|Year : 2019 | Volume
| Issue : 3 | Page : 148-151
Hemoglobin-D Punjab—rare hemolytic anemia in the elderly: a case report
Tushar Kanti Biswas, Anupa Pillai
Department of Geriatrics, MGM Medical College and Hospital, Kamothe, Maharashtra, India
|Date of Submission||21-Jan-2020|
|Date of Acceptance||21-Jan-2020|
|Date of Web Publication||16-Mar-2020|
Dr. Tushar Kanti Biswas
Dr. Tushar K. Biswas, Department of Geriatrics, MGM Medical College and Hospital, Kamothe, Navi Mumbai, Maharashtra.
Source of Support: None, Conflict of Interest: None
A 62-year-old woman with no comorbidity presented with dyspnea since 2 months and fatigue since 1 month. She was having severe anemia with hepatosplenomegaly and icterus. Anemia due to blood loss was ruled out. With a history of blood transfusions and episodes of jaundice in the past, evaluation of hemolytic anemia was carried out. Her serum iron level was normal. Serum lactate dehydrogenase level was raised, and extracorpuscular causes were absent. Hemoglobin electrophoresis was performed in view of suspected hemoglobinopathy. It showed hemoglobin-D Punjab homozygous type, which is very rare. Its presentation in older age is even rarer to warrant this report.
Keywords: Electrophoresis, hemoglobin-D Punjab homozygous, hemoglobinopathy, hemolytic anemia
|How to cite this article:|
Biswas TK, Pillai A. Hemoglobin-D Punjab—rare hemolytic anemia in the elderly: a case report. MGM J Med Sci 2019;6:148-51
| Introduction|| |
Hemoglobin D (Hb-D) hemoglobinopathy occurs mainly in the northwest India (Punjab), Pakistan, and Iran. Hb-D was first discovered in the early 1950s in a mixed British and American family of Indian origin from the Los Angeles area and hence the original Hb-D was called Hb-D Los Angeles, but it was later found to be identical to the Hb-D Punjab found in India and Pakistan. Hb-D Punjab arises from the substitution of glutamine for glutamic acid in the 121st position of the β chain. Hb-D disease can occur in four different forms, including heterozygous Hb-D trait, Hb-D thalassemia, Hb-SD disease, and very rarely homozygous Hb-D disease. Heterozygous Hb-D disease is a benign condition with no apparent illness, but when Hb-D is associated with Hb-S or beta-thalassemia, clinical conditions such as sickling disease, moderate hemolytic anemia may be observed. Homozygous Hb-D results when the gene for Hb-D is inherited from both parents. Homozygous Hb-D disease is a rare disease and usually presents with mild hemolytic anemia and mild-to-moderate splenomegaly. Hb-D does not sickle.
| Case report|| |
A 62-year-old lady from rural Maharashtra, with no comorbid illness came with shortness of breath, which was insidious in onset and gradually progressive since 2 months. She also had dizziness and generalized weakness. It was also accompanied with left-sided abdominal pain since 2 months and passing dark colored stools intermittently for 1 month. She had no history of chest pain or palpitations or weight loss or hematuria or hematochezia or hematemesis. She also had no history of leg ulcers or dark-colored urine. She gave a history of 1–2 episodes of jaundice in the past. She had a history of blood transfusion 20 years back and recently 6 month back. No history of postmenopausal bleeding or bleeding piles was observed. She had two children: one girl and one boy who had died at the age of 6 months each, with episodes of jaundice. No history of consanguineous marriage was reported in her family.
On general examination, no feature of hemolytic facies was observed [Figure 1]. She had marked pallor and mild icterus. Her pulse was 84/min and blood pressure was 110/64mm Hg. However, there was no edema, cyanosis, clubbing, or lymphadenopathy. Systemic examination revealed hepatosplenomegaly. Liver was palpable 4cm below the right costal margin (anterior hepatic span, 14cm), and spleen was palpable 8cm below the left costal margin. Her rectal examination showed no hemorrhoid. Cardiovascular, respiratory, and nervous systems were normal.
Her initial investigations showed markedly low Hb (6.3 g/dl) with a low packed cell volume (PCV) of 20.70%; Mean corpuscular volume (MCV) 74.20 fL; Mean corpuscular hemoglobin (MCH) 22.60 pg/cell; Mean corpuscular hemoglobin concentration (MCHC) 30.40 g/dL; thus blood indices indicating microcytic hypochromic anemia. TLC 5970/mm3 differential count (DLC) Polymorphs 75 %, Lymphocytes 20%, Monocytes 4%, Eosinophils 1%, Platelet 2,34,000/mm3. Reticulocyte count was 1.5%. Peripheral smear showed microcytic hypochromic anemia; no malarial parasites seen. Serum LDH was high, 324 U/L (reference range, <247 U/L); serum bilirubin total was 6.18mg/dL, direct was 0.74mg/dL and indirect was 5.44mg/dL, thus indicating indirect hyperbilirubinemia in favor of hemolytic jaundice. Serum total protein level was 7.51g/dL, albumin was 4.34g/dL, globulin was 3.17g/dL, Albumin/Globulin (A/G) ratio was 1.37; serum glutamic-oxaloacetic transaminase (SGOT) was 23.0 U/L, and serum glutamic-pyruvic transaminase (SGPT) was 12.0 U/L, thus ruling out any hepatocellular jaundice. The level of serum iron was 133 μg/dL (reference, 60–180 μg/dL in female), serum ferritin was 554.90ng/mL (reference, 11.0–306.8ng/mL in female), and serum vitamin B12 level was 801.0 pg/mL (reference 211–911 pg/mL). Other hematological investigations were as follows: direct and indirect Coombs tests were negative, ruling out autoimmune hemolytic anemia. Osmotic fragility test was normal, serum G6PD test was normal, and sickling test was negative. Serum immunoglobulin G level was 14.4g/L (reference, 7.51–14.60g/L) and immunoglobulin M level was 2.05g/L (reference 0.46–3.04 gm/L), which were normal. Her urine routine analysis was normal, and stool routine examination did not show any occult blood or ova, parasite, or cyst. Other blood biochemistry levels were as follows: blood urea, 11.0mg/dL (reference, 13–43mg/dL), serum creatinine, 0.51mg/dL (reference, 0.51–0.95mg/dL), serum sodium, 137.0 meq/L (reference, 136–145 meq/L), and serum potassium 4.0 meq/L (reference, 3.5–5.1 meq/L). Random blood sugar level was 115mg/dL. Serum thyroid-stimulating hormone level was normal.
Ultrasonography of abdomen [Figure 2] showed cholelithiasis (9-mm-sized gall stone with posterior acoustic shadow) and hepatosplenomegaly (liver span, 14.4cm and splenic span, 16.6cm). Upper gastrointestinal endoscopy was normal except axial hiatus hernia grade I. Two-dimensional echocardiography was normal.
After clinical examination and subsequent investigations, possibility of hemoglobinopathy was considered as the cause of hemolytic anemia. Hemoglobin electrophoresis was ordered on blood sample collected before blood transfusion, and it showed homozygous Hb-D Punjab disease [Figure 3], with Hb-A, 30.1%, Hb-F, 10.6%, Hb-D Punjab, 55.7%, and Hb-A2, 1.6%. She was given two PCV transfusion and folate supplements. The patient was counseled regarding her diagnosis and was discharged on day 5 with advice to be on regular follow-up. On discharge, her Hb was 7.6 g/dl.
| Discussion|| |
Hb-D Punjab is one of the most common subvariants (55%) of Hb-D derived from a point mutation in the beta globin gene. Hb-D Punjab is quite prevalent in northwestern India, specifically in Punjab and Gujarat regions, due to cultural practices of consanguineous marriages. Approximately 3% of Sikhs from Punjab are affected. This patient hails from Maharashtra (part of western India), a border state of Gujarat.
Hb-D Punjab can be inherited as a homozygous component or as a heterozygous trait with normal Hb-A. The trait presents with no clinical or hematological alterations. However, when co-inherited with another variant of Hb such as sickle cell or thalassemia, it may present with clinically significant conditions often requiring hospital admissions and blood transfusions. Although Hb-D is not uncommon in India, its homozygous form is very rare and very few cases have been reported. Hb variants usually are the consequence of single amino acid substitutions caused by point mutations in genes encoding globin chains, resulting in a tetramer with different physicochemical characteristics.
According to the Globin Gene Server database, 1198 Hb variants were described until September 2014. Most of the Hb variants described do not cause symptomatic clinical manifestations; however, in some cases, they can be associated to relevant pathophysiology, for example, Hb-S. Hb-S is the most frequent Hb variant in the world; its clinical outcome is severe in homozygous or in association with other relatively common hemoglobinopathies, such as beta-thalassemia, Hb-C, or Hb-D. The homozygous component Hb-DD, the rarest form of inheritance, is not commonly related to symptomatic cases, but occasionally individuals with this profile can develop mild-to-moderate hemolytic anemia., This particular case was a homozygous Hb-D Punjab, which presented with moderately severe anemia, moderate splenomegaly, and mild hepatomegaly. The patient also had cholelithiasis, which is commonly seen with hemolytic anemia.
Low-dose hydroxyurea (10mg/kg/day) was found to be effective in reducing the clinical severity in patients with Hb-SD Punjab without any short-term toxicity, but there has been no trial in patients with homozygous Hb-D Punjab. Some patients may eventually benefit from splenectomy.
| Conclusion|| |
This was a case of late presentation of hemolytic anemia due to homozygous Hb-D Punjab hemoglobinopathy in a young old category (60–69 years) of an older adult. Such cases can easily be missed if not clinically suspected for.
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Das R. Disorders of haemoglobin structure and synthesis. In: Saxena R, Pati HP, Mahapatra M, editors. de Gruchy’s Clinical Haematology in Medical Practice. 6th ed. New Delhi, India: Wiley India; 2013. p. 120-45.
Pandey S, Mishra RM, Pandey S, Shah V, Saxena R. Molecular characterization of hemoglobin D Punjab traits and clinical-hematological profile of the patients. Sao Paulo Med J 2012;130:248-51.
Jain RC. Hemoglobin D disease: Report of a case. Am J Clin Pathol 1971;56:40-2.
de Souza Torres L, Okumura JV, da Solva DGH, Bonini-Domingos CR. Hemoglobin D-Punjab: Origin, distribution and laboratory diagnosis. Rev Bras de Hematol Hemoter 2015;37: 120-6.
Adekile A, Mullah-Ali A, Akar NA. Does elevated hemoglobin F modulate the phenotype in Hb SD-Los Angeles? Acta Haematol 2010;123:135-9.
Taghavi Basmanj M, Karimipoor M, Amirian A, Jafarinejad M, Katouzian L, Valaei A. Co-inheritance of hemoglobin D and β-thalassemia traits in three families: Clinical relevance. Arch Iran Med 2011;14:61-3.
Patel S, Purohit P, Mashon RS, Dehury S, Meher S, Sahoo S, et al
. The effect of hydroxyurea on compound heterozygotes for sickle cell-hemoglobin D-Punjab—A single centre experience in eastern India. Pediatr Blood Cancer 2014;61:1341-6.
[Figure 1], [Figure 2], [Figure 3]