Congenital Non-spherocytic Haemolytic Anaemia Variants with Primary and Secondary Pyruvate Kinase Deficiency

The patterns of survival of isotope-labelled erythrocytes were examined in patients suffering from two variants of congenital non-spherocytic haemolytic anaemia with decreased erythrocyte pyruvate kinase (PK) activity. In one variant, with primary PK defect (PPKD) random destruction of erythrocytes was predominant in the process of haemolysis. In the second variant, with primary magnesium activated adenosine triphosphatase (ATP-ase) (Mg++) deficiency and a secondary decrease in PK activity, erythrocytes were destroyed by senescence. Two subpopulations of labelled erythrocytes with different destruction rates were observed in all patients examined, except one with the second variant, with very mild haemolysis. Splenectomy, performed on two patient, was successful only in the variant with PPKD.     

Chronic Haemolytic Anaemia in Two Patients Heterozygous for Erythrocyte Pyruvate Kinase Deficiency

Two patients with mild chronic haemolytic anaemia, a mother and her son, were found to be heterozygous for erythrocyte pyruvate kinase deficiency. In the red blood cells the enzymatic activity was reduced by about 50 % and the residual PK had normal kinetic properties, stability and electrofocusing pattern. The PK antigen concentration was also decreased by half, so that the ratio of the enzymatic activity to the immunological reactivity (i.e. the molecular specific activity) was normal. In the son's liver PK enzymatic activity was slightly reduced and, above all, an abnormal active form, more anodic than normal PK, was detected by electrofocusing. The propositus's liver PK was also slightly thermo-unstable. It is suggested that the patients were heterozygous for an unstable PK variant which is found in liver, nucleated tissue actively synthesizing proteins, but which disappeared from the erythrocytes because of its unstability.     

Haemolytic Anaemia with Hereditary Pyruvate Kinase Instability Developing Acute Leukaemia

The case of a 27-year-old woman with pancytopenia, revealing acute monocytic leukaemia and haemolytic anaemia, is described in detail. The underlying cause for the red cell destruction was found to be a pyruvate kinase (PK) instability. Further investigation into three generations of her family (n = 12) disclosed a hereditary PK instability. This was proven by performing biochemical studies to elucidate mutants representing a structurally defective enzyme. Since conversions of pancytopenia with acquired red cell enzyme deficiency into leukaemia have been described, our observation emphasizes that hereditary red cell enzymopathy might also be associated with adult acute leukaemia.     

Erythrocyte Populations in Pyruvate Kinase Deficiency Anaemia Following Splenectomy

S ummary . Light and scanning electron microscopic examination of fresh erythrocytes from the blood of four patients splenectomized for severe pyruvate kinase (PK) deficiency haemolytic anaemia has revealed three morphologically different cell populations. Most striking in these patients was the presence of crenated red cells (30–50% of total) which fit current criteria for definition as cchinocytes, but also with unusual surface retraction compatible with the existence of intracellular shrinkage, a phenomenon known to occur after incubation of PK deficient red cells in vitro. Additional cell types include immature reticulocytes (7–8% of total) and thin macrocytic discocytes (45–65% of total) none of which are considered specific for the disease. These morphological findings are in sharp contrast with the paucity of red cell shape abnormalities usually described in PK deficient patients before splenectomy and may provide insight into the mechanisms leading to accelerated erythrocyte destruction in this disease.     

Simultaneous Inheritance of Mutant Isoenzymes of Erythrocyte Pyruvate Kinase Associated with Chronic Haemolytic Anaemia

SUMMARY The heterogeneity of pyruvate kinase (PK) deficiency associated with hereditary haemolytic anaemia is emphasized by studies of a kindred harbouring two distinct mutant forms of this enzyme, both of which were kinetically defective with markedly decreased affinities for the substrate, phosphoenolpyruvate. The two isoenzymes, designated PK-Vancouver₁ and PK-Vancouver₂, were primarily distinguishable from one another by differences in maximum in vitro activities and by variations in response to fructose-1,6-diphosphate activation. When combined in proband erythrocytes to the exclusion of any normal PK, the isoenzymes were associated with a severe chronic haemolytic process with many of the features of PK deficiency of the more common quantitative type. Clinical laboratory screening tests for detecting PK deficiency may be falsely negative or equivocal in such cases.     

Congenital Stomatocytosis and Chronic Haemolytic Anaemia

A new case of congenital stomatocytosis associated with haemolytic anaemia, increased autohaemolysis, abnormalities in the erythrocyte metabolism, increased osmotic fragility and shortened erythrocyte survival is described. Intracellular cation concentrations are abnormal: Red cell sodium is high, and potassium is low. The pump rate for monovalent cations is increased.     

A Congenital Haemolytic Anaemia with Thermal Sensitivity of the Erythrocyte Membrane

Microspherocytes, measuring 2-3 mum in diameter, and cells with blunted projections or triangular in shape characterized the erythrocoyte morphology in three children with congenital haemolytic anaemia. Since the erythrocyte morphology resembled that associated with thermal injury, heat-induced changes in erythrocyte morphology and membrane composition were studied. Erythrocytes developed filaments and spheroid bodies which fragmented, resulting in microspherocyte transformation. Normal cells required exposure to 49 degrees C, whereas the patients' cells fragmented at 45 degrees C. Fragmentation was also observed during incubation of patients' cells at 37 degrees C for 17h. The heat-induced transformation of the patients' cells was associated with an increase in the membrane cholesterol:phospholipid and cholesterol:protein ratios. The phospholipid:protein ratio was unchanged. This suggests that fragmentation produces a selective loss of membrane components. Splenectomy ameliorated the haemolytic process. We propose that the patients' red-cell morphology is the result of in vivo fragmentation, and that the spleen is the major site of microspherocyte and poikilocyte destruction.     

A Case of Haemolytic Anaemia due to Phenacetin Allergy

A case of haemolytic anaemia due to phenacetin allergy is described, with an account of the serological investigation of the antibody and the allergen.

Résumé

Les auteurs décrivent un cas d'anémie hémolytique due à une allergie à la phénacétine et font un compte rendu sur les investigations sérologiques de l'anticorps et de l'allergène.

Zusammenfassung

Es wird ein Fall von Phenacetinallergie beschrieben, wobei die Ereignisse der Untersuchungen des Antikürpers und des Allergens ausführlich dargelegt werden.     

A New Variant of Glucosephosphate Isomerase Deficiency with Mild Haemolytic Anaemia (GPI-MYTHO)

A new case of glucosephosphate isomerase deficiency with mild haemolytic anaemia was observed in a 6-year-old girl. Deficient enzyme was characterized by a profoundly decreased activity in the red cells, a normal electrophoretic phenotype, normal isoelectric point, normal optimum pH, a molecular instability and a clearly decreased Michaelis constant for fructose-6-phosphate. Propositus was double heterozygote for a ‘silent gene’ inherited from the mother and an abnormal enzyme from the father. Because this abnormal enzyme has undescribed characteristics, it responds to a new variant for which we propose the name GPI-MYTHO.     

Non-spherocytic Haemolytic Anaemia in Mother and Son Associated with Hexokinase Deficiency

The case history, laboratory findings and properties of the enzyme in a patient with hexokinase deficiency are reported. The mother had a haemolytic disorder of similar severity. In these cases the expression of the disease in both mother and son suggests a dominant mode of inheritance. This family further illustrates the necessity of taking the reticulocyte level into account when interpreting red cell enzyme levels.     

Decreased Deformability of Erythrocytes in Haemolytic Anaemia Associated with Glucosephosphate Isomerase Deficiency

Deformability of erythrocytes from four patients with different types of glucosephosphate isomerase (D-glucose-6-phosphate ketoisomerase, GPI) deficiency has been determined by cell filtration. Young as well as whole erythrocyte populations had a markedly increased rigidity and an abnormally strong attachment of haemoglobin to the inner surface of isolated membranes. Acidic environment may enhance membran rigidity in vitro and also during passage of the erythrocytes through the spleen. The decrease of deformability at a pH of 6.8 was most pronounced in the splenectomized patients, and likewise in erythrocytes from the splenic artery, which were obtained from one patient during splenectomy. It is suggested that the metabolic environment of the spleen, with its low pH, impairs the deformability of GPI-deficient erythrocytes and predisposes them to splenic sequestration. The clinical improvement of all patients following splenectomy which is accompanied by an increase of the erythrocyte survival time and by unchanged reticulocyte counts, is in accordance with this view.     

Atypical Intraerythrocytic Pyruvate Kinase in some Haematological Diseases

An atypical pyruvate kinase (PK) in erythrocytes was studied in a family with several different haematological diseases: non-spherocytic haemolysis, thrombocytopenia, myelofibrosis and polycythaemic traits. Atypical intraerythrocytic PK was also found in a group of non-related patients with myelofibrosis and polycythaemia vera. The atypical PK was characterised by abnormal urea inhibition and other relevant biochemical parameters.     

Haemolytic Anaemia of Pregnancy

Haemolytic anaemia apparently induced by pregnancy is reported in an otherwise healthy woman, with a negative family history. Folate deficiency, haemoglobino-pathies, enzymopathies, hereditary spherocytosis, paroxysmal nocturnal haemoglobin-uria, interstitial haematomata, hypertensive toxaemia, auto-immunity and infections were excluded. The autohaemolysis test showed increased lysis in the presence of added glucose. This abnormality was corrected by insulin when excess glucose was present, but not by insulin alone. It is suggested that this patient's erythrocytes may have been altered by placental lactogen and/or prolactin in such a way as to make them abnormally dependent on insulin for the uptake of glucose.     

Penicillin-Induced Haemolytic Anaemia Associated with Microangiopathy

Summary: Penicillin-induced haemolytic anaemia associated with microangiopathy. A. J. McPherson, J. D. Parkin and R. Hope, Aust N.Z. J. Med. , 1976, 6 , pp. 152–155.
The development of a penicillin-induced haemolytic anaemia was studied in a patient with microangiopathy following an average daily dose of five million units of penicillin G (total dose 46 million units). It has been proposed that the combination of the benzylpenicilloyl hapten with exposed or altered erythrocyte antigens, induces an autoimmune response. In this particular case, it is suggested that erythrocyte membrane damage has predisposed to immune drug-mediated red cell damage.