Congenital Factor XIII Deficiency With the Presence of Inhibitor: A Case Study

Abstract

Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor with additional roles in wound healing and interactions between the decidua and fetus. Congenital FXIII deficiency is rare bleeding disorder. Inhibitor development against FXIII in inherited FXIII deficency is also uncommon, but may cause severe, life-threatening bleeding. FXIII is the last step in the coagulation cascade with normal coagulation paramaters (PT, aPTT), the detection of inhibitor to FXIII is quite difficult. The treatment of inhibitor-positive congenital FXIII deficiency is challenging due to the lack of a role of by-pass agents such as FVII. The best known ways of treatment in these cases are the use of high-dose FXIII concentrates and immunosuppression. Herein, we report the management of postoperative bleeding diathesis in a patient with FXIII deficiency who developed inhibitors, and to follow the clinical course of the disease with FXIII concentrate and immunosuppression.

Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking

“…Previously reported anti-FXIII-A antibodies, including allo-and auto-Abs, are catalytic FXIII inhibitors. [15][16][17][18][19][20][21][22][23][24][25][26][32][33][34][35][36][37] There have been few studies on anti-FXIII-B antibodies, 31,32,38 which did not mention their inhibitory effects on the catalytic function of FXIII; however, one anti-FXIII-B mAb was found to inhibit heterotetramer assembly. 31 To our knowledge, our current study is the first to report that anti-FXIII-B allo-Abs "indirectly" affect the crosslinking function of FXIII by blocking the FXIII-B role in anchoring FXIII A 2 B 2 on fibrinogen despite they do not target the active site of FXIII.…”

“…Although allo-Abs to FXIII are rare, anti-FXIII-A allo-Abs have been reported in at least 10 patients. [15][16][17][18][19][20][21][22][23][24][25][26] Contrastingly, to our knowledge, only one Japanese male patient with hereditary FXIII-B deficiency has been reported to develop anti-FXIII-B allo-Abs after therapeutic FXIII infusion. 27 We previously reported no inhibition of amine incorporation activity in a five-step cross-mixing test between the patient's and normal control plasma, which indicated a factor-deficient pattern.…”

Factor XIII deficiency – where we can save

“…У пациентов с дефицитом FXIII возможно образование ингибиторов, что может сильно повлиять на терапию. Протоколов лечения ингибиторной формы на данный момент не существует [14].…”

Treatment of rare bleeding disorders

“…Протоколов лечения ингибиторной формы на данный момент не существует. Применяются следующие препараты с различным успехом: кортикостероиды, ритуксимаб, внутривенный иммуноглобулин, сиролимус [15].…”