WEEK 1 HEMATO

Brigita Vania Ilenadea 00000008156

HEMOGLOBINOPATHIES CHAP. 7

Source : Lange

Normal globin chemistry

The globin portion of hemoglobin can be defined according to combination of , , ,

globin chains. Impaired in globin synthesis produce microcytic, hypochromic
anemia and changes in pairing of several globin chains. Kalau ada amino acid
subtitution bisa merubah struktur dan fungsi hemoglobin.
Normalnya Hb terdiri dari 2 dan 2 globin chains. Kalo ada perubahan dari susunan
ini bisa mempengaruhi afinitas o2 -> polycitemia dan tidak stabil -> hemolysis

Normal Hemoglobins
Hemoglobin A. This is the designation for the normal hemoglobin that exists after
birth. Hemoglobin A is a tetramer with two alpha chains and two beta chains
(a2b2).
Hemoglobin A2. This is a minor component of the hemoglobin found in red cells
after birth and consists of two alpha chains and two delta chains (a2d2).
Hemoglobin A2 generally comprises less than 3% of the total red cell
hemoglobin.
Hemoglobin F. Hemoglobin F is the predominant hemoglobin during fetal
development. The molecule is a tetramer of two alpha chains and two gamma
chains (a2g2).
Thalassemia
The thalassemias are a group of disorders in which the normal hemoglobin protein is
produced in lower amounts than usual. The genes are defective in the amount of
hemoglobin they produce, but that which they produce (generally) is normal. The
thalassemias are a complex group of disorders because of the genetics of hemoglobin
production and the structure of the hemoglobin molecule.
CLINICAL FEATURES
1. Sickle cell anemia

Bentuk homozygote hemoglobin S disease

Muncul di awal kehidupan dengan severe hemolytic anemia
Vasooculsive disease involving marrow, spleen, kidney, and CNS
Di anak : sakit saat nangis, bone / joint paint, illness lain
Bias spleen infarc
Resiko infeksi Streptococcus, Haemophilus
Di dewasa : vasooculsive cries, bone and joint disease, aseptic necrosis

2. Compound hemoglobinopathies

Kombinasi S dan C jadi SC disease (gross hematuria)

Atau kombinasi B dan thalassemia (variable hematuria)

3. Hemoglobin C disease
Homozygote hemoglobin C ( well compensated anemia)
No vasooculsive disease
Increase rate of RBC destruction -> bisa jaundice

LAB STUDIES

Key test: CBC, HPLC (high performance liquid chromatography), hemoglobin

electrophoresis. Tambahan: LDH dan indirect bilirubin

1. RBC and morphology

- Although most hemoglobinopathies normocytic normochromic anemia. MCV bias
turun pada keadaan sickle cell anemia. Pada keadaan kombinasi dengan thalassemia
atau Hemoglobin E MCV biasa turun. Tapi , kalau udh di barengi folic acid
deficiency -> ini kan megaloblastic maka hasil MCV nya bias seakan normal. Maka
perlu dilakukan peripheral film.
- Cell morphology : sickle cell -> banana / crescent moon ( fragments of the cells and
partially distorted cells with sharp pointed extensions)
- Hemoglobin S : rigid crystal like structure
- Kalo merusak spleen (sickle cell) : Howel Jolly bodies and nucleated orthochromatic
normoblats
- Heinz bodies
- Hemoglobin C: blok like crystal like in center of RBC
2. Hb Electrophoresis
Best by HPLC analysis (detect and quantify any abnormal Hb)
3. Isopropanol stability test
Unstable hemoglobin usually precipitates with in 5-20 min
Normalnya 40 -60 min
4. Heat stability test
Unstable hemoglobin akan presipitasi pada suhu 50
5. Detection of intracellular inclusion bodies
Brilliant cresyl blue: diffuse cobblestone type stippling of RBC
Methyl violet stain: Heinz bodies ( pada thalassemia dan G6PD juga di temukan)

DIAGNOSIS
1. Hemoglobin S disease
Sickle cell trait
Heterozygote form of hemoglobin S not associated with anemia or clinical disease.
The only abnormality that has been associated is self limited episodes of pain less
hematuria.

Sickle cell anemia

Homozygote form of hemoglobin S. Muncul di infant pada usia 6 bulan karena
sebelum itu masih ada fetal hemoglobin.
Classic symptoms and sign:
Recurrent painful crises secondary to intravascular sickling, small vessel occlusion,
and tissue infarc.
Young children: acute dactylitis secondary to marrow necrosis in small bones of hand
and feet.
Older children: recurrent bone and joint pain, abdominal pain-> spleen infarc
Sepsis
Severity
Tergantung dari konsentrasi hemoglobin S dan F
Ada tendensi untuk dehidrasi
Viskositas darah menigkat
Rate hemolysis berbeda beda
Risk for sudden and repeated aplastic crises
Complications
Growth retardation
Delayed puberty
Women have no difficulty bearing children
Men : priapism
Proliferative retinopathy
Gallstones, aseptic necrosis, leg ulcers, renal insuf, acute chest syndrome

Hemoglobin SC disease
Mirip sickle cell manifestasinya tapi vasoocclusive manifestation lebih sedikit
Gross hematuria
Ada crystal formation tendency spherocytes
Peningkatan MCHC

Hemoglobin B- thalassemia
Severity tergantung dari kadar hemoglobin F
Mirip sickle cell trait

Other

2. Hemoglobin C disease
Homozygote hemoglobin C disease
Mild to moderate hemolytic disease
Do not have vasoocclusive problems

3. Hemoglobin D disease
Heterozygote are not anemic
Homozygote mild anemia

4. Unstable
Heinz bodies

THERAPY
Sickle cell anemia
a. Painful sickle crises
Pake nonsteroid analgesic, acetaminophen, narcotics
Fluid intake must be maintain
RBC transfusion
In severe bisa hydrated with dextrose and normal saline
Morphine
b. Prevention for painful crises
Transfusin -> darahnya di diluted makanya symptom berkurang
At least 2 U PRBC must be transfused every 2-4 weeks
Hati2 iron overload makanya untuk long term bisa di damping dengan oral chelator,
deferasirox, or deferoxamine
Berikan juga supplementasi Vit E
Induction of hemoglobin F (ada 4 obat tapi yang sering dipakai hydroxyurea (10-15
kg/BB/d))
Reduction of intracel HB concentration
Bone marrow transplantation

Management of other complications

Pigmen gallstonesand cholecytitis and cholangitis -> cholecystectomy
Aseptic necrosis -> pain medication
Acute chest syndrome -> RBC exchange transfusion, fluid resuscitation,
oxygen, antibiotics, anticoagulant
Priapism-> pain medications
Leg ulcer -> Unna boot
Infeksi -> suntiok meningococcal and pneumococcal
NOTES: BUKA BUKU HALAMAN 82 GAMBAR
Hasil lab halaman 80,81,83
Clinical features halaman 84