Clinical features of 32 new Japanese cases with autoimmune haemorrha‐philia due to anti‐factor XIII antibodies

Ichinose, Akitada; Osaki, Tsukasa; Souri, Masayoshi

doi:10.1111/hae.12677

Cited by 26 publications

(38 citation statements)

References 20 publications

(41 reference statements)

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“…In contrast, autoimmune hemophilia-like disease (hemorrhaphilia) caused by anti-FXIII autoantibodies (AH13) is a considerably rare and life-threatening bleeding disorder that occurs most frequently in the elderly [6,7,8,9]. The majority of AH13 patients have autoantibodies against FXIII-A [10,11]. Diagnosis of AH13 is difficult because routine coagulation screening tests, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), are usually normal [1,3].…”

Section: Introductionmentioning

confidence: 99%

“…In the 21st century, the number of diagnosed AH13 cases has been on the rise, at least in Japan because the Japanese Collaborative Research Group on AH13 (JCRG) has been conducting a nationwide survey. Accordingly, there were more diagnosed Japanese AH13 cases [10,11] than non-Japanese cases [12,13,14]. In order to save the lives of AH13 patients, prompt examinations, a correct diagnosis, and proper treatment are necessary [15].…”

Section: Introductionmentioning

confidence: 99%

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Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Ogawa

Yanagisawa²,

Souri³

et al. 2017

Acta Haematol

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Autoimmune hemophilia-like disease (hemorrhaphilia) due to anti-factor XIII (FXIII) antibodies (AH13) is a very rare, life-threatening bleeding disorder. A 77-year-old woman developed macrohematuria and a right renal pelvic hematoma. The coagulation times were not prolonged, but FXIII activity and antigen levels were severely and moderately reduced to 9 and 29% of normal values, respectively. Accordingly, the FXIII-specific activity turned out to be low. FXIII inhibitor and anti-FXIII-A subunit autoantibodies were detected by a 1:1 crossmixing test and immunoblot and immunochromatographic assays. She was therefore diagnosed with “definite AH13” and treated with plasma-derived FXIII concentrates to arrest the hemorrhage. In addition to a highly compressed inferior vena cava by a huge renal pelvic hematoma, deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) were identified by systemic computed tomography. The patient was immediately started on anticoagulation therapy with low-dose heparin. Emboli disappeared quickly, probably because under-crosslinked thrombi caused by severe FXIII deficiency are vulnerable to fibrinolysis. After about 1.5 years, anti-FXIII-A subunit autoantibodies still remained despite the use of rituximab, steroid pulse therapy, oral prednisolone, and oral cyclophosphamide treatments. In conclusion, an extremely rare AH13 case complicated by DVT and PE was successfully managed by balancing anticoagulation therapy with hemostatic therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Ogawa

Yanagisawa²,

Souri³

et al. 2017

Acta Haematol

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“…FXIII autoantibodies have been reported in a rising number of case studies in recent years, particularly in Japan (Ichinose et al , ). A recent study investigating autoantibody‐mediated acquired FXIII deficiency describe three types of inhibitor: Type Aa, which inhibits FXIII by blocking the assembly of the A and B subunits, and also dissociates the A subunit from the B subunit.…”

Section: Discussionmentioning

confidence: 99%

Defective α₂antiplasmin cross‐linking and thrombus stability in a case of acquired factor XIII deficiency

et al. 2017

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Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition that is often misdiagnosed or missed completely. A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. Low activated FXIII (FXIIIa) activity levels and abnormal urea clot stability led to diagnosis of acquired FXIII deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose of FXIII concentrate and immunosuppression with prednisolone induced remission. A subsequent relapse was treated with combined prednisolone and Rituximab resulting in a prolonged, ongoing remission. Here we analyse the mechanisms underlying this idiopathic case of acquired FXIII deficiency. Prospective analysis of patient plasma revealed minimal FXIIIa activity and antigen in presentation and relapse samples. Thrombi formed from these samples lysed rapidly and showed an absence of cross-linked α AP. Western blotting revealed the presence of FXIII-B, indicating only FXIII-A and FXIII-A B were affected. FXIII activity and antigen levels normalised on remission. Our data suggest the presence of inhibitor-induced clearance of FXIII from plasma. As a consequence, reduced thrombus stability was evident due to defective α AP cross-linking, thereby explaining symptoms of excessive bleeding.

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“…At high inhibitor titer, the administration of FXIII concentrate is without effect, and the main aim of the therapy should be the eradication of the autoantibody. In spite of all efforts, the mortality rate is between 20% and 30% . Here, we describe the severe bleeding diathesis of an elderly patient caused by anti‐FXIII‐A autoantibody in the absence of underlying disease.…”

Section: Introductionmentioning

confidence: 98%

“…Deficiency of the protective FXIII‐B results in a decreased FXIII‐A level with moderate bleeding diathesis. Among the acquired FXIII deficiencies, the most severe forms are caused by autoantibodies against either of the FXIII subunits (reviewed in ). This is a rare clinical condition, although the number of diagnosed patients has recently increased in Japan .…”

Section: Introductionmentioning

confidence: 99%

Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome – characterization of the antibody

Pénzes

Rázsó

Katona

et al. 2016

Journal of Thrombosis and Haemostasis

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HungaryTo cite this article: P enzes K, R azs o K, Katona E, Ker enyi A, Kun M, Muszbek L. Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome -characterization of the antibody. J Thromb Haemost 2016; 14:1517-20. Essentials• Autoantibody against factor XIII (FXIII) is a rare but severe acquired hemorrhagic diathesis.• In an elderly patient, anti-FXIII-A antibody led to severe bleedings with fatal outcome.• The neutralizing autoantibody bound to FXIII with high affinity (Ka%10).• The dominant effect of the autoantibody was the inhibition of activated FXIII.Summary. Autoantibodies may develop against the catalytic A subunit of factor XIII (FXIII-A) or the carrier B subunit (FXIII-B). Autoimmune FXIII-A deficiency was diagnosed in an elderly (75 years) patient with severe bleeding symptoms. The patient had 3% FXIII activity, and unmeasurable FXIII-A 2 B 2 and FXIII-A antigens in the plasma, whereas, in the platelet lysate, activity and FXIII-A antigen values were normal. As revealed by western blotting, FXIII antigen was present in the plasma, but the autoantibody interfered with the immunoassays. A mixing study indicated the presence of inhibitor with a titer of 63.2 Bethesda units (BU). The patient's IgG bound to FXIII-A 2 B 2 and to FXIII-A 2 with equally high affinity (K a in the range of 10 9 M À1). It exerted a multiple inhibitory effect on FXIII activation/ activity (IC50: 50 lg mL À1 ). Immunosupressive therapy gradually decreased the autoantibody titer to 8.0 BU, but FXIII activity remained very low, and, owing to recurrent bleeding, the patient died.

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Clinical features of 32 new Japanese cases with autoimmune haemorrha‐philia due to anti‐factor XIII antibodies

Abstract: Physicians/haematologists must raise the awareness of AH13 as a life-threatening disease. This report represents the only experience of a nationwide survey, and may contribute to a diagnosis on potentially overlooked non-Japanese AH13 patients in other countries in the world.

Cited by 26 publications

References 20 publications

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Defective α₂antiplasmin cross‐linking and thrombus stability in a case of acquired factor XIII deficiency

Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome – characterization of the antibody

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Clinical features of 32 new Japanese cases with autoimmune haemorrha‐philia due to anti‐factor XIII antibodies

Abstract: Physicians/haematologists must raise the awareness of AH13 as a life-threatening disease. This report represents the only experience of a nationwide survey, and may contribute to a diagnosis on potentially overlooked non-Japanese AH13 patients in other countries in the world.

Cited by 26 publications

References 20 publications

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

Defective α2antiplasmin cross‐linking and thrombus stability in a case of acquired factor XIII deficiency

Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome – characterization of the antibody

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Defective α₂antiplasmin cross‐linking and thrombus stability in a case of acquired factor XIII deficiency