David P. Tukey

A Hypothesis for the Increased Oxygen Affinity in Haemoglobin Malmö

Haemoglobin Malmöβ97HisGln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxy‐haemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the ‐SH proton of the β93 cysteine and the amide of oxygen of the substituted β97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malmö.

Erythrocyte carnitine: A study of erythrocyte fractions isolated by discontinuous density gradient centrifugation☆

Erythrocyte fractions of varying density were isolated by discontinuous density gradient centrifugation of washed erythrocytes of five subjects (three adults and two cord bloods). Free and total carnitine concentrations were determined in each gradient fraction to compare the carnitine content of less dense with more dense erythrocytes. Erythrocyte, leukocyte, and reticulocyte counts and hemoglobin were measured on all fractions of each gradient. The density gradient studies showed that the highest proportion of reticulocytes were associated with the least dense gradient fractions of all five subjects. Linear regression analyses revealed significant positive correlations (r = 0.94 to 0.99, P less than 0.02 to P less than 0.001) between the number of reticulocytes per fraction and the total or free carnitine concentrations per fraction for all subjects. No correlation was found between free or total carnitine and hemoglobin, number of erythrocytes, or number of leukocytes per fraction. It appears that erythrocyte carnitine is localized in circulating reticulocytes which have mitochondria and carnitine-dependent fatty acid metabolism.

Complex α-thalassemia-like syndrome: A cause of neonatal normoblastemia**

A previously unrecognized hypochromic anemia associated with marked normoblastemia during the newborn period is reported. One male and two female siblings and a first cousin had a hypochromic anemia and marked normoblastemia (300 to 900 normoblast index per 100 white blood cells) at birth. Globin chain synthesis studies on peripheral blood of the proband at birth indicated the presence of α-thalassemia trait with possible reduced γ chain synthesis. Studies of globin chain synthesis on the father, two older affected siblings of the proband, and the proband at 1.5 years of age revealed α-thalassemia trait. The data suggest this complex α-thalassemia-like condition as a new syndrome associated with marked neonatal normoblastemia.

877 FETAL RED CELLS (FC) DIFFER IN ELASTICITY, VISCOSITY, AND ADHESION FROM ADULT RED CELLS (AC)

Blood hyperviscosity occurs in 3-5% of full-term infants, usually accompanies central venous hematocrit (HCT)>65%, but may occur at HCT 60-65%. Small differences in red cell deformability have major influence on blood viscosity at high HCT. We studied the whole cell deformability of washed FC and AC by counting the % cells aspirated more than 10μm into 2μm pore diameter nuclepore filters. FC were more deformable with 88±7% having aspiration length >10μm compared to 19±4% for AC (p<.01). More extensible membranes have lower membrane elasticity (μ in 10-3 dyne/cm); μ was calculated from small nipple extensions into 0.6μm pore diameter nuclepore filters. FC had lower μ than AC (μFC=4.39, μAC=8.06; p<.05). Subpopulations of FC separated by density gradient showed invariant μ with increasing MCHC and decreasing cell volume. Work from a collaborating laboratory (Blackshear et al, 1980 Gotenburg Filtration Symposium) has shown increased membrane viscosity (η) of FC (ηFC=6×10-4; ηAC=3×10-4 poise-cm). More FC were adherent to the filter than AC in the special, purged filter chamber (FC 9.0%, AC 0.3%). The altered whole cell deformability and membrane elasticity of FC would ameliorate the flow retardation influences of FC membrane viscosity and adhesion. Evaluation of these rheological properties in newborn hyperviscosity syndrome may determine who would benefit from phlebotomy.