Monocyte expression of tissue factor and adhesion molecules: the link withaccelerated coronary artery disease in patients with chronic renal failure

Objective-To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to loo k for any correlation with thrombin generation and Lp(a) lipoprotein. Design-A study of MTF expression and adhesion molecules, prothrombin fragme nts 1+2 (PTfl + 2), an index of thrombin generation, and lipoproteins in pa tients with CRF and in normal control subjects. Background-Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes a re potent activators of blood coagulation through the generation of MTF, wh ich was recently implicated in the aetiology of acute coronary ischaemic sy ndromes. Methods-MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor anti body and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in pla sma were measured by enzyme linked immunosorbent assay (ELISA). Patients-70 patients with CRF without documented coronary artery disease (3 0 patients with CRF undialysed, 20 patients undergoing chronic ambulatory p eritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. Results-The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf u nit/100 monocytes in controls, p = 0.04) was more pronounced in patients un dergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf uni t/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotei n. Lp(a) lipoprotein was significantly increased in both dialysis groups co mpared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Mo nocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). Conclusion-This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These fi ndings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.