thromboplastin and Colonic-Diseases

The association between cancer and thromboembolic disease has been known for over a century. Increased tissue factor expression by endothelial cells, monocytes or macrophages is implicated. Thus, monocyte tissue factor measurements may reflect disease presence or progression.. Using a 2 stage kinetic chromogenic assay, monocyte tissue factor levels were assessed in normal controls (n=60), patient controls (hernia or cholecystectomy, n=60) and in patients with benign and malignant disease of the bladder (n=73), prostate (n=81), breast (n=83) and colorectum (n=62). This was performed as baseline (resting cells) and after 6 hours incubation with (stimulated) and without (unstimulated) lipopolysaccharide. Each benign disease group was sub-divided into inflammatory and non-inflammatory categories.. The relative operating characteristic curve for the lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer, the area under the curve being 0.71. The control groups and the benign non-inflammatory groups gave similar results and were pooled for further analysis. Each malignant group showed higher monocyte tissue factor levels than the control groups for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). All benign inflammatory groups apart from breast, showed increased monocyte tissue factor levels over controls for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). In all cases there was no significant difference between the malignant and the benign inflammatory groups. Monocyte tissue factor levels were related to tumor grade or stage, patients' survival time, serum prostate specific antigen and static bone scan images. Levels were also higher in patients with bladder cancer recurrence and in those who subsequently died.. Lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer compared to controls. Monocyte tissue factor levels are raised in malignant groups compared to controls and non-inflammatory diseases but not when compared with inflammatory conditions. Stimulated cells give better discrimination between the groups and may be useful in identifying high risk individuals. Monocyte tissue factor levels were related to tumor progression.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Case-Control Studies; Colonic Diseases; Colorectal Neoplasms; Discriminant Analysis; Disease Progression; Female; Humans; Inflammation; Male; Middle Aged; Monocytes; Prostatic Diseases; Prostatic Neoplasms; Risk Factors; Sensitivity and Specificity; Thromboembolism; Thromboplastin; Urinary Bladder Diseases; Urinary Bladder Neoplasms

Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy.

Topics: Arthritis, Rheumatoid; Blotting, Western; Colonic Diseases; Colonoscopy; Colorectal Neoplasms; Humans; Molecular Weight; Proctocolitis; Rectal Diseases; Thromboplastin