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.

Airway Compromise and Perioperative Management of a Patient with Acquired Factor XIII Inhibitor.

Perioral hematomas can lead to acute airway compromise and can present significant challenges in both direct and indirect approaches to airway instrumentation. In patients with normal cell counts and routine coagulation tests, spontaneous hematomas are rare, but when encountered, they elicit a limited differential diagnosis that includes von Willebrand factor deficiency, platelet dysfunction, and the acquired factor XIII (FXIII) deficiency. Although spontaneous hematoma formation resulting from FXIII inhibition has been reported, we describe what may be the first reported case of FXIII inhibitor-related hematoma leading to acute airway compromise. Successful management of this patient required multidisciplinary cooperation among anesthesiologists, intensivists, otolaryngologists, and hematologists.