Erythro-Thrombocytopoiesis in Hemodialysis Patients: Possible Interaction between Thrombopoietin and Erythropoietin? Is there a Role for Arterio-Venous Fistula?

This study was carried out to evaluate the thrombopoietic status of patients with ESRD, to postulate possible causes of altered thrombopoiesis (if any), to verify the clinical significance of endogenous thrombopoietin on both erythropoiesis and thrombopoiesis as well as to assess the contribution of arteriovenous fistula on TPO activity. It included 60 subjects divided into two groups. Group (A) included 40 patients with ESRD on regular hemodialysis three times a week. All included patients had no history of thrombosis (local or systemic, arterial or venous) or a hemorrhagic event within the previous 6 months and they were negative for hepatitis B antigen (HBsAg) and for hepatitis C virus RNA (HCV-RNA) and have normal aminotransferases for the previous 6 months. Patients with a history of malignancy, autoimmune disease, or a documented infection were not included in this study. None of the patients received medication known to interfere with haemostasis (i.e. oral contraceptives, anticoagulants) except for heparin administered during hemodialysis as well as antihypertensives (but not angiotensin-converting enzyme inhibitor or angiotensin II-receptor antagonist) when indicated. Group (A) patients were further subdivided into two subgroups according to their need to rHu-Epo therapy; group (AI) included 19 hemodialysis patients treated with recombinant erythropoietin at a dose of 170±30 U/kg/sc per week, and group (All) included 21 patients treated only with oral iron supplementation. Group (B) included 20 age-and sex-matched healthy as the control group. Both patients and control groups were subjected to the following tests: Complete blood count (including blood smear), BUN, serum creatinine, ALT, AST, serum iron, total iron binding capacity (TIBC), serum ferritin, serum erythropoietin (EPO), serum thrombopoietin (TPO) and absolute reticulated platelets count. Furthermore, serum TPO was measured from both the venous return of the AVF and the contra-lateral peripheral vein in each patient with ESRD. Serum erythropoietin was significantly lower (p 0.01) in HD patients (7.6±0.8) than in the control group (10.1+1.3). Also, serum thrombopoietin was significantly lower (p 0.001) in the HD patients (60.6±6.9) than in the control group (120.7±50.9). Furthermore, the absolute count of reticulated platelets (xl03/cmm) was significantly lower (p 0.01) in the HD patients (9.4±3.7) than in the control group (21.7±4.3). Hemoglobin and hematocrit were slightly higher in Group All (10.2±0.8, 32.7±5.2, respectively) than in group AI (10.1±0.9, 32.5±4.3, respectively). Such difference was not significant. Platelet count (xl03/cmm) was signifi¬cantly higher (p 0.01) in group AI (190±24.6) than in group All (150±30.8). On the other hand, the absolute count of reticulated platelets (xl03/cmm) was lower in group AI (8.8±1.5) than group All (9.3±1.1), and such difference was not significant. Furthermore, serum TPO was significantly higher (p 0.05) in group All (64.7+5.9) than group AI (55.6±6.8). The serum EPO level was significantly higher (p 0.01) in group AI (8.3±1.1) than in group All (6.3±0.7). In hemodialysis patients, comparative studies showed significant positive correlation between s.TPO and hematocrit and retic¬ulated platelet count particularly group All (p 0.02 and p 0.01 respectively). But there was insignificant inverse correlation between s.TPO and platelet count in HD patients. On the other hand, there was significant inverse correlation between s.TPO and endogenous s.EPO in dialysis patients (p 0.01). In HD patients, s.TPO concentrations in AVF samples were significantly lower than in the peripheral veins (60.6±6.9 vs 40.4±3.9, p 0.01). These data confirm the presence of impaired erythro-thrombocytopoiesis in HD patients. This could be partly due to impaired thrombopoietin production and/or increased thrombopoietin destruction and partly due to impaired bone marrow response to the endogenous thrombopoietin. Thrombopoietin appears to induce marrow erythropoiesis either directly or indirectly by augmenting the action of endogenous ery thropoietin. Also, it suggests possible involvement of the arteriovenous fistula in the production and/or catabolism of this growth factor. These findings serve as a starting point for further studies to determine the regulatory mechanisms of TPO levels and its precise erythro- thrombocytopoietic role in end-stage renal disease.