BENEFICIAL EFFECT OF TREATMENT WITH A MONOCLONAL ANTITUMOR NECROSIS FACTOR-ALPHA ANTIBODY ON MARKERS OF COAGULATION AND FIBRINOLYSIS IN PATIENTS WITH ACTIVE CROHNS-DISEASE

Crohn's disease has frequently been associated with coagulation abnorm alities, causing intravascular deposition of fibrin and local infarcti on which can subsequently compromise the gut mucosa. Also, arterial an d venous thromboembolic complications of larger vessels appear to be a ssociated with Crohn's disease. Coagulation activation in patients wit h Crohn's disease could be a result of increased serum and tissue leve ls of cytokines, as reported. We prospectively studied parameters of c oagulation and fibrinolysis in 10 patients with active Crohn's disease , who were subsequently treated with a monoclonal anti-tumor necrosis factor-a (TNF) antibody. Ten consecutive patients with active Crohn's disease (CDAI > 150), not responding to a daily dose of at least 20 mg prednisolone, received a single infusion of human/mouse chimeric anti -TNF antibody cA2. All evaluable patients attained complete clinical a nd endoscopic remission within 4 weeks. Pretreatment plasma concentrat ions of markers of thrombin generation, thrombin-antithrombin (TAT) co mplexes and F1 + 2, were increased (22.1 +/- 11.8 mu g/l and 3.46 +/- 1.2 nmol/l, respectively). After treatment with cA2, these levels almo st completely normalized within 2 weeks. D dimer plasma levels were in creased at baseline (377 +/- 61.3 mu g/l) and decreased to normal leve ls 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 uncha nged. Von Willebrand factor (vWf) levels were increased at baseline (1 59 +/- 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 fin dings support the notion that active Crohn's disease is associated wit h the activation of coagulation and may indicate that this coagulation activation is mediated by TNF.