A comprehensive study on hemostasis in CAPD patients treated with erythropoietin.
OBJECTIVE
Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin (EPO) may shift the precarious balance of the hemostatic system toward thrombosis. Platelets and tissue factor (TF) play a major role in plug formation. Tissue factor pathway inhibitor (TFPI) appears to play a primary role in regulating TF-induced coagulation. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. The aim of the study was to assess whether 6 months of EPO therapy affects platelet function, that is, platelet aggregation and P-selectin level; moieties of the extrinsic coagulation pathway: TF, TFPI, and TFPI/Xa complexes, and factors VII and X; markers of ongoing coagulation: thrombin-antithrombin complexes (TAT) and prothrombin fragments 1+2; a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes (PAP); fibrinolytic activity: euglobulin clot lysis time (ECLT); and markers of endothelial cell injury: von Willebrand factor, thrombomodulin, E-selectin, and TAFI, in continuous ambulatory peritoneal dialysis (CAPD) patients.


METHODS
22 patients on CAPD were given EPO 6,000 U/week. 12 patients with chronic renal failure and 12 healthy volunteers served as control groups. All parameters were studied before, and after 1, 3, and 6 months of EPO therapy.


METHODS
Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Poland.


RESULTS
Platelet aggregation in whole blood did not change significantly during EPO treatment. A significant rise in arachidonic acid-induced platelet aggregation in platelet-rich plasma was observed after 3 and 6 months, and in collagen-induced platelet aggregation after 6 months of EPO therapy, compared to the baseline values. The TFPI concentration decreased significantly after 6 months of EPO therapy. The activity of factor VII increased transiently after 1 month of EPO therapy, compared to the baseline values. The TAFI concentration and activity in the CAPD group were significantly higher than in the control group. Erythropoietin therapy resulted in a significant decrease in TAFI concentration and activity after 6 months of EPO treatment. The ECLT was shortened significantly as early as after 1 month of EPO therapy. Thrombomodulin, von Willebrand factor concentration and activity, PAP, TAT, TFPI/Xa complexes, prothrombin fragments 1+2, factor X activity, P-selectin, E-selectin, and lipoprotein(a) did not change significantly during EPO treatment.


CONCLUSIONS
Erythropoietin treatment has a minimal effect on hemostasis in CAPD patients. A tendency toward a decline in TAFI is of unknown clinical relevance so far, and awaits further research.
Malyszko
Jolanta
J
Department of Nephrology and Internal Medicine, Bialystok University School of Medicine, Bialystok, Poland. jolmal@poczta.onet.pl
Suchowierska
Ewa
E
Malyszko
Jacek S
JS
Mysliwiec
Michal
M
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000032:analysis* / Q000187:drug effects; D025901:Carboxypeptidase B2 / Q000187:drug effects; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D013997:Time Factors
D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D004921:Erythropoietin; D025901:Carboxypeptidase B2