p–ISSN: 2723 - 6609 e-ISSN: 2745-5254

Vol. 5, No. 6 June 2024 http://jist.publikasiindonesia.id/

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2834

Obstetric and Gynecology Department of RSUD Dr.

Soedono Provinsi Jawa

Reny Faristin Putri Arifin

, Wildan Firmansyah

RSUD dr. Soedono Provinsi Jawa Timur, Indonesia

Email: [email protected]

, [email protected]

*Correspondence

ABSTRACT

Keywords: Anemia,

Pregnancy, Thalassemia.

Anemia is a condition in which the number of red blood cells

or the hemoglobin concentration within them is lower than

normal. Thalassemia is a Mutation of the globin gene that

can cause changes in the globin chain, e.g. structural

hemoglobinopathy or changes in the rate of synthesis or the

production ability of certain globin chains. Epidemiological

research in Indonesia found that the frequency of the beta

thalassemia gene ranges from 3-10%. Case report of patient

Mrs. T, 27 years old, HPHT: 01-10-2023, routine ANC

examination every month, ANC examination results in 18-

19 weeks no complaints, and laboratory examination results

in Hb 4.7. Patients with thalassemia beta major and

intermediate need to be given regular transfusions and keep

their hemoglobin levels above 10 mg/dl. All patients with

homozygous thalassemia should receive folic acid

supplements.

Introduction

Anemia is a condition in which the number of red blood cells or the hemoglobin

concentration within them is lower than normal. Haemoglobin is needed to carry oxygen

and if you have too few or abnormal red blood cells or not enough hemoglobin, there will

be a decreased capacity of the blood to carry oxygen to the body’s tissues. This results in

symptoms such as fatigue, weakness, dizziness, and shortness of breath, among others.

The optimal hemoglobin concentration required to meet physiologic needs varies by age,

sex, elevation of residence, smoking habits, and pregnancy status (SUDIARTA, RIZKA,

RIZAL, ABIGAIL, & PRATAMA, 2022). Anemia may be caused by several factors:

nutrient deficiencies through inadequate diets or inadequate absorption of nutrients,

infections (e.g. malaria, parasitic infections, tuberculosis, HIV), inflammation, chronic

diseases, gynecological and obstetric conditions, and inherited red blood cell disorders.

The most common nutritional cause of anemia is iron deficiency, although deficiencies

in folate, vitamins B12, and A are also important causes (Sanif & Husin, 2017).

Anemia is a serious global public health problem that particularly affects young

children, menstruating adolescent girls and women, and pregnant and postpartum women.

WHO estimates that 40% of children 6–59 months of age, 37% of pregnant women, and

Obstetric and Gynecology Department of RSUD Dr. Soedono Provinsi Jawa

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2835

30% of women 15–49 years of age worldwide are anemic (Budiardjo & Irwiensyah,

2015).

Hemolytic anemia is a lack of hemoglobin levels due to the breakdown of

erythrocyte cells faster than the bone marrow's ability to replace them. Based on the

involvement of immunoglobulins in hemolysis events, hemolytic anemia is divided into

immune hemolytic anemia and non-immune hemolytic anemia. In immune hemolytic

anemia, hemolysis occurs due to the involvement of antibodies, usually IgG or IgM that

are specific to erythrocyte antigens (autoantibodies). Meanwhile, in non-immune

hemolytic anemia, hemolysis occurs without the involvement of immunoglobulins, such

as molecular defect factors, membrane structure abnormalities, hemoglobinopathy, etc.,

which do not include immunological mechanisms. Thalassemia itself is included in one

of the types of hemoglobinopathy.

Haemoglobinopathy is a disorder caused by impaired hemoglobin synthesis due to

mutations in or near globin genes. Mutations in globin genes can cause changes in globin

chains, e.g. structural hemoglobinopathy or changes in the rate of synthesis or the ability

to produce certain globin chains called thalassemia (Guntur et al., 2014).

Thalassemia is a defect or damage to hemoglobin (Hb) due to mutations or deletions

of genes that regulate the formation of alpha or beta globin chains that are usually

autosomally recessively derived (Daniel et al., 2019). In Southeast Asia, symptomatic

anemia occurs at 0.66 per 1,000 births with an incidence of 20,420 per year and is almost

entirely dependent on transfusions (Sandjaja, Nafisa, & Manurung, 2020). Beta

thalassemia is commonly found in Mediterranean populations, while alpha thalassemia is

commonly found in Asian and African populations (Mishra, Lakhera, Negi, & Pandey,

2022). In the world, thalassemia beta is widely distributed in Mediterranean populations,

the Middle East, India, Pakistan, Southeast Asia, Southern Russia, and China, and is

rarely found in Africa except Liberia, and some parts of North Africa are sporadic in all

races. As for alpha thalassemia, it is widely distributed from Africa to the Mediterranean,

the Middle East, East Asia, and Southeast Asia (Guntur et al., 2014).

Thalassemia is a hereditary disease or genetic disorder due to red blood cell

abnormalities that result in patients having to undergo blood transfusions throughout their

lives. Thalassemia is a genetic disease that has the most types and frequencies in the world

with varying clinical manifestations. Data from the World Bank shows that 7% of the

world's population is a carrier of thalassemia. Every year about 300,000-500,000 babies

are born with severe hemoglobin abnormalities, and 50,000 to 100,000 children die from

thalassemia. Indonesia is one of the countries with a high frequency of genes or carriers

of thalassemia. Epidemiological research in Indonesia found that the frequency of the

thalassemia beta gene ranges from 3-10% (National Guidelines for Thalassemia

Management Medical Services, 2018). Based on data from the Thalassemia Indonesia

Foundation, there has been a continuous increase in thalassemia cases. From 2012 to June

2021, there were 10,973 cases of thalassemia in Indonesia (Sehat Negeriku Editorial,

2022).

Reny Faristin Putri Arifin, Wildan Firmansyah

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2836

According to (Rediyanto, 2023) states that thalassemia is differentiated into alpha

thalassemia if the synthesis of the alpha globin chain decreases and thalassemia beta if

there is a decrease in the synthesis of the beta-globin chain. Thalassemia can occur from

mild to severe (Wishnuwardhana, Fernandez, Trixie, Jovito, & Gabriella, 2022). Beta

thalassemia is inherited from both parents who carry thalassemia and shows the most

severe clinical symptoms, this condition is also called thalassemia major. Patients with

thalassemia major will experience anemia due to the destruction of hemoglobin and

patients have to undergo a lifetime blood transfusion once a month. Thalassemia cases

in Madiun City number 39 people.

Method

The method used is a case report.

Results and Discussion

Case report of patient Mrs. T, 27 years old, HPHT: 01-10-2023, routine ANC

examination every month, ANC examination results in 18-19 weeks no complaints, and

laboratory examination results in Hb 4.7. The patient's previous disease history was

transfused when he was still in high school with 1 blood bag with complaints of frequent

dizziness, and then never transfused again. The patient was treated at Dr. Soedono

Madiun with G1P0A0 18/19 weeks + Severe Anemia (Hb 4.7).

Weight 44.7 kg, Height 155 cm. Vital signs of blood pressure 120/80 mmHg,

Breath rate 20 x/min, pulse 110 x/min, temperature 36.7 °C, SpO2 99% room water.

Physical examination found anemis in the conjunctiva of the eye.

Status Obstetri

Inspection : Distended abdomen, no surgical scars, stria gravidarum (-)

Leopold I : teraba ballotement. TFU: 14 cm

Leopold II : the ballotement. DJJ: 150x times/minute

Leopold III : teraba ballotement

Leopold IV: not yet entered the upper door of the pelvis

Fetal motility: There is fetal movement

His : (-)

VT : VT Ø -/ eff 0% /ket (-)/kep/SSmell/H-I

DJ: 150 x/min

The ANA test was negative. Hematology examination showed Ferritin 821.7

(Hyperferritin), Hematocrit 16.3% (Hypohematocrit), Erythrocytes 2.24 (low), MCV

72.8 (low), MCH 22.3 (low), MCHC 30.7 (low), Reticulocytes 10.7 (increased).

Peripheral blood deletion indicates the conclusion of Hypochrome microcytic severe

anemia with an elevated erythropoietic system, a suspect of iron differentiation with

Obstetric and Gynecology Department of RSUD Dr. Soedono Provinsi Jawa

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2837

active bleeding or hemolytic processes. Blood chemistry test of total Billirubin 3.05

(increased), Billirubin decreased by 1.10 (increased).

Thalassemia is an inherited disorder syndrome and is included in the

hemoglobinopathy group, which is a disorder caused by disruption of hemoglobin

synthesis due to mutations in or near the globin gene. This mutation in the globin gene

can cause two changes in the globin chain, namely:

Changes in the structure of the amino acid chains of certain globin chains called

structural hemoglobinopathy, or Changes in the rate of synthesis or the ability to produce

certain globin chains, are called thalassemia.

Adults have HbA hemoglobin consisting of alpha globin 2 and beta 2 chains, while

fetuses have HbF consisting of alpha 2 and gamma 2 globin chains (Paloma, 2023). The

decrease in beta globin chain production in beta thalassemia increases alpha globin chain

production resulting in an excess of alpha globin chain. Beta globin chains in adults and

gamma globin chains that are still produced after birth cannot bind to the entire

overproduced alpha globin chain, so excess alpha globin chains are characteristic of the

pathogenesis of beta-thalassemia.

A study of 48 thalassemic women β showed that 72.9% of transfusion-dependent

patients during pregnancy, 18.75% ended up in premature labor, 14.5% of patients

underwent cesarean delivery, 45.8% of patients experienced fetal growth restriction and

8.3% of pregnancies ended in stillbirth. The patient's and family's history is very

important in diagnosing thalassemia because, in populations with certain races and

ethnicities, there is a high frequency of specific types of abnormal thalassemia genes. On

physical examination, symptoms and pale signs are found that indicate abnormal cell

pooling, and skeletal deformity, especially in beta-thalassemia which shows expansion of

the bone marrow cavity, in thalassemia major.

Excessive alpha chains that cannot bind to other globin chains will precipitate

precursors of blood cells in the bone marrow and progenitor cells in peripheral blood,

causing impaired maturation of erythroid precursors and erythropoiesis and causing

erythrocyte lifespan to be shortened. The activity is anemia. Anemia causes continuous

proliferation of erythroids in the bone marrow resulting in bone marrow expansion which

then leads to skeletal deformities and various growth and metabolic disorders.

Furthermore, anemia also results in splenomegaly so that more abnormal blood cells are

trapped and then destroyed by the phagocyte system. Bone marrow hyperplasia then leads

to increased iron absorption and load. In addition, regular transfusions carried out by

thalassemia patients will also increase the iron load so that there is iron accumulation in

various organ tissues which will be followed by organ damage and end with death if this

iron is not immediately removed (Guntur et al., 2014).

Hemoglobinopathy found clinically, whether in children or adults, is caused by

mutations in the globin α or β gene. Meanwhile, mutations in the weight of globin genes

ζ, ε, γ can cause death at the beginning of gestation.

A decrease in the synthesis rate or production capacity of one or more globin chains

a or b, or other globin chains, may cause a partial or complete production defect of the

Reny Faristin Putri Arifin, Wildan Firmansyah

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2838

globin chain. As a result, thalassemia occurs which is of the type according to the globin

chain whose production is disrupted, as shown below (Daniel et al., 2019). Thalassemia

α occurs due to reduced or no production at all of the production of globin chains α.

1. Thalassemia β occurs due to reduced or no production at all of the production of globin

chain β.

2. Thalassemia σβ occurs due to reduced or no production at all of the production of both

globin chains σ and β.

3. Double heterozygous thalassemia α or β with hemoglobin thalassemia variant.

Patients with thalassemia have a history that varies from asymptomatic to clear

complaints of anemia. There is a family history, of complaints of weakness, enlargement

of the liver and spleen, growth disorders, sexual maturity disorders, and heart failure

(Maulina, 2018). In alpha thalassemia, there are two main phenotypes. The elimination

of the fourth α-globinogen chain (-/-) characteristic homozygous α-thalassemia. Because

the chain forms fetal hemoglobin, the fetus in the womb is affected. Without α-globin

chains, Bart's hemoglobin and H hemoglobin are formed as abnormal tetramers. Fetal

death occurs either in the womb or immediately after birth.

Homozygous alpha thalassemia is a common cause of hydrops fetalis in Southeast

Asia. HbH(β4) diseases are compatible with extrauterine life. Abnormal red cells at birth

contain a mixture of Bart hemoglobin, H hemoglobin, and hemoglobin A. Neonates

appear both at birth but soon develop hemolytic anemia. Some of Bart's hemoglobin

present at birth is replaced postnatally by hemoglobin H. The disease is characterized by

hemolytic anemia, which may be severe and similar to α-thalassemia major. Anemia in

women usually worsens during pregnancy.

Deletion of two clinically occurring genes in α-thalassemia minor, which is

characterized by minimal to moderate hypochromic microcytic anemia. Thus, the

genotype may be - / - or - /. Patients with β thalassemia intermedia are at increased risk

of complications during pregnancy, which include, worsening anemia and

thrombocytopenia, miscarriage, intra-uterine fetal death, premature labor, cesarean

section, and intrauterine growth restriction (Nassar et al., 2006). There is no specific

therapy for β-thalassemia minor during pregnancy. Prophylactic iron and folic acid are

administered. Prenatal diagnosis of thalassemia using chorionic villus sampling can be

done at 9 to 13 weeks.

In order for a pregnancy to occur normally, what must be considered is that women

with thalassemia must have an optimal health status and not experience organ damage

(heart, liver, and others) due to excess iron. Liver function and heart function tests are

done before planning a pregnancy. Diet is also considered so as not to consume foods that

contain excessive iron.

Pregnant patients with thalassemia beta minor do not need to be given specific

therapy and generally tolerate pregnancy well. Iron supplementation is given if there is

an indication, while folic acid is recommended to be given when planning a pregnancy or

immediately after pregnancy. If anemia becomes severe. Then the administration of

transfusions can be considered. Patients with thalassemia beta major and intermediate

Obstetric and Gynecology Department of RSUD Dr. Soedono Provinsi Jawa

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2839

need to be given regular transfusions and keep their hemoglobin levels above 10 mg/dl.

All patients with homozygous thalassemia should receive folic acid supplements.

Therapy of iron chelation with deferoxamine in pregnancy is still controversial. Female

patients suffering from alpha thalassemia HbH, in general, can have a good pregnancy,

but often cause acute exacerbations of chronic anemia and require blood transfusions.

Conclusion

Patients develop severe hypochrome microcytic anemia characterized by a low red

blood cell count (low erythrocytes), a small average red blood cell volume (low MCV),

and a low hemoglobin concentration per red blood cell (low MCHC), accompanied by

hyperferitinemia (very high ferritin levels) and increased reticulocytes indicating an

increase in red blood cell production by the bone marrow in response to anemia. An

increase in total and indirect bilirubin levels indicates the presence of excessive

breakdown of red blood cells, while high reticulocytes indicate that the bone marrow

responds rapidly to anemia, which is consistent with hemolysis. Hyperferitinemia usually

indicates the presence of iron hoarding, but in the context of anemia and very high ferritin

levels, this can indicate a problem with the efficient use of iron in the body. This disorder

may be caused by the inability of the alpha globin chain to bind to other globin chains,

leading to the deposition of alpha chains in erythroid progenitor cells in the bone marrow

and red blood cells in peripheral blood, resulting in impaired maturation of red blood cells

(erythropoiesis) and shortening the lifespan of red blood cells. Despite a negative ANA

test, autoimmune hemolytic anemia should still be considered due to an indirect increase

in reticulocytes and bilirubin, while globin production disorders such as thalassemia,

especially alpha thalassemia, and siderobastic anemia can also cause similar symptoms

and laboratory results. To ensure a proper diagnosis, it is recommended to carry out

further examinations such as direct and indirect Coombs tests to evaluate the presence of

antibodies that cause hemolysis, hemoglobin analysis (hemoglobin electrophoresis) to

evaluate the possibility of thalassemia or other hemoglobinopathy, and bone marrow

biopsies to assess the status of erythropoiesis and the presence of abnormal cells or iron

deposits. With a more precise diagnosis, appropriate therapy can be given to overcome

anemia and improve the patient's quality of life.

Reny Faristin Putri Arifin, Wildan Firmansyah

Jurnal Indonesia Sosial Teknologi, Vol. 5, No. 6, June 2024 2840

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