The effect of erythropoietin on platelet function in uraemic children on haemodialysis.
The effect of 1-year erythropoietin (rHu-EPO) treatment on the bleeding time, platelet aggregation, ATP and thromboxane B2 (TXB2) release, cyclic AMP (cAMP) concentration and platelet surface positive charge were studied in 8 haemodialysed children with chronic uraemia and 8 controls. The pre-dialysis haematocrit (Hct) was 0.21 + 0.01 before and 0.36 + 0.01 following 1 year of rHu-EPO therapy. At the end of this period the pre-dialysis bleeding time became normal (P < 0.05); this was associated with a significant increase in platelet aggregability (P < 0.05), ATP release (P < 0.05) and TXB2 production (P < 0.01), and with a significant decrease in platelet cAMP concentration (P < 0.01). A further increase in platelet aggregation, ATP release and TXB2 production and a decrease in platelet cAMP concentration was observed following bicarbonate haemodialysis (BHD) (P < 0.01). There was a significant positive correlation between platelet aggregation and ATP release (r = 0.78, P < 0.05), as well as platelet aggregation and TXB2 production (r = 0.68, P < 0.05). A significant negative correlation was found between platelet aggregability and cAMP concentration (r = -0.7, P < 0.05). The platelet surface positive charge, which was significantly lower in the patients than in the controls (P < 0.01), did not change during rHu-EPO therapy, nevertheless BHD resulted in a significant increase (P < 0.05), suggesting the surface charge may influence platelet aggregation. In an in vitro and an in vivo study, rHu-EPO and the higher Hct did not increase platelet aggregation directly. Long-term administration of rHu-EPO stimulated complex functional and biochemical changes in the platelets of uraemic patients, which resulted in an improved aggregability.
Turi
S
S
Department of Paediatrics, Albert Szent-Györgyi Medical University, Hungary.
Soos
J
J
Torday
C
C
Bereczki
C
C
Havass
Z
Z
D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D001639:Bicarbonates / Q000627:therapeutic use; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005470:Fluorometry; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000008:administration & dosage; D006435:Renal Dialysis; D013929:Thromboxane B2 / Q000378:metabolism; D014511:Uremia / Q000097:blood / Q000473:pathology / Q000628:therapy*
D001639:Bicarbonates; D011994:Recombinant Proteins; D004921:Erythropoietin; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D000242:Cyclic AMP