Acquired Factor XIII (FXIII) deficiencies, stemming from autoantibodies against FXIII subunits, are recognized as severe bleeding disorders, albeit rare. While alloantibodies in FXIII-deficient individuals can also precipitate life-threatening bleeding episodes, their occurrence is exceedingly uncommon. This review delves into the diagnosis and classification of anti-FXIII antibodies, analyzing data from 48 patients with autoimmune FXIII deficiency and four additional FXIII-deficient patients who developed anti-FXIII alloantibodies, gathered from peer-reviewed publications.
Predominantly, with only two exceptions in the reviewed cases, the identified antibodies targeted FXIII-A. Diagnostic complexities inherent in FXIII deficiency when anti-FXIII antibodies are present necessitate a robust classification system. A functional classification scheme is proposed, categorizing anti-FXIII antibodies into three primary groups: neutralizing antibodies, non-neutralizing antibodies, and antibodies exhibiting a combined effect.
Methods employed for both detecting and quantifying the inhibitory impact on FXIII activation, alongside the transglutaminase activity of activated FXIII, are crucial for accurate diagnosis. Techniques for classifying neutralizing anti-FXIII antibodies are essential for understanding the mechanism of action. The significance of clearance studies in these clinical scenarios cannot be overstated, providing insights into antibody dynamics. Furthermore, binding assays are invaluable for identifying non-neutralizing and combined type antibodies; their diagnostic power is demonstrated through clinical examples documented in existing literature.
The most prevalent bleeding manifestations observed in patients with anti-FXIII antibodies are soft tissue hemorrhages. Intracranial bleeding, while occurring, is less frequent compared to cases of inherited FXIII deficiency. Therapeutic intervention in these patients presents substantial challenges. The primary therapeutic objective should be the eradication of the causative antibody to restore normal FXIII function and mitigate bleeding risk.
