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Heinz Body
Definition/Introduction
Heinz bodies, initially known as Heinz-Erlich bodies, were first described by Dr. Robert Heinz in 1890. Heinz bodies are indicative of oxidative injury to the erythrocyte. They are inclusions of irreversibly denatured hemoglobin attached to the erythrocyte cell membrane. Studies have shown that anti-oxidants may reduce Heinz body formation.[1]
Oxidative damage may be incurred by external substances or due to hereditary enzyme or hemoglobin defects.[2][3] More significant oxidative damage is believed to increase Heinz body formation and adhesion to the erythrocyte inner cellular membrane. Heinz bodies decrease the elasticity and the deformability of the erythrocyte, increasing the probability of splenic destruction. Splenic macrophages remove the damaged portions of the erythrocyte membrane, resulting in the formation of bite cells. Bite cells and the resulting spherocytes are at increased risk of extravascular hemolysis, which may lead to oxidant-induced hemolytic anemia.
Heinz body production may also produce reactive oxygen species, which can cause intravascular hemolysis leading to hemoglobinemia and hemoglobinuria. In addition, oxidative stress can result in methemoglobinemia; ferrous iron is oxidized to ferric iron, decreasing the oxygen-carrying capacity of hemoglobin.
Heinz bodies may be small or relatively large and prominent. In some instances, a single erythrocyte may have several small Heinz bodies. Heinz bodies stain the same red-pink color of mature erythrocytes with common Wright stains and are basophilic with Diff-Quik stain. Laboratory stains can create confusion with other inclusion anomalies, including the reticulofilamentous material of reticulocytes, Pappenheimer bodies (basophilic iron deposits), Howell-Jolly bodies (nuclear fragments), and Hemoglobin H inclusions (beta-chain tetrameric precipitates).[4] These otherwise difficult-to-visualize inclusions are readily observable in supravital stains like methylene blue.
On microscopy, Heinz bodies are small, dark, round, basophilic masses. They are typically located near the inner membrane of the red blood cell.[5]
Issues of Concern
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Issues of Concern
Heinz bodies increase the risk of hemolytic anemia, which can present with symptoms including jaundice, dyspnea, tachycardia, hematuria, fatigue, and even hypotension. These symptoms must be recognized as early as possible to limit the severity of the anemia and its related complications.[6][7][8]
Clinical Significance
Heinz body formation, precipitation, and resulting cellular membrane damage is an etiology of hemolytic anemia. In addition, Heinz body hemolytic anemia may be associated with exposure to toxins such as propylene glycol, brassica species, and henna [9].
Cases of Heinz body hemolytic anemia may also result from genetic defects in the molecular milieu that acts to protect erythrocytes from oxidative damage. Heinz bodies may be present in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and those with methemoglobinemia.[10] Heinz bodies may also indicate unstable hemoglobins such as Hb Koeln or Hb Wien; they are evident in the beta-thalassemias.[11][12] Heinz body production is amongst the dysmorphisms brought on by the oxidative stress of COVID infection.[13][14]
Erythrocyte oxidative damage with resulting Heinz body formation can occur in various clinical conditions, especially in patients experiencing diabetic ketoacidosis.[15] Drugs acting as oxidants also cause Heinz body formation; examples include acetaminophen, vitamin K1, propafol, and phenothiazines. Mineral deficiency, for example, selenium, also increases susceptibility to oxidative damage and Heinz body formation.
The presence of Heinz bodies can ultimately result in hemolytic anemia, and the ability to recognize signs and symptoms of hemolytic anemia is the best way to maximize patient-centered care. Although hemolytic anemia is often diagnosed through laboratory assessment, it is crucial to recognize classic signs of anemia: fatigue, dyspnea, pallor, jaundice, and organomegaly. Being well-versed in identifying these clinical presentations maximizes patient safety and quality of care.[16]
There is no treatment for oxidation-induced erythrocyte damage beyond the removal of the offending agent and supportive care. If chronic hemolysis is present, bilirubin gallstones and iron overload may be present; splenectomy is the treatment of choice for some causes of hemolytic anemia.[11] Patients with hemoglobinopathies may benefit from genetic counseling.
Nursing, Allied Health, and Interprofessional Team Monitoring
Because the formation of Heinz bodies may precipitate hemolytic anemia, the patient evaluation must include screening for the pertinent signs and symptoms, including but not limited to fatigue, dyspnea, tachycardia, hypoxia, icterus, jaundice, and organomegaly. Although other signs or symptoms may be present, appropriate laboratory evaluation is critical.[16][17]
References
Palasuwan A, Soogarun S, Lertlum T, Pradniwat P, Wiwanitkit V. Inhibition of Heinz body induction in an in vitro model and total antioxidant activity of medicinal Thai plants. Asian Pacific journal of cancer prevention : APJCP. 2005 Oct-Dec:6(4):458-63 [PubMed PMID: 16435991]
Reinhart WH, Sung LP, Chien S. Quantitative relationship between Heinz body formation and red blood cell deformability. Blood. 1986 Dec:68(6):1376-83 [PubMed PMID: 3779102]
Jacob H, Winterhalter K. Unstable hemoglobins: the role of heme loss in Heinz body formation. Proceedings of the National Academy of Sciences of the United States of America. 1970 Mar:65(3):697-701 [PubMed PMID: 5267148]
Gaur M, Sehgal T. Reticulocyte count: a simple test but tricky interpretation! The Pan African medical journal. 2021:40():3. doi: 10.11604/pamj.2021.40.3.31316. Epub 2021 Sep 2 [PubMed PMID: 34650653]
Christopher MM, White JG, Eaton JW. Erythrocyte pathology and mechanisms of Heinz body-mediated hemolysis in cats. Veterinary pathology. 1990 Sep:27(5):299-310 [PubMed PMID: 2238384]
Level 3 (low-level) evidencePhillips J, Henderson AC. Hemolytic Anemia: Evaluation and Differential Diagnosis. American family physician. 2018 Sep 15:98(6):354-361 [PubMed PMID: 30215915]
Dhaliwal G, Cornett PA, Tierney LM Jr. Hemolytic anemia. American family physician. 2004 Jun 1:69(11):2599-606 [PubMed PMID: 15202694]
Guillaud C, Loustau V, Michel M. Hemolytic anemia in adults: main causes and diagnostic procedures. Expert review of hematology. 2012 Apr:5(2):229-41. doi: 10.1586/ehm.12.3. Epub [PubMed PMID: 22475291]
Khefacha L, Berrayana N, Rouag H, Benhamida H, Sassi M. Henna-induced Heinz bodies in glucose-6-phosphate dehydrogenase-deficient newborn. International journal of laboratory hematology. 2022 Feb:44(1):59-60. doi: 10.1111/ijlh.13713. Epub 2021 Sep 29 [PubMed PMID: 34585532]
Ballin A, Brown EJ, Zipursky A. Idiopathic Heinz body hemolytic anemia in newborn infants. The American journal of pediatric hematology/oncology. 1989 Spring:11(1):3-7 [PubMed PMID: 2712239]
Level 3 (low-level) evidenceHilbert S, Voill-Glaninger A, Höller B, Minkov M. Hemolytic anemia due to the unstable hemoglobin Wien: manifestations and long-term course in the largest pedigree identified to date. Haematologica. 2020 May:105(5):e253-e255. doi: 10.3324/haematol.2019.236562. Epub 2020 Feb 6 [PubMed PMID: 32029504]
Sagar CS, Kumar R, Sharma DC, Kishor P. DNA damage: beta zero versus beta plus thalassemia. Annals of human biology. 2015:42(6):585-8. doi: 10.3109/03014460.2014.990921. Epub 2014 Dec 26 [PubMed PMID: 25541274]
Perrin J, Gérard D. Heinz bodies in COVID-19. International journal of laboratory hematology. 2022 Dec:44(6):1013-1014. doi: 10.1111/ijlh.13926. Epub 2022 Jun 25 [PubMed PMID: 35751427]
Zamd M, Mtioui N, Maoujoud O, Ramdani B. An unorthodox pathophysiology of severe cases of COVID-19 the weak heme hypothesis. American journal of blood research. 2020:10(6):305-310 [PubMed PMID: 33489438]
Level 3 (low-level) evidenceChristopher MM, Broussard JD, Peterson ME. Heinz body formation associated with ketoacidosis in diabetic cats. Journal of veterinary internal medicine. 1995 Jan-Feb:9(1):24-31 [PubMed PMID: 7891359]
Level 3 (low-level) evidenceRuiz EF, Cervantes MA. Diagnostic approach to hemolytic anemias in the adult. Revista brasileira de hematologia e hemoterapia. 2015 Nov-Dec:37(6):423-5. doi: 10.1016/j.bjhh.2015.08.008. Epub 2015 Oct 9 [PubMed PMID: 26670408]
Kim Y, Park J, Kim M. Diagnostic approaches for inherited hemolytic anemia in the genetic era. Blood research. 2017 Jun:52(2):84-94. doi: 10.5045/br.2017.52.2.84. Epub 2017 Jun 22 [PubMed PMID: 28698843]