BACKGROUND: The exposure of phosphatidylserine (PS) on the outer leaflet of the erythrocyte membrane may have several pathophysiological consequences, including the development of a procoagulant phenotype, a finding that seems relevant to the thrombotic risk seen in many disorders. METHODS: Because PS externalization increases in erythrocytes from patients suffering from chronic uraemia, which is frequently associated with a prothrombotic state, the possible relationship between erythrocyte PS exposure, erythrocyte procoagulant activity and plasma levels of several haemostatic markers was studied in a group of haemodialysed patients. RESULTS: Uraemic erythrocytes displayed increased procoagulant activity, which proved to be correlated directly with erythrocyte PS exposure. Pre-incubation of uraemic erythrocytes with annexin V, a protein with high affinity and specificity for PS, strongly inhibited in vitro thrombin generation induced by erythrocytes as compared with untreated red cells. Thrombin generation and activation of fibrinolysis were found to occur in uraemic patients, as substantiated by increased plasma levels of markers for thrombin generation (prothrombin fragment F1.2 and thrombin-antithrombin complex) and fibrinolysis (D-dimer and plasmin-antiplasmin complex), respectively. Significant correlations between prothrombin fragment F1.2 and D-dimer suggested that hyperfibrinolysis was secondary to thrombin generation. Correlations were also found between erythrocyte PS levels and plasma levels of haemostatic markers, including prothrombin fragment F1.2 (P = 0.007), thrombin-antithrombin complex (P = 0.00009), plasmin-antiplasmin complex (P = 0.0009) and D-dimer (P = 0.005). CONCLUSIONS: Our study suggests that increased PS exposure may cause a pathological erythrocyte procoagulant phenotype, which may be a factor inducing a hypercoagulable state in uraemia.
BACKGROUND: The exposure of phosphatidylserine (PS) on the outer leaflet of the erythrocyte membrane may have several pathophysiological consequences, including the development of a procoagulant phenotype, a finding that seems relevant to the thrombotic risk seen in many disorders. METHODS: Because PS externalization increases in erythrocytes from patients suffering from chronic uraemia, which is frequently associated with a prothrombotic state, the possible relationship between erythrocyte PS exposure, erythrocyte procoagulant activity and plasma levels of several haemostatic markers was studied in a group of haemodialysed patients. RESULTS: Uraemic erythrocytes displayed increased procoagulant activity, which proved to be correlated directly with erythrocyte PS exposure. Pre-incubation of uraemic erythrocytes with annexin V, a protein with high affinity and specificity for PS, strongly inhibited in vitro thrombin generation induced by erythrocytes as compared with untreated red cells. Thrombin generation and activation of fibrinolysis were found to occur in uraemic patients, as substantiated by increased plasma levels of markers for thrombin generation (prothrombin fragment F1.2 and thrombin-antithrombin complex) and fibrinolysis (D-dimer and plasmin-antiplasmin complex), respectively. Significant correlations between prothrombin fragment F1.2 and D-dimer suggested that hyperfibrinolysis was secondary to thrombin generation. Correlations were also found between erythrocyte PS levels and plasma levels of haemostatic markers, including prothrombin fragment F1.2 (P = 0.007), thrombin-antithrombin complex (P = 0.00009), plasmin-antiplasmin complex (P = 0.0009) and D-dimer (P = 0.005). CONCLUSIONS: Our study suggests that increased PS exposure may cause a pathological erythrocyte procoagulant phenotype, which may be a factor inducing a hypercoagulable state in uraemia.
Authors: Natalia Di Pietro; Annalisa Giardinelli; Vittorio Sirolli; Chiara Riganti; Pamela Di Tomo; Elena Gazzano; Sara Di Silvestre; Christina Panknin; Miriam M Cortese-Krott; Csaba Csonka; Malte Kelm; Péter Ferdinandy; Mario Bonomini; Assunta Pandolfi Journal: Mol Cell Biochem Date: 2016-05-20 Impact factor: 3.396