THALASSEMIA MAYOR

Case report Amalia Khairunisa Hsb (090100006) Albert (090100212) Pembimbing dr. Hj. Rita Evalina, Sp.A (K)

a heterogeneous group of inherited conditions characterized by defects in the synthesis of one or more of the globin chains that form the haemoglobin tetramer disorders of Hb synthesis

thalasemia---common in Southeast Asia

Thalassemia

Worldwide ----- 3% carry thalassemia genes 15 millions have clinical features

thalassemia ---common in southern Europe, India, Africa

P A T O P H Y S I

O L O G Y

22 Hbf
Selective survival of HbFcontaining Cell

Excess Precipitati on Hemolysis

Destructio n of red blood cell precursor s Ineffective erythropoie sis

High oxygen affinity of red celis

Splenomegaly (pooling, plasma volume expansion) Tissue hypoxia Erytropoietin Marrow expansion Anemia Increased iron absorption

Transfusion

Bone deformity increased metabolic rate Wasting Goul Folate deficiency

Iron loading
Endocrine deficiencies Cirrhosis Cardiac failure Death

Classification
-thalassemia
USUAL GENOTY PES GENE NUMB ER CLINIC AL FEATUR ES NORMA L HEMOGLOBIN ELECTROPHORESIS BIRTH > 6 MO

-thalassemia
0
Homozygous or compound heterozygous (0 0) total lack of Chain production total failure to produce Hb A

+
Homozygous (++) some productions of Hb A.

NORMAL

NORMAL

- /

SILENT CARRIE R

0 3% Hb Barts

NORMAL

-- / or - / - -- / -

- THAL TRAIT Hb H DISEAS E FETAL HYDRO PS

2 10% Hb Barts

NORMAL

Heterozygosity - Thal trait

15 30% Hb Barts > 75% Hb Bart,s

Hb H PRESENT

Thal minor

Homozygosity - Thal major transfusion dependent Thalassemia Intermedia

4

-- / --

Clinical Manifestations
Failure to thrive

Laboratory Diagnostics
Anemia : hypochromic,microcytic

Anemia

Reticulocytosis

Jaundice, gallstones Abnormal facies, prominence of malar eminences, exposure of upper central teeth Growth retardation, delayed puberty

Hb electrophoresis: Hb F and A2 increased

Blood film: variation in red cell size and shape, pale (hypochromic) red cells, target cells,basophillic stippling,nucleated red cells

Chromatography: HPLC

Leg ulcers

Bone marrow: megaloblastic (due to folate depletion) ,erythroid hyperplasia

Skin bronzing
DNA analysis

Complications
1. 2. 3. 4. Chronic anemia in undertransfused or in untranfused thalasemia intermedia patients Chronic transfusion with resultant hemosiderosis and hemochromatosis Hyperplastic marrow,extramedullary hematopoiesis Increased iron absorption and iron overload Fibrosis/cirrhosis of the liver liver failure Endocrine disturbances : growth retardation , pituitary failure with impaired gonadotropins, hypothyroid, delayed puberty Skin hyperpigmentation Cardiac hemochromatosis cardiac failure

5.

Hypersplenism: plasma volume expansion, shortened red cell life, leukopenia

,thrombocytopenia

6.

Osteoporosis
6

Treatment & Prognosis

Keep post transfusionHb not higher than 14 15 g/dL

Transfusion to maintain the pre-transfusion haemoglobin level above 9 - 10,5 g/dL

Give ABO,Rh(D) compatible blood

Leucoreduced PRC or washed red cells

Treatment
Keep record of red cell antibodies,transfusion reaction

Chelation Therapy

Used: 1.Desferrioxamine (Desferal) iv,sc 2.Deferiprone :oral

Small dose of vit C may enhance the efficacy of iron chelation

The prognosis of patients with thalassemia major is highly dependent on the patient's adherence to longterm treatment programs, namely the hypertransfusion program and lifelong iron chelation.

Prognosis

The prognosis depends on the type and severity of thalassemia.

Medical Record

CASE REPORT
: AFJ : 10 years old : Male : December, 6th 2013 : Pasar barus village of general hospital street

Name Age Sex Date of Admission Address

Main Complaint (Alloanamnesis) Pale (+) History :

Pale was happened since 5 days before the patient came to the hospital.History of fever was found in the past 1 week ago. The characteristic of fever was recurrent, subfebris, and decreased with antipiretic drug. Fever was not found when the patient came to the hospital History of defecating and urinating was found normally. History of cough was not found. History of spontan bleeding was not found. History of diarrhea was not found. History of vomiting was not found. History of illness was not found. History of family illness was not found. History of occupation was a student. This patient was HematologyOncolgys patient with Thalasemia Mayor diagnosed and got routine blood transfusion

Physical Examination Generalized status Body weight : 20 Kg Body length : 125 cm

BW/BL : 68,9% BW/Age : 80% BL/Age : 97,6%

Presens status Sensorium : compos mentis Blood Pressure : 90/60 mmHg Heart Rate : 128 bpm Temperature : 36, 7 oC Respiratory rate : 28 bpm Anemic (+/+), Icteric (+), Edema (-), Dyspnea (-), Cyanosis (-). Localized status Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (+/+) Ear/Mouth/Nose : normal Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax : Symmetrical fusiformis. Epigastrial retraction (-). HR : 128 bpm, reguler, murmur (-) RR : 28 bpm, regular, crackles (-/-)

Abdomen

Extremities Urogenital

: Soepel. Peristaltic (+) normal. Liver was palpabled, 3 cm under arcus costae dextra. Spleen : S V - VI : Pulse 128 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) : Male, normal in appearance

Differential Diagnosis Thalasemia Mayor Working Diagnosis Thalasemia Mayor Management IVFD D 5% NaCl 0,45 % 10 gtt/ mikro R/ Blood Transfusion 60 cc Necessity of PRC (Hb target : 10 g%) PRC 4 x BW x Hb 4 x 20 kg x (10 3,9 g%) 488 cc (500 cc) Transfusion capability with Hb < 5 = 3 cc/ kgBW 60 cc / transfusion

Complete Blood Count (September, 03rd 2013) Examination

Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) Hematokrit Trombosit (PLT) MCV MCH MCHC RDW MPV PCT PDW Diftel Count Neutrofil Limfosit Monosit Eosinofil Basofil % % % % % 53.60 33.80 11.20 0.20 1.20 37 80 20 40 28 16 01 g% 106/ mm3 103/ mm3 % 103/ mm3 Fl Pg g% % fL % fL

Unit
3.2

Result
1.34 5.20 11.50 243 85.80 23.90 27.80 24.50 10.90 0.27 14.4

Normal
11.7 15.5 4.20 - 4.87 4.5 11.0 38 44 150 450 85 95 28 32 33 - 35 11.6 14.8 7.0 10.2

Kimia klinik (September, 03rd 2013)

Ginjal Ureum Kreatinin mg/ dL mg/ dL 9.10 0.25 < 50 0.5 0.9

Neutrofil Absolut
Limfosit Absolut Monosit Absolut

103/L
103/L 103/L

2.79
1.76 0.58

2.7 6.5
1.5 3.7 0.2 0.4

Eosinofil Absolut

103/L

0.01

0 0.10

Basofil Absolut 103/L 0.06 0 0.1 Morfology Erythrocyte : Hypochromic Microcytic, tear drops (+) pencil cell (+) Leucocyte : Normal Thrombocyte : Normal

December, 08th 2013 (2nd Day)

December, 07th 2013 (1nd Day)

S O Pale (+)

S O

Pale (+)

Sensorium: Compos Mentis, T: 36.8 oC Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (+/+). Ear/Mouth/Nose : Normal. Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax: Symmetrical fusiformis. Epigastrial retraction (-). HR : 94 bpm, reguler, murmur (-). RR : 24 bpm, regular, crackles (-/-) Abdomen: Soepel. Peristaltic (+) normal. Liver was palpabled, 3 cm under arcus costae dextra. Spleen : S V - VI Extremities : Pulse 94 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) Urogenital : Male, normal in appearance

Sensorium: Compos Mentis, T: 36.8 oC Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (+/+). Ear/Mouth/Nose : Normal. Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax: Symmetrical fusiformis. Epigastrial retraction (-). HR : 94 bpm, reguler, murmur (-). RR : 24 bpm, regular, crackles (-/-) Abdomen: Soepel. Peristaltic (+) normal. Liver was palpabled, 3 cm under arcus costae dextra. Spleen : S V - VI Extremities : Pulse 94 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) Urogenital : Male, normal in appearance

A P

Thalasemia Mayor

A P

Thalasemia Mayor

-IVFD D5% Nacl 0,45% 10 gtt/ micro -PRC transfusion 60 cc (I)

-IVFD D5% Nacl 0,45% 10 gtt/ micro -PRC transfusion 60 cc (II)

Complete Blood Count (September, 07th 2013) Examination Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) Hematokrit Trombosit (PLT) MCV MCH MCHC RDW Diftel Count g% 106/ mm3 103/ mm3 % 103/ mm3 Fl Pg g% % Unit Result 6.60 2.50 4.43 21.20 201 84.80 26.40 31.10 16.30 Normal 11.7 15.5 4.20 - 4.87 4.5 11.0 38 44 150 450 85 95 28 32 33 - 35 11.6 14.8

Kimia klinik (September, 07th 2013) Liver Function Total Bilirubin Direct Bilirubin mg/dL mg/dL 8.19 3.83 150 82 91 <1 0 0.2 < 157 < 32 < 31

Alkali Phospatase (ALP) U/L AST/SGOT ALT/SGPT Elektrolit Calsium (Ca) Phospor Magnesium (Mg) Imunoserologi FSH ng/mL mg/dL mEq/L mEq/L U/L U/L

8.5 4.7 2.39

9.2 11.2 3.4 6.2 1.3 1.8

3.36

Follicular phase : 3.5 12.5

Neutrofil
Limfosit Monosit Eosinofil Basofil Neutrofil Absolut Limfosit Absolut Monosit Absolut Eosinofil Absolut

%
% % % % 103/L 103/L 103/L 103/L

68.00
26.40 4.70 0.90 0.200 3.01 1.16 0.21 0.04 0.01

37 80
20 40 28 16 01 2.7 6.5 1.5 3.7 0.2 0.4 0 0.10 0 0.1
LH g/L 0.72

Follicular phase : 2.4 12.6

Hepatitis HBsAg Tiroid T3 Total T4 Total TSH ng?mL g/dL IU/mL 1.60 9.45 2.260 0.8 2 5 14 0.27 4.2 Negatif Negatif

Hepatitis A Profile
Anti HAV IgM Hepatitis C Anti HCV Negatif Negatif Negatif Negatif

Basofil Absolut 103/L Morfology Erythrocyte : normochrom normocytic Leucocyte : Normal

December, 09th 2013 (3nd Day) S O Pale (+) Decreased, Fever

December, 10th 2013 (4nd Day) S O Pale (+) Decreased, Fever

Sensorium: Compos Mentis, T: 36.8 oC Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (+/+). Ear/Mouth/Nose : Normal. Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax: Symmetrical fusiformis. Epigastrial retraction (-). HR : 94 bpm, reguler, murmur (-). RR : 24 bpm, regular, crackles (-/-) Abdomen: Soepel. Peristaltic (+) normal. Liver was palpabled, 3 cm under arcus costae dextra. Spleen : S V - VI Extremities : Pulse 94 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) Urogenital : Male, normal in appearance

Sensorium: Compos Mentis, T: 36.8 oC Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (+/+). Ear/Mouth/Nose : Normal. Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax: Symmetrical fusiformis. Epigastrial retraction (-). HR : 94 bpm, reguler, murmur (-). RR : 24 bpm, regular, crackles (-/-) Abdomen: Soepel. Peristaltic (+) normal. Liver was palpabled, 3 cm under arcus costae dextra. Spleen : S V - VI Extremities : Pulse 94 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) Urogenital : Male, normal in appearance

A P

Thalasemia Mayor

A P

Thalasemia Mayor
-IVFD D5% Nacl 0,45% 10 gtt/ micro -Ceftazidine injection 1 gr/12 hours/IV -Paracetamol 3 x 250 mg -Exjade 250 mg 1-1-1 -As folat 1x1 -Vit C 1x1 -Vit E 1x1 -PRC transfusion 100 cc (IV)

-IVFD D5% Nacl 0,45% 10 gtt/ micro -PRC transfusion 60 cc (III) -Culture Blood and urine - Ceftazidine injection 1 gr/12 hours/IV

R/

Complete Blood Count (September, 10th 2013)

Examination
Hemoglobin (HGB) Eritrosit (RBC) Leukosit (WBC) Hematokrit Trombosit (PLT) MCV MCH MCHC RDW Diftel Count g%

Unit

Result
10.50 3.80 3.61 31.50 222 82.90 27.60 33.30 14.90

Normal
11.7 15.5 4.20 - 4.87 4.5 11.0 38 44 150 450 85 95 28 32 33 - 35 11.6 14.8

106/ mm3 103/ mm3 % 103/ mm3 Fl Pg g% %

Bone Age Result Bone age was appropriate for the 14 years old girl Normal bone modelling Average girl Estradiol pg/mL g/dL 52.1 Follicular phase :

Neutrofil
Limfosit Monosit Eosinofil Basofil Neutrofil Absolut Limfosit Absolut Monosit Absolut Eosinofil Absolut Basofil Absolut Faal Hemostasis Ferritin

%
% % % % 103/L 103/L 103/L 103/L 103/L

52.50
38.00 7.80 1.40 0.300 1.90 1.37 0.28 0.05 0.01

37 80
20 40 28 16 01 2.7 6.5 1.5 3.7 0.2 0.4 0 0.10 0 0.1

12.5 - 166
Cortisol 19.6 6.2 19.4

ng/mL

4431.00

15 - 3000

September, 10th 2013 (8th Day) S O Pale (-), icteric sclera (+/+) Sensorium: Compos Mentis, T: 37 oC, BW: 24 kg Head Eye : Light reflex (+/+), isochoric pupil, Icteric sclera (+/+), Paleness of inferior Palpebral conjunctiva (-/-). Ear/ Nose : normal. Mouth: Lip mucous pale (+). Neck : Lymph node enlargement (-), muchal rigidity (-) Thorax:Symmetrical fusiformis. Epigastrial retraction (-). HR : 102 bpm, reguler, murmur (-). RR : 26 bpm, regular, crackles(-/-) Abdomen: Soepel. Peristaltic (+) normal. Liver was palpabled, 4 cm under arcus costae dextra. Spleen : S III - IV Extremities : Pulse 102 bpm, regular, adequate pressure and volume, warm acral, CRT < 3, paleness of plantar and palmar (+/+) Urogenital : Female, normal in appearance A P Thalasemia Mayor IVFD D5% Nacl 0,45% 10 gtt/ micro Folic Acid 1 x 1 tab Usual diet 1580 kcal + 48 gr of protein - Vit C 1 x 1 - Vit E 1 x 1

Endocrinology S : never get menstruate, hair airmpit and hair genital was not found.

Modul

O : sensorium : compos mentis T : 36.8 oC

Thorax : SF, retraction (-), HR : 102 bpm, reg, murmur (-). RR : 26 bpm, regular, crackles (-/-) Puberty status : Tanner Stage A1M2P1 A : delayed puberty + short stature + thalasemia mayor P : waiting for bone age result

Hematology modul

IVFD Desferol 1000 mg IV (dose : 50 mg/kgBW/day 24 kg x 50 mg = 1200 mg) Available : 500 mg/vial

Therapy for 30 days -

Desferol 50 vial, 1x2 vial Vit C 1x1, 30 tab Vit E 1x1, 30 tab Folic acid 1x1, 30 tab

Discussion
The clinical manifestations of beta thalasemia include anemia Jaundice failure to thrive Hepatosplenomegaly abnormal facies fractures due to marrow expansion and abnormal bone structure, generalized osteoporosis growth retardation, delayed puberty, primary amenorrhea in female, and other endocrine disturbance secondary to anemia and iron overload. In this patient the skin is pallor that resuts from the anemia (Hb =3,2 mg/dl) , and jaundice from hyperbilirubinemia.(total bilirubin = 8,19 mg/dl, bilirubin direct = 3,83 mg/dl). hepatomegaly and splenomegaly.
Hepatomegaly may be related to significant extramedullary hematopoiesis or this patient who have already receive routine blood transfusions may have hepatomegaly or chronic hepatitis due to iron overload. Splenomegaly typically is observed as part of the extramedullary hematopoiesis or as a hypertrophic response related to the extravascular hemolysis.

delayed puberty ( Tanner A1M2P1) and primary amenorrhea also short stature that
may results from endocrine disturbance as a result of iron overload complications in routine transfused patients. (hypogonadism (35-55%)).

Therapy of beta thalasemia include

Transfusion to maintain the pretransfusion haemoglobin level above 9 - 10,5 g/dL Chelation Therapy Used: 1.Desferrioxamine (Desferal) iv,sc 2.Deferiprone :oral Small dose of vit C may enhance the efficacy of iron chelation

In this patient
oxygen -1 L/minute IVFD D5% Nacl 0,45% 10 gtt/i micro folic acid 1x1 tab vit c 1x1 vit E 1x1 PRC transfusion
the PRC transfusion is given 3 times because the hemoglobin need to be maintained until above 9,5 mg/dl, when the patient came the hb was 3,2 and after three times tranfusion, the Hb level is 10,5 and already approaches the goals of therapy

desferol 1000 mg iv
iron chelator therapy desferol to prevent iron overload ( this patient already have endocrine complications of iron overload such as hypogonadism, short stature, primary amenorhea)

after patients discharged, the patients is given therapy for 30 days desferol 50 vial 1x2 vial/day and vit C 1x1, 30 tablets.

---TERIMA KASIH ---