Heinz body hemolytic anemia

V Padma; Abhilash B Nair; S Sarath Bhaskar

doi:10.4103/joah.joah_163_20

CASE REPORT

Year : 2022 | Volume : 13 | Issue : 2 | Page : 103-106

Heinz body hemolytic anemia

V Padma¹, Abhilash B Nair¹, S Sarath Bhaskar²
¹ Department of General Medicine, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India
² Junior Resident, Sree Balaji Medical College Hospital, Chrompet, Chennai, Tamil Nadu, India

Date of Submission	07-Sep-2020
Date of Decision	20-Oct-2020
Date of Acceptance	14-Nov-2020
Date of Web Publication	04-Aug-2022

Correspondence Address:
Dr. V Padma
No 49, Mahalakshmi Street, East Tambaram, Chennai - 600 059, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/joah.joah_163_20

Abstract

Anemia is a common finding in our population. Females are highly predisposed to develop anemia. Evaluation of anemia due to a single cause may be straightforward in most of the situations, however rare causes cannot be ruled out. In this case report, we present to you a case of a 35-year-old female who came with complaints of breathlessness. On further evaluation, she had pallor, icterus, and mild splenomegaly. Her hemoglobin (Hb) was later found to be 8.1 g/dl, pyruvate kinase activity was normal, normal liver enzymes, Heinz body positive, and elevated retics count. Thus, she was found to have a rare form of anemia, i.e., Heinz body hemolytic anemia. She was advised for splenectomy and started on medications. Following the procedure, her Hb started to rise to 9.6 g/dl and reached to 13.8 in the following months.

Keywords: Anemia, hemoglobin, Heinz body anemia

How to cite this article:
Padma V, Nair AB, Bhaskar S S. Heinz body hemolytic anemia. J Appl Hematol 2022;13:103-6

How to cite this URL:
Padma V, Nair AB, Bhaskar S S. Heinz body hemolytic anemia. J Appl Hematol [serial online] 2022 [cited 2023 Sep 22];13:103-6. Available from: https://www.jahjournal.org/text.asp?2022/13/2/103/353273

Introduction

Anemia may be classified into various categories based on various criteria. It can be divided into nutritional, hemolytic, aplastic anemia, or can be categorized as hypochromic, hyperchromic, microcytic, or macrocytic. It can be divided into anemia due to blood loss or impaired production or increased destruction. Various causes of anemia are present. Even though it is very common, especially in our population, a careful evaluation is required sometimes as a rare form or type of presentation may be missed on routine evaluation. There are various types of unstable or abnormal forms of hemoglobin (Hb) and may be associated with varying degree of hemolytic anemia.

Case Report

A 35-year-old female came to the outpatient department with complaints of breathlessness. Breathlessness was not associated with any aggravating or relieving factors. She also complained of generalized weakness and tiredness and complained of easy fatiguability. There was also a history of left-sided abdominal pain with no aggravating or relieving factors. No history of chest pain or altered sensorium was there. She did not have any episode of loss of consciousness or any history suggestive of reduced renal output or any drug allergy. There were no similar complaints in her family. Her appetite and sleep were normal; bowel and bladder habits were regular.

On examination, she was moderately built and nourished. She looked pale and icteric. She looked dehydrated. She was conscious, oriented, and afebrile. There was no cyanosis, clubbing, lymphadenopathy, or edema. Cardiorespiratory system examination was normal with S1 and S2 heard, no murmurs were present, and bilateral air entry was there, no added sounds were present. Central nervous system examination did not reveal any significant findings with no focal neurological deficit. However, per abdomen examination did reveal tenderness and splenomegaly on palpation.

All routine investigations were done. Tests showed Hb of 8.1 g/dl, total bilirubin was 2.17 mg/dl with indirect bilirubin of 1.35 mg/dl, aspartate aminotransferase 32.4 IU/L, alanine aminotransferase (ALT) 59.6 IU/L, alkaline phosphatase 86.1 IU/L, and GGT 29.0 IU/L. Ultrasonography (USG) of the abdomen showed moderate splenomegaly. A provisional diagnosis of hemolytic anemia was made. Furthermore, her reticulocyte count was 8.0%, smear study showed normocytic normochromic red blood cell (RBC) with moderate anisocytosis and polychromatophilic RBC, mild leukopenia with no immature cells and adequate platelets, and no hemoparasites. She was given ursodeoxycholic acid, multivitamins, and folic acid. Repeat Hb after 2 weeks also did not show further increase in Hb and so further investigations were advised. She was not under any medications or drug consumption and so drug-induced cause was ruled out. ANA antibody was negative, serum ferritin was 376.37 ng/ml, direct Coombs test was positive, and no occult blood was present. She was started on steroids.

Hb repeated after 2 weeks was found to be 7.1 g/dl and ALT was 48.7 IU/L. Urine routine was normal, although epithelial cells and calcium oxalate crystals were seen. Multivitamins and antioxidants were continued and the dose of steroids was decreased. Further evaluation for hemolytic anemia was advised. Other liver function and renal function tests were within the normal range. Red cell glucose-6-phosphate dehydrogenase enzyme screening test was normal, isopropanol stability test for unstable Hb and Ham's test were negative and so were sucrose lysis test and stool for occult blood. Hb electrophoresis done was normal, retics count was 0.5%, HIV, HCV antibody, and HBsAg were negative; bone marrow biopsy showed hypercellular marrow with gross erythroid hyperplasia. Bone marrow aspiration cytology showed hypercellular marrow with moderate erythroid hyperplasia with binucleate normoblast and now a provisional diagnosis of congenital dyserythropoietic anemia type 2/nutritional deficiency anemia was also thought of.

The patient was advised for review after 1 month. Now, when she came, her Hb was 4.9 md/dl and other tests were normal. She was advised 2 packed cell transfusions and restarted on steroids. Her pyruvate kinase activity was normal and was advised for splenectomy (if the symptoms persisted). The patient came back after 1 month and this time, her Hb was 8.1 g/dl, total bilirubin 2.2 mg/dl, direct bilirubin of 0.80 mg%, indirect Hb of 1.4 mg%, and normal liver enzyme levels. However, the direct Coombs test turned out to be positive (1+), Heinz bodies positive, and retics of 17.46%. She was thus diagnosed to have congenital nonspherocytic Heinz body hemolytic anemia.

She came for follow-up after a month and her Hb was found to be 7.0 g/dl. Her Hb further fell to 4.9 g/dl in two weeks' time. She was advised for USG abdomen which showed moderate splenomegaly. She was advised 1 packed cell transfusion, restarted on steroids, and splenectomy was advised.

She got admitted for the procedure in a couple of weeks' times and was transfused with 3 packed cells preoperatively. Her pre- and posttransfusion Hb were 5.2 and 7.7 g/dl. Lap converted to open splenectomy was done for her. Splenectomy specimen was 560 grams in weight, measured 15.5 cm × 11 cm × 6 cm. The capsule was smooth, gray brown, and intact. The serial cut section was gray brown in color, homogeneous, congested, no nodules, and no pale areas were seen. Congestion in splenic parenchyma and follicles with prominent germinal centers present. Post splenectomy, her Hb increased to 9.6 g/dl and then finally 11.1 g/dl. The drain was removed on the 5^th day and subsequently, she was discharged.

She has been under regular follow-up and her Hb after month was 10.7 g/dl, followed by 13.1, 13.8, 13.1, 13.6, and 13.7 g/dl in the following months. There was mild elevation of liver enzymes initially which was managed by giving urodeoxycholic acid and subsequently it reduced. She was being managed with multivitamins, folic acid, and zinc supplements.

Discussion

The presence of hemolytic anemia with red cell inclusion bodies has been documented for a long time. The cause can be congenital or acquired which are mostly drugs as in following potassium chlorate poisoning, sulphonamides, etc. It was Cathie (in 1952) who first described a child with persistent hemolysis and had a high frequency of red cell Heinz bodies for which she underwent splenectomy.^[1],[2],[3] Similar cases were later on discovered and found to be associated with hereditary deficiency of various enzymes. The cause was believed to be due to abnormal Hb such as Hb Koln, Hb Ube-I, and Hb Seattle.^[4],[5],[6]

They may carry charges different from normal alpha and beta chains of HbA or carry the same charge. Splenectomy may be beneficial, more so in patients with clinical symptoms. Their Hb may not be as equal as the normal range and may be still anemic but would be stable enough to have a normal lifestyle without any problems in their day to day activities. They may have a negative family history with normal Hb levels in their parents. They are more commonly seen in females than males. Incidence is more common in early childhood, however late cases are also reported. In some Heinz, bodies are not seen till after splenectomy which may be attributed to splenetic sequestration of the spleen.^{[7],[8],[9],[10],[11]} Fine intracytoplasmic granules in the cells lining the splendid sinusoids may be present. Some patients may have raised level of HbF or may have methemoglobinemia. Some patients have been found to excrete dark-colored urine possibly due to Hb breakdown to dipyrrole compounds. It is necessary to do family studies in such patients.

Certain abnormal Hb includes Hb Zurich in which the beta 63 histidine to arginine replacement occurs.^[12] In Hb Seattle, the site of the problem lies at beta T-9, an alanyl being replaced by a glutamyl residue at either position 70 or 76. In Hb Ube-I, the reactive cysteine at position 93 is blocked and in Hb Koln, beta at position 98 (valine to methionine) and in Hb Hammersmith, phenylalanine is replaced by serine at position 42.^{[11],[13],[14],[15],[16]}

The majority of unstable Hbs are inherited as autosomal dominant traits, and affected individuals are heterozygous for the mutation; however, homozygosis may rarely also occur, especially for the more common variants or in populations with a high degree of consanguinity. Some Hbs are so unstable that they are either barely detectable or undetectable in the hemolysate, e.g., Hb Petah Tikva, Hb Indianapolis, Hb Bristol-Alesha, Hb Toms River, etc.

Heinz bodies are intraerythrocytic Hb precipitates that form when Hb denatures and produces hemichromes. Hemichromes are molecules generated when the heme dissociates from the heme pocket and rebinds elsewhere in the globin molecule after the alpha or beta chains have undergone some degree of uncoiling or denaturation. The formation of irreversible hemichromes appears to be an indispensable stage in the formation of Heinz bodies.^{[17],[18],[19]}

Heinz bodies adhere at least partially to the cytosolic (internal) surface of the RBC membrane by hydrophobic interactions. Heinz bodies may also cause adjacent portions of the RBC membrane to be excised in the spleen (a process known as “pitting”), leading to the formation of “bite” or “blister” cells.

Patients with unbalanced Hbs can present with congenital nonspherocytic type of hemolytic anemia with clinical features like splenomegaly and pigmented gallstones. They may be associated with Heinz body hemolytic anemia with increased sensitivity to oxidant drugs such as sulphonamides and may be associated with or without mild/minimal anemia with reticulocytosis out of proportion to the Hb level. In cases of the hyper unstable variants, a thalassemia-like peripheral blood picture with hypochromic RBCs increased the formation of met Hb.^[20],[21] Most patients present in childhood or adolescence, but many are diagnosed as adults because chronic mild hemolytic anemia was unappreciated or attributed to another condition. The differential diagnosis includes RBC enzymatic defects, RBC membrane/cytoskeletal defects, AIHA, and PNH. Treatment includes folic acid, avoidance of oxidant drugs, and prevention of infection. In patients, resistant to these transfusions may be required. Splenectomy is advised to patients with frequent transfusions.

Conclusion

Any structural changes in Hb structure can result in its instability and thus decrease the oxygen-carrying capacity and other vital functions. It, thus, leads to clinical manifestations which can vary from asymptomatic to life-threatening ones. As we saw in this patient she was apparently asymptomatic till adulthood and manifested at the age of 35, it is vital for every clinician to keenly observe, investigate, and come to a conclusion or diagnosis even for common symptoms like anemia.

Acknowledgment

The authors would like to acknowledge Bharath University, Sree Balaji Medical College and Hospital for providing all the infrastructure needed for the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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