Acquired Factor XIII Inhibitor Research Articles

Perioperative therapeutic plasma exchange in a patient with rare Factor XIII inhibitor

IntroductionFactor 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). Patient and methodTo 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. ResultsThe 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. ConclusionsTPE is useful in removing XIII inhibitory factor, but the effects are only short term.

Acquired FXIII inhibitor: Patient characteristics and treatment outcome, a case series in Taiwan

Acquired factor XIII (FXIII) inhibitor is a rare but possibly underdiagnosed bleeding disorder. To date, less than one hundred cases have been reported, but the number has increased rapidly in recent years, especially in Japan. Because of the rarity of this disorder, no treatment guidelines are available. In some reports, physicians treated the bleeding with cryoprecipitate or factor XIII concentrate and eradicated the inhibitor with various immune suppressants. From January 2015 to December 2018, we collected consecutive patients diagnosed as having acquired FXIII inhibitor. FXIII activity and inhibitor were measured by a fluorescent factor XIII assay using isopeptidase reaction catalyzed by activated factor XIII and the Bethesda method, respectively. Factor XIII antigen was measured by latex-enhanced immunoassay. We found five adult patients with detectable FXIII inhibitor. Four of them were older than 70. Two had systemic lupus erythematosus. All the patients presented with ecchymosis and intramuscular hematoma. No life-threatening bleeding was observed. Delayed diagnosis was common with varied time periods needed to achieve a correct diagnosis. All bleedings were treated and improved by cryoprecipitate. Steroids were given to all patients and cyclophosphamide, rituximab, and other immune suppressants were also used. FXIII inhibitor was totally resolved in three, partially resolved in one, and persisted in one patient. We documented five patients with acquired FXIII inhibitor, found over 4 years. The most common presentations were ecchymosis and intramuscular hematomas. Cryoprecipitate was effective in controlling most bleeds. Steroid, cyclophosphamide and rituximab were effective in eradicating inhibitor in some patients.

Spontaneous remission of acquired factor XIII inhibitor concurrent to development of IgA-λ type multiple myeloma

Coagulation factor XIII is a fibrin-stabilizing factor that leads to the crosslinking of fibrin when activated by thrombin. Acquired factor XIII inhibitor is caused when antibodies are generated against factor XIII, reducing its activity. Here we report a case of acquired factor XIII inhibitor. Although prednisolone was administered, factor XIII activity was not recovered. Interestingly, the activity normalized following the onset of multiple myeloma. The presence of inhibitors was evaluated in the patient's plasma by absorption tests and enzyme-linked immunosorbent assay. Immunoglobulin G inhibitors of factor XIII were present at admission, but later decreased with the onset of the IgA-λ-type myeloma. Thus, it is possible that the level of factor XIII inhibitors and polyclonal immunoglobulins could have been suppressed by the progression of myeloma, resulting in the normalization of factor XIII activity.

Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series.

Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII deficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagulation test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcutaneous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in patients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobulin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvious lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients (27%) having partial resolution; 9 of these patients (14%) had a relapse. Thirteen patients (20%) died (7 from internal hemorrhage). Completeness of reporting varied for specific CAse REport items. Patient demographics, clinician-assessed outcomes, and laboratory test results were reported in all case reports. Least reported items included informed consent (6%), patient perspective (3%), and a title containing the words case report (9%). Our systematic review provides the most complete overview of published reports of FXIII acquired inhibitor to date. There is a paucity of data available on FXIII acquired inhibitor, and the available data may be limited by variable reporting. Despite multimodal therapy, a significant proportion of patients with FXIII acquired inhibitor have a large burden of morbidity and mortality.

Severe Bleeding Diathesis From Acquired Factor XIII Inhibitor Secondary to SLE

Severe Bleeding Diathesis From Acquired Factor XIII Inhibitor Secondary to SLE

Efficacy of rituximab in acquired factor XIII inhibitor after arterial rFVIIa‐induced thrombosis

Efficacy of rituximab in acquired factor XIII inhibitor after arterial rFVIIa‐induced thrombosis

Acquired factor XIII inhibitor: clinical features, treatment, fibrin structure and epitope determination

Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature.

57 Acquired factor XIII inhibitor: multimodal therapeutic approach with finally including immunoadsorption

57 Acquired factor XIII inhibitor: multimodal therapeutic approach with finally including immunoadsorption

Acquired factor XIII inhibitor in monoclonal gammopathy of undetermined significance: characterization and cross-linked fibrin ultrastructure

Acquired factor XIII inhibitor in monoclonal gammopathy of undetermined significance: characterization and cross-linked fibrin ultrastructure

Case Report of an Acquired Factor Xiii Inhibitor: Diagnosis and Management

A 57-year-old man presented with a spontaneous upper-extremity hematoma and compartment syndrome. The patient experienced excessive bleeding following evacuation of the hematoma, and the results of routine coagulation studies were normal. Factor XIII activity was undetectable using a photometric assay, and the presence of an inhibitor was detected with mixing studies. Bleeding was controlled with infusions of fresh frozen plasma and cryoprecipitate. Cyclophosphamide was started on the 16th hospital day, and four weekly doses of the monoclonal anti-CD20 antibody, rituximab, were begun 3 weeks later. One week after the initial dose of rituximab, the inhibitor was no longer detectable and the factor XIII level increased to 28%. After completion of the rituximab therapy, the factor XIII activity was 58% with no inhibitor present. This case illustrates the need to check for unusual defects such as factor XIII deficiency if a bleeding tendency is evident—even if routine studies are unrevealing.

Intracerebral haemorrhage due to acquired factor XIII inhibitor???successful response to factor XIII concentrate

A 63-year-old woman presented with extensive bruising. An inhibitor to factor XIII was detected. Subsequent subcutaneous bruising and soft tissue haemorrhage into the left foot were treated with infusions of pasteurized factor XIII concentrate with good effect. Immunosuppression with cyclophosphamide was attempted but in spite of this she suffered a right cerebral haemorrhage necessitating further intensive therapy with factor XIII concentrate. This overcame the inhibitor, adequate post-infusion factor XIII levels were achieved and she made an excellent recovery. Factor XIII concentrate was well tolerated with no evidence of transmission of hepatitis or HIV infection. The inhibitor appeared to interfere with haemostasis by hindering the fibrin binding site of factor XIII, resulting in interference in clot-solubility tests. Subsequently the inhibitor resolved.

Hemorrhagic disorder due to an isoniazid-associated acquired factor xiii inhibitor in a patient with waldenstrom's macroglobulinemia

A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenström's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid. The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter. Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity. Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor. A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption. The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein. The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody. The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein. Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal. Isoniazid was discontinued after the patient was admitted to the hospital. Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50%. Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further. Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity. Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer. This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid.

Hemorrhagic disorder due to an isoniazid-associated acquired factor XIII inhibitor in a patient with waldenström's macroglobulinemia

A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenström's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid. The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter. Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity. Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor. A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption. The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein. The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody. The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein. Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal. Isoniazid was discontinued after the patient was admitted to the hospital. Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50%. Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further. Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity. Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer. This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid.