ERYTHROPOIETIN POTENTIATES THROMBUS DEVELOPMENT IN A CANINE ARTERIOVENOUS SHUNT MODEL

Erythropoietin (EPO) has been previously shown to affect platelet as w ell as red cell production. In addition, recent studies demonstrated t hat platelets from EPO-treated dogs are hyperreactive towards thrombin when compared to age-matched, control platelets. This report extends these observations by quantitating the thrombogenic potential of EPO i n dogs. Dogs with arterio-venous (A-V) shunts received 100 U EPO/kg/da y for 6 days, and thrombogenicity was serially monitored by insertion of a thrombotic surface into the A-V shunt. The resulting experimental thrombi were analyzed for platelet and erythrocyte content after form alin-fixation and chymotrypsin digestion, a technique which allows non -isotopic quantitation of cellular components. By day 5 of EPO-adminis tration all animals demonstrated a significant increase in platelet an d red cell content of the experimental thrombi; the average increase i n platelet number was 2.94 +/- 0.12 fold (mean +/- 1 SE; n = 3; p = 0. 006) above baseline while that for red cells was 2.46 +/- 0.18 fold ab ove baseline (p = 0.023). After cessation of EPO, thrombogenicity retu rned to normal. During EPO-treatment, the percentage of thiazole orang e-positive (TO+) platelets increased significantly to 17.2 +/- 1.68 (m ean +/- 1 SE; n = 3) on day 5 compared to a pre-treatment level of 8.5 +/- 0.9% (p = 0.029). Although the percentage of TO+ erythrocytes als o increased during the short course of EPO administration, the change was not significant. Despite the increases in TO+ Cells, total platele t and erythrocyte counts did not change significantly within the time frame of these experiments. Fibrin/fibrinogen content of the experimen tal thrombi was unaltered with EPO-treatment. These data demonstrate t hat human EPO is pro-thrombotic in dogs and, in conjunction with earli er studies, suggest that hyperreactive platelets may be responsible fo r the potentiated thrombogenicity.