thromboplastin and Crohn-Disease

Topics: Blood Coagulation; Cell-Derived Microparticles; Colitis, Ulcerative; Crohn Disease; Female; Humans; Male; Thrombin; Thromboplastin; Venous Thromboembolism

Patients with inflammatory bowel disease (IBD) have a higher risk for venous thromboembolism compared with non-IBD subjects. The pathogenic mechanisms of the thrombotic events are not fully understood. We investigated levels of circulating microparticles and their influence on thrombin generation in pediatric patients with IBD during active and quiescent disease compared with healthy controls.. Plasma samples were collected from 33 pediatric patients with Crohn disease (CD), 20 pediatric patients with ulcerative colitis (UC), and 60 healthy controls. Microparticles' procoagulant activity was measured by enzyme-linked immunosorbent assay, and the dependency of thrombin generation on microparticles-derived tissue factor was determined by means of calibrated automated thrombography.. The procoagulant function of microparticles was significantly increased in patients with active and inactive CD, and active UC compared with controls. Endogenous thrombin potential was significantly higher in patients with CD and UC compared with controls. A minor influence of microparticles on thrombin generation was only observed for patients with active UC.. Our study shows increased procoagulant function of microparticles in pediatric patients with active and quiescent CD and active UC compared with controls, but demonstrates that they are not a major cause for the higher thrombin generation in pediatric patients with IBD.

Topics: Adolescent; Austria; Blood Coagulation; Blood Coagulation Tests; Cell-Derived Microparticles; Child; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kinetics; Male; Prothrombin; Risk; Severity of Illness Index; Thrombin; Thromboplastin; Venous Thromboembolism

Topics: Adult; Antifibrinolytic Agents; Colitis, Ulcerative; Crohn Disease; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Polymorphism, Genetic; Thromboplastin

Inflammatory bowel diseases (IBD) are characterized by an increased thrombotic risk of uncertain etiology. Endogenous thrombin potential (ETP), a parameter of the thrombin generation curve, represents a new tool in the evaluation of thrombotic and bleeding disorders.. To study ETP in IBD patients and to correlate the results with clinical and biochemical features.. Seventy-four IBD patients (37 ulcerative colitis and 37 Crohn's disease) and 74 sex- and age-matched healthy individuals. ETP was measured upon activation of coagulation with small amounts of tissue factor and phospholipids in the presence or absence of thrombomodulin; results were expressed as nM thrombin.minutes.. Mean+/-SD ETP values were significantly higher in patients (1,499+/-454) than controls (1,261+/-385) (p<0.001) only when the test was performed in the presence of thrombomodulin. ETP evaluated as ratio (with/without thrombomodulin), taken as an index of hypercoagulability, was significantly higher in patients (0.69+/-0.14) than controls (0.62+/-0.18) (p<0.006). Patients with increased C-reactive protein (CRP) had significantly higher mean ETP (1,721+/-458) than those with normal CRP (1,357+/-394) or controls (1,261+/-385) (p<0.001). Patients who at the time of blood sampling were classified as having a clinically active disease had ETP higher than those who were quiescent (1,655+/-451 versus 1,388+/-427, p<0.001) or controls (1,261+/-385, p<0.001).. ETP measured in the presence of thrombomodulin or as ratio (with/without thrombomodulin) is increased in IBD patients, mainly in those with increased CRP or active disease. It may be considered as a candidate test for prospective studies aimed at assessing the risk of thrombosis in IBD patients.

Topics: Adult; C-Reactive Protein; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Factor VIII; Female; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Phospholipids; Prospective Studies; Thrombin; Thrombomodulin; Thromboplastin

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Crohn Disease; Factor XIa; Female; Humans; Male; Middle Aged; Prognosis; Thromboplastin; Young Adult

Procoagulant membrane microparticles can be released from activated or apoptotic cells in response to various environmental stimuli. The aim of this study was to investigate the presence of microparticles in Crohn's disease and to assess their variations after infliximab therapy. We compared the levels of circulating microparticles in 38 patients with Crohn's disease, 16 patients with ulcerative colitis, 7 patients with infectious colitis, and 17 control subjects. The evolution of microparticle levels was assessed after infliximab therapy in 13 patients with Crohn's disease. Circulating microparticle levels were elevated in patients with Crohn's disease (9.31+/-0.66 nmol/L phosphatidylserine equivalent [PS Eq]) or infectious colitis (10.71+/-0.92 nmol/L PS Eq) compared to patients with ulcerative colitis (5.75+/-0.59 nmol/L PS Eq) and control subjects (4.06+/-0.37 nmol/L PS Eq) (P = 0.001). Infliximab induced a significant diminution of the amounts of circulating microparticles, from 10.33+/-1.20 to 6.45+/-0.90 nmol/L PS Eq (P = 0.002). Generation of circulating microparticles occurs in Crohn's disease; infliximab induces significant diminution. Release of microparticles could be linked to the type of inflammatory response underlying Crohn's disease.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Apoptosis; Biomarkers; Case-Control Studies; Cohort Studies; Colitis; Colitis, Ulcerative; Crohn Disease; Female; Humans; Infliximab; Male; Middle Aged; Particle Size; Prognosis; Sensitivity and Specificity; Thromboplastin

To investigate the localisation of tissue factor expression in normal and inflamed intestine.. Serial cryostat sections of tissue taken from patients with Crohn's disease (n = 8), ulcerative colitis (n = 5), and from controls (n = 5) were stained with haematoxylin and eosin and immunostained for tissue factor, collagen type IV, fibrinogen and platelet glycoprotein IIIa.. In control tissues tissue factor was present as a continuous layer along the epithelial basal lamina: sections from controls did not immunostain for fibrinogen or platelets. In non-ulcerated inflamed mucosa, tissue factor staining intensified in cases of Crohn's disease and was associated with fibrin deposition. Staining for tissue factor was either patchy or absent in cases of ulcerative colitis and there was no fibrin deposition. This change accompanied the early destruction of the epithelial basal lamina in ulcerative colitis that was not seen in Crohn's disease. In both diseases tissue factor expression in severely inflamed and ulcerated mucosa was present on lamina propria macrophages and vascular endothelium and was associated with fibrin or platelet thrombi. In three of eight cases of Crohn's disease tissue factor expression and thrombi were evident in areas of submucosal vasculitis. These were not seen in adjacent normal vessels.. These observations are consistent with a tissue factor haemostatic barrier in the intestine: this barrier seems to be incomplete or defective in ulcerative colitis. Tissue factor expression by macrophages and endothelial cells may be important, particularly in the microvascular thrombosis and induration which are characteristic of Crohn's disease.

Topics: Adult; Aged; Aged, 80 and over; Colitis, Ulcerative; Collagen; Crohn Disease; Female; Fibrinogen; Humans; Immunohistochemistry; Intestinal Mucosa; Intestine, Large; Intestine, Small; Male; Platelet Membrane Glycoproteins; Thromboplastin

The etiology of Crohn's disease is unknown. Observations suggest that some sort of luminal agent enters the intestinal mucosa and elicits the special inflammatory reaction. Immunological mechanisms seem to be important. A related but so far largely unrecognised reaction is local activation of the external coagulation system by induction of thromboplastin (tissue factor) activity on the surface of endothelial cells and macrophages. This local procoagulant activity might initiate the formation of thromboses in small arteries in the intestinal wall. Recent studies indicate that microinfarcts due to arterial thromboses at the level of the muscularis propria may be an important pathogenetic mechanism in Crohn's disease.

Topics: Crohn Disease; Humans; Intestinal Mucosa; Thromboplastin; Thrombosis

We have examined the relationships among activation of blood coagulation, generation of monocyte procoagulant activity, and clinical activity in patients with Crohn's disease. Subclinical activation of blood coagulation was measured using a radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels were strongly correlated with the level of disease activity as measured by the Crohn's disease activity index. Patients with active disease who were successfully treated either medically or surgically demonstrated a reduction of fibrinopeptide A levels. Failure of fibrinopeptide A to return to the normal range predicted an early relapse. Monocyte tissue factor generation was assessed in both unstimulated and lipopolysaccharide-stimulated mononuclear cell cultures obtained from the peripheral blood of patients with Crohn's disease. A strong correlation (r = 0.89) was observed between plasma fibrinopeptide A levels and monocyte tissue factor generation. These results suggest that monocyte procoagulant generation may contribute to the activation of blood coagulation in this inflammatory bowel disease. Moreover, fibrinopeptide A levels in Crohn's disease may provide a useful quantitative measure of inflammatory activity.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Coagulation Factors; Crohn Disease; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Monocytes; Thromboplastin; Time Factors