Beneficial Effect of Treatment with a Monoclonal Anti-Tumor Necrosis Factor-α Antibody on Markers of Coagulation and Fibrinolysis in Patients with Active Crohn’s Disease

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Abstract
Crohn’s disease has frequently been associated with coagulation abnormalities, causing intravascular deposition of fibrin and local infarction which can subsequently compromise the gut mucosa. Also, arterial and venous thromboembolic complications of larger vessels appear to be associated with Crohn’s disease. Coagulation activation in patients with Crohn’s disease could be a result of increased serum and tissue levels of cytokines, as reported. We prospectively studied parameters of coagulation and fibrinolysis in 10 patients with active Crohn’s disease, who were subsequently treated with a monoclonal anti-tumor necrosis factor-α (TNF) antibody. Ten consecutive patients with active Crohn’s disease (CDAI > 150), not responding to a daily dose of at least 20 mg predniso-lone, received a single infusion of human/mouse chimeric anti-TNF antibody cA2. All evaluable patients attained complete clinical and endoscop-ic remission within 4 weeks. Pretreatment plasma concentrations of markers of thrombin generation, thrombin-antithrombin (TAT) complexes and Fl + 2, were increased (22.1 ± 11.8 μg/1 and 3.46 ± 1.2 nmol/l, respectively). After treatment with cA2, these levels almost completely normalized within 2 weeks. D dimer plasma levels were increased at baseline (377 ± 61.3 μg/1) and decreased to normal levels after cA2 treatment. The levels of plasminogen activator inhibitor (PAI-1) were elevated before treatment and slowly decreased hereafter. The levels of tissue-type plasminogen activator (t-PA) remained unchanged. Von Willebrand factor (vWf) levels were increased at baseline (159 ± 21%) and showed a downward trend after 2 weeks (121.3 ± 24%, NS). In conclusion, anti-TNF antibody infusion resulted in a decrease of thrombin generation and endothelium activation markers in patients that were suffering from steroid-refractory Crohn’s disease. These findings support the notion that active Crohn’s disease is associated with the activation of coagulation and may indicate that this coagulation activation is mediated by TNF.

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