thromboplastin and Kidney-Calculi

Coagulation activation is a recognized complication of cancer in which increased tissue factor (TF) is implicated. TF can be detected in urine (uTF). This study assesses uTF levels in benign and malignant urological disease and correlates the results with conventional markers of tumour progression.. Using a simple and reproducible kinetic chromogenic assay, we determined uTF levels in controls (normal volunteers (n = 57) and patients with renal stones (n = 30)), benign and malignant bladder (n = 75) or prostate (n = 106) disease and in patients with or without recurrent bladder cancer (n=30). Each benign disease group was stratified as inflammatory (cystitis or prostatitis) or non-inflammatory (negative cystoscopy following haematuria or benign prostatic hypertrophy).. The controls and the benign non-inflammatory results were indistinguishable. The malignant and inflammatory groups showed raised uTF levels over controls (P<0.001 bladder and P<0.01 prostate). The difference between malignant and benign inflammatory disease was only significant for the bladder group. uTF levels were significantly related to histological tumour grading, prostate serum specific antigen, static bone scan images and recurrence status.. uTF levels can distinguish, statistically but not without overlap, patients with malignancy from normal controls and benign non-inflammatory conditions. Discrimination between inflammatory and malignant disease has only been demonstrated in the bladder. uTF levels showed a significant association with markers of tumour progression or metastasis and may be useful in predicting bladder tumour recurrence.

Topics: Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Case-Control Studies; Cystitis; Disease Progression; Humans; Kidney Calculi; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Thromboplastin; Urinary Bladder Neoplasms

Activation of blood coagulation is a common complication of cancer in man and experimental animals. The causes of such activation may be multifactorial, but increased production of tissue factor (TF) by the host mononuclear cells may be involved. TF is not only produced by human monocytes (mTF) and tumour cells, but is also found in urine (uTF), where measurements might be clinically important. Using a highly reproducible (intra-assay CV 2.3 per cent and inter-assay CV 8.1 per cent) one-stage kinetic chromogenic assay (KCA) developed by this group, uTF levels were measured in controls [healthy volunteers (n = 57), patients with renal stones and a normal ESR (n = 30)] and in patients with benign and malignant diseases of the breast (n = 94) and large bowel (n = 62). Each benign disease group was sub-divided into inflammatory and non-inflammatory categories. There were no significant differences between the controls and the benign non-inflammatory groups, so they were unified for further analysis. Malignant groups, irrespective of tumour types, showed significantly higher uTF levels than controls (p < 0.001 for breast and p < 0.01 for large bowel). Similarly, breast and colorectal benign inflammatory groups showed significant increases over controls (p < 0.01 and p < 0.001, respectively). Patients with malignant disease showed uTF activity above the upper quartile range of the normal control group for breast, 77.3 per cent, and large bowel, 73 per cent. uTF levels were related to histological tumour grading and were higher in non-surviving patients. In conclusion, uTF levels are raised in malignant and inflammatory disease compared with controls and patients with non-inflammatory conditions. uTF levels may reflect tumour progression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Child; Child, Preschool; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Kidney Calculi; Male; Middle Aged; Neoplasm Proteins; Survival Rate; Thromboplastin

Monocyte and urinary tissue factors (mTF and uTF) are both elevated in a number of pathologic conditions, including cancer. This study validates the best available uTF and mTF assays as diagnostic tools for cancer and examines if uTF levels reflect monocyte activation. Using kinetic chromogenic assays for uTF and mTF (measured on fresh resting cells [baseline], unstimulated cells, and lipopolysaccharide [LPS]-stimulated cells), we assessed TF levels in normal individuals, surgical controls, and patients with benign and malignant diseases. Each benign disease group was stratified as inflammatory or noninflammatory. Controls and benign noninflammatory results were indistinguishable. The malignant and inflammatory groups showed raised uTF levels over controls (p < 0.001). mTF levels differ similarly. For mTF and uTF assays, there was no significant difference between the malignant and inflammatory groups. The relative operating characteristic (ROC) curve plots sensitivity against false positive rate (1-specificity) for all possible cutoff values of a diagnostic test. Assay performance is assessed as the area under the curve (AUC). The ROC curve for the uTF assay displayed both sensitivity and specificity for cancer, the AUC being 0.83. Of the three mTF levels, LPS-stimulated cells gave the optimum curve (AUC = 0.71). uTF showed a weak to moderate association with mTF levels but correlated best and was statistically significant when compared with levels in the LPS-stimulated cells. uTF represents an intrinsic, kidney-derived, physiologic concentration rather than that of preactivated or postactivated monocytes. In conclusion, both uTF and LPS-stimulated mTF levels showed sensitivity and specificity in detecting cancer and inflammatory diseases. However, the two forms of TF appear to be independently derived.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers, Tumor; Breast Neoplasms; Child; Child, Preschool; Cholelithiasis; Colorectal Neoplasms; Diagnosis, Differential; False Positive Reactions; Female; Hernia, Inguinal; Humans; Inflammation; Kidney Calculi; Lipopolysaccharides; Male; Middle Aged; Monocytes; Neoplasms; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity; Thromboplastin; Urinary Bladder Neoplasms

To investigate the significance of urinary tissue factor (uTF) concentrations in patients with glomerulonephritis.. Urine samples were collected from normal subjects (n = 57), patients with uncomplicated renal stones (n = 30), and patients with glomerulonephritis (n = 150). Samples were then centrifuged and the pellets solubilised in n-octyl-beta-glucopyranoside. uTF concentrations were determined using a one stage kinetic chromogenic assay.. The uTF concentration was higher in patients with glomerulonephritis than in normal controls (p < 0.01) or in patients with renal stones (p < 0.05). uTF activity correlated with the protein creatinine index (PCI, r = 0.41, p < 0.001) and seven patients with glomerulonephritis and a PCI < or = 0.1 g/mmol had raised uTF. Glomerulonephritis patients were subdivided into two groups depending on the PCI: < 0.2 g/mmol creatinine (mild to moderate proteinuria, group I) and > or = 0.2 g/mmol creatinine (heavy proteinuria, group II). In group I, uTF concentrations were higher in patients with either immune complex (IC) glomerulonephritis (p < 0.01) or non-IC (p < 0.05) glomerulonephritis than in normal controls. In group II, the IC glomerulonephritis group had higher uTF concentrations than normal controls (p < 0.001) or patients with renal stones (p < 0.01); and non-IC glomerulonephritis patients had higher uTF than normal controls (p < 0.01). When the glomerulonephritis groups were divided into broad WHO subtypes, the significance level varied with the type of glomerulonephritis.. uTF is increased in patients with glomerulonephritis, and its concentration may reflect the aetiopathogenesis of glomerulonephritis.

Topics: Biomarkers; Creatinine; Glomerulonephritis; Humans; Kidney Calculi; Proteinuria; Thromboplastin