Seizures,
hypertensive encephalopathy,
transient ischemic attacks, and
thrombosis of
hemodialysis accesses occurred in early clinical trials with recombinant human
erythropoietin. To determine if these events may be caused by the increased hematocrit value or some direct effect of the recombinant human
hormone, 10 transfusion-dependent
hemodialysis patients were divided into two groups of five according to their serum
ferritin concentration: group A. less than 800 microgram/liter, and group B. greater than 800 micrograms/liter. After a month of placebo administration, recombinant human
erythropoietin was given (150 U/kg intravenously thrice weekly) for four months and then stopped for one month. Hematocrit values were maintained at 0.33 +/- 0.02 (mean +/- SD) by dose adjustment in group A and at 0.26 +/- 0.02 by thrice weekly phlebotomies in group B, who received a constant dose of
erythropoietin. Viscosity increased from subnormal to normal in group A (P less than 0.02) and cerebral blood flow decreased from above normal to normal (P less than 0.02). In group B minor, statistically insignificant, changes in viscosity and reciprocal changes in cerebral blood flow also occurred. There was no change in either group in transcutaneous
oxygen tension. Bleeding time decreased toward normal in both groups during recombinant human
erythropoietin administration but the changes did not reach statistical significance.
Fibrinogen levels were increased in all patients but remained unchanged. No other significant coagulation-related changes were observed. Recombinant
erythropoietin in the dosage and schedule of administration described in this study did not lead directly or indirectly to changes likely to precipitate
seizures or intravascular
thrombosis.