Abstract
Factor XIII is one of the twelve coagulation factors and also known as a fibrin-stabilizing factor. In 2012, we encountered a male RA patient with hemorrhagic factor XIII deficiency who had been treated with tocilizumab for two years. There are few reports regarding the relationship between tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)) and factor XIII. We measured the factor XIII activity levels in the plasma of 40 RA patients (10 patients treated without biologics, 30 patients treated with biologics (15 patients treated with necrosis factor inhibitors and 15 patients treated with tocilizumab)) and 19 healthy controls. Consequently, the tocilizumab group exhibited lower levels than the other three groups according to the Steel-Dwass test (P<0.01). Furthermore, we compared the plasma factor XIII activity levels and the plasma factor XIII concentrations in the RA patients treated with biologics. Pearson's correlation test was used to assess the relationship between the factor XIII activity levels and the plasma factor XIII concentrations (r = 0.449, P = 0.019). According to the multiple regression analysis, the treatment with tocilizumab is an independent risk factor for plasma factor XIII reduction in RA patients. In conclusion, RA patients treated with tocilizumab, an IL-6R blocker, are at risk of developing acquired factor XIII deficiency. The mechanisms underlying the reduced factor XIII activity observed in RA patients treated with tocilizumab may result from the quantitative reduction in the plasma. These data imply that IL-6 plays an important role in maintaining the factor XIII activity level.
Highlights
Factor XIII is one of the twelve coagulation factors and known as a fibrin-stabilizing factor
rheumatoid arthritis (RA) patients with the following background factors were excluded: (a) complications of liver cirrhosis, leukemia or disseminated intravascular coagulation (DIC), (b) patients who had been treated with biologics for less than six months, (c) patients treated with more than two biologics simultaneously and (d) patients who had undergone surgery within the previous two months
In 2012, we experienced a 40-year-old male RA patient treated at Dohgo Spa Hospital who suffered from intra-pelvic hemorrhage without a history episode of trauma or contusion
Summary
Factor XIII is one of the twelve coagulation factors and known as a fibrin-stabilizing factor. Factor XIII circulates in the plasma in tetrameric form (FXIII-A2B2) and consists of two catalytic A subunits (FXIII-A) and two carrier/inhibitory B subunits (FXIII-B) [1,2,3,4,5]. FXIII-A is a protransglutaminase and exhibits potential enzymatic activity. The FXIII-A dimer is present in the cytoplasm of several cells, including platelets, megakaryocytes and monocytes/macrophages [6,7,8]. The concentration of FXIII-A is 100-fold higher in the cytoplasm of platelets than in the plasma. Both platelets and monocytes lack FXIII-B in their cytoplasm. FXIII-B is a glycoprotein that is secreted by hepatocytes [9]
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