Platelet (dys)function and plasma plasminogen levels in hemodialysis patients

The factors contributing to platelet dysfunction in hemodialysis patients are still not completely known. We explored whether the fibrinolytic system influences platelet function in hemodialysis patients. We measured standard fibrinolytic parameters and markers of fibrinolysis/coagulation activation, and correlated them to platelet aggregation in 15 hemodialysis patients. Fifteen healthy age-matched volunteers served as controls. Hemodialysis patients had significantly decreased levels of plasminogen (0.76 [0.64-0.86] vs. 0.98 [0.87-1.08] rel, P < 0.001), and increased levels of fibrinogen (4.6 [3.9-5.5] vs. 4.0 [3.4-4.6] g/L, P < 0.05), whereas tissue-type plasminogen activator antigen and plasminogen activator inhibitor (PAI)-1 antigen and PAI activity were comparable to controls. Furthermore, elevated levels of markers of fibrinolysis/coagulation were found in hemodialysis patients: D-dimer (280 [170-460] vs. 135 [120-150] ng/mL, P < 0.01), prothrombin fragments 1 + 2 (1.7 [1.4-1.9] vs. 1.1 [1.0-1.2] nmol/L, P < 0.001), and thrombin-antithrombin complexes (5.2 [4.2-17.7] vs. 0 [0-4.2]microg/L, P < 0.01). The aggregation of platelets (induced by adenosine diphosphate) was slightly impaired in patients compared to controls (72 [43-79] vs. 83 [73-88]%, P = 0.08). Analysis showed that platelet aggregation positively correlated with plasminogen levels (r = 0.48, P < 0.01). No correlation with other fibrinolytic parameters or markers of activation was found. In hemodialysis patients platelet (dys)function appears to be associated with both the fibrinolytic and coagulation systems. We found that platelet aggregation significantly correlates with plasma plasminogen levels. This relation, which has not been hitherto described, seems to be causal and clinically important. Further exploration of this may help us to better understand the mechanisms of platelet dysfunction in hemodialysis patients.