Haemostatic derangement in advanced peripheral occlusive arterial disease

Background. Dysbalance of the coagulation and fibrinolysis system was suspe cted to be a further risk factor for the progression of peripheral occlusiv e arterial disease (POAD). Reports on disturbed platelet function in advanc ed disease, however, were contradictory. Therefore, we studied haemostasis parameters and platelet function in symptomatic patients with peripheral ar terial disease. Methods. 60 peripheral arterial disease patients hospitalised for invasive diagnostic procedures were included into this comparative study. Patients w ere clinically stratified according to the criteria for chronic limb ischem ia (grade I: n=36; grade II: n=11; grade III: n=13). Plasma fibrinogen, ant ithrombin III, von Willebrand factor, tissue plasminogen activator (tPA), p lasminogen activator inhibitor-1 (PAI-1) prothrombin time, and activated pa rtial thromboplastin time were determined using standard methods. We measur ed flow cytometrically, the platelet activation marker P-selectin on nonsti mulated, ADP- and TRAP-6-stimulated platelets. Angiographic data were asses sed using the Bollinger score. Results. Plasma levels of the procoagulant proteins fibrinogen (grade I: 3. 7/grade II: 3.9/grade III: 4.0 g/l) and vWF (158/156/178%) increased and of antithrombin III (109/103/102%) and the PAI-1/tPA ratio (5.2/5.0/4.1) decr eased with progressive disease. Highest platelet activation levels were obs erved in the CLI grade II subgroup. A significant correlation of disease se verity was seen with the ankle-brachial pressure index (p=0.006; r=0.39) an d with the Bollinger score (p=0.002; r=-0.41). Conclusions. Progressive peripheral obstructive arterial disease was associ ated with platelet hyper-reactivity, haemostatic dysbalance of pro- and ant icoagulant proteins, and a counterregulatory increase of fibrinolytic activ ity. Therapeutic concepts should include these pathogenetic mechanisms.