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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2983-2989
Effects of erythropoietin on platelet reactivity and
thrombopoiesis in humans
Petra Jilma Stohlawetz,
Larisa Dzirlo,
Nicole Hergovich,
Edith Lackner,
Christa Mensik,
Hans Georg Eichler,
Eva Kabrna,
Klaus Geissler, and
Bernd Jilma
From the Department of Clinical Pharmacology-The Adhesion Research
Group Elaborating Therapeutics (TARGET); Blood Group Serology and
Transfusion Medicine, Division of Transfusion Medicine; and Department
of Internal Medicine I, Division of Hematology, Vienna University
School of Medicine, Vienna, Austria.
A recent study in dogs suggested that erythropoietin (EPO) not only
promotes the synthesis of increased numbers of reticulated platelets
but that these newly produced platelets are hyperreactive compared with controls. Because of the increasing
use of EPO in the perioperative setting, we characterized the
effects of EPO on platelet reactivity in healthy human volunteers. In a
randomized, controlled trial, we studied the effects of EPO on platelet
reactivity, thrombopoiesis, and endothelial activation in circumstances
similar to those of autologous blood donation. Thirty healthy
male volunteers received placebo or EPO (100 or 500 U/kg of body weight
given intravenously) three times a week for 2 weeks and underwent
phlebotomy on days 8 and 15. Thrombin receptor-activating peptide
induced expression of P-selectin, and CD63 increased 2- to 3-fold
during EPO treatment. The enhanced platelet reactivity was also
reflected by a 50% increase in soluble P-selectin in plasma. Plasma
E-selectin levels increased in a dose-dependent fashion by more than
100% during EPO treatment, indicating substantial activation of
endothelial cells. A 10% to 20% increase in platelet counts was
observed in both EPO groups on day 5. In the placebo group, platelets
increased only several days after the first phlebotomy. The increase in platelet counts was not reflected by changes in the amounts
of reticulated platelets or circulating progenitor cells.
In summary, we found that EPO markedly enhances endothelial activation
and platelet reactivity, which may adversely affect patients at
cardiovascular risk. However, the increased platelet reactivity could
be exploited in patients with platelet dysfunction.
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