Summary
In the present study, uremic patients on chronic maintenance hemodialysis were treated
with recombinant erythropoietin. Before and after 20 weeks of treatment, platelet
adhesion and aggregation were studied with perfusions over a sprayed collagen surface
and over matrix of cultured endothelial cells with high tissue factor activity. The
influence of the erythropoietin induced raise in hematocrit on platelet transport
and adhesion was excluded by performing the perfusions at a standard red blood cell
concentration. The present study clearly demonstrates that erythropoietin treatment
improves platelet adhesion and aggregation in addition to and independent of its effect
on the hematocrit.
Studies with control platelets resuspended in plasma of untreated patients showed
that a uremic plasma factor reduced adhesion and thrombin- and collagen-dependent
aggregation. Patient platelets resuspended in control plasma showed no defects. After
erythropoietin treatment, the plasma-induced inhibition of adhesion and aggregation
had almost completely disappeared from patient plasma.
The beneficial effect of the erythropoietin treatment on uremic hemostasis is therefore
twofold. The increase of the red blood cell mass improves transport of platelets,
and thus adhesion to the vessel wall. The intrinsic defect due to the presence of
an inhibitory toxin in uremic plasma is, in large part, corrected. Improved neutralization
of uremic toxins by red blood cells or less production of toxins by better oxygenated
tissue might play a role in the observed phenomena.