Gen and INTEM-MCF, there were no correlations between ROTEM parameters and the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15957913 other variables in the control group.Discussion As far as we know, this is the first report on the use of ROTEM and CAT in the study of the procoagulant state in BD. The present study has shown that thrombin generation and blood clotting capacity were increased in BD patients, even in the absence of thrombosis. Additionally, we found significant correlations between the ROTEM parameters, plasma ES levels and DA, which suggests links between the procoagulant state, endothelial inflammation and severity of symptoms of the disease. We found increased levels of fibrinogen in our group of patients with BD. This result is consistent with those observed in previous studies [19-21] and is not surprising considering that 78 of our patients were in an active state and that fibrinogen is an acute phase reactant [22]. The procoagulant effect of fibrinogen on ROTEM parameters has been reported previously PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/23410069 [23], and our results are in agreement with this effect. We observed that fibrinogen levels were significantly correlated with INTEM-MCF in both patients and controls, which suggests that increased levels of fibrinogen in the BD group might be involved in the group's hypercoagulable profile, as determined by the ROTEM test. Surprisingly, although INTEM-MCF correlated significantly with the fibrinogen levels and DA, we did not observe any dependence between the fibrinogen 2-Bromo-4-fluoro-5-methylbenzoic acid levels and DA. This issue, which was also observed by Hampton et al. 3,3-Dimethyl-7-nitro-2,3-dihydrobenzo[b][1,4]oxazepin-4(5h)-one [19], is intriguing but may be the result of the high variability of the fibrinogen synthesis route due to alternative mRNA processing, post-translational modifications and proteolytic degradation, which may lead to different levels of fibrinogen in response to similar inflammatory states [24]. Fibrinogen may also affect thrombin generation. Dielis et al. have shown that fibrinogen may produce not only an anticoagulant effect by increasing LT but also a procoagulant effect by heightening ETP and PH values in normal populations [25]. This dual anticoagulant/procoagulant effect can be explained by the spatial distribution of the thrombin's binding sites and the kinetics of interaction with its multiple substrates. Increased fibrinogen levels may prolong LT because of this molecule's ability to bind to thrombin through exosite II, which is needed for the thrombin-mediated FVIII activation. This fibrinogen binding leads to anFern dez-Bello et al. Orphanet Journal of Rare Diseases 2013, 8:81 http://www.ojrd.com/content/8/1/Page 5 ofTable 2 Demographic features, ROTEM and CAT results of both groupsCharacteristics Age at inclusion (year) Female gender ( ) INTEM- (degree) ROTEM INTEM-CFT (sec) INTEM-MCF (mm) Platelet contribution-MCF ( ) Lag-time (min) Time-to-peak (min) CAT Peak height (nM) ETP (nM ?min) Velocity index (nM/min) Platelet count (?03/l) Erythrocyte count (?06/l) Fibrinogen (mg/l) TAT (ng/l) Other parameters D-dimer (g/l) tPA (antigen) (ng/ml) PAI-1 (antigen) (ng/ml) E-selectin (g/l) C-reactive protein (mg/dl) BD patients (N = 23) 49 ?15 78 77 ?3 66 ?15 61 ?4 78 (69?9) 6.7 ?1.8 9.6 ?1.9 292 ?65 1543 ?331 102 (83?27) 217 (189?87) 4.2 ?0.4 321 ?53 19 (17?1) 293 ?65 17.2 ?7.2 19.9 ?8.6 24.2 ?9.3 0.2 (0.1-0.5) Controls (N = 33) 43 ?10 63 74 ?2 80 ?14 57 ?4 79 (77?1) 5.6 ?1.1 9.0 ?1.4 213 ?67 1286 ?292 55 (42?0) 227 (199?47) 4.3 ?0.4 280 ?42 15 (12?7) 270 ?86 12.4 ?5.2 12.6 ?6.0 16.8 ?8.4 0.1 (0.1-0.4) p-value 0.082 0.241 <0.010 <0.010.