INVERSE RELATIONSHIPS BETWEEN HEMOGLOBIN AND RISTOCETIN-INDUCED PLATELET-AGGREGATION IN HEMODIALYSIS-PATIENTS UNDER ERYTHROPOIETIN THERAPY

Background. Amelioration of the anaemia of chronic renal failure and s ubsequent improved haemorheology result in correction of bleeding diat hesis as evidenced by shortening of the skin bleeding time (BT). Howev er, the relationship between the haematocrit and platelet-vessel wall interactions in haemodialysis (HD) patients under recombinant human er ythropoietin (rHuEpo) therapy, assessed by platelet aggregation in res ponse to ristocetin is more complex and somewhat inconsistent. Methods . We investigated the relationship between haemoglobin (Hb) levels and whole blood ristocetin-induced platelet aggregation (electric impedan ce method) in 28 HD patients treated with rHuEpo, and with normal BT. The measurements were repeated in 16 subjects after having reduced pla telet aggregability with orally administered ketanserin. Results. Rist ocetin-induced platelet aggregation in the whole group was comparable to those found in 21 age-matched healthy subjects (normals) and in 25 HD patients not treated with rHuEpo (uraemics). Interestingly, a signi ficant inverse correlation between this aggregation and Hb concentrati on was found (r= -0.392, P < 0.05). In the group of 16 patients, the p re-ketanserin aggregation was more intensive than in the normals and u raemics (P < 0.05). Ketanserin produced a fall in ristocetin-induced p latelet aggregation (P < 0.02), prolongation of the BT (P < 0.02) and, unexpectedly, a decrease in serum Epo concentration (P < 0.0002) and the Hb level (P < 0.001). Again, an inverse correlation between depres sed ristocetin-induced platelet aggregation and lowered Hb concentrati on was found(r= -0.590, Pt < 0.02). Moreover, a strong positive correl ation between the extent of pre-ketanserin platelet aggregation and th e decrease in the intensity of this process that followed the trial wa s observed (r=0.919, P < 0.000005). There were no changes in other hae matological parameters or arterial blood pressure. Conclusions. Consid ering the role of von Willebrand factor and fibrinogen in mediating ri stocetin-induced platelet aggregation, and enhanced synthesis and/or r elease of these macromolecules in response to uraemia or inflammation, we suggest that exaggerated whole-blood platelet aggregability to ris tocetin points to blunted erythropoiesis in HD patients on rHuEpo ther apy.