Long-Term Effects of Recombinant Human Erythropoietin on Macro-and Microcirculation in Chronic Hemodialysis Patients

Abstract

Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an increase in systemic vascular resistance and to a decrease in cardiac index and skin microcirculatory flow. Long-term adaptive changes might occur. We studied the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8 normotensive and normovolemic hemodialysis patients before and after, respectively, 4 and 14 months of treatment. The reported macrocirculatory changes at short term were at long term not significantly different as compared with the initial values. The mean arterial pressure remained unaltered, as might be explained by the slow correction of the hematocrit and the decrease in cardiac output in all initially long-lasting normotensive patients who were maintained normovolemic. Left ventricular end-diastolic dimensions decreased, and also the left ventricular muscle mass decreased, depending on the initial left ventricular muscle mass. The skin oxygenation improved, whereas the maximal capillary flow decreased both at short- and long-term ReHuEpo treatment. The number of capillaries in the nail fold remained unchanged. However, the percentage of tortuosity decreased significantly during ReHuEpo therapy.

Effects of Epoetin Alfa on Hemostasis in Chronic Renal Failure

“…Protein S antigen decreased 14 and 45% in two studies [52,53], but was unchanged in a third study [54]. Of the proteins examined, the data on ATIII appear to be the most consistent, with a 9-36% decrease noted in four of seven studies [7,22,40,48], and no change noted in three other studies [17,21,32]. In one of the latter studies, ATIII increased 5% but remained within the normal reference range [17].…”

“…The increase in platelet count was not affected by the rate at which the hemoglobin concentration or hematocrit increased or by the hematocrit achieved. The rates at which the hemoglobin concentration increased ranged from 0.17 to 0.44 g/ dl/week in the studies that reported an increase in the platelet count [14,21] and did not differ from those in which platelet count did not change significantly (range 0.17-0.36 g/dl/week) [26,32]. Similarly, hematocrits of 36 and 37% were achieved in studies in which the platelet counts increased [14] or remained static [23,25], respectively.…”

“…(table 5) The effect of Epoetin alfa on fibrinolysis also is difficult to interpret. Tissue-type plasminogen activator (t-PA) antigen was increased in three studies, varying from 16 to 180% [26,33,55]; however, it was unchanged in two other studies [32,46]. Aunsholt et al [46] reported belownormal t-PA activity in hemodialysis patients, and this was unaffected by Epoetin alfa therapy.…”

“…However, measurements of PT and PTT are not clinically useful for determining hypercoagulable disorders, but rather are better suited for evaluating patients with hemorrhagic diathesis. (table 4) Nine studies, ranging in sample size from 8 to 34 patients, evaluated the effect of Epoetin alfa on the coagulation inhibitors protein C, protein S, ATIII, · 2 -antiplasmin, and · 2 -macroglobulin [7,17,21,22,27,32,40,46,48]. Interpretation of these data is hindered by the variability of the results and the small number of studies.…”

“…For example, protein C antigen was reported to be decreased in two studies [22,32], unchanged in one [21], and increased in another [27], while protein C activity did not change in three [21,22,46] of the five studies in which it was determined [7,21,22,32,46]. Levels of protein C antigen varied, from a 13% increase reported by Takayama [27] to a 42% decrease in another report [22]; protein C activity increased by 35% in one study [7] but decreased by 13% in another [32]. Protein S antigen decreased 14 and 45% in two studies [52,53], but was unchanged in a third study [54].…”