In patients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins

Several studies have shown that patients with venous thrombosis have elevated levels of factor VIII (FVIII) at an increased frequency. Most such patients also have high von Willebrand factor (vWF) levels. Since vWF is synthesized by the vascular endothelium, we hypothesized that elevated FVIII levels would also be associated with an increase of other endothelial cell-derived coagulation proteins suggesting perturbation of the endothelium. In 100 healthy individuals and 129 patients with venous thromboembolism, we have determined antigenic FVIII levels along with several endothelial proteins including vWF, soluble thrombomodulin (sTM), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). Levels of FVIII, vWF, PAI-1 and t-PA were significantly increased in patients compared with the controls (FVIII, vWF, and PAI-1, P < 0.001; t-PA, P < 0.05). Levels of sTM, however, were higher in the controls than in the patients (P < 0.001). Whereas the FVIII levels correlated well with the vWF levels in the patients (correlation, 0.61;P < 0.001) and the controls (correlation, 0.70;P < 0.001), there was neither a relevant correlation between FVIII and sTM, PAI-1, and t-PA, nor between vWF and sTM, PAI-1, and t-PA in the patients and the controls. In conclusion, although levels of PAI-1 and t-PA can be found, on average, at increased levels in patients with thrombosis, FVIII levels correlate only with vWF but not other endothelial cell-derived coagulation and fibrinolysis proteins including sTM, PAI-1, and t-PA.