Inverse relationships between haemoglobin and ristocetin-induced platelet aggregation in haemodialysis patients under erythropoietin therapy

BACKGROUND.: Amelioration of the anaemia of chronic renal failure and subsequentimproved haemorheology result in correction of bleeding diathesisas evidenced by shortening of the skin bleeding time (BT). However,the relationship between the haematocrit and platelet-vesselwall interactions in haemodialysis (HD) patients under recombinanthuman erythropoietin (rHuEpo) therapy, assessed by plateletaggregation in response to ristocetin is more complex and somewhatinconsistent. METHODS.: We investigated the relationship between haemoglobin (Hb) levelsand whole blood ristocetininduced platelet aggregation (electricimpedance method) in 28 HD patients treated with rHuEpo, andwith normal BT. The measurements were repeated in 16 subjectsafter having reduced platelet aggregability with orally administeredketanserin. RESULTS.: Ristocetin-induced platelet aggregation in the whole group wascomparable to those found in 21 age-matched healthy subjects(normals) and in 25 HD patients not treated with rHuEpo (uraemics).Interestingly, a significant inverse correlation between thisaggregation and Hb concentration was found (r = –0.392,P<0.05). In the group of 16 patients, the preketanserin aggregationwas more intensive than in the normals and uraemics (P<0.05).Ketanserin produced a fall in ristocetin-induced platelet aggregation(P<0.02), prolongation of the BT (P<0.02) and, unexpectedly,a decrease in serum Epo concentration (P<0.0002) and theHb level (P<0.001). Again, an inverse correlation betweendepressed ristocetin-induced platelet aggregation and loweredHb concentration was found (r= –0.590, P<0.02). Moreover,a strong positive correlation between the extent of preketanserinplatelet aggregation and the decrease in the intensity of thisprocess that followed the trial was observed (r=0.919, P<0.000005).There were no changes in other haematological parameters orarterial blood pressure. CONCLUSIONS.: Considering the role of von Willebrand factor and fibrinogenin mediating ristocetin-induced platelet aggregation, and enhancedsynthesis and/or release of these macromolecules in responseto uraemia or inflammation, we suggest that exaggerated whole-bloodplatelet aggregability to ristocetin points to blunted erythropoiesisin HD patients on rHuEpo therapy.