Biology Reference
In-Depth Information
sions of the left ventricle in both systole and diastole decrease after rHuEPO
therapy, and cardiac size therefore progressively diminishes [15]. Finally, exer-
cise physiology improves after rHuEPO therapy: exercise capacity, maximum
oxygen consumption, anaerobic threshold, and carbon monoxide transfer fac-
tor have all been shown to increase [12, 17].
Other systems
The list of secondary effects associated with rHuEPO therapy is impressive
(Tab. 2). Studies on the coagulation and hemostatic pathways, prompted by the
early observation of possible increased vascular-access thrombosis with
rHuEPO, have documented a reduction in bleeding time along with improve-
ments in platelet function, both aggregation and adhesion to endothelium [18].
The standard coagulation tests are unaffected by rHuEPO, as are measure-
ments of the coagulation factors. A prothrombotic state may develop, howev-
er, possibly contributed to by increased blood viscosity [19], reductions in pro-
tein C and protein S concentrations [20], and increases in thrombin-antithrom-
bin III levels [21], Factor VIII-related activities [22], and plasminogen activa-
tor inhibitor-1 production after rHuEPO therapy.
The hematocrit is the major determinant of whole blood viscosity, and thus
an rHuEPO-induced increase in red cell mass inevitably causes an increase in
blood viscosity. Furthermore, the relationship between hematocrit and blood
viscosity is exponential, such that a linear increase in the former results in a
disproportionate increase in the latter. Detailed rheological studies have indi-
cated that the increase in blood viscosity occurs solely as a result of the larger
quantity of circulating red cells, without any change in plasma viscosity or the
rheology of the red cells themselves in terms of their deformability or aggre-
gability [19].
Objective assessments of quality of life parameters [23] and of brain and
cognitive function [24, 25] have shown improvements after rHuEPO therapy.
Patients report subjective improvements in memory, concentration, and other
cerebral functions. Electrophysiological studies have shown an increase in
amplitude of the P3 component of the brain event-related potential [24], and
Table 2. Non-cardiovascular effects of recombinant human erythropoietin (rHuEPO) therapy
Improved quality of life
•
Improved brain/cognitive function
•
Decreased uremic bleeding tendency
•
Improved platelet function
•
Improved sexual function
•
Improved endocrine function
•
Enhanced immune function
•
Decreased uremic pruritus
•
