RECOMBINANT-HUMAN-ERYTHROPOIETIN SHORTENS THE BLEEDING-TIME AND CORRECTS THE ABNORMAL PLATELET-AGGREGATION IN HEMODIALYSIS-PATIENTS

Uremia may be associated with abnormal hemostasis characterized by a p rolonged bleeding time and abnormal in-vitro platelet aggregation. The mechanisms underlying these derangements are not fully elucidated. Th e present study examined the effect of correction of anemia by recombi nant human erythropoietin (r-HuEPO) on these abnormalities in eight di alysis patients. Prior to r-HuEPO therapy the patients had low hematoc rits (Hct) (20%+/-0.7), abnormal bleeding times (23+/-1.2 minutes), an d marked impairment in platelet aggregation induced by adenosine dipho sphate (ADP), epinephrine (Epi), thrombin (Th) and collagen. After cor rection of the anemia to a Hct of 32%+/-0.9 over 5+/-0.9 months, there were a) significant shortening of the bleeding time (from 23+/-1.2 to 10.6+/-2.4 minutes, p <0.01), L) an inverse correlation between the H ct and the bleeding time (r=-0.89, p <0.001) and c) significant improv ement, or normalization of platelet aggregation in response to both co ncentrations of epinephrine [Epi(2)(5.4 x 10(-6) M), 45%+/-10.5 vs 73. 5%+/-7.3, p <0.01, and Epi(l) (5.4 X 10(-5) M), 49%+/-10.6 vs 64%+/-6. 6, p <0.05)], both concentrations of ADP [ADP(C) (2 X 10(-6) M), 31%+/ - 5.9 vs 60%+/-9.3, p <0.05, and ADP(B) (2 x 10-5), 69.5%+/-7.6 vs 99% +/-4.8, p <0.01], and both concentrations of thrombin [Th-C (0.22 u/ml ) 28.6%+/-8.9 vs 80.4%+/-8.3, p <0.01, and TH50/50 (0.44 u/ml), 57.8%/-6.7 vs 83,3%+/-9.2, p <0.01)]. The in-vitro addition of r-HuEPO to p latelets did not affect their aggregability. The data show that the co rrection of the anemia by r-HuEPO reversed not only the prolonged blee ding time but also the abnormality in platelet aggregation.