|Year : 2019 | Volume
| Issue : 2 | Page : 111-113
Anemia in pregnancy: Think beyond iron deficiency
Faisal A Memon, Vikram A Londhey, Raju J Nagara
Department of General Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai, Maharashtra, India
|Date of Submission||26-Feb-2019|
|Date of Decision||02-May-2019|
|Date of Acceptance||03-May-2019|
|Date of Web Publication||24-May-2019|
Dr. Vikram A Londhey
Department of General Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
We hereby describe a rare case of delta beta (δβ)-thalassemia as a cause of anemia in a 2-month pregnant female who was diagnosed as homozygous δβ-thalassemia after gene mutation studies. δβ-thalassemia is an unusual variant of thalassemia with elevated level of fetal hemoglobin. Homozygous patients of this disorder, unlike β-thalassemia, show mild anemia and give a clinical picture similar to that of thalassemia intermedia. However, δβ-thalassemia heterozygotes clinically show the characteristics of thalassemia minor.
Keywords: Delta beta-thalassemia, fetal hemoglobin, hereditary persistence of fetal hemoglobin, high-performance liquid chromatography
|How to cite this article:|
Memon FA, Londhey VA, Nagara RJ. Anemia in pregnancy: Think beyond iron deficiency. Indian J Med Spec 2019;10:111-3
| Introduction|| |
Thalassemias are a group of congenital anemias that have in common deficient synthesis of one or more of the globin subunits of the normal human hemoglobin (Hb). According to the type of globin chain involved, thalassemia can be divided into α-, β-, δβ-thalassemias and hereditary persistence of fetal hemoglobin (HPFH). Fetal hemoglobin (HbF) is a globular protein composed of two α- and two γ-globin chains (α2 γ2). δβ-thalassemia is characterized by the persistent expression of γ-globin genes in adults in association with decreased or absence of δ- and β-globin gene expression, leading to increased HbF concentrations, and presence of hypochromic and microcytic erythrocytes.
| Case Report|| |
A 27-year-old female in her first trimester of pregnancy got admitted for community-acquired pneumonia and anemia. On questioning, the patient gave a history of easy fatigability since many years and a history of single episode of jaundice 3 years back. She had no history of blood transfusion in the past.
Physical examination did not reveal any bony deformities of thalassemia. Pallor and icterus were present; a firm spleen was palpable 6 cm below the left costal margin. On investigations, she had Hb 7.5 gm%, hematocrit 22.5%, mean corpuscular volume 68.1 fL, mean corpuscular Hb (MCH) 22.7 pg, MCH concentration 33.3 g/dL, red blood cell count 3.3 × 106/μL, and red cell distribution width19.1%. Giemsa-stained peripheral smear examined for red cell morphology showed microcytic hypochromic red cells. On peripheral smear examination, reticulocyte count was <1%. Liver function tests showed raised levels of serum total bilirubin (3.2 mg/dL) and indirect bilirubin (2.2 mg/dL). Serum iron chemistry showed low serum iron, high total iron-binding capacity, and low transferrin saturation. Quantitative test was performed to determine the levels of HbA, HbA2, and HbF by high-performance liquid chromatography (HPLC). It showed 99.1% HbF in patient's blood sample with complete absence of HbA2.
Provisional diagnosis of δβ-thalassemia versus HPFH was considered.
Consequently, a HPLC was performed for both parents who were apparently healthy and had no history of blood transfusions which showed high HbF and normal HbA2. Hematological and molecular investigations were performed of the patient and parents. Hematological and molecular details of the patient and parents are mentioned in [Table 1].
|Table 1: Results of high-performance liquid chromatography of patient and parents|
Click here to view
Results [Table 1] confirmed diagnosis of homozygous δβ-thalassemia in the patient, whereas the parents were heterozygous δβ-thalassemia.
Our patient was managed conservatively; the blood was transfused during her ward stay to build up the Hb to around 10 gm%; she was started on oral iron and folic acid supplementations.
No data is available of pregnancy outcome in our patient as she did not follow up after discharge.
| Discussion|| |
The synthesis of Hb depends on two gene clusters: (1) The α locus, which contains the embryonic ζ gene plus the two adult α genes and (2) the β cluster, which contains the embryonic ∈, the fetal Gγ and Aγ, and the adult δ and β genes.
δβ-Thalassemia is a group of disorders characterized by decreased or absent production of both δ- and β-globin chains and by a variable increase in γ-chain synthesis; there is deletion of variable extent of the β-like globin cluster, which involves the δ- and β-globin genes. Based on the presence of one (Gγ) or both (G and Aγ) globin genes, two groups of δβ0-thalassemia have been identified: Gγ(Aγδβ) 0 and GγAγ(δβ) 0-thalassemia.
During early childhood, the level of HbF normally declines to <1% of total Hb; however, in some genetic conditions, increased levels of HbF are found in adult life. The hereditary persistence of HbF and δβ-thalassemia are heterogeneous disorders characterized by increased levels of HbF in adult life. The distinction between these two conditions is not always possible with routine hematologic analysis. Molecular analysis of these conditions has demonstrated many deletion and nondeletion types of these two conditions.
Heterozygotes for δβ-thalassemia have hypochromic microcytic red cells, with the levels of HbF ranging from 5% to 20%, and in contrast, HPFH heterozygotes have normal blood indices with higher HbF (15%–30%).
Homozygotes of HPFH are asymptomatic, whereas δβ-thalassemia homozygotes have thalassemia intermedia-like features.
There is a thin line of clinical and hematological difference between HPFH and δβ-thalassemia. Therefore, the level of HbF alone sometimes cannot differentiate the two conditions and DNA analysis of the molecular defect is required.
Our patient, who was initially suspected to have anemia of pregnancy, turned out to be a case of homozygous δβ-thalassemia (proved by molecular investigations) with superimposed iron deficiency. Our patient was managed conservatively with blood transfusion along with oral iron and folic acid supplements.
The decision to start such pregnant patients with clinical phenotype of thalassemia intermedia on regular transfusion regimen is clinical, based on the woman's symptoms and fetal growth. If there is worsening maternal anemia or evidence of fetal growth retardation, regular transfusions should be started aiming for maintenance of pretransfusion Hb concentration above 10 gm%.
Initially, 2–3 units of blood should be transfused with additional units of blood transfusion if necessary in the following week until the Hb reaches 12 gm%.
The Hb should be monitored after 2–3 weeks and a 2-unit transfusion administered if the Hb has fallen below 10 gm%. Each woman's Hb falls at different rates after transfusion, so close surveillance of pretransfusion Hb concentrations is required.
Our patient was poorly built and nourished and had poor socioeconomic status; this along with increased iron requirement by fetoplacental unit contributed to superimposed iron deficiency on δβ-thalassemia, leading to exaggeration in amount of anemia from δβ-thalassemia per se.
Thalassemia syndromes and iron deficiency anemias are the two most common etiologies of microcytic hypochromic anemias. Most physicians neglect the possible coexistence of an iron deficiency with thalassemia syndromes and do not treat the iron deficiency accordingly. However, various studies have shown the occurrence of iron deficiency in patients with β-thalassemia, especially β-thalassemia trait., Hence, patients with thalassemia trait and depleted iron stores should receive iron supplementation; hence, our patient was started on oral iron.
Primary preventive measures in the form of carrier screening, genetic counseling, prenatal diagnosis, and selective pregnancy termination appear to be the most effective tool for the control of such type of hemoglobinopathies.
Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done preconceptionally or as early as possible in the pregnancy.
Genetic counseling provides information for individuals and at-risk couples (i.e., both carriers) regarding the mode of inheritance, the genetic risk of having affected children, and the natural history of the disease including the available treatment and therapies under investigation.
Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis, usually performed at approximately 15–18 weeks' gestation or chorionic villi sampling at 11 weeks' gestation.
An extensive literature search was done to determine the incidence of δβ-thalassemia reported from different parts of the world; however, owing to the rarity of this Hb variant, only anecdotal case reports were identified from across the globe.,
| Conclusion|| |
Since Hb HPLC has readily become available at more institutions across the country, this rare disorder should be kept in mind in cases with elevated HbF. Differential diagnosis of these conditions is therefore important for providing appropriate treatment and genetic counseling to the patient. Identification of these abnormalities also facilitates in prevention and control program of thalassemia as well as in prenatal and newborn screening for hemoglobinopathies in the region.
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|| |
Greer J, Foerster J. Thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis. In: Wintrobes Clinical Hematology. 12th
ed. Philadelphia, United States: Lippincott Williams and Wilkins; 2009. p. 1084-9.
Rees DC, Porter JB, Clegg JB, Weatherall DJ. Why are hemoglobin F
levels increased in HbE/beta thalassemia? Blood 1999;94:3199-204.
Baysal E. HPFH and δβ-thalassemia conditions. Hemoglobin 1993;17:575-9.
Rochette J, Craig JE, Thein SL. Fetal hemoglobin levels in adults. Blood Rev 1994;8:213-24.
Bollekens JA, Forget BG. Delta beta thalassemia and hereditary persistence of fetal hemoglobin. Hematol Oncol Clin North Am 1991;5:399-422.
Royal College of Obstetricians and Gynaecologists. Management of Beta Thalassaemia in Pregnancy. Green-Top Guideline No. 66. London: Royal College of Obstetricians and Gynaecologists; 2014. p. 1-17.
Hegde UM, Khunda S, Marsh GW, Hart GH, White JM. Thalassaemia, iron, and pregnancy. Br Med J 1975;3:509-11.
Verma S, Gupta R, Kudesia M, Mathur A, Krishan G, Singh S. Coexisting iron deficiency anemia and beta thalassemia trait: Effect of iron therapy on red cell parameters and hemoglobin subtypes. ISRN Hematol 2014;2014:293216.
Verma S, Bhargava M, Mittal S, Gupta R. Homozygous delta-beta thalassemia in a child: A rare cause of elevated fetal hemoglobin. Iran J Ped Hematol Oncol 2013;3:222-7.
Ramot B, Ben-Bassat I, Gafni D, Zaanoon R. A family with three beta-delta-thalassemia homozygotes. Blood 1970;35:158-65.