Heinz body hemolytic anemia

Petry H (1966) Uhrglasnagel und Trommelschlegelfinger bei Asbestose. Int Arch Geweberpath, Gewerberghyg 22 55-59 Pinkus J, Djadetti M, Joshua H, et al. (1963) Sulfhemoglobinemia and acute hemolytic anemia with Heinz bodies following... 

May precipitate a Heinz body hemolytic anemia or methemoglobinemia... 

Regarding its effect on hemolysis and formation of Heinz bodies, methemaglobinemia, and hemolytic anemia, it is likely that either additive or S5mergistic interaction would occur with other oxidants, such as aniline and acrolein, which are known to inhibit G6PD. 

No biomarkers of effects caused by cresols have been identified in humans or animals. It may be possible to use methemoglobinemia and Heinz body formation, which precede hemolytic anemia in humans (Chan et al. 1971 Cote et al. 1984), as biomarkers for the hemolytic effects of cresols, although these changes may be too general and occur at too high doses to be useful for this purpose. 

No biomarkers of effect have been identified for cresols. Studies designed to investigate subtle effects might discern these biomarkers, which would enable finer delineation of the dose-response relationship for an effect and allow better estimation of the levels of cresols to which people could be exposed without risk. Case reports in humans have reported methemoglobinemia and Heinz body formation that may be predictive of hemolytic anemia (Chan et al. 1971 Cote et al. 1984). 

The presence of precipitates of oxidized, denatured hemoglobin (Heinz bodies) helps distinguish the hemolytic anemia caused by of G6PD deficiency from that caused by pyruvate kinase deficiency. 

Fia. 11. Scheme of the pathogenesis of congenital Heinz body hemolytic anemia. From (J4), H. S. Jacob, Seminars in Hematology 341 (1970), with permission of the author and publisher. 

Sabine, represent spontaneous mutations. The effect of the substitution can be extremely mild (Hb-Richmond, Hb-I-Toulouse) to severe (Hb-Bibba, Hb-Hammersmith). Subjects with Hb-Zurich are asymptomatic unless exposed to oxidant drugs causing an acute hemolytic episode with formation of Heinz bodies. Particularly severe is the lesion in Hb-Hammersmith because the removal of phenylalanine GDI is accompanied by the introduction of the polar OH group of serine which probably facilitates the entry of water into the heme pocket which causes the heme group to drop out (P14). Substitution of this phenylalanine by leucine, as in Hb-Louisville, results in a much less severe anemia (K9). 

Significant neonatal morbidity can occur after transabdominal infusion of methylthioninium chloride to diagnose premature rupture of fetal membranes, to stain the amniotic fluid in twin pregnancies, or after postpartum administration of methylthioninium chloride. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possible desquamation of the skin. In most cases it appears that toxicity was the result of an overdose of methylthioninium chloride (6-9). 

Shis MR, Zinkham WH. Methylene blue-induced Heinz body hemolytic anemia. Arch Pediatr Adolesc Med 1994 148(3) 306-10. 

Kirsch IR, Cohen HJ. Heinz body hemolytic anemia from the use of methylene blue in neonates. J Pediatr 1980 96(2) 276-8. 

Chronic megadoses of vitamin C may precipitate formation of calcium oxalate renal stones, oxalate nephropathy, and renal failure. The amount required to cause this is variable from 2 to 8gday . Bone oxalate deposits have also been reported. Esophageal and dental erosion are possible with tablet ingestion. Heinz body hemolytic anemia has been seen in premature infants. 

Hydroxylamine acts as a reducing agent when absorbed systemically, producing methemoglobin and the formulation of Heinz bodies in the blood. It can induce hemolytic anemia. It inhibits platelet aggregation and is a nitric oxide vasodilator. Oxy-Imines such as hydroxylamine and methoxylamine disturb DNA replication and act as potent mutagens, causing nucleotide transition from one purine to another or one pyrimidine to another. 

The use of high doses of naturally occurring vitamin K (Kj and K2) appears to have no untoward effect however, menadione (K3) treatment can lead to the formation of erythrocyte cytoplasmic inclusions known as Heinz bodies and hemolytic anemia. With severe hemolysis, increased bilirubin formation and undeveloped capacity for its conjugation may produce kernicterus in the newborn. 

Oxidative damage to hemoglobin may lead to its precipitation (e.g., by acetaminophen) and present as Heinz bodies that can be detected by morphological evaluation of blood smears. Heinz body is a rounded, often retractile, projection from the surface of the RBC that is due to oxidation and denatur-ation of hemoglobin. Typically, the detection of Heinz bodies associated with hemolytic anemia is believed to be indicative of nonimmune-mediated anemia. In contrast, supportive evidence of the involvement of immune system components in anemic animals could include a positive autoagglutination of blood cells. 

Ohno H,Tojo H, Kakihata K, Nomura M,Takayama S. Heinz body hemolytic anemia induced by DQ-2511, a new anti-ulcer drug, in dogs. Fundam Appl Toxicol 1993 20(2) 141-146. 

I. Mechanism of toxicity. Toxic effects ate caused by the P 50 metabolites and include methemoglobinemia, sulfhemoglobinemia, and Heinz-body hemolytic anemia—all of which decrease the oxygen-carrying capacity of the blood. 

Cfinkal ns are typical of acute hemolytic disease depression, icterus, anemia, hemr oUnemia, arxl hemoglobinuria. Polypnea and tachycardia may result from severe anemia, and cyanosb may also be present CO Laboratory dagnosis of Uood reveals a low pa ed cell volume (PCV), mild methemoglobinemia, Heinz bodies, hyperbilirubinemia, and. sometimes, increased creatine phosphokinase. 

Some 56 hemoglobin variants are known which denature and precipitate within the red blood cell, forming a so-called Heinz body. There is an associated hemolytic anemia of varying severity, which is termed congenital Heinz body hemolytic anemia (Bunn et al., 1977). Examination of the structures of the abnormal hemoglobins suggests that instability can be attributed to five mechanisms (Perutz and Lehmann, 1968 Morimoto et al., 1971). There may be (1) amino acid substitution in the vicinity of the heme pocket (2) disruption of secondary structure (3) substitution in the interior of the subunit (4) amino acid deletions and (5) elongation of the subunit. 

Bunn, H. F., Forget, B. G., and Ranney, H. M. 1977, Unstable hemoglobin variants— congenital Heinz body hemolytic anemia, in Human Hemoglobins pp. 282-311, W. B. Saunders, Philadelphia. 

Jacob, H. S., Brain, M. C., and Dacie, J. V., 1968a, Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital Heinz body hemolytic anemia, /. Clin. Invest. 47 2664. 

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