Linda Forman

Elevated pyruvate kinase activity in patients with hemolytic anemia due to red cell pyruvate kinase “deficiency”☆

Two patients with non-spherocytic hemolytic anemia were found to have elevated red blood cell pyruvate kinase activities commensurate with the decreased mean red cell age, but the residual pyruvate kinase had marked kinetic abnormalities. Accumulation of metabolic intermediates before pyruvate kinase and reduced levels of activity of the red blood cells of the parents of both patients supported the diagnosis of an inherited abnormal pyruvate kinase causing hemolytic anemia. Although it was observed in two unrelated persons, review of enzyme assays performed on the red blood cells of 651 patients with hereditary non-spherocytic hemolytic anemia suggests that this occurrence is rare.

Glucose-6-phosphate dehydrogenase Durham : A de novo mutation associated with chronic hemolytic anemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect. We report a new variant, G6PD Durham713G, that is associated with chronic nonspherocytic hemolytic anemia. The G6PD Durham713G variant has a unique biochemical and enzymatic profile and a novel A-->G substitution mutation at nucleotide 713, changing lysine to arginine at amino acid 238. This mutation was not found in the mother of our patient, indicating that G6PD Durham713G resulted from a de novo mutation.

Coexistence of α-Thalassemia and a New Pyruvate Kinase Variant: PK Fukien

A 12-year-old male of Chinese ancestry had life-long hemolytic anemia attributed to α -thalassemia. Restriction endonuclease mapping of his DNA revealed that in reality, he had three

Mechanism of improved maintenance of 2,3-diphosphoglycerate in stored blood by the xanthone compound 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C).

The effect of the xanthone derivative 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C) on red cells was studied. When added to stored red cells at a concentration of 6 mM, greatly improved preservation of 2,3-diphosphoglycerate (2,3-DPG) was observed. There was no effect on internal pH of the erythrocyte. At a concentration 0.500 mM, many red cell enzyme activities were inhibited completely. At a 0.500 mM concentration, however, inhibition of pyruvate kinase and diphosphoglycerate phosphatase was most striking. Inhibition of either of these enzymes could result in elevation of 2,3-DPG levels. BW A440C in concentrations which elevated 2,3-DPG levels in humans caused a decrease in 2,3-DPG levels in rabbits and markedly impaired the viability of 21-day stored rabbit erythrocytes.