A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy.

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.

[The action of the sodium salt of galbanic acid in experimental erythrocyte hyperaggregation]. / Deistvie natrievoi gal'banovoi kisloty pri éksperimental'noi giperagregatsii éritrotsitov.

During in vitro experiments a sodium salt of galbanic acid was shown to prevent the development of erythrocyte hyperaggregation induced by ATP, thrombin, histamine, adrenaline and acetylcholine. In the intact organisms of dogs at preventive intravenous administration of the compound before bloodletting it prevented the development of experimental erythrocyte hyperaggregation and at administration against the background of bloodletting relieved it.

[Clinical results after hemodilution with hydroxyethyl starch in pregnancy]. / Klinische Ergebnisse nach Hämodilution mit Hydroxyäthylstärke in der Schwangerschaft.

Plasma volume contraction in pregnancy is diagnosed by an increase of hematocrit above 38%. Hydroxyethylstarch was administered to 30 patients with hemoconcentration alone, to 36 patients with fetal growth weight retardation and to two patients with pre-eclampsia. In the present study the tolerance and effectiveness of middle molecular hydroxyethylstarch as volume replacement was studied. The data presented a significant decrease in the incidence of small for date babies (from 52% to 34%). In addition to these findings, hematocrit, erythrocyte aggregation and plasma viscosity were decreased and cardiac output was increased. By twenty three women we registered a newborn weight below the 10th percentile according to Hohenauer. The impaired rheological properties of blood in this group were associated with a decrease of cardiac output. We conclude that hydroxyethylstarch is a safe (no maternal-fetal transfer and only a small incidence of starch storage (1.4% of patients) in the placenta) and effective colloid substance for plasma volume expansion in pregnancy.

Effect of intravascular cellular aggregate dissolution in postoperative patients.

It was the purpose of this study to confirm whether the increase in packed cell (PC) viscosity that occurs in humans after elective surgery is accompanied by a decrease in total body O2 consumption as previously noted in animals, and further to define the effect of resolution of intravascular cellular aggregates (ICA) on these parameters. Thirty nine patients were studied. Total body O2 consumption was 76% of normal 6 hours postop, 81% of normal 24 hours postop and 87% of normal 48 hours postop. Twenty four hours after operation PC viscosity and increased markedly. Saline infusion had no significant effect on total body O2 consumption or PC viscosity, either pre- or postop, but WB viscosity decreased linearly in proportion in the drop in hematocrit. Resolution of ICA by dextran-40 infusion was associated with return of total body O2 consumption and PC viscosity to normal; a decrease in WB viscosity was disproportionately greater than would have been seen had the decrease been due solely to the drop in hematocrit. It is concluded that in humans surgical trauma causes an increase in PC viscosity and microcirculatory impairment as evidenced by a decrease in total body O2 consumption. Resolution of ICA by dextran-40 infusion reverses that detrimental changes.

Preliminary report: treatment of the hemolytic-uremic syndrome with aspirin and dipyridamole.

Three children with the hemolytic-uremic syndrome were treated with heparin, aspirin, and dipyridamole. Two of the children had remained profoundly thrombocytopenic in spite of platelet transfusion and heparin therapy. All three patients responded with prompt elevation of their platelet counts and apparent termination of the pathologic consumption of platelets. Our experience suggests not only that primary platelet consumption may play a critical role in the pathogenesis of the HUS, but also that such patients may benefit from therapy with drugs which inhibit platelet function.