losartan-potassium and Sickle-Cell-Trait

While the crucial role of haemoglobin in aerobic exercise has been well accepted, there is still a great deal of controversy about the optimal haematological parameters in the athletic population. The initial part of this review will examine the question of anaemia in athletes. The most common finding in athletes is a dilutional pseudoanaemia that is caused by a plasma volume expansion, rather than an actual blood loss. It is not a pathological state and normalises with training cessation in 3 to 5 days. This entity should be distinguished from conditions associated with lowered blood counts, such as intravascular haemolysis or iron deficiency anaemia. The evaluation of true anaemia states in the athlete must take into account not only blood losses secondary to exercise, such as foot strike haemolysis or iron losses through sweat, but non-athletic causes as well. Depending on the age and sex of the athlete, consideration must be given to evaluation of the gastrointestinal or genitourinary systems for blood loss. Finally, a comprehensive nutritional history must be taken, as athletes, especially women, are frequently not consuming adequate dietary iron. The second section of the paper will deal with the very contentious issue of sickle cell trait. While there have been studies demonstrating an increased risk of sudden death in people with sickle cell trait, it is still quite rare and should not be used as a restriction to activity. Further, studies have demonstrated that patients with sickle cell trait have an exercise capacity that is probably normal or near normal. However, in the cases of sudden death, it has been secondary to rhabdomyolysis occurring among sickle cell trait athletes performing at intense exertion under hot conditions, soon after arriving at altitude. The recommendations are that athletes with sickle cell trait adhere to compliance with the general guidelines for fluid replacement and acclimatisation to hot conditions and altitude. The final section of the paper examines the issue of haematological manipulation for the purposes of ergogenic improvement. Although experiments with blood doping revealed improvements in running time to exhaustion and maximal oxygen uptake, the introduction of recombinant erythropoietin has rendered blood doping little more than a historical footnote. However, the improvements in performance are not without risk, and the use of exogenous erythropoietin has the potential for increased viscosity of the blood a

Topics: Adaptation, Physiological; Anemia; Blood Volume; Doping in Sports; Erythropoietin; Hemolysis; Humans; Iron; Iron Deficiencies; Recombinant Proteins; Sickle Cell Trait; Sports; Sports Medicine

We have studied the effects of hydroxyurea on growth and differentiation of early erythroid progenitor cells (BFU-e) from peripheral blood of sickle cell disease patients (five SS and two Hb S/beta-thalassemia) in the presence or absence of exogenous stimulating factors. When the mononuclear cells from the sickle cell disease patients were cultured at diagnosis (before hydroxyurea treatment), there was an increased number of BFU-e in relation to controls (p < 0.05, Wilcoxon test) when cells were grown in the presence or absence of 5637 conditioned medium and erythropoietin. Colonies that developed in the absence of added growth factors were considered "spontaneous". A significant difference was observed after hydroxyurea treatment in the number of BFU-e obtained in the presence and absence of stimulus, with a higher reduction in the spontaneous BFU-e number. As expected, there was an increased Hb F level in these patients when compared with their pretreatment levels. There was no correlation between spontaneous BFU-e and hemoglobin levels in all patients studied.

Topics: Anemia, Sickle Cell; Antisickling Agents; beta-Thalassemia; Blood Cell Count; Cell Differentiation; Cell Division; Cells, Cultured; Culture Media, Conditioned; Erythroid Precursor Cells; Erythropoietin; Heterozygote; Humans; Hydroxyurea; Sickle Cell Trait

Administration of hydroxyurea in sickle cell disease is associated with a dramatic increase of HbF along with a significant clinical improvement and, occasionally, increased total hemoglobin levels. The underlying mechanisms are not yet fully elucidated.. We report the response of three patients with homozygous sickle cell disease and 10 patients with compound HbS/beta-thalassemia (four with beta(o)thal/HbS and six with beta(+)thal/HbS respectively) to hydroxyurea treatment with regards to their serum erythropoietin levels (sEpo).. Baseline sEpo levels varied from 33.0 to 284.0 IU/L and showed a significant negative correlation with the respective Hb values (P<0.007). Two to three weeks after initiation of treatment, the sEpo values started to increase and reached levels three to 31 times higher than the baseline two to three weeks later. Thereafter, in most cases the Epo values decreased and remained at intermediate levels throughout the rest of hydroxyurea administration, while in a few cases, they returned to baseline. An inappropriate increase of sEpo following treatment with various cytostatic drugs, independently of anemia induced by cytostatic agents, has already been reported in the literature. The cytostatics included cyclophosphamide, anthracyclines, cytosine arabinoside etc., but not hydroxyurea. The results described here with hydroxyurea are virtually similar, ie, they show a significant sEpo increase five to ten days post therapy with no apparent cause. Pulses of high dose Epo have been reported to promote proliferation of erythroid precursors with HbF synthesizing capacity.. Our hypothesis is that a similar phenomenon may occur here also, in the sense that peaks of endogenous Epo may promote proliferation of erythroid precursors which maintain the capacity to synthesize HbF.

Topics: Adolescent; Adult; Anemia, Sickle Cell; beta-Thalassemia; Erythroid Precursor Cells; Erythropoietin; Female; Fetal Hemoglobin; Gene Expression Regulation; Humans; Hydroxyurea; Kidney; Liver; Male; Middle Aged; Sickle Cell Trait; Time Factors

The ability of circulating progenitor cells to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin) in 63 patients with sickle cell disease (SCD) (36 homozygotes for hemoglobin [Hb] S, 13 double heterozygotes for Hb S and beta thalassemia, and 14 SC patients) in Southeast Brazil. In the presence of growth factors, SCD patients (all genotypes) presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5 x 10(5) MNC), when compared with control subjects. However, when the progenitor cells were cultured in the absence of added stimulus, high numbers of BFU-E were observed only in the genotypes SS and S/beta thalassemia. SC patients presented a similar response to the control subjects. Moreover, there was an inverse correlation between spontaneous (without stimulus) BFU-E and Hb levels in SCD patients. These results suggest that the formation of spontaneous BFU-E observed in SCD may be due to an expanded erythropoiesis secondary to hemolysis.

Topics: Adult; Anemia, Sickle Cell; beta-Thalassemia; Brazil; Cell Differentiation; Cell Division; Colony-Forming Units Assay; Erythroid Precursor Cells; Erythropoietin; Genotype; Hemoglobin SC Disease; Humans; Recombinant Proteins; Sickle Cell Trait

Topics: Anemia; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Recombinant Proteins; Sickle Cell Trait

The erythropoietin response to anaemia was compared in 30 children with haemolytic anaemia and in 5 children with Fanconi's hypoproliferative anaemia. Serum erythropoietin was measured by radioimmunoassay. In children with haemolytic anaemia the serum erythropoietin concentration increased exponentially with decreasing haematocrit values (r = 0.74; p less than 0.001). Serum erythropoietin levels also correlated with reticulocyte counts (r = 0.62; p less than 0.001). Children with Fanconi's hypoproliferative anaemia had considerably higher serum erythropoietin levels than children with haemolysis for the same degree of anaemia. These data indicate that erythropoietin production in Fanconi's anaemia may be dependent on other factors in addition to the degree of anaemia and relative hypoxaemia.

Topics: Adolescent; Anemia, Aplastic; Anemia, Sickle Cell; Cell Count; Child; Child, Preschool; Erythropoietin; Fanconi Anemia; Female; Hematocrit; Humans; Male; Radioimmunoassay; Reticulocytes; Sickle Cell Trait