A model of hemopoietic stress in a lactate dehydrogenase mouse mutant with hemolytic anemia

1986 ◽  
Vol 52 (3) ◽  
pp. 179-183 ◽  
Author(s):  
J.-P. Kremer ◽  
T. Datta ◽  
P. D�rmer
2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
W. Barcellini ◽  
B. Fattizzo

Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20–40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans’ syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions.


Author(s):  
Amrapali L. Gaikwad ◽  
D. S. Jadhav

Background: Megaloblastc anemia corresponds to severe macrocytic anemia with hypersegmented neutrophils and very high serum Lactate Dehydrogenase (LDH). The present study was undertaken to evaluate the utility of serum LDH and chloroform inhibited serum LDH in the diagnosis of megaloblastic anemia and to observe if this can be used to differentiate megaloblastic anemia from iron deficiency anemia and hemolytic anemia.Methods: The present study was carried out on 75 patients of anemia categorised on bone marrow examination (into megaloblastic and non-megaloblastic anaemia) to evaluate the efficacy of total serum LDH levels and LDH isoenzyme pattern in the diagnosis of megaloblastic anemia. About 25 healthy adults were taken as controls.Results: In megaloblastic anemia, total serum LDH level was found to be increased to about nineteen folds and in hemolytic anemia it was found to increased four folds as compared to normal. On statistical analysis this increased total serum LDH level in megaloblastic anemia and hemolytic anemia as compared to control group was found to be significant.In the present study serum LDH level above 3000IU/L was associated with megaloblastic anemia and serum LDH level below 900IU/L was suggestive of iron deficiency anemia. The chloroform inhibition test was less than 25% in megaloblastic anemia and more than 25% in hemolytic anemia and these differences were found to be statistically significant (t=9.62, df=49, p<0.001).Conclusions: Total serum LDH levels more than 3000IU/L are diagnostic of megaloblastic anemia. Reversed LDH isoenzyme pattern (LDH1>LDH2) by chloroform inhibition test is an adjuvant in the diagnosis where total serum LDH levels are between 451-3000IU/L and can also differentiate megaloblastic anemia from hemolytic anemia.


2000 ◽  
Vol 74 (13) ◽  
pp. 6045-6049 ◽  
Author(s):  
Mory Meite ◽  
Sabine Léonard ◽  
Mohammed El Azami El Idrissi ◽  
Shozo Izui ◽  
Pierre L. Masson ◽  
...  

ABSTRACT Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases.


Genetics ◽  
1993 ◽  
Vol 135 (1) ◽  
pp. 161-170 ◽  
Author(s):  
W Pretsch ◽  
S Merkle ◽  
J Favor ◽  
T Werner

Abstract A procarbazine hydrochloride-induced mutation at the Ldh-1 structural locus encoding the A subunit of lactate dehydrogenase (LDH) was used to study the molecular and metabolic basis of severe hemolytic anemia due to LDH-A deficiency in the mouse. The mutant allele designated Ldh-1a-m1Neu codes for an enzyme that as homotetramer differs from the wild-type enzyme by a marked instability, acidic shift of the pH profile, increased Km for pyruvate and altered inhibition by high concentrations of this substrate. Except for the latter, all these altered properties of the mutant protein contribute to the diminished LDH activity in heterozygous and homozygous mutant individuals. Impaired energy metabolism of erythrocytes indicated by a relatively low ATP concentration is suggested to result in cell death at the end of the reticulocyte stage leading to the expression of hemolytic anemia with extreme reticulocytosis and hyperbilirubinemia. Despite the severe anemia, affected homozygous mutants exhibit approximately normal body weight and do not show noticeable impairment of viability or fertility. To date no such condition is observed in man. This discrepancy is likely due to the fact that in human erythrocytes both LDH-A and LDH-B subunits are expressed such that homozygotes for a LDH-A or LDH-B deficiency would not result in a comparably extreme LDH activity deficiency.


1975 ◽  
Vol 135 (10) ◽  
pp. 1293-1300 ◽  
Author(s):  
J. V. Dacie

1976 ◽  
Vol 136 (9) ◽  
pp. 1067a-1067
Author(s):  
E. P. Gabor
Keyword(s):  

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  

2006 ◽  
Vol 12 (3) ◽  
pp. 148-151
Author(s):  
Noriko Ihara ◽  
Ikuo Murohashi ◽  
Masako Itho ◽  
Ikuo Amino ◽  
Katsuhiko Yoshida ◽  
...  

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