Heinz bodies (also referred to as "Heinz-Ehrlich bodies") are inclusions within

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s composed of denatured

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...

. They are not visible with routine blood staining techniques, but can be seen with

supravital staining Supravital staining is a method of staining used in microscopy to examine living cells that have been removed from an organism. It differs from intravital staining, which is done by injecting or otherwise introducing the stain into the body. Thu ...

. The presence of Heinz bodies represents damage to

and is classically observed in

G6PD deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...

, a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

that causes

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...

. In

veterinary medicine Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...

, Heinz bodies may be seen following the consumption of foods containing

thiosulfate Thiosulfate ( IUPAC-recommended spelling; sometimes thiosulphate in British English) is an oxyanion of sulfur with the chemical formula . Thiosulfate also refers to the compounds containing this anion, which are the salts of thiosulfuric acid, ...

and

propylene glycol Propylene glycol (IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. Containing two alcohol groups, it is classed as a diol. It i ...

compounds by cats, dogs and certain primates.

History

They are named after Robert Heinz (1865–1924), a German physician who in 1890 described these inclusions in connection with cases of

Form and appearance

Heinz bodies appear as small round inclusions within the red cell body, though they are not visible when stained with Romanowsky dyes. They are visualized more clearly with supravital staining (e.g., with

new methylene blue is an organic compound of the thiazine class of heterocycles. It is used as a stain and as an antimicrobial agent. It is classified as an azine dye, and the chromophore is a cation, the anion is often unspecified. Applications NMB is a staini ...

crystal violet Crystal violet or gentian violet, also known as methyl violet 10B or hexamethyl pararosaniline chloride, is a triarylmethane dye used as a histological stain and in Gram's method of classifying bacteria. Crystal violet has antibacterial, antif ...

bromocresol green Bromocresol green (BCG) is a dye of the triphenylmethane family (triarylmethane dyes). It belongs to a class of dyes called sulfonephthaleins. It is used as a pH indicator in applications such as growth mediums for microorganisms and titrations. ...

Causes

Heinz bodies are formed by damage to the

component molecules, usually through

oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...

by administered drugs, or from an inherited mutation (i.e. change of an internal amino acid residue). As a result, an electron from the hemoglobin is transferred to an oxygen molecule, which creates a

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS) that can cause severe cell damage leading to premature cell lysis. Damaged cells are cleared by macrophages in the

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, where the precipitate and damaged membrane are removed, leading to characteristic "

bite cells A degmacyte or bite cell is an abnormally shaped mature red blood cell with one or more semicircular portions removed from the cell margin, known as "bites". These "bites" result from the mechanical removal of denatured hemoglobin during splenic f ...

". The denaturing process is irreversible and the continual elimination of damaged cells leads to

Heinz body anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

. There are several pathways leading to the hemoglobin damage. * NADPH deficiency can cause a dysfunction in

glutathione peroxidase Glutathione peroxidase (GPx) () is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid h ...

which is an enzyme that converts

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...

) into water. * G6PD (

glucose-6-phosphate dehydrogenase Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalyzes the chemical reaction : D-glucose 6-phosphate + NADP+ + H2O 6-phospho-D-glucono-1,5-lactone + NADPH + H+ This enzyme participates in the pentose phospha ...

) deficiency exacerbated by administration of oxidant drugs (e.g.,

primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to ''Plasmodium vivax'' and '' Plasmodium ovale'' along with other medications and for prevention if oth ...

, dapsone,

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

) can also result in Heinz bodies. G6PD deficient red cells in combination with high levels of oxidants causes a cross-linking of sulfhydryl groups on globin chains which causes a denaturing and formation of Heinz body precipitates. * Heinz bodies can also be found in

chronic liver disease Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease ...

. *

Alpha-thalassemia Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes '' HBA1'' and '' HBA2''. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule ...

. Normal adult

is composed of two alpha and two beta chains. Alpha thalassemia patients have partial or complete defects in alpha globin production, leading to a relative abundance of beta globin chains in the cell. These excess beta globin chains aggregate to form HbH, which has decreased

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

and precipitates in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

. This is not direct damage to hemoglobin per se, but rather a perturbation in the

quaternary structure Protein quaternary structure is the fourth (and highest) classification level of protein structure. Protein quaternary structure refers to the structure of proteins which are themselves composed of two or more smaller protein chains (also refe ...

of hemoglobin. The presence of Heinz bodies may also be a feature of hyposplenism or

asplenia Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism. ''Functional'' a ...

, when a damaged or absent spleen cannot remove these damaged cells from circulation.

Veterinary

, Heinz bodies are associated with the consumption of paracetamol (acetaminophen), garlic, and

onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onio ...

s by

cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...

s, and various

primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians ( monkeys and apes, the latter including ...

Thiosulfate Thiosulfate ( IUPAC-recommended spelling; sometimes thiosulphate in British English) is an oxyanion of sulfur with the chemical formula . Thiosulfate also refers to the compounds containing this anion, which are the salts of thiosulfuric acid, ...

compounds in the flesh of onions have been identified as the cause.

Propylene glycol Propylene glycol (IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. Containing two alcohol groups, it is classed as a diol. It i ...

was once a common ingredient in soft moist cat food. According to the FDA "It was known for some time that propylene glycol caused Heinz Body formation in the red blood cells of cats (small clumps of proteins seen in the cells when viewed under the microscope), but it could not be shown to cause overt anemia or other clinical effects. However, recent reports in the veterinary literature of scientifically sound studies have shown that propylene glycol reduces the red blood cell survival time, renders red blood cells more susceptible to oxidative damage, and has other adverse effects in cats consuming the substance at levels found in soft-moist food."Heinz Body Anemia in Cats"
Tarigo-Martinie, Jaime and Krimer, Paula (accessed Sept. 2006) In light of this new data, CVM amended the regulations to expressly prohibit the use of propylene glycol in cat foods."

Treatment

There is no specific treatment for Heinz bodies; however, they are important as a diagnostic indicator for the causative conditions listed above.

References

{{Abnormal clinical and laboratory findings for blood Abnormal clinical and laboratory findings for RBCs