Red blood cells may contribute to hypercoagulability in uraemia via enhanced surface exposure of phosphatidylserine.
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.
Bonomini
Mario
M
Institute of Nephrology, Department of Medicine, G. d'Annunzio University, Chieti, Italy. m.bonomini@nephro.unich.it
Sirolli
Vittorio
V
Merciaro
Gabriele
G
Antidormi
Teresa
T
Di Liberato
Lorenzo
L
Brummer
Uwe
U
Papponetti
Marco
M
Cappelli
Paolo
P
Di Gregorio
Patrizia
P
Arduini
Arduino
A
D017304:Annexin A5 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000494:pharmacology*; D012016:Reference Values; D006435:Renal Dialysis
D017304:Annexin A5; D015415:Biomarkers; D010718:Phosphatidylserines