RESUMEN
Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV-infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p < 0.001). Patients with a history of inhibitor (INB+) presented a mixed immune profile characterized by higher levels of pro-and anti-inflammatory cytokines than those without a history of inhibitor (INB-). The highest levels of CCL2 and CXCL8 were seen in HCVINB- , whereas CXCL9 and CXCL10 in HCVINB+ . Heatmap analysis of the set of cytokines and chemokines concentration distributed HCV patients into two distinct clusters, HCVINB+ and HCVINB- , both characterized by low concentrations of IL-4, while noninfected patients were grouped in a single block regardless of inhibitor development history (NIINB-/INB+ ). This finding suggests that the strong association between HCV infection and low levels of factor VIII inhibitors might be due to the modulation of the cytokine and chemokine network established by the antiviral response.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/uso terapéutico , Factor VIII/antagonistas & inhibidores , Hemofilia A/complicaciones , Hepatitis C Crónica/complicaciones , Adolescente , Adulto , Quimiocinas/metabolismo , Citocinas/metabolismo , Femenino , Hemofilia A/terapia , Hepatitis C Crónica/terapia , Humanos , Masculino , Persona de Mediana Edad , Plasma , Adulto JovenRESUMEN
Recombinant factor VIII (FVIII) products represent a life-saving intervention for patients with hemophilia A. However, patients can develop antibodies against FVIII that prevent its function and directly increase morbidity and mortality. The development of anti-FVIII antibodies varies depending on the type of recombinant product used, with previous studies suggesting that second-generation baby hamster kidney (BHK)-derived FVIII products display greater immunogenicity than do third-generation Chinese hamster ovary (CHO)-derived FVIII products. However, the underlying mechanisms responsible for these differences remain incompletely understood. Our results demonstrate that BHK cells express higher levels of the nonhuman carbohydrate α1-3 galactose (αGal) than do CHO cells, suggesting that αGal incorporation onto FVIII may result in anti-αGal antibody recognition that could positively influence the development of anti-FVIII antibodies. Consistent with this, BHK-derived FVIII exhibits increased levels of αGal, which corresponds to increased reactivity with anti-αGal antibodies. Infusion of BHK-derived, but not CHO-derived, FVIII into αGal-knockout mice, which spontaneously generate anti-αGal antibodies, results in significantly higher anti-FVIII antibody formation, suggesting that the increased levels of αGal on BHK-derived FVIII can influence immunogenicity. These results suggest that posttranslational modifications of recombinant FVIII products with nonhuman carbohydrates may influence the development of anti-FVIII antibodies.
Asunto(s)
Anticuerpos , Formación de Anticuerpos , Inhibidores de Factor de Coagulación Sanguínea , Factor VIII , Polisacáridos , Procesamiento Proteico-Postraduccional/inmunología , Animales , Anticuerpos/genética , Anticuerpos/inmunología , Inhibidores de Factor de Coagulación Sanguínea/genética , Inhibidores de Factor de Coagulación Sanguínea/inmunología , Células CHO , Cricetinae , Cricetulus , Factor VIII/inmunología , Factor VIII/farmacología , Hemofilia A/genética , Hemofilia A/inmunología , Ratones , Ratones Noqueados , Polisacáridos/genética , Polisacáridos/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/farmacologíaRESUMEN
COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/terapia , SARS-CoV-2/inmunología , Antiinflamatorios/sangre , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , Autoanticuerpos/sangre , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factores de Coagulación Sanguínea/análisis , Reacciones Cruzadas , Vesículas Extracelulares , Humanos , Inmunización Pasiva/efectos adversos , Factores Inmunológicos/sangre , Inmunosupresores/sangre , Sueroterapia para COVID-19RESUMEN
To investigate the current experience and expertise for haemophilia inhibitor patient management in haemophilia treatment centres (HTCs) in mainland China. Questionnaires were distributed to 'tertiary tier A' hospital HTCs across China to collect information on treatment preferences for bleeding control, prophylaxis and inhibitor eradication, as well as their regimens in real-world clinical practice. Of 40 questionnaires distributed, 39 were returned. In all, 38 were analysable for treatment preferences and 34 for actual clinical practice. For haemostatic treatment, 76·3% (29/38) HTCs preferred activated recombinant human Factor VII (rFVIIa). In clinical practice, the most widely used by-pass agent was prothrombin complex concentrate (26 HTCs). Although 65·8% (25/38) of HTCs believed prophylaxis treatment was necessary, it was prescribed in only 12. Similarly, 65·8% (25/38) of HTCs believed immune tolerance induction (ITI) therapy was necessary but only 14·8% (92/622) of patients in 19 HTCs received low-dose ITI treatment. HTCs in relatively economically developed cities (with higher-than-average per-capita gross domestic product) had better access to haemostatic treatment, coagulation testing and were more likely to provide prophylaxis and ITI in practice. The present survey showed there were gaps in haemophilia inhibitor care between the HTC physicians' preferences and their actual clinical practice. More specific care guidelines, education and clinical decision support tools are needed to guide clinical practice.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Hemostáticos/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Factor VIIa/uso terapéutico , Hemofilia A/sangre , Hemofilia A/epidemiología , Hemofilia B/sangre , Hemofilia B/epidemiología , Hemorragia/sangre , Hemorragia/tratamiento farmacológico , Hemorragia/epidemiología , Humanos , Lactante , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Adulto JovenRESUMEN
Acquired coagulation factor V (FV) inhibitors are rare disorders in which antibodies against FV develop under various conditions. We herein report the case of a 71-year-old woman with FV inhibitor during radiochemotherapy for pancreatic cancer. Multiple purpuras suddenly appeared on her bilateral upper limbs with prolonged coagulation data (APTT 97.3 seconds). The FV activity was less than 3% and the FV inhibitor was positive (1.7 B.U./mL). Oral prednisolone induced a rapid normalization of the coagulation data and FV activity and a rapid disappearance of FV inhibitor within 7 days. Early diagnosis and treatment may therefore be important in cases of FV inhibitor.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea , Factor V , Corticoesteroides , Anciano , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Femenino , HumanosRESUMEN
Background and Purpose: Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH). Methods: ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days. Results: A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population). Conclusions: Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor Xa/administración & dosificación , Hemostasis , Hemorragias Intracraneales , Proteínas Recombinantes/administración & dosificación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hemorragias Intracraneales/sangre , Hemorragias Intracraneales/tratamiento farmacológico , Masculino , Pirazoles/administración & dosificación , Piridonas/administración & dosificación , Rivaroxabán/administración & dosificaciónRESUMEN
The development of anti-drug antibodies (ADAs) is a serious outcome of treatment strategies involving biological medicines. Coagulation factor VIII (FVIII) is used to treat haemophilia A patients, but its immunogenicity precludes a third of severe haemophiliac patients from receiving this treatment. The availability of patient-derived anti-drug antibodies can help us better understand drug immunogenicity and identify ways to overcome it. Thus, there were two aims to this work: (i) to develop and characterise a panel of recombinant, patient-derived, monoclonal antibodies covering a range of FVIII epitopes with varying potencies, kinetics and mechanism of action, and (ii) to demonstrate their applicability to assay development, evaluation of FVIII molecules and basic research. For the first objective we used recombinant antibodies to develop a rapid, sensitive, flexible and reproducible ex vivo assay that recapitulates inhibitor patient blood using blood from healthy volunteers. We also demonstrate how the panel can provide important information about the efficacy of FVIII products and reagents without the need for patient or animal material. These materials can be used as experimental exemplars or controls, as well as tools for rational, hypothesis-driven research and assay development in relation to FVIII immunogenicity and FVIII-related products.
Asunto(s)
Anticuerpos Monoclonales/química , Anticuerpos Neutralizantes/química , Inhibidores de Factor de Coagulación Sanguínea/química , Factor VIII/química , Hemofilia A/sangre , Anticuerpos Monoclonales/sangre , Anticuerpos Neutralizantes/sangre , Inhibidores de Factor de Coagulación Sanguínea/sangre , Humanos , Proteínas Recombinantes/químicaRESUMEN
BACKGROUND People with hemophilia A have shown osteomuscular complications that have a significant impact on their quality of life (QoL) and on health care costs. Patients with hemophilia A with inhibitors living in developing countries such as Chile face a high disease and treatment burden. Emicizumab, a humanized bispecific monoclonal antibody, is associated with improvements in QoL and reduction in the financial impact of the disease related to treatment. This case report describes the impact of emicizumab on a patient with severe hemophilia A with inhibitors in terms of breakthrough bleeding control, improvements in QoL, and reduced financial impact after a year of treatment, in a country where this medication is not routinely available. CASE REPORT A 10-year-old child with severe hemophilia A with inhibitors had several restrictions in his daily life due to multiple incidences of breakthrough bleeding. He was on episodic treatment with bypassing agents, and in the year prior to treatment with emicizumab he had 18 bleeding episodes. After 1 year on prophylaxis treatment with emicizumab, the patient had only 1 bleeding episode (94.4% of reduction), improved pain control (5-point reduction on the visual analogue scale), a decrease in the Hemophilia Joint Health Score from 39 to 19, the QoL perception increased by 86% on the standardized Haemo-QoL-kids, and a 70% reduction in treatment costs versus the costs of episodic treatment with bypassing agents. CONCLUSIONS After 1 year of treatment with emicizumab, this patient had substantial improvements in the evaluated parameters. Further investigations with emicizumab are needed to assess its possible effects on public health policies.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de Factor de Coagulación Sanguínea , Hemofilia A/tratamiento farmacológico , Metrorragia , Calidad de Vida/psicología , Niño , Chile , Factor VIII , Femenino , Hemofilia A/psicología , Humanos , MasculinoRESUMEN
In patients with severe haemophilia receiving clotting factor concentrates, the risk of immunisation against their usual treatment is still patent and feared. New haemophilia drug treatments with an extended half-life have become available over the past few years. The risk of inhibitor development to these new treatments is unclear. We report the case of a 51-year-old man with severe haemophilia A, who was previously treated with no history of inhibitor development. Soon after a switch in his treatment to efmoroctocog alfa he developed an inhibitor against this recombinant Fc fusion extended half-life FVIII (rFc-FVIII) product. The patient was on an on-demand treatment regimen and was treated for mucosal bleeding. The inhibitor was characterised as type I, with classical epitope mapping. The spontaneous evolution of this inhibitor was favourable, but an anamnestic response led to a switch in his treatment to emicizumab.
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Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIII/administración & dosificación , Hemofilia A , Proteínas Recombinantes de Fusión/administración & dosificación , Factor VIII/efectos adversos , Francia , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/efectos adversosRESUMEN
INTRODUCTION: Inhibitor formation is the greatest challenge facing persons with haemophilia treated with factor concentrates. The gold standard testing methodologies are the Nijmegen-Bethesda assay (NBA) for FVIII and Bethesda assay (BA) for FIX inhibitors, which are affected by pre-analytical and inter-laboratory variability. AIMS: To evaluate inhibitor testing methodology and assess correlation between self-reported and actual methodology. METHODS: Methodology was evaluated using a survey distributed alongside a UK National External Quality Assessment Service Blood Coagulation external quality assurance (EQA) exercise for FVIII and FIX inhibitor testing. RESULTS: Seventy four survey and EQA exercise responses were received (response rate 63.2%), with 50 paired survey/EQA results. 47.1% (33/70) reported using the NBA and 42.9% (30/70) the BA for FVIII inhibitor testing. Review of FVIII inhibitor assay methodology demonstrated discrepancy (self-reported to actual) in 64.3% (BA reporting) and 27.6% (NBA reporting). Pre-analytical heat treatment was used by 32.4%, most commonly 56°C for 30 minutes. Assay cut-offs of 0.1-1.0 BU/mL were reported. EQA samples (acquired FVIII and congenital FIX) demonstrated titres and coefficients of variation (CV) of 3.1 BU/mL (0.7-15.4 BU/mL; CV = 43%) and 18.0 BU/mL (0-117 BU/mL; CV = 33%), respectively. No significant assay or laboratory factors were found to explain this variance, which could have resulted in change in management for 6 patients (5 misclassified high-titre FVIII inhibitors and 1 false negative for a FIX inhibitor). CONCLUSIONS: Heterogeneity was seen at each stage of assay methodology. No assay-related factors were found to explain variation in inhibitor titres. Further standardization is required to improve inhibitor quantification to guide patient care.
Asunto(s)
Factor VIII , Hemofilia A , Inhibidores de Factor de Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Humanos , Reino UnidoRESUMEN
Inhibitors of factor VIII (FVIII) remain the most challenging complication of FVIII protein replacement therapy in hemophilia A (HA). Understanding the mechanisms that guide FVIII-specific B cell development could help identify therapeutic targets. The B cell-activating factor (BAFF) cytokine family is a key regulator of B cell differentiation in normal homeostasis and immune disorders. Thus, we used patient samples and mouse models to investigate the potential role of BAFF in modulating FVIII inhibitors. BAFF levels were elevated in pediatric and adult HA inhibitor patients and decreased to levels similar to those of noninhibitor controls after successful immune tolerance induction (ITI). Moreover, elevations in BAFF levels were seen in patients who failed to achieve FVIII tolerance with anti-CD20 antibody-mediated B cell depletion. In naive HA mice, prophylactic anti-BAFF antibody therapy prior to FVIII immunization prevented inhibitor formation and this tolerance was maintained despite FVIII exposure after immune reconstitution. In preimmunized HA mice, combination therapy with anti-CD20 and anti-BAFF antibodies dramatically reduced FVIII inhibitors via inhibition of FVIII-specific plasma cells. Our data suggest that BAFF may regulate the generation and maintenance of FVIII inhibitors and/or anti-FVIII B cells. Finally, anti-CD20/anti-BAFF combination therapy may be clinically useful for ITI.
Asunto(s)
Factor Activador de Células B/inmunología , Inhibidores de Factor de Coagulación Sanguínea/inmunología , Factor VIII/inmunología , Hemofilia A/inmunología , Adolescente , Adulto , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Factor Activador de Células B/genética , Inhibidores de Factor de Coagulación Sanguínea/genética , Niño , Preescolar , Factor VIII/antagonistas & inhibidores , Factor VIII/genética , Factor VIII/uso terapéutico , Femenino , Células HEK293 , Hemofilia A/tratamiento farmacológico , Hemofilia A/genética , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Lactante , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Persona de Mediana EdadRESUMEN
Emicizumab reduces bleeding in patients with hemophilia A and inhibitors (PwHA-I). Coagulation potential during the perioperative period in emicizumab-treated PwHA-I undergoing surgery remains to be evaluated. We describe a 14-year-old boy with HA-I receiving emicizumab prophylaxis who experienced arthroscopic synovectomy. He was treated with a bolus infusion of recombinant factor VIIa (rFVIIa; 80 µg/kg) immediately before surgery, and treatment continued at the same dose every 3 h on day 1, every 4 h on day 2, and every 6 h on day 3. Treatment with rFVIIa was discontinued on day 4. No perioperative bleeding or thrombotic events were observed. Coagulation potential throughout the perioperative period was retrospectively assessed with an easy-to-use clot waveform analysis (CWA). Measurements from CWA returned to within or near the normal range, suggesting successful hemostatic management. Coagulation potentials assessed by CWA showed a significant correspondence with those from a thrombin generation assay (TGA) that is already in use. CWA and TGA could both provide useful data for assessing coagulation potential in the perioperative hemostatic management of emicizumab-treated PwHA-I.
Asunto(s)
Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIIa/administración & dosificación , Hemofilia A , Hemostasis , Sinovectomía , Adolescente , Pruebas de Coagulación Sanguínea , Hemofilia A/sangre , Hemofilia A/terapia , Humanos , Masculino , Proteínas Recombinantes/administración & dosificaciónRESUMEN
Emicizumab reduces bleeding in hemophilia A patients with inhibitor (HA-inh). A combination of immune tolerance induction therapy (ITI) and emicizumab prophylaxis may provide additional benefits, but coagulation potential during this treatment remains unknown. We assessed coagulation potentials in simulated ITI models in vitro using modified-clot waveform analysis. Factor (F)VIII-deficient plasma preincubated with anti-A2 and anti-C2 monoclonal antibodies was reacted with emicizumab (50 µg/mL) (emicizumab-HA-plasma), then spiking bypassing agents (BPAs): activated prothrombin complex concentrates (aPCC 1.3 IU/mL; 50 IU/kg), recombinant factor (rF)VIIa (2.2 µg/mL; 90 µg/kg), and FVIIa/FX (1.5 µg/mL; 60 µg/kg), and/or FVIII (100, 200 IU/dL). Coagulation potentials in emicizumab-HA-plasma (10 BU/mL) remained within the normal range when BPA and FVIII were both present. In emicizumab-HA-plasma (1 BU/mL) with BPA and FVIII (200 IU/dL), they were near or beyond the normal range, but those with a half concentration of rFVIIa based on the half-life in blood were within the normal range. In samples without inhibitor, coagulation potentials with combined BPA and FVIII were far beyond the normal range but with FVIII (100 IU/dL) and rFVIIa at half concentration they remained within the normal range. These results may provide information on the feasibility of concurrent ITI under emicizumab prophylaxis.
Asunto(s)
Anticuerpos Biespecíficos/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Inhibidores de Factor de Coagulación Sanguínea/inmunología , Desensibilización Inmunológica , Hemofilia A , Modelos Inmunológicos , Animales , Células CHO , Cricetulus , Hemofilia A/inmunología , Hemofilia A/patología , Hemofilia A/prevención & control , HumanosRESUMEN
Treating patients with hemophilia and inhibitors is often problematic. The presence of inhibitors negatively impacts the effectiveness of treatment to achieve hemostasis especially in patients with hemophilia B, owing mainly to allergic reactions to factor IX (FIX) concentrates and the low success rate of immune tolerance therapy. A 9-month-old boy had intracranial hemorrhage and was diagnosed with hemophilia B. After replacement therapy, he developed inhibitors and an allergic reaction to FIX. Prophylactic therapy was initiated with recombinant activated factor VII (rFVIIa) and later switched to pdFVIIa/factor X (FX; 120 µg/kg as the FVII dose, every other day) because of a recurrence of intracranial hemorrhage. Since then, he remained well without life-threatening bleeding for more than 2 years. Our case suggests that pdFVIIa/FX may be useful for prophylactic therapy in hemophilia B complicated by inhibitors and allergic reaction to FIX concentrates.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIIa/uso terapéutico , Factor X/uso terapéutico , Hemofilia B/tratamiento farmacológico , Hipersensibilidad/diagnóstico , Factor IX/efectos adversos , Factor IX/genética , Factor IX/uso terapéutico , Hemorragia , Humanos , Hipersensibilidad/etiología , Lactante , Masculino , Polimorfismo de Nucleótido Simple , Tomografía Computarizada por Rayos XRESUMEN
Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor with additional roles in wound healing and interactions between the decidua and fetus. Congenital FXIII deficiency is rare bleeding disorder. Inhibitor development against FXIII in inherited FXIII deficency is also uncommon, but may cause severe, life-threatening bleeding. FXIII is the last step in the coagulation cascade with normal coagulation paramaters (PT, aPTT), the detection of inhibitor to FXIII is quite difficult. The treatment of inhibitor-positive congenital FXIII deficiency is challenging due to the lack of a role of by-pass agents such as FVII. The best known ways of treatment in these cases are the use of high-dose FXIII concentrates and immunosuppression. Herein, we report the management of postoperative bleeding diathesis in a patient with FXIII deficiency who developed inhibitors, and to follow the clinical course of the disease with FXIII concentrate and immunosuppression.