Erythropoetintherapie während häufiger Blutspenden Eine Dosisfindungsstudie

Zusammenfassung

Tierexperimentell und in ersten klinischen Studien konnte die Effektivität von rekombinantem humanen Erythropoetin (rHuEPO) bei Patienten, die präoperativ Eigenblut spenden, dokumentiert werden. In einer kontrollierten, multizentrischen und randomisierten Studie erhielten 49 Patienten, die vor orthopädischen oder gefäßchirurgischen Eingriffen einmal wöchentlich Eigenblut (je 450 ml) spendeten, 0 (n=9), 200 (n=10), 300 (n=11), 400 (n=10) oder 500 (n=9) U/kg rHuEPO subkutan zweimal wöchentlich sowie 2·100 mg Eisensulfat p.o. täglich. Nur in der Kontrollgruppe kam es zu einem signifikanten (ANOVA) Abfall der Hämatokritwerte. In der 400 und 500 U/kg Gruppe waren die Hämatokrit- und Hämoglobinwerte bei Studienende signifikant besser als in der Kontrollgruppe (s. Tabelle 9). Zusammenfassend kann gefolgert werden, daß die Therapie mit rHuEPO während häufiger Blutspenden dosisabhängig zu einer signifikanten Abschwächung der Verminderung der Hämoglobin- und Hämatokritwerte führt. Unerwünschte Nebenwirkungen wurden nicht beobachtet.

Abstract

Avoidance of homologous blood products and patients' demand for preoperative autologous blood donation programs are increasing. As many of these patients are older, with a compromised cardiovascular system and a slow response of the erythropoietic system when anemia occurs, the feasibility and benefit of autologous blood donation is often limited. Augmentation of preoperative blood donation by therapy with recombinant human erythropoietin (rHuEPO) has been described in animal models and in patients.

Methods. In a multicenter, controlled, randomized trial, 49 patients scheduled for orthopaedic or vascular surgery received 0 (control group, n=9), 200 (n=10), 300 (n=11), 400 (n=10) or 500 (n=9) U/kg rHuEPO (Erypo, Cilag, Sulzbach, distributor Fresenius, Oberursel, Germany) subcutaneously twice a week for 3 weeks while every week 450 ml blood was collected. Iron sulphate 100 mg was prescribed orally twice a day. Patients were ineligible if they had uncontrolled hypertension, recent myocardial infarction, haematological disorders or a history of seizures. Blood donation had to be cancelled if the haematocrit was below 30%.

Results. There was a significant (ANOVA) drop of the haematocrit value only in the control group, and end-point values for haematocrit and haemoglobin were significantly elevated in the 400 and 500 U/kg groups compared with the control group (Table 9).

Discussion. The erythropoietic stimulus of phlebotomy for autologous blood donations is often not efficient enough to guarantee a constant haematocrit. Lowering of the preoperative haematocrit jeopardizes the aim of avoidance of homologous blood transfusions. rHuEPO increased the efficiency of autologous blood collections, as predonation haematocrit values could be preserved in the high-dosage groups. As a consequence, homologous transfusions could be avoided. However, there were broad interindividual differences in the erythropoietic response, possibly due to limitations in iron availability. Adverse effects of rHuEPO therapy, such as hypertension, thrombosis or neurologic disorders, are mostly reported in patients with terminal kidney failure. No such disturbances were observed in the present study.

Conclusion. rHuEPO ameliorates the preoperative decrease of haemoglobin and haematocrit values due to autologous blood donations in a dose-related fashion. The individually adjusted dosage of rHuEPO and iron supplementation merits further investigation.