Red blood cell aggregation changes are depended on its initial value: Effect of long-term drug treatment and short-term cell incubation with drug.

This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group - adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb < 100 g/L). After 4 weeks of pentoxifylline treatment the red cell aggregation increased (p < 0.05) in the patients with initially low RBCA. On the other hand in the patients with initially high RBCA treatment with pentoxifylline reduced it markedly (p < 0.01). In vitro experiments with pentoxifylline RBC incubation resulted in a decrease of the initially high RBCA by 47% (p < 0.01), whereas in the sub-group with initially low RBCA it increased. It was observed that after 4 weeks of epoetin-beta treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p < 0.01). At the same time 25% of the study patients had a significant RBCA increase (p < 0.05) after treatment. The initially low red cell aggregation after incubation with epoetin-beta was markedly increased by 122% (p < 0.05). On the contrary initially high RBCA was reduced by 47% (p < 0.05). When forskolin (10 µM) was added to the RBC suspensions the RBCA was increased in sub-group of subjects with initially low aggregation and it was decreased in sub-group with initially high one. The similar RBCA changes were observed when RBC suspensions were incubated with vinpocetine, calcium ionophore (A23187), Phorbol 12-myristate 13-acetate (PMA) as a protein kinase C (PKC) stimulator. A major finding of this study is that the red cell aggregation effects of some drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism.

Comparative efficiency and hemorheological consequences of hemotransfusion and epoetin therapy in anemic cancer patients.

The aim of our study was to compare hemorheological consequences of hemotransfusion and recombinant human erythropoetin treatment in anemic cancer patients. Forty anemic patients with solid nonmyeloid malignancies were enrolled in this prospective, open-label study. Both prior to and following treatment (epoetin beta, 10,000 units subcutaneously thrice weekly, for four weeks and transfusion of 400 ml of erythrocyte mass) hemorheological measurements including blood and plasma viscosity, hematocrit (Hct), hemoglobin, red blood cell aggregation (RBCA) and deformability were completed. It was found an increase of Hb from 76.07+/-3.68 g/l to 87.86+/-4.26 g/l after the transfusion. It was accompanied by Hct rise by 25% (from 23.67+/-1.85 to 29.50+/-1.96%, p<0.05). Under these conditions the whole blood viscosity (BV) was increased by 19% (p<0.05). Plasma viscosity did not change markedly. Therefore the main cause of the whole blood viscosity rise was an increase of Hct. After erythrocyte mass transfusion there were some increases of red cell deformability and aggregation (by 7%, p>0.05). Under these conditions the Hct/BV ratio as an index of oxygen transport efficiency was changed after transfusion only slightly. While after four weeks of epoetin treatment the hematocrit/viscosity ratio was raised by 14% (p<0.05), in spite of the high blood viscosity. In addition RBCA decreased (p<0.01) and their deformability was increased by 14% (p<0.05). In vitro microrheological data permit to suggest that epoetin has a direct effect on the microrheological properties of red cells due to activation of the cellular signal transduction system including the tyrosine kinases and phosphatases. Thus, Epoetin beta administered s.c. thrice weekly, during four weeks, increased hemoglobin levels, improved hemorheological profile and especially its microrheological part as well as the blood transport capacity in anemic cancer patients who were receiving chemotherapy and its hemorheological effect was more positive than under hemotransfusion.

Hemorheological changes in solid tumor patients after treatment with recombinant erythropoetin.

The subject of this study was the effect of erythropoetin (Epoetin) treatment of anemic patients (n=30) with solid tumors on parameters of hemorheological profile. Both prior to and following Epoetin treatment (10,000 units subcutaneously thrice weekly) for four weeks hemorheological measurements included plasma and red blood cell (RBC) suspension viscosity; high and low shear whole blood viscosity; hematocrit (Hct), hemoglobin, RBC aggregation (RBCA) and deformation. It was found that the patients had reduced Hb up to 92.96+/-2.99 g/l, and the Hct - 28.2%. These parameters were significant increased after four weeks of Epoetin treatment: Hb by 28% (p<0.01) and Hct by 31% (p<0.01). In macrorheological part of the profile, both the high shear blood viscosity, and the low one were increased by 23 and 27% (p<0.05), respectively. These changes were mainly associated with the Hct rise. As for microrheological part of profile after Epoetin treatment, RBCA was decreased by 25% (p<0.05). While the red cell rigidity index (Tk) was lowered only slightly (by 8%). RBC incubation with Epoetin (10.0 I.E./ml) was accompanied by 10% decrease of Tk. It is important to note that before Epoetin treatment incubation with it led to decrease of RBCA by 30% (p<0.05), whereas after four week of the treatment period a 27% (p<0.05) rise of aggregation was found in majority of patients. Thus these results suggest that Epoetin is an effective, safe and convenient therapy for the management of anaemia in patients with cancer. And this drug has a moderate positive hemorheological effect on RBC and on the microrheological properties in particular. These data suggested that Epoetin has an effect on the membrane properties regulating RBC aggregation and deformation and affects by the signal transduction system, including Ca2+-dependant signaling pathway and tyrosine kinase and phosphotase activity change.