Recombinant human erythropoietin treatment improves platelet function in uremic patients

Abstract

The effect of recombinant human erythropoietin (rHuEPO) on primary hemostasis was tested in 19 hemodialyzed patients. Bleeding time, platelet aggregation and platelet interaction with vessel subendothelium (SE) under flow conditions were determined before treatment and after patients reached hematocrits greater than or equal to 30%. Two thrombotic events (an acute myocardial infarction and an AV fistula clotting) were recorded during the early stages of treatment. A shortening of average bleeding times (P less than 0.01), an increase in platelet count (P less than 0.01) and an improvement of platelet aggregation (P less than 0.01) and of platelet-SE interaction (P less than 0.01) were observed. A low correlation index was found between hematocrit and bleeding time (r = -0.351, P less than 0.05). To assess a possible effect of rHuEPO on platelet function, the same parameters were evaluated before and after receiving three doses of rHuEPO (40 U/kg i.v. post-hemodialysis) in 14 of the patients. No changes in platelet or erythrocyte counts were observed, the mean bleeding time remained unchanged, but platelet aggregation induced by arachidonic acid (P less than 0.05), ADP (P less than 0.01) and ristocetin (P less than 0.05) improved. Perfusion studies confirmed moderate but significant increases in the parameters that quantify platelet-SE interaction (P less than 0.05). Improvement of ADP-induced aggregation correlated with the increase of platelet adhesion to SE (r = 0.675, P less than 0.05). We conclude that rHuEPO treatment improves primary hemostasis in uremia through an increase of red cell mass but also through a beneficial effect on platelet function, which is independent of the hematocrit rise.

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“…rHuEPO treatment corrects anemia in uremic patients and improves primary hemostasis through the hematocrit rise [6,7]. Although anemia is an important factor, it is not the sole determinant of uremic bleeding because rHuEPO can improve platelet function independently of the effect of rHuEPO on hematocrit [8][9][10][11]. We confirmed an improvement in platelet response to several agonists detected after only three doses of rHuEPO and before any effect on hematocrit was observed.…”

“…The mechanisms of such early improvement of platelet function with rHuEPO are unknown. In a previous report, our group suggested a release to the blood of young platelets, which are metabolically more active, to explain this fact [10]. Young platelets can be identified by their increased ribonucleic acid (RNA) contents [12].…”

“…Recombinant human erythropoietin (rHuEPO) effectively corrects the anemia of uremic patients and improves platelet function ''in vivo,'' mainly through increasing hematocrit and blood viscosity [6,7]. Furthermore, improvement of platelet aggregability has been reported during rHuEPO treatment [7][8][9][10] and amelioration of platelet function has also been observed in the early stages of treatment, when an effect on hematocrit is still not reached [10,11]. The mechanisms of such early improvement of platelet function with rHuEPO are unknown.…”

Effect of erythropoietin use on mean platelet volume in children undergoing chronic dialysis

“…Eritropoezde temel rol oynayan ve kronik böbrek hastalığı (KBH) olan hastalardaki aneminin tedavisinde yaygın kullanılan eritropoetin (EPO)'in önemli bir yan etki olarak trombotik olayları artırdığı bilinmektedir [2,3,4]. EPO'nun pro-trombotik etki mekanizmasının; eritrosit kütle artışı, genç ve büyük trombositlerin kemik iliğinden salınımının artması, endotelial hücre aktivasyonu, tirozin kinaz bağımlı sinyal iletim yolağının aktivasyonu ve trombositlerdeki uyarılmış sitozolik ve bazal kalsiyum seviyelerinin artması ile tetiklendiği düşünülmektedir [5,6,7]. EPO'yla birlikte artan protrombotik etkiler ile kronik hemodiyaliz (HD) hastalarında yüksek oranda greft trombozu gelişmekte ve mortalite artışına katkıda bulunmaktadır [2,3,4].…”

Neurocritical Care for Patients with Kidney Dysfunction

“…Anemia in advanced CKD can further exacerbate platelet dysfunction. Erythropoietin improves platelet function not only by improving blood cell counts, but also has direct effects via increasing the density of GPIIb/IIIa surface receptors and enhancing phosphorylation of platelet proteins [121,122].…”