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The anti‐neoplastic drug 5‐fluorouracil produces echinocytosis and affects blood rheology
Author(s) -
Baerlocher G. M.,
Beer J. H.,
Owen G. Rh.,
Meiselman H. J.,
Reinhart W. H.
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.4003212.x
Subject(s) - fluorouracil , drug , medicine , pharmacology , cancer research , oncology , chemotherapy
The anti‐neoplastic agent 5‐fluorouracil (5‐FU) in high therapeutic doses can induce angina pectoris and myocardial infarction. The pathophysiological mechanism of this side‐effect has not yet been elucidated. We analysed the influence of 5‐FU on blood rheology in vitro . Whole blood, blood cell suspensions and plasma were incubated with increasing concentrations of 5‐FU (final concentrations 0, 0.08, 0.4, 2, 10 and 25 mg/ml 5‐FU) at 37°C. Erythrocyte morphology was analysed after fixation with glutaraldehyde. Viscosity was measured at high and low shear rates (94 and 0.1 s −1 ). Erythrocyte aggregation and the cell transit times of erythrocytes through 5 μm pores and polymorphonuclear leucocytes through 8 μm pores were determined. 5‐FU induced a dose‐dependent formation of echinocytes within minutes and was reversible upon removal of 5‐FU, which reflected a preferential intercalation of the drug in the outer hemileaflet of the cell membrane. High shear blood viscosity was increased at the highest 5‐FU concentration (148 ± 12%), and at low shear rate a dose‐dependent decrease was found (0 mg/ml: 100%, 0.08 mg/ml: 87 ± 10%, 0.4 mg/ml: 80 ± 19%, 2 mg/ml: 70 ± 15%, 10 mg/ml: 40 ± 19%, 25 mg/ml: 33 ± 5%). Erythrocyte aggregation was decreased by the 5‐FU‐induced echinocytosis. The transit time of erythrocytes through narrow pores was increased in a dose‐dependent manner by 5‐FU, whereas the transit time of polymorphonuclear leucocytes was initially decreased at 10 mg/ml and returned to control after 60 min incubation. We conclude that 5‐FU interacts with the cell membrane, induces echinocytosis and vesiculation and affects blood rheology in several ways which may contribute to cardiovascular complications.