THROMBUS FORMATION AND PLATELET-VESSEL WALL INTERACTION IN THE NEPHROTIC SYNDROME UNDER FLOW CONDITIONS

Increased in vitro platelet aggregability and hypercoagulability are g enerally held to be main determinants in the prethrombotic state in ne phrosis. In vivo, however, thrombotic events depend on the dynamic int eraction of flowing blood with the vessel wall. The present study conf irms that aggregability of platelets of nephrotic patients is signific antly increased by mere stirring or by exogenous stimuli as adenosine diphosphate and arachidonic acid. Moreover, the nephrotic patients hav e high von Willebrand factor and decreased red blood cell deformabilit y, which normally increase platelet-vessel wall interaction. However, perfusion studies under well-defined flow conditions, in which anticoa gulated nephrotic blood was exposed to deendothelialized human umbilic al artery segments and sprayed collagen, showed normal platelet adhesi on and only a modest increase in the deposition of platelet aggregates . This suggests that some factor counteracts platelet-vessel wall inte raction under flow conditions in the nephrotic syndrome. When tissue f actor associated with endothelial extracellular matrix (ECM) was allow ed to generate thrombin, perfusions with nephrotic blood over this ECM resulted in a strong increase in fibrin generation. The capacity of p atient blood to form increased amounts of fibrin appeared strongly cor related with the level of hyperfibrinogenemia. Platelet adhesion as we ll as aggregation in these experiments was even decreased below contro l values. This suggests that fibrin coverage may block the direct cont act between blood platelets and matrix. We therefore also studied the isolated effect of high fibrinogen on platelet-vessel wall interaction by increasing fibrinogen concentrations in normal blood. Modulation o f fibrinogen concentrations in normal blood could mimic all the observ ations in nephrotic blood: platelet aggregation in suspension increase d with increasing concentrations of fibrinogen, while platelet adhesio n and aggregate formation under flow conditions decreased. In perfusio ns over tissue factor-rich matrix, fibrin deposition increased. Theref ore, our observations indicate that nephrotic hyperaggregability in su spension is not associated with increased platelet vessel wall-interac tion under flow conditions. The latter is probably counteracted by hig h levels of fibrinogen. Our observations further suggest that hyperfib rinogenemia may be a major thrombotic risk factor in nephrosis by indu cing more fibrin depositions.