Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears
a risk of thrombotic complications. Therefore in the present study an attempt has
been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic
parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8
and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered
with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a
week. Bleeding time was shortened significantly as early as after 1 week of the therapy,
whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout
the study. Only a transient rise in platelet count, collagen-induced platelet aggregation,
beta-thromboglobulin and VIII:C activity were observed during therapy relative to
baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to
be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in
platelet aggregation in response to ristocetin was found, starting from the 2nd week
of the therapy. It lasted throughout the study and correlated inversely with the bleeding
time and positively with a rise in both blood and platelet serotonin. rHuEPO did not
alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein
C activity and euglobulin clot lysis time. A decline in protein C and S concentrations
and antithrombin III activity observed during the therapy were counterbalanced by
a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen
activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall
interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors
of fibrinolysis may be regarded as a protection against a general tendency to thrombosis
during rHuEPO therapy.