Erythropoietin administration increases production and reactivity of platelets in dogs.
Administration of erythropoietin (EPO) to adult dogs resulted in a dramatic increase in the number of thiazole orange-positive (TO+) platelets, also referred to as reticulated platelets. Pre-treatment level of TO+ platelets was 6.2 +/- 0.5% (mean +/- 1 SE: n = 5); following day 5 of treatment with 500 U EPO/kg/day, the percentage of TO+ platelets peaked at 16.8 +/- 2.3% (n = 5; p <0.02). After cessation of the hormone, the number of TO+ platelets fell rapidly to below starting levels. Unexpectedly, there was a significant decline in total platelet count during EPO administration despite an increased level of TO+ platelets. To assess platelet reactivity, total platelets and TO+ platelets from EPO-treated dogs were analyzed for thrombin-responsiveness as quantitated by P-selectin expression on the cell surface; reactivity was expressed as a thrombin EC50, the thrombin concentration required to activate 50% of platelets. Both total and TO+ platelets were hyperreactive during EPO treatment when compared either to pre-treatment values or to control animals. Thrombin EC50 values for total and TO+ platelets on day 5 fell to 66.5 +/- 5.4% (mean +/- 1 SE; n = 5; p <0.02) and 62.2 +/- 8.7% (n = 5; p <0.025), respectively, of pre-treatment levels. These data indicate that EPO not only promotes the synthesis of increased numbers of TO+ platelets in the dog but that these newly produced platelets are hyperreactive when compared to TO+ platelets from control animals.
Wolf
R F
RF
Department of Medicine and W.K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Peng
J
J
Friese
P
P
Gilmore
L S
LS
Burstein
S A
SA
Dale
G L
GL
D000818:Animals; D052160:Benzothiazoles; D001792:Blood Platelets / Q000166:cytology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006410:Hematopoiesis / Q000187:drug effects; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D011804:Quinolines; D012156:Reticulocytes / Q000166:cytology; D013194:Staining and Labeling; D013844:Thiazoles; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D052160:Benzothiazoles; D005456:Fluorescent Dyes; D019007:P-Selectin; D011804:Quinolines; D013844:Thiazoles; C051000:thiazole orange; D004921:Erythropoietin; D013917:Thrombin