Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients.
An increased incidence of fistula thrombosis has been reported in haemodialysis patients treated with recombinant human erythropoietin (rHuEpo). The present study sought to investigate this problem by measuring fistula blood flow, blood viscosity, and a variety of tests of coagulation and haemostasis in a group of ten haemodialysis patients treated with rHuEpo. Fistula blood flow did not alter during the first 12 months of rHuEpo despite a significant increase in whole-blood viscosity. Bleeding time improved in all ten patients after 4 months of therapy, and this improvement was maintained at 12 months. There were no significant changes in one-stage prothrombin time, kaolin cephalin clotting time, whole-blood clotting time, prothrombin consumption index, plasma fibrinogen factor VII, factor VIII, antithrombin III, or platelet aggregability to ADP over the first 4 months of rHuEpo. In contrast, protein C decreased from 84.3 to 66.4% (P less than 0.01) and protein S from 124.1 to 68.3% (P less than 0.001) over the first 4 months. By 8 and 12 months, the concentrations of these substances had returned to pretreatment values. The levels of protein C and S attained at 4 months are known to predispose to thrombosis, and it is possible that this effect may contribute to the increased incidence of fistula thrombosis observed in haemodialysis patients treated with rHuEpo.
Macdougall
I C
IC
Institute of Nephrology, University of Wales College of Medicine, Cardiff Royal Infirmary, UK.
Davies
M E
ME
Hallett
I
I
Cochlin
D L
DL
Hutton
R D
RD
Coles
G A
GA
Williams
J D
JD
D000328:Adult; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D017293:Protein S; D006435:Renal Dialysis / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology
D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D004921:Erythropoietin