Challenge in diagnosis of hemoglobin E/beta thalassemia during pregnancy: A case report

Abstract

Introduction

Beta thalassemia (β-thalassemia) in pregnant women increases the risk of obstetric problems such as premature birth and low birth weight, so caution is needed in its management; these cases are usually asymptomatic.

Presentation of case

A pregnant Indonesian female (gestational age of 36 weeks), 21 years old, complained of general weakness. The patient experienced anemia several times during this pregnancy and received several blood transfusions. Her parents also have β-thalassemia. A physical examination of the patient showed pale conjunctiva and slight icteric sclera. Laboratory examination showed abnormal included hemoglobin (Hb) of 6.7 g/dL, hematocrit of 207 %, mean corpuscular volume (MCV) of 60.1 fL, mean corpuscular hemoglobin (MCH) of 19.3 pg, mean corpuscular hemoglobin concentration (MCHC) of 32.1 g/dL, albumin of 3.06 g/dL, direct bilirubin of 0.75 mg/dL, and total bilirubin of 1.78 mg/dL. Peripheral blood smear examination showed β-thalassemia. She received a high-calorie and protein diet with extra eggwhite of 2100 kcal/day, leukodepleted packed red blood cell (LD-PRBC) transfusion of 2 × 250 cc/day, folic acid of 3 × 1 mg/day, and methylprednisolone of 3 × 62.5 mg/day. The patient gave birth to a baby girl spontaneously. She received methylprednisolone of 3 × 16 mg with tapering off every week and folic acid of 3 × 1 mg. The patient's prognosis showed improvement.

Discussion

Pregnancy weakens the immune system; therefore β-thalassemia is frequently discovered during this time, and keeping the mother's Hb ≥10 g/dL prevents complications.

Conclusion

Maintaining Hb ≥10 g/dL minimizes complications for mother and baby.

Highlights

• •Pregnant women must maintain Hb ≥10 g/dL.
• •Woman with β-thalassemia minor is often detected during pregnancy.
• •Thalassemia screening is recommended for couples before marriage.

1. Introduction

Beta thalassemia (β-thalassemia) is a hereditary disorder characterized by a decrease in the synthesis of β-globin chains that reduces hemoglobin (Hb) in erythrocytes, low erythrocyte production, and anemia [1]. β-Thalassemia is a health problem that is commonly found in Asian countries such as India (1.4 %) and Kuwaiti (2.12 %) [2,3]. β-Thalassemia in pregnant increases the risk of obstetric problems such as premature birth and low birth weight. Females with β-thalassemia trait (BTT) are usually asymptomatic, do not appear anemic, and tolerate hematological changes due to pregnancy as well [4]. Hb E is one of the most common mutations worldwide, resulting in a heterogeneous group of disorders whose phenotypes range from asymptomatic to severe [5]. The study's aim was to examine a pregnant patient with Hb E/β-thalassemia. The report is based on the surgical case report (SCARE) guideline 2020 [6].

2. Presentation of case

An Indonesian female, 21 years old, complained of general weakness from 1 month before. The patient was 36 weeks pregnant. During this pregnancy, she experienced anemia several times and received several packed red blood cells (PRBC) transfusions (at 10 weeks, 15 weeks, 25 weeks, and 31 weeks gestational age). Fever, nausea, vomiting, cough, chest tightness, and sore throat were not found. She had no problem in eating or drinking. The patient is a housewife. The patient has no history of allergies and chronic disease. The patient also experienced paleness, general weakness, and Hb of 8.2 g/dL when she was 5 years old. She was diagnosed with β-thalassemia and received PRBC transfusion. She had never experienced such symptoms or had any complaints again prior to this pregnancy. Her parent's medical history also has a β-thalassemia minor for father and heterozygote Hb E and Hb D minor for mother (Fig. 1), with no previous history of transfution.

Fig. 1.

A. Her father's Hb electrophoresis showed decreased Hb A fraction and increased Hb A2 fractions; B. Her mother's Hb electrophoresis showed decreased Hb A fraction and increased Hb D, Hb E, and Hb A2 fractions.

Physical examination of the patient revealed anemic conjunctiva and slight icteric sclera. Obstetric examination revealed a fetal heart rate of 146 ×/min. Laboratory examination showed abnormality including Hb of 6.7 g/dL, hematocrit of 20.7 %, mean corpuscular volume (MCV) of 60.1 fL, mean corpuscular hemoglobin (MCH) of 19.3 pg, mean corpuscular hemoglobin concentration (MCHC) of 32.1 g/dL, albumin of 3.06 g/dL, direct bilirubin of 0.75 mg/dL, and total bilirubin of 1.78 mg/dL. Radiological examination was within normal limits. Peripheral blood smear examination showed β-thalassemia (Fig. 2). She was diagnosed with β-thalassemia and a differential diagnosis of autoimmune hemolytic anemia (AIHA).

Fig. 2.

Hypochromic microcytic anisopoikilositosis anemia, Leukocytes with immature granulocyte and atypical lymphocyte.

She received a high-calorie and protein diet with extra eggwhite of 2100 kcal/day, leukodepleted packed red blood cells (LD-PRBC) transfusion of 2 × 250 cc/day, and folic acid of 3 × 1 mg/day. On the 2nd day of admission, there were several abnormal laboratory results, including Hb of 6.9 g/dL, total iron binding capacity (TIBC) of 248 μg/dL, serum iron (SI) of 296 μg/dL, reticulocytes of 2.37 %, positive direct coomb test, and positive indirect coomb test. Patients received additional treatment of methylprednisolone of 3 × 62.5 mg/day and other treatments were continued. On the 3rd day, the patient complained of slight weakness, slight pale conjunctiva, slight icterus, and Hb of 9.5 g/dL. Hb electrophoresis test showed β-thalassemia and hemoglobinopathies E (Fig. 3). On the 4th day, the patient experienced increased uterine contractions, slight anemic conjunctiva, and Hb of 10.3 g/dL. We changed the methylprednisolone dose from 3 × 62.5 mg/day (intravenous) to 3 × 16 mg/day (orally) and continue other treatments. The patient also underwent labour observation.

Fig. 3.

Hb electrophoresis showed decreased Hb A fraction and increased Hb F, Hb E, and Hb A2 fractions.

On the 5th day, the patient complained of stomach tightening and rupture of membranes. The patient is in a stable condition so vaginal delivery is performed and there is no sign that a delivery caserean section is required. The patient gave birth to a baby girl spontaneously with a body length of 47 cm and a body weight of 2300 g, heart rate of 148×/min, respiratory rate of 46×/min, SpO2 of 98 %, temperature of 36.7 °C, and Apgar score of 8–9. On the 6th day, the patient was discharged and received folic acid of 3 × 1 mg/day, paracetamol of 3 × 500 mg/day, and methylprednisolone of 3 × 16 mg. On the 3rd day of discharge, the patient was stable condition. Patients received methylprednisolone therapy of 3 × 16 mg with tapering off every week (to be 16 mg–16 mg-0 during 1 week, continued to be 16 mg-0-0 for 1 week, continued to 8 mg-0-0 during 1 week, continued to 4 mg-0-0 for 1 week) and folic acid of 3 × 1 mg. The patient's prognosis showed improvement.

3. Discussion

Patient and family history are significant in diagnosing β-thalassemia because they are related to certain races and ethnicities. Physical examination leads to the diagnosis of thalassemia if there are symptoms and signs, such as paleness indicating anemia, hemolytic jaundice, and splenomegaly indicating an accumulation of abnormal cells. Patients with thalassemia syndrome generally show decreased Hb and hematocrit levels, relatively high red blood cell count, very low MCV, and slightly decreased MCHC. In homozygous and multiple heterozygous β-thalassemia, extreme poikilocytosis includes target cells, elliptocytes, polychromasia, basophilic stippling, and nRBC. The reticulocyte count was found to be elevated, indicating that the bone marrow is responding to the hemolytic process [7]. Hemolytic anemia in β-thalassemia is associated with arginase release, impaired nitric oxide availability and endothelial dysfunction [8]. Positive Coomb test results can be found due to antibodies from the maternal circulation that cross the placenta and attack fetal erythrocytes [9]. Electrophoresis with cellulose acetate at alkaline pH is essential for screening the diagnosis of β-thalassemia minor, Hb H, Bart's, Constant Spring, Lepore, HPFH, and other variants of β-thalassemia [7,10].

The low Hb level in β-thalassemia minor/Hb E may contribute to the poor obstetric outcome [11,12]. Pregnancy with β-thalassemia minor/Hb E has a relative risk of fetal growth restriction of 2.8 times greater than controls, the incidence of preterm birth is 2.7 times greater than controls, and the incidence of low birth weight is 5.6 times bigger than control. A study also found that as many as 35 % of the patients had never received a blood transfusion before [13]. This could be related to the increase in plasma volume during pregnancy which accelerates the occurrence of anemia in these patients [14].

Pregnancy is one of the indications for blood transfusions in the management of anemia in thalassemia patients. The target maternal Hb level during pregnancy is around 10 g/dL to ensure optimal fetal development [14]. Thalassemia patients are at risk for iron overload associated with repeated transfusions, so chelation therapy is one of the main components in managing the patient's disease. During pregnancy, chelation therapy should be limited to some instances where the potential benefit outweighs the potential risk to the fetus. If a patient exhibits symptoms of myocardial dysfunction during pregnancy, continuing chelation therapy should be discussed by a multidisciplinary team [15].

The prognosis for variant thalassemia depends on the clinical phenotype. Patients with a milder phenotype tend not to require treatment and frequent transfusions [16]. Most Hb E/β-thalassemia patients' Hb fall moderately, with stable Hb levels between 6 and 7 g/dL. Clinically, patients in this category usually do not require blood transfusion unless an infection leads to anemia, which sometimes must be accompanied by chelation therapy. Patients in this group often have a shorter lifespan, but with careful monitoring and management may have a better prognosis [17]. Patients with severe Hb E/β-thalassemia requires chronic red blood cell transfusions and iron chelation therapy, causing economic burden to countries with a high disease prevalence. Prenatal diagnosis and neonatal screening are essential parts of strategies to reduce disease burden and improve patient care [8]. In general, severe anemia that is not adequately managed can lead to high-output heart failure and bone changes related to intramedullary erythroid expansion, such as thinning of the bone cortex. The destruction associated with the fragility of red blood cells in the long-term causes hyperbilirubinemia and gallstones containing bilirubin. The increased iron deposition resulting from repeated transfusions and increased iron absorption result in secondary iron overload. This causes clinical problems similar to primary hemochromatosis, e.g., endocrine, hepatic, and cardiac dysfunction [16,18].

The risk of pregnancy-specific complications included placental ischemic disease, placental abruption, gestational hypertension, kidney stones, cholelithiasis, and urinary tract infection [19]. Most of these complications require surgery and are life-threatening for the mother and baby, so preventive efforts are essential. Hb E/thalassemia is a disease that is often found in Asia, but it is rarely screened. This disease is often found when it is showing symptoms, so healthcare providers need to be more aware during examination and treatment of these patients to minimize the occurrence of complications [20].

4. Conclusion

An Indonesian pregnancy, aged 21 years with history of transfusion as a child and no recurrence of the disease until the first pregnancy, with clinical suspicion of thalassemia characterized by complaints of weakness and frequent transfusions at the previous hospital. The examination shows increased indirect bilirubin, increased total bilirubin, positive direct coomb test, positive indirect coomb test, and Hb electrophoresis suggesting a Hb E/β-thalassemia. The patient is given methylprednisolone injection therapy, LD-PRBC transfusion, and oral folic acid. During treatment, clinical symptoms improved, and the patient give birth to a healthy baby with normal Hb electrophoresis results according to age. When healthcare providers are presented with patients with signs and symptoms of thalassemia, they should be more aware because the prevalence is relatively high in Asia and can be life-threatening if complications occur.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Funding

N/A.

Credit authorship contribution statement

Median Brahmantyo: data curation, supervision, visualization, investigation, drafting; Merlyna Savitri: conceptualization, methodology, drafting, editing, revising and reviewing.

Guarantor

Merlyna Savitri is the person in charge of the publication of our manuscript.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Declaration of competing interest

N/A.