Auto‐ and alloantibodies against factor XIII: laboratory diagnosis and clinical consequences

Abstract

Acquired FXIII deficiencies caused by autoantibodies against FXIII subunits represent rare but very severe bleeding diatheses. Alloantibodies in FXIII-deficient patients also cause life-threatening bleeding complications, but they develop extremely rarely. In this review we provide an overview of the diagnosis and classification of anti-FXIII antibodies and analyze 48 patients with autoimmune FXIII deficiency and four additional FXIII-deficient patients who developed anti-FXIII alloantibody. The patients were collected from peer-reviewed publications from which relevant data could be extracted. With the exception of two cases the antibodies were directed against FXIII-A. The difficulties in the diagnosis of FXIII deficiency in the presence of anti-FXIII antibodies are discussed and a scheme for the functional classification of the anti-FXIII antibodies is recommended. The three main categories are neutralizing and non-neutralizing antibodies and antibodies with combined effect. The methods being used for detecting and quantifying the inhibitory effect on FXIII activation and on the transglutaminase activity of activated FXIII are summarized and techniques for the classification of neutralizing anti-FXIII antibodies are outlined. The importance of clearance studies in these cases is emphasized. Binding assays, useful for the identification of non-neutralizing and combined type antibodies, were collected from the literature and their informative power is demonstrated by examples. The most frequently occurring bleeding symptoms in patients with anti-FXIII antibodies were soft tissue bleeding; intracranial bleedings also occurred, but less frequently than in inherited FXIII deficiency. Treatment of such patients is extremely challenging; the main aim should be eradication of the antibody.

Laboratory Assessment of Coagulation Factor XIII

“…3 In recent years, a large number of autoimmune FXIII deficiencies have been reported. 13,21 In suspected autoimmune acquired FXIII Fig. 1 Recommended diagnostic workup for suspected FXIII deficiency, based on the recommendations on the diagnosis and classification of FXIII deficiencies published by the Factor XIII and Fibrinogen SSC Subcommittee of the ISTH.…”

Autoimmune factor XIII deficiency with unusual laboratory and clinical phenotype

“…In this case the inhibition of FXIIIa by the patient's IgG was moderate: 44% of the transglutaminase activity was inhibited by 300 μg/mL IgG (Figure S1C) suggesting that the inhibition of transglutaminase activity only partially contributed to the combined inhibition of Ca 2+ induced activation and FXIIIa activity. According to the proposed classification the neutralizing anti‐FXIII‐A autoantibody is of combined type (type IV) 6 …”

Autoimmune Acquired Factor XIII Deficiency: A Case Report

“…2 Inhibitor development against FXIII in inherited FXIII deficiency in patients receiving FXIII replacement therapy is also infrequent but may induce severe bleeding. 3 However, acquired FXIII deficiency is more common and can be classified as immune and non-immune disease. Acquired immune-mediated FXIII deficiency implies the presence of an autoantibody targeting FXIII epitopes which may lead to severe bleeding.…”