. However, cases of mild deficiency (factor XIII activity levels of 30–60%) have been reported in which abnormal posttraumatic bleeding may occur. Treatment ranges from specific F XIII concentrate or fresh frozen plasma to antifibrinolytic drugs in mild cases. Methods: A 78-year-old patient, no toxic habits, with a history of high blood pressure, dyslipidaemia, type II diabetes mellitus, and ischemic heart disease. Two episodes of hospitalization for anemia of digestive origin. He had undergone transurethral resection of the prostate, infrarenal aortic aneurysm repair with endoprosthesis, and cataract surgery in both eyes without hemorrhagic complications. He was being treated with rosuvastatin, valsartan, bisoprolol, furosemide, and linagliptin. He required surgery for senile entropion of the lower eyelid of the right eye under local anesthesia. Preoperative tests, including a complete blood count, biochemistry, and coagulation, showed normal values. A lateral tarsal strip was performed to anchor the outer edge of the eyelid to the orbit to tighten it. Forty-eight hours after the operation, the patient presented with continuous bleeding from the surgical wound, hyposphagma, and a large hematoma on the lower eyelid. The surgical wound was examined on three occasions and, despite local compression and hemostatic measures, recurrent bleeding continued in the surgical bed for 2 weeks, requiring urgent attention on several occasions. Results: Subsequently, the study was expanded to include plasma factor determination, finding only a Factor XIII value of 42%. After ruling out other causes of hemorrhagic diathesis, Factor XIII deficiency was considered to be the cause of the condition. Treatment with tranexamic acid at a dose of 1 g every 8 hours orally helped to resolve the condition. Conclusion: Outpatient entropion surgery resulted in moderate hemorrhagic complications that complicated the postoperative period. The mild Factor XIII deficiency caused recurrent bleeding that required interventional and pharmacological treatment with antifibrinolytics. Publication History Article published online: 31 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-08-01 | Comparison of outcomes in autoimmune acquired factor XIII deficiency with and without underlying diseases: a systematic review.
Autoimmune acquired factor XIII deficiency (AiF13D) is an exceptionally rare and serious bleeding disorder. This condition may occur idiopathically or in association with comorbidities, such as malignancies or autoimmune diseases. Data comparing these distinct etiological subgroups remain limited. Therefore, we conducted a systematic literature review of published case reports, case series, and cohort studies on AiF13D indexed in PubMed, Web of Science, and Scopus up to December 2023. We compared the clinical characteristics, treatment modalities, and outcomes between patients with AiF13D associated with underlying disorders and those with idiopathic AiF13D. Our analysis revealed a higher proportion of female patients in the AiF13D group with underlying diseases compared to the idiopathic group. Statistically significant differences were observed that patients with underlying diseases exhibited slightly higher inhibitor levels and a greater frequency of Grade III bleeding events. Furthermore, fewer AiF13D patients with underlying diseases received combination therapy (prednisone plus rituximab or cyclophosphamide) compared to the idiopathic group. Additionally, this group experienced higher rates of relapse and/or mortality. Collectively, these findings indicated that AiF13D patients with underlying diseases experience more severe bleeding manifestations and poorer outcomes. Consequently, clinicians managing concomitant conditions should maintain vigilance for potential AiF13D development. Regular monitoring of FXIII activity and inhibitor titers is essential, coupled with prompt initiation of anti-inhibitor therapy when indicated.
2025-06-13 | Immune-Related and Non-Immune-Related Acquired Factor XIII Deficiency.
Coagulation factor XIII (FXIII) is an essential protein that stabilizes the hemostatic plug formed in the final stage of the coagulation reaction and controls its dissolution. In the blood, it exists as a heterotetramer consisting of A subunit dimers and B subunit dimers. Genetic defects in each subunit result in a congenital deficiency, which causes fatal or mild bleeding symptoms. Acquired FXIII deficiency can develop owing to reduced production or increased consumption of FXIII, and its severe form can cause various bleeding symptoms. In particular, autoimmune FXIII deficiency (AiF13D) causes fatal bleeding symptoms due to the suppression of FXIII activity by anti-FXIII autoantibodies and/or accelerated clearance of FXIII. AiF13D is characterized by extremely severe FXIII deficiency and severe bleeding symptoms. It is associated with the highest hemorrhagic mortality rate among autoimmune coagulation factor deficiencies, making it essential to differentiate it from other non-immune FXIII deficiencies (NiF13D), such as those arising from liver cirrhosis or leukemia. The probable and definitive diagnosis of AiF13D require the presence of FXIII inhibitors and anti-FXIII autoantibodies, respectively. FXIII inhibitors can be detected by a general FXIII activity assay in the mixed plasma of patients and healthy controls, and can be measured in a regular laboratory. In contrast, immunological assays are conducted in limited research facilities because they are not commercially available. NiF13D is usually treated by hemostatic therapy with FXIII concentrates, but AiF13D requires hemostatic therapy plus autoantibody eradication therapy with immunosuppressants. Since the disease often becomes resistant to treatment, long-term follow-up is strongly recommended.
2024-12-31 | Unexplained acute bleeding in chronic phase of chronic myeloid leukaemia due to acquired factor XIII deficiency induced hyperfibrinolysis – Experience at National Hospital of Sri Lanka, Colombo
Chronic Myeloid Leukaemia (CML) is a significant myeloproliferative neoplasm, making up about 15% of all leukaemias, with an incidence rate of 1-2 cases per 100,000 adults. It is marked by the presence of the BCR-ABL1 fusion gene, which leads to the overproduction of a constantly active tyrosine kinase, driving the development of leukaemia. CML progresses through three phases, with bleeding complications more frequent in the accelerated and blast phases due to bone marrow infiltration and thrombocytopenia. The report highlights three cases of CML in the chronic phase, each presenting with unexplained acute bleeding due to isolated factor XIII deficiency-induced hyperfibrinolysis, a rare occurrence in this phase: A 49-year-old man with spontaneous intramuscular haematoma and severe leukocytosis, diagnosed with acquired factor XIII deficiency, managed with cryoprecipitate transfusion and imatinib mesylate, achieving complete remission before progressing to the blast phase. A 39-year-old man who developed multiple haematomas post-bone marrow biopsy, diagnosed with factor XIII deficiency, with bleeding resolving upon imatinib therapy, though he later progressed to the blast phase. A 53-year-old woman who presented with haematomas following a bone marrow biopsy, with diagnosis and management similar to the previous cases, achieving successful control of bleeding and remission. These cases emphasize the importance of recognizing and diagnosing acquired coagulopathy in CML patients with unexplained bleeding. Proper management involves specific factor replacement along with targeted CML therapy, as failure to diagnose can lead to significant morbidity and mortality.
2024-12-02 | Diagnosis and Management of an Acquired Factor XIII Deficiency in a Limited Resource Setting: A Case Report
Factor XIII deficiency, a rare bleeding disorder, can be either immunemediated or non -immune and present significant challenges due to potential life-threatening bleeding.This report underscores the importance of targeted management in FXIII deficiency, particularly in lowresource setting where advanced testing may be inaccessible. Case ReportThe case centers on 16-year-old boy with a history of mild bleeding who -presented with a subdural hemorrhage after a fall.Initial tests, including standard clotting profiles and screening for von Willebrand factor deficiency, were normal, prompting further investigation.A positive clot solubility test suggested Factor XIII deficiency.Due to limited facilities, FXIII assays were unavailable, so the patient was managed with fresh frozen plasma, cryoprecipitate, and tranexamic acid.Post-surgery bleeding revealed potential FXIII inhibitors, which were managed with additional plasma, cryoprecipitate, and oral prednisolone.The patient responded well and remained asymptomatic after discharge.
proteins
2026-07-01 | EP1T6_1 Acquired Factor XIII deficiency incidence in polytrauma
Acquired Factor XIII (FXIII) after trauma is underdiagnose, and can lead to increase bleeding events, blood transfusions and prolonged wound healing. FXIII deficiency becomes more relevant in the post-acute phase after trauma, which underlines the clinical relevance when planning definitive surgical care requiring increase blood transfusions, despite normal coagulation tests.
2026-06-22 | Factor XIII Supplementation Suppresses Recurrent Hemorrhages Due to Acquired Factor XIII Deficiency Secondary to Severe Acute Pancreatitis: A Case Report.
Hemorrhagic complications associated with severe acute pancreatitis significantly worsen the prognosis. Acquired factor XIII (FXIII) deficiency can lead to delayed tissue repair and associated recurrent bleeding, yet its clinical impact in the context of pancreatitis remains poorly understood. A 69-year-old woman with severe acute pancreatitis developed recurrent hemorrhagic shock due to multiple arterial bleeding episodes, including the splenic and left gastric arteries. Despite repeated transcatheter arterial embolization and massive blood transfusions, hemorrhagic events recurred during the subacute phase. Laboratory investigations revealed an acquired FXIII deficiency with FXIII activity levels of 56-59%. Repeated administration of FXIII concentrates administration suppresses the hemorrhagic complications gradually. This report suggests that FXIII concentrate administration may be a beneficial therapeutic option for managing recurrent hemorrhagic complications and stabilizing the clinical course in patients with severe acute pancreatitis and acquired FXIII deficiency.
2026-02-19 | Acquired Factor XIII deficiency presenting as intramuscular haemorrhage in an elderly patient
Ryohei Kishi, MD, Takuya Otsuki, MD, PhD, Kosuke Ishizuka, MD, PhD, FHGM, Tatsuya Masuyama, MD, Iori Motohashi, MD, MPH, Kenya Ie, MD, PhD, MPH, Yoshiyuki
2026-02-04 | Unexplained bleeding related to acquired factor XIII deficiency: A case report
Introduction: Acquired factor XIII (F XIII ) deficiency is a rare and often underdiagnosed bleeding disorder. Because standard coagulation tests typically yield normal results, diagnosis and treatment are often delayed in patients with unexplained hemorrhage. Case Presentation: We report the case of a 56-year-old man who presented with severe, recurrent epistaxis unresponsive to conventional management. Initial coagulation tests—including prothrombin time, international normalized ratio, activated partial thromboplastin time, and fibrinogen levels—were all within normal limits. Despite interventional radiology and surgical measures, bleeding persisted. An F XIII activity assay revealed a mild deficiency (48.7%; reference range: 60–130%). Administration of recombinant F XIII (catridecacog, 10 IU/kg) led to rapid clinical improvement and resolution of bleeding. Discussion: This case illustrates the diagnostic challenge posed by acquired F XIII deficiency and underscores the importance of including it in the differential diagnosis of unexplained bleeding, especially when standard coagulation parameters are unremarkable. Conclusion: Prompt recognition and targeted replacement therapy with recombinant F XIII can be life-saving in acquired F XIII deficiency. F XIII activity testing should be considered early in patients with persistent bleeding of unknown origin.
2026-01-24 | Perioperative factor XIII and viscoelastic measurements of open compared to minimal invasive major upper gastrointestinal surgery- A prospective observational study.
Acquired Factor XIII (FXIII) deficiency is prevalent in hospitalized or surgical patients, with FXIII activity <70% in over 20% of cases. A decrease in FXIII has been linked with postoperative bleeding, anastomotic insufficiency, and a greater likelihood of requiring reoperation. This study aims to identify patients at increased risk for postoperative complications by comparing open versus minimally invasive pancreatic and esophageal surgery. This prospective, monocentric observational study was conducted at Heidelberg University Hospital (Germany). Inclusion criteria consisted of age ≥ 18 years, the ability to provide informed consent, and scheduled esophageal or pancreatic surgery. A coagulation panel was performed preoperatively, directly after surgery and on postoperative day (POD) 1, 2, 3, 4, 7, 10, and 13, along with repeated thromboelastography (ClotPro®) Tests. Finally, 112 patients were enrolled (n = 77 open and n = 35 minimally invasive). FXIII activity showed a more pronounced decrease in the open surgery group until day 7; in both groups, the lowest FXIII activity occurred between days 4 and 7. There were no significant group differences in readmissions, reoperations, or severe perioperative complications according to the Clavien-Dindo classification. Open surgery was associated with a significant decline in FXIII activity, with a nadir estimated to occur between POD 4 and 7. FXIII activity also remained significantly reduced until day 7 after surgery. Viscoelastic testing was not able to detect mild acquired FXIII deficiencies. The extent to which routine testing of FXIII activity should be performed prior to reoperation must be evaluated in further studies. German Clinical Trials Register (DRKS00028547, registration date: April 14, 2022).
antibodies
2024-09-25 | Development and Epitope Mapping of Seven Mouse Anti-Human Coagulation Factor XIII-B Subunit Monoclonal Antibodies.
Coagulation factor XIII (FXIII) is an enzyme that strengthens hemostatic clots, and its deficiency can cause life-threatening bleeding. We immunized mice with human plasma-derived FXIII to generate monoclonal antibodies (mAbs) against the B subunit (FXIII-B), which stabilizes the A subunit (FXIII-A) of FXIII, and analyzed their properties. The epitopes of the seven mouse antihuman FXIII-B mAbs obtained were found to be the 3rd, 5th, 6th, 9th, and 10th Sushi domains. One of these mAbs, mAb 5-6C, recognized the 10th Sushi domain and inhibited the fibrin cross-linking reaction without affecting the amine incorporation activity of FXIII. We previously reported that the 10th Sushi domain is the site where FXIII-B binds to fibrin and functions to bring FXIII-A closer to the substrate fibrin. Except for mAb 5-6C, mouse mAbs with high yields were used to measure the amount of FXIII-B antigen by an immunochromatography test (ICT), which showed a high correlation with enzyme-linked immunosorbent assay-obtained results. In addition, we developed a prototype ICT to detect anti-FXIII-B autoantibodies using mAb 1-3C, which showed good results in measuring the amount of FXIII-B antigen. Thus, mouse mAbs may be useful for clinical applications. mAb 5-6C targeting the 10th Sushi domain may also be useful for inhibiting thrombosis progression when humanized as antibody medicines.
2023-10-01 | PB0240 Possible Autoimmune Acquired Factor 13 Deficiency : Tailoring Management in a Resource Constrained Setting in India, ACase Report
change from pretreatment baseline (%Change) in cynomolgus macaques receiving combination treatment of both anti-VWF nanobody and anti-FVIII with and without administration of VGA039.Vertical black dotted lines represent repeat subcutaneous anti VWF nanobody (Anti-VWF) injections at 5 mg/kg at -96, -72, -48, -24, 0, 24, and 48 hr, respectively, and coadministration of intravenous anti-FVIII mAb at 0.1 mg/ kg on Day 1 (0 hr).The vertical red dashed line represents administration of a vehicle (Control) or intravenous VGA039 at 10 mg/kg. Conclusion(s):Efficacy of VGA039 was demonstrated in a novel NHP model of acquired VWD.This proof-of-concept study supports clinical evaluation of VGA039 for the treatment of VWD.
2023-08-29 | Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking.
Coagulation factor XIII (FXIII) is a proenzyme of plasma transglutaminase. It comprises two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). We previously reported that alloantibodies against FXIII-B could promote FXIII clearance in a patient with congenital FXIII-B deficiency who had received infusions of plasma-derived human FXIII (A2B2 heterotetramer). We aimed to investigate whether anti-FXIII-B antibodies affect the catalytic function of FXIII. FXIII activation and fibrin crosslinking were examined in the presence of patient plasma, isolated patient IgG, or rat anti-FXIII-B monoclonal antibodies. Alloantibody levels were increased by repeated infusions of plasma-derived A2B2 heterotetramer, which enhanced binding to the functionally important FXIII-B sushi domains. The patient plasma strongly inhibited cleavage of the FXIII-A activation peptide, amine incorporation, and fibrin crosslinking in normal plasma. Furthermore, anti-FXIII-B alloantibodies blocked the formation of the complex of FXIII-B with FXIII-A, and fibrinogen. Rat monoclonal antibodies against the 10th sushi domain of FXIII-B inhibited the incorporation of FXIII-B to fibrin, FXIII activation (i.e., cleavage of FXIII-A activation peptide), and ultimately fibrin crosslinking in normal plasma, independent of their effect on heterotetramer assembly with FXIII-A. Alloantibody binding to the A2B2 heterotetramer blocked the access of thrombin to the FXIII-A cleavage site, as indicated by the reaction of the alloantibodies to the A2B2 heterotetramer and FXIII-B, but not to FXIII-A. Anti-FXIII-B antibodies binding to the A2B2 heterotetramer and FXIII-B inhibited FXIII activation and its crosslinking function despite being directed against its noncatalytic subunit (FXIII-B).
2023-05-10 | Epitope analysis of human monoclonal antibodies from a patient with autoimmune factor XIII deficiency reveals their inhibitory mechanisms.
Autoimmune coagulation factor XIII (FXIII) deficiency (AiF13D) is a bleeding disorder caused by anti-FXIII autoantibodies. Recently, we generated human monoclonal antibodies (mAbs) from the peripheral blood of an AiF13D patient and classified them into three groups: FXIII-dissociation inhibitor, FXIII-assembly inhibitor, and non-neutralizing/inhibitory mAbs. However, the epitope region and molecular inhibitory mechanism of each mAb remain unknown. Here, we localized the epitope regions of the representative inhibitory mAbs A69K (dissociation inhibitor) and A78L (assembly inhibitor) to the β-barrel-2 domain and boundary of β-barrel-1&2 domains, respectively, of the FXIII-A subunit, by combining a binding assay using its synthesized peptides and a protease-protection assay. Our findings suggest that A69K inhibits the activation-related conformational changes and dissociation of FXIII and that A78L competitively inhibits FXIII-assembly.
2023-02-14 | Cloning of human anti-factor XIII monoclonal antibody dissects mechanisms of polyclonal antibodies in a single patient.
Coagulation factor XIII (FXIII) consists of 2 A (FXIII-A) and 2 B (FXIII-B) subunits that cross-link and strengthen the hemostatic fibrin thrombus; thus, abnormal bleeding occurs when FXIII is significantly reduced. Autoimmune-acquired FXIII deficiency (AiF13D) is characterized by lethal bleeding secondary to the development of autoantibodies against FXIII. However, since anti-FXIII autoantibodies are polyclonal, the mechanism underlying FXIII dysfunction is unclear. The objective of this study was to dissect the inhibitory mechanisms of polyclonal anti-FXIII autoantibodies. In this study, we prepared the human monoclonal antibodies (hmAbs) from the peripheral blood of an 86-year-old man with AiF13D by using a new complementary DNA cloning method and analyzed the properties of each autoantibody. Seventeen clones obtained from hmAbs were divided into the following 3 groups: dissociation inhibitors of FXIII-A2B2 (6 clones), assembly inhibitors of FXIII-A2B2 (3 clones), and nonneutralizing/inhibitory hmAbs (8 clones). Dissociation inhibitors strongly inhibited fibrin cross-linking and amine incorporation. Assembly inhibitors extracted FXIII-A from FXIII-A2B2, strongly inhibited binding of FXIII-A to FXIII-B, and activation peptide cleavage. However, the patient's plasma presented a strong inhibition of A2B2 heterodimer assembly but only a slight inhibition of thrombin-Ca2+-dependent dissociation, suggesting that the assembly inhibitors concealed the effect of dissociation inhibitors in plasma. By contrast, nonneutralizing antibodies had little effect on the function of FXIII, suggesting that nonneutralizing hmAbs (and/or dissociation inhibitors and/or assembly inhibitors) promoted the clearance of FXIII-A from the blood. Cloning of anti-FXIII autoantibodies enabled us to not only elucidate the mechanism and pathophysiology of AiF13D but also develop a completely new type of anticoagulant.
cell therapies
2023-06-01 | Perioperative therapeutic plasma exchange in a patient with rare Factor XIII inhibitor
Factor XIII deficiency is a rare bleeding disorder which could be severe if inherited or less severe if acquired. We report a case of acquired Factor XIII inhibitor in a 75-year-old male with a suspicious left renal mass treated perioperatively with therapeutic plasma exchange (TPE).To perform kidney biopsy and ablation of the renal mass, six daily TPE treatments were performed before and after biopsy to minimize bleeding risk because the patient did not respond to drug therapy. Both thromboelastography (TEG) and laboratory-based coagulation tests were performed to assess coagulation status prior to and after TPE.The biopsy indicated oncocytoma which was removed by surgical procedure. Factor XIII activity remained below 15 % throughout TPE treatments, but Factor XIII inhibitor titer reduced from initial positive value of 1:40 to negative following the third TPE and remained negative through the sixth TPE. Unfortunately, the inhibitor titer was positive at 1:20 in the fifth month and 1:5 in the sixth month during follow-up.TPE is useful in removing XIII inhibitory factor, but the effects are only short term.
small molecules
2025-11-01 | Postsurgical Hemorrhage in Senile Entropion Due to Factor XIII Deficiency
Background: When diagnosing postsurgical bleeding with normal coagulation tests, factor XIII (F XIII) deficiency must be ruled out. This circulates in plasma, mainly bound to fibrinogen, and has a half-life of 7 to 14 days. F XIII acts as a fibrin stabilizer and is involved in tissue repair and healing. In F XIII deficiency, coagulation tests are normal because it does not participate in thrombus formation but rather in its stabilization, both in congenital and acquired deficiency. Patients with FXIII levels below 1 U/dL are at high risk of early onset bleeding (with umbilical cord hemorrhage). With factor levels between 1 and 4 U/dL, the hemorrhagic phenotype is severe or moderate. With values above 5 U/dL, hemorrhagic symptoms are occasional. However, cases of mild deficiency (factor XIII activity levels of 30–60%) have been reported in which abnormal posttraumatic bleeding may occur. Treatment ranges from specific F XIII concentrate or fresh frozen plasma to antifibrinolytic drugs in mild cases. Methods: A 78-year-old patient, no toxic habits, with a history of high blood pressure, dyslipidaemia, type II diabetes mellitus, and ischemic heart disease. Two episodes of hospitalization for anemia of digestive origin. He had undergone transurethral resection of the prostate, infrarenal aortic aneurysm repair with endoprosthesis, and cataract surgery in both eyes without hemorrhagic complications. He was being treated with rosuvastatin, valsartan, bisoprolol, furosemide, and linagliptin. He required surgery for senile entropion of the lower eyelid of the right eye under local anesthesia. Preoperative tests, including a complete blood count, biochemistry, and coagulation, showed normal values. A lateral tarsal strip was performed to anchor the outer edge of the eyelid to the orbit to tighten it. Forty-eight hours after the operation, the patient presented with continuous bleeding from the surgical wound, hyposphagma, and a large hematoma on the lower eyelid. The surgical wound was examined on three occasions and, despite local compression and hemostatic measures, recurrent bleeding continued in the surgical bed for 2 weeks, requiring urgent attention on several occasions. Results: Subsequently, the study was expanded to include plasma factor determination, finding only a Factor XIII value of 42%. After ruling out other causes of hemorrhagic diathesis, Factor XIII deficiency was considered to be the cause of the condition. Treatment with tranexamic acid at a dose of 1 g every 8 hours orally helped to resolve the condition. Conclusion: Outpatient entropion surgery resulted in moderate hemorrhagic complications that complicated the postoperative period. The mild Factor XIII deficiency caused recurrent bleeding that required interventional and pharmacological treatment with antifibrinolytics. Publication History Article published online: 31 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2025-08-01 | Comparison of outcomes in autoimmune acquired factor XIII deficiency with and without underlying diseases: a systematic review.
Autoimmune acquired factor XIII deficiency (AiF13D) is an exceptionally rare and serious bleeding disorder. This condition may occur idiopathically or in association with comorbidities, such as malignancies or autoimmune diseases. Data comparing these distinct etiological subgroups remain limited. Therefore, we conducted a systematic literature review of published case reports, case series, and cohort studies on AiF13D indexed in PubMed, Web of Science, and Scopus up to December 2023. We compared the clinical characteristics, treatment modalities, and outcomes between patients with AiF13D associated with underlying disorders and those with idiopathic AiF13D. Our analysis revealed a higher proportion of female patients in the AiF13D group with underlying diseases compared to the idiopathic group. Statistically significant differences were observed that patients with underlying diseases exhibited slightly higher inhibitor levels and a greater frequency of Grade III bleeding events. Furthermore, fewer AiF13D patients with underlying diseases received combination therapy (prednisone plus rituximab or cyclophosphamide) compared to the idiopathic group. Additionally, this group experienced higher rates of relapse and/or mortality. Collectively, these findings indicated that AiF13D patients with underlying diseases experience more severe bleeding manifestations and poorer outcomes. Consequently, clinicians managing concomitant conditions should maintain vigilance for potential AiF13D development. Regular monitoring of FXIII activity and inhibitor titers is essential, coupled with prompt initiation of anti-inhibitor therapy when indicated.
2025-06-13 | Immune-Related and Non-Immune-Related Acquired Factor XIII Deficiency.
Coagulation factor XIII (FXIII) is an essential protein that stabilizes the hemostatic plug formed in the final stage of the coagulation reaction and controls its dissolution. In the blood, it exists as a heterotetramer consisting of A subunit dimers and B subunit dimers. Genetic defects in each subunit result in a congenital deficiency, which causes fatal or mild bleeding symptoms. Acquired FXIII deficiency can develop owing to reduced production or increased consumption of FXIII, and its severe form can cause various bleeding symptoms. In particular, autoimmune FXIII deficiency (AiF13D) causes fatal bleeding symptoms due to the suppression of FXIII activity by anti-FXIII autoantibodies and/or accelerated clearance of FXIII. AiF13D is characterized by extremely severe FXIII deficiency and severe bleeding symptoms. It is associated with the highest hemorrhagic mortality rate among autoimmune coagulation factor deficiencies, making it essential to differentiate it from other non-immune FXIII deficiencies (NiF13D), such as those arising from liver cirrhosis or leukemia. The probable and definitive diagnosis of AiF13D require the presence of FXIII inhibitors and anti-FXIII autoantibodies, respectively. FXIII inhibitors can be detected by a general FXIII activity assay in the mixed plasma of patients and healthy controls, and can be measured in a regular laboratory. In contrast, immunological assays are conducted in limited research facilities because they are not commercially available. NiF13D is usually treated by hemostatic therapy with FXIII concentrates, but AiF13D requires hemostatic therapy plus autoantibody eradication therapy with immunosuppressants. Since the disease often becomes resistant to treatment, long-term follow-up is strongly recommended.
2024-12-31 | Unexplained acute bleeding in chronic phase of chronic myeloid leukaemia due to acquired factor XIII deficiency induced hyperfibrinolysis – Experience at National Hospital of Sri Lanka, Colombo
Chronic Myeloid Leukaemia (CML) is a significant myeloproliferative neoplasm, making up about 15% of all leukaemias, with an incidence rate of 1-2 cases per 100,000 adults. It is marked by the presence of the BCR-ABL1 fusion gene, which leads to the overproduction of a constantly active tyrosine kinase, driving the development of leukaemia. CML progresses through three phases, with bleeding complications more frequent in the accelerated and blast phases due to bone marrow infiltration and thrombocytopenia. The report highlights three cases of CML in the chronic phase, each presenting with unexplained acute bleeding due to isolated factor XIII deficiency-induced hyperfibrinolysis, a rare occurrence in this phase: A 49-year-old man with spontaneous intramuscular haematoma and severe leukocytosis, diagnosed with acquired factor XIII deficiency, managed with cryoprecipitate transfusion and imatinib mesylate, achieving complete remission before progressing to the blast phase. A 39-year-old man who developed multiple haematomas post-bone marrow biopsy, diagnosed with factor XIII deficiency, with bleeding resolving upon imatinib therapy, though he later progressed to the blast phase. A 53-year-old woman who presented with haematomas following a bone marrow biopsy, with diagnosis and management similar to the previous cases, achieving successful control of bleeding and remission. These cases emphasize the importance of recognizing and diagnosing acquired coagulopathy in CML patients with unexplained bleeding. Proper management involves specific factor replacement along with targeted CML therapy, as failure to diagnose can lead to significant morbidity and mortality.
2024-12-02 | Diagnosis and Management of an Acquired Factor XIII Deficiency in a Limited Resource Setting: A Case Report
Factor XIII deficiency, a rare bleeding disorder, can be either immunemediated or non -immune and present significant challenges due to potential life-threatening bleeding.This report underscores the importance of targeted management in FXIII deficiency, particularly in lowresource setting where advanced testing may be inaccessible. Case ReportThe case centers on 16-year-old boy with a history of mild bleeding who -presented with a subdural hemorrhage after a fall.Initial tests, including standard clotting profiles and screening for von Willebrand factor deficiency, were normal, prompting further investigation.A positive clot solubility test suggested Factor XIII deficiency.Due to limited facilities, FXIII assays were unavailable, so the patient was managed with fresh frozen plasma, cryoprecipitate, and tranexamic acid.Post-surgery bleeding revealed potential FXIII inhibitors, which were managed with additional plasma, cryoprecipitate, and oral prednisolone.The patient responded well and remained asymptomatic after discharge.
proteins
2026-07-01 | EP1T6_1 Acquired Factor XIII deficiency incidence in polytrauma
Acquired Factor XIII (FXIII) after trauma is underdiagnose, and can lead to increase bleeding events, blood transfusions and prolonged wound healing. FXIII deficiency becomes more relevant in the post-acute phase after trauma, which underlines the clinical relevance when planning definitive surgical care requiring increase blood transfusions, despite normal coagulation tests.
2026-06-22 | Factor XIII Supplementation Suppresses Recurrent Hemorrhages Due to Acquired Factor XIII Deficiency Secondary to Severe Acute Pancreatitis: A Case Report.
Hemorrhagic complications associated with severe acute pancreatitis significantly worsen the prognosis. Acquired factor XIII (FXIII) deficiency can lead to delayed tissue repair and associated recurrent bleeding, yet its clinical impact in the context of pancreatitis remains poorly understood. A 69-year-old woman with severe acute pancreatitis developed recurrent hemorrhagic shock due to multiple arterial bleeding episodes, including the splenic and left gastric arteries. Despite repeated transcatheter arterial embolization and massive blood transfusions, hemorrhagic events recurred during the subacute phase. Laboratory investigations revealed an acquired FXIII deficiency with FXIII activity levels of 56-59%. Repeated administration of FXIII concentrates administration suppresses the hemorrhagic complications gradually. This report suggests that FXIII concentrate administration may be a beneficial therapeutic option for managing recurrent hemorrhagic complications and stabilizing the clinical course in patients with severe acute pancreatitis and acquired FXIII deficiency.
2026-02-19 | Acquired Factor XIII deficiency presenting as intramuscular haemorrhage in an elderly patient
Ryohei Kishi, MD, Takuya Otsuki, MD, PhD, Kosuke Ishizuka, MD, PhD, FHGM, Tatsuya Masuyama, MD, Iori Motohashi, MD, MPH, Kenya Ie, MD, PhD, MPH, Yoshiyuki
2026-02-04 | Unexplained bleeding related to acquired factor XIII deficiency: A case report
Introduction: Acquired factor XIII (F XIII ) deficiency is a rare and often underdiagnosed bleeding disorder. Because standard coagulation tests typically yield normal results, diagnosis and treatment are often delayed in patients with unexplained hemorrhage. Case Presentation: We report the case of a 56-year-old man who presented with severe, recurrent epistaxis unresponsive to conventional management. Initial coagulation tests—including prothrombin time, international normalized ratio, activated partial thromboplastin time, and fibrinogen levels—were all within normal limits. Despite interventional radiology and surgical measures, bleeding persisted. An F XIII activity assay revealed a mild deficiency (48.7%; reference range: 60–130%). Administration of recombinant F XIII (catridecacog, 10 IU/kg) led to rapid clinical improvement and resolution of bleeding. Discussion: This case illustrates the diagnostic challenge posed by acquired F XIII deficiency and underscores the importance of including it in the differential diagnosis of unexplained bleeding, especially when standard coagulation parameters are unremarkable. Conclusion: Prompt recognition and targeted replacement therapy with recombinant F XIII can be life-saving in acquired F XIII deficiency. F XIII activity testing should be considered early in patients with persistent bleeding of unknown origin.
2026-01-24 | Perioperative factor XIII and viscoelastic measurements of open compared to minimal invasive major upper gastrointestinal surgery- A prospective observational study.
Acquired Factor XIII (FXIII) deficiency is prevalent in hospitalized or surgical patients, with FXIII activity <70% in over 20% of cases. A decrease in FXIII has been linked with postoperative bleeding, anastomotic insufficiency, and a greater likelihood of requiring reoperation. This study aims to identify patients at increased risk for postoperative complications by comparing open versus minimally invasive pancreatic and esophageal surgery. This prospective, monocentric observational study was conducted at Heidelberg University Hospital (Germany). Inclusion criteria consisted of age ≥ 18 years, the ability to provide informed consent, and scheduled esophageal or pancreatic surgery. A coagulation panel was performed preoperatively, directly after surgery and on postoperative day (POD) 1, 2, 3, 4, 7, 10, and 13, along with repeated thromboelastography (ClotPro®) Tests. Finally, 112 patients were enrolled (n = 77 open and n = 35 minimally invasive). FXIII activity showed a more pronounced decrease in the open surgery group until day 7; in both groups, the lowest FXIII activity occurred between days 4 and 7. There were no significant group differences in readmissions, reoperations, or severe perioperative complications according to the Clavien-Dindo classification. Open surgery was associated with a significant decline in FXIII activity, with a nadir estimated to occur between POD 4 and 7. FXIII activity also remained significantly reduced until day 7 after surgery. Viscoelastic testing was not able to detect mild acquired FXIII deficiencies. The extent to which routine testing of FXIII activity should be performed prior to reoperation must be evaluated in further studies. German Clinical Trials Register (DRKS00028547, registration date: April 14, 2022).
antibodies
2024-09-25 | Development and Epitope Mapping of Seven Mouse Anti-Human Coagulation Factor XIII-B Subunit Monoclonal Antibodies.
Coagulation factor XIII (FXIII) is an enzyme that strengthens hemostatic clots, and its deficiency can cause life-threatening bleeding. We immunized mice with human plasma-derived FXIII to generate monoclonal antibodies (mAbs) against the B subunit (FXIII-B), which stabilizes the A subunit (FXIII-A) of FXIII, and analyzed their properties. The epitopes of the seven mouse antihuman FXIII-B mAbs obtained were found to be the 3rd, 5th, 6th, 9th, and 10th Sushi domains. One of these mAbs, mAb 5-6C, recognized the 10th Sushi domain and inhibited the fibrin cross-linking reaction without affecting the amine incorporation activity of FXIII. We previously reported that the 10th Sushi domain is the site where FXIII-B binds to fibrin and functions to bring FXIII-A closer to the substrate fibrin. Except for mAb 5-6C, mouse mAbs with high yields were used to measure the amount of FXIII-B antigen by an immunochromatography test (ICT), which showed a high correlation with enzyme-linked immunosorbent assay-obtained results. In addition, we developed a prototype ICT to detect anti-FXIII-B autoantibodies using mAb 1-3C, which showed good results in measuring the amount of FXIII-B antigen. Thus, mouse mAbs may be useful for clinical applications. mAb 5-6C targeting the 10th Sushi domain may also be useful for inhibiting thrombosis progression when humanized as antibody medicines.
2023-10-01 | PB0240 Possible Autoimmune Acquired Factor 13 Deficiency : Tailoring Management in a Resource Constrained Setting in India, ACase Report
change from pretreatment baseline (%Change) in cynomolgus macaques receiving combination treatment of both anti-VWF nanobody and anti-FVIII with and without administration of VGA039.Vertical black dotted lines represent repeat subcutaneous anti VWF nanobody (Anti-VWF) injections at 5 mg/kg at -96, -72, -48, -24, 0, 24, and 48 hr, respectively, and coadministration of intravenous anti-FVIII mAb at 0.1 mg/ kg on Day 1 (0 hr).The vertical red dashed line represents administration of a vehicle (Control) or intravenous VGA039 at 10 mg/kg. Conclusion(s):Efficacy of VGA039 was demonstrated in a novel NHP model of acquired VWD.This proof-of-concept study supports clinical evaluation of VGA039 for the treatment of VWD.
2023-08-29 | Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking.
Coagulation factor XIII (FXIII) is a proenzyme of plasma transglutaminase. It comprises two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). We previously reported that alloantibodies against FXIII-B could promote FXIII clearance in a patient with congenital FXIII-B deficiency who had received infusions of plasma-derived human FXIII (A2B2 heterotetramer). We aimed to investigate whether anti-FXIII-B antibodies affect the catalytic function of FXIII. FXIII activation and fibrin crosslinking were examined in the presence of patient plasma, isolated patient IgG, or rat anti-FXIII-B monoclonal antibodies. Alloantibody levels were increased by repeated infusions of plasma-derived A2B2 heterotetramer, which enhanced binding to the functionally important FXIII-B sushi domains. The patient plasma strongly inhibited cleavage of the FXIII-A activation peptide, amine incorporation, and fibrin crosslinking in normal plasma. Furthermore, anti-FXIII-B alloantibodies blocked the formation of the complex of FXIII-B with FXIII-A, and fibrinogen. Rat monoclonal antibodies against the 10th sushi domain of FXIII-B inhibited the incorporation of FXIII-B to fibrin, FXIII activation (i.e., cleavage of FXIII-A activation peptide), and ultimately fibrin crosslinking in normal plasma, independent of their effect on heterotetramer assembly with FXIII-A. Alloantibody binding to the A2B2 heterotetramer blocked the access of thrombin to the FXIII-A cleavage site, as indicated by the reaction of the alloantibodies to the A2B2 heterotetramer and FXIII-B, but not to FXIII-A. Anti-FXIII-B antibodies binding to the A2B2 heterotetramer and FXIII-B inhibited FXIII activation and its crosslinking function despite being directed against its noncatalytic subunit (FXIII-B).
2023-05-10 | Epitope analysis of human monoclonal antibodies from a patient with autoimmune factor XIII deficiency reveals their inhibitory mechanisms.
Autoimmune coagulation factor XIII (FXIII) deficiency (AiF13D) is a bleeding disorder caused by anti-FXIII autoantibodies. Recently, we generated human monoclonal antibodies (mAbs) from the peripheral blood of an AiF13D patient and classified them into three groups: FXIII-dissociation inhibitor, FXIII-assembly inhibitor, and non-neutralizing/inhibitory mAbs. However, the epitope region and molecular inhibitory mechanism of each mAb remain unknown. Here, we localized the epitope regions of the representative inhibitory mAbs A69K (dissociation inhibitor) and A78L (assembly inhibitor) to the β-barrel-2 domain and boundary of β-barrel-1&2 domains, respectively, of the FXIII-A subunit, by combining a binding assay using its synthesized peptides and a protease-protection assay. Our findings suggest that A69K inhibits the activation-related conformational changes and dissociation of FXIII and that A78L competitively inhibits FXIII-assembly.
2023-02-14 | Cloning of human anti-factor XIII monoclonal antibody dissects mechanisms of polyclonal antibodies in a single patient.
Coagulation factor XIII (FXIII) consists of 2 A (FXIII-A) and 2 B (FXIII-B) subunits that cross-link and strengthen the hemostatic fibrin thrombus; thus, abnormal bleeding occurs when FXIII is significantly reduced. Autoimmune-acquired FXIII deficiency (AiF13D) is characterized by lethal bleeding secondary to the development of autoantibodies against FXIII. However, since anti-FXIII autoantibodies are polyclonal, the mechanism underlying FXIII dysfunction is unclear. The objective of this study was to dissect the inhibitory mechanisms of polyclonal anti-FXIII autoantibodies. In this study, we prepared the human monoclonal antibodies (hmAbs) from the peripheral blood of an 86-year-old man with AiF13D by using a new complementary DNA cloning method and analyzed the properties of each autoantibody. Seventeen clones obtained from hmAbs were divided into the following 3 groups: dissociation inhibitors of FXIII-A2B2 (6 clones), assembly inhibitors of FXIII-A2B2 (3 clones), and nonneutralizing/inhibitory hmAbs (8 clones). Dissociation inhibitors strongly inhibited fibrin cross-linking and amine incorporation. Assembly inhibitors extracted FXIII-A from FXIII-A2B2, strongly inhibited binding of FXIII-A to FXIII-B, and activation peptide cleavage. However, the patient's plasma presented a strong inhibition of A2B2 heterodimer assembly but only a slight inhibition of thrombin-Ca2+-dependent dissociation, suggesting that the assembly inhibitors concealed the effect of dissociation inhibitors in plasma. By contrast, nonneutralizing antibodies had little effect on the function of FXIII, suggesting that nonneutralizing hmAbs (and/or dissociation inhibitors and/or assembly inhibitors) promoted the clearance of FXIII-A from the blood. Cloning of anti-FXIII autoantibodies enabled us to not only elucidate the mechanism and pathophysiology of AiF13D but also develop a completely new type of anticoagulant.
cell therapies
2023-06-01 | Perioperative therapeutic plasma exchange in a patient with rare Factor XIII inhibitor
Factor XIII deficiency is a rare bleeding disorder which could be severe if inherited or less severe if acquired. We report a case of acquired Factor XIII inhibitor in a 75-year-old male with a suspicious left renal mass treated perioperatively with therapeutic plasma exchange (TPE).To perform kidney biopsy and ablation of the renal mass, six daily TPE treatments were performed before and after biopsy to minimize bleeding risk because the patient did not respond to drug therapy. Both thromboelastography (TEG) and laboratory-based coagulation tests were performed to assess coagulation status prior to and after TPE.The biopsy indicated oncocytoma which was removed by surgical procedure. Factor XIII activity remained below 15 % throughout TPE treatments, but Factor XIII inhibitor titer reduced from initial positive value of 1:40 to negative following the third TPE and remained negative through the sixth TPE. Unfortunately, the inhibitor titer was positive at 1:20 in the fifth month and 1:5 in the sixth month during follow-up.TPE is useful in removing XIII inhibitory factor, but the effects are only short term.
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