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Anwar Zaben Arwa Maqboul Eias Al-ashhab Majd Barahmeh Ra’ed Mashalah

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Presentation on theme: "Anwar Zaben Arwa Maqboul Eias Al-ashhab Majd Barahmeh Ra’ed Mashalah"— Presentation transcript:

1 Anwar Zaben Arwa Maqboul Eias Al-ashhab Majd Barahmeh Ra’ed Mashalah
Hemoglobinopathies Anwar Zaben Arwa Maqboul Eias Al-ashhab Majd Barahmeh Ra’ed Mashalah

2 Qualitative Sickle cell anemia Hb C disease Hb SC disease Qauntitative Thalassemias (α and )


4 Hemoglobin Gene

5 HBB Gene – Hb S Variant

6 Testing

7 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A + Normal

8 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A + Normal Hb SS

9 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A+ Normal Hb SS Hb AS

10 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A+ Normal Hb SS Hb AS Hb SC

11 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A+ Normal Hb SS Hb AS Hb SC Hb CC

12 Secondary Laboratory Investigation Cellulose Acetate Hb Electrophoresis
- A2/C S F A+ Normal Hb SS Hb AS Hb SC Hb CC HB AD

13 Genetics of Sickle Cell
Sickle cell is an autosomal recessive disease. Therefore, the child can only get Sickle cell if both parents are carriers, not if only one is and the other is normal. They have a 25% chance of getting it if both are carriers


15 HBB Gene Continued…

16 Sickle Cell Disease This results when both copies of the hemoglobin beta gene have an S mutation. All of this person’s beta subunits are replaced by beta S. Hemoglobin Alpha Beta S


18 An infant doesn’t start show symptoms until sufficient Hb F has been replaced by Hb S

19 Glutamate is replaced by valine
Protrusion on β-globin at low [o2] Hb polymerizes Normal RBCs can squeezes itself but sickled RBCs cant



22 symptoms

23 1-Sickle cell crises : pain episodes
RBCs assume the sickle-like shape They clog at the capillaries and block the blood flow Those sickle-like shape cant squeeze like normal RBCs Tissue are not oxygenated resulting in tissue injury or tissue death Pain episodes crises

24 Organs that can be affected by sickle crises:
Brain : could cause a stroke spleen and kidney : renal and splenic dysfunction Muscle ,bone and joint Lungs : acute chest syndrome


26 Sickled RBCs have shorter lifetime
2- hemolytic anemia : Sickled RBCs have shorter lifetime span ( 20 days instead of 120 days ) . It causes to decrease the number of RBCs anemia

27 3-hyperbilirubinemia:
RBCs breakdown in spleen Heme group breakdown produces bilirubin We can get rid of bilirubin by liver and kidney Elevated levels of bilirubin causes to color the skin and eyes with yellow color

28 4- increased susceptibility to infections:
Blood blockage in splenic tissue damages the tissue making the patient more susceptible to infections Spleen is responsible for activating immune respond

29 The proportion of sickle –like shape cells is enhanced by factors that increase the deoxy- Hb S :
PCO2 [2,3-BPG] dehydration

30 treatment

31 -Analgesics to reduce pain
-Antibiotics ( ex : penicillin) reduces morbidity and mortality due to bacterial infections -Blood transfusion if the patient has chronic anemia Blood transfusion complications : -blood borne infections -hemosiderosis (accumulation of iron in heart ,liver and endocrine organs )

32 Advantages of sickle cell disease :
1 of 500 newborn African Americans have the homozygous Hb S genes 1 of 12 newborn African American have the trait sickle cell disease The parasite causing malaria has lifetime span as the normal RBC but sickled RBCs have shorter lifetime span the parasite dies before causing malaria

33 Hemoglobinpathies Over 800 different mutations of globin chains of human hemoglobin have been discovered Mutations are classified by the type of mutation. Examples: Insertion Deletion Base change Base mismatch (translocation Duplication Inversion

34 These mutations can affect the structure of the protein leading to a deformed protein with malfunction (e.g.: Mutation in alpha chain, and beta chain)

35 Hemoglobin C Hemoglobin C (Hb C) is a beta globin chain mutation, it is caused by the amino acid substitution of lysine instead of glutamine at the Beta-6 position, making the Hb C a less soluble protein than Hb A which is the most abundant hemoglobin protein in adults (around 90% of total hemoglobin in adults.)


37 Since Hb C is a less soluble hemoglobin than Hb A, this means that Hb C forms hexagonal crystals in the infected blood cell


39 When Hemoglobin C is present in any of its states (homozygous Hb C, heterozygous Hb SC, and Hb AC) it induces red cell dehydration


41 Hemoglobin C disease Some characteristics of homozygous hemoglobin C disease (Hb CC) include: Cell dehydration Target cells Mild hemolysis with no significant anemia (mild anemia) While heterozygous Hemoglobin C patients are phenotypically normal and the above symptoms doesn’t apply

42 In homozygous hemoglobin C patients, the Hb C amount in a blood cell is about 100%, while in heterozygous hemoglobin C patients (Hb AC), the percentage of the Hemoglobin C protein is about 35-45% and the rest is normal Hemoglobin (Hb A)

43 Cell dehydration Dehydration is caused by abnormal cellular Potassium loss by the K-Cl cotransport pathway (Potassium – Chloride cotransporter) due to interactions between the abnormally positive charged hemoglobin protein and the cell membrane causing an elevated K-Cl cotransport activity


45 Hemoglobin SC disease This disease is caused by having double heterozygotes for Beta S and Beta C in patients. In Hb SC disease, Hb C increases K-Cl cotransport activity, this causes the high intraerythrocytic concentration of Hb S to make polymers, giving the red cell it’s sickled shape In Hb SC disease, the cell contains 50% of Hb S and 50% of Hb C, no normal hemoglobin is present (Hb A)


47 Some Hb SC symptoms Some of the Hb SC disease symptoms include:
Retinopathy Ischemic necrosis of bone Mild painful crisis Possible asplenia (about 45% of patients older than 25) leading to sepsis (lowering B.P, dysfunction in kidneys, liver, lungs and CNS)



50 Methemoglobin Normal hemoglobin contains ferrous ions on the center of the heme groups Methemoglobin is formed when ferrous oxidized to ferric Our blood contains normally about 1% Hb M

51 Methemoglobinemia

52 Causes Drugs ( nitrates)
Endogenous products (reactive o intermediates) Inherited defects (mutations) Deficiency of NADH- Hb M reductase

53 Effects and Symptoms Functional Anemia Chocolate cyanosis
Chocolate-cholored blood Tissue hypoxia → anxiety, headache , dyspnoea , weakness , lightheadache . Rare cases → coma , death.

54 Treatment Methylene blue

55 Hemoglobin Synthesis Adult hemoglobin - 96% HbA (α2β2)
Clinically significant variant hemoglobins - usually β abnormalities α β α β

56 Thalassemia Absent or  Synthesis of Globin Chains (Quantitative)
Most Frequent in Mediterranean, African, or Asian Populations  - Thalassemia -   Chain Synthesis (Gene Mutations)  - Thalassemia -   Chain Synthesis (1-3 of 4 Genes Deleted) (SE Asians)

57 Global Distribution of Thalassemia

58 Carrier Frequencies for Common Hemoglobin Disorders/WHO- percent
α⁺ thalassemia α◦ thalassemia  - Thalassemia Region 0-40 0-5 0-3 Americas 1-60 0-2 2-18 Easter Mediterranean 0-12 1-2 0-19 Europe 3-40 1-30 0-11 S Asia 10-50 Sub-Saharan Africa 2-60 0-13 W Pacific

59  - Thalassemia's α⁺ thalassemia (common /milder form)→ mild hypochromic anemia in homozygous α◦ thalassemia's → stillbirth, with toxemic and postpartum complications α ⁺ + α◦ thalassemia's → Hb H , varies in severity

60 Classification & Terminology Alpha Thalassemia
Silent carrier Minima Minor Intermedia Major

61 Symbolism Alpha Thalassemia
Greek letter used to designate globin chain:

62 Symbolism Alpha Thalassemia
/ : Indicates division between genes inherited from both parents: / Each chromosome 16 carries 2 genes. Therefore the total complement of  genes in an individual is 4

63 Symbolism Alpha Thalassemia
- : Indicates a gene deletion: -/

64 Classification & Terminology Alpha Thalassemia
Normal / Silent carrier - / Minor -/- --/ Hb H disease --/- Barts hydrops fetalis --/--

65 Silent Carrier of α- Thalassemia
are clinically and hematologically healthy may have mild reductions in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Normal Hb electrophoresis Detected by gene analysis

66 α-thalassemia trait minimal to no anemia and a low MCV and MCH.
Normal electrophoresis May show microcytosis and target cells Identified by gene analysis

67 Hb H disease / Hb (4) disease
marked variability in degree of anemia patients may range from asymptomatic to needing periodic transfusions to having severe anemia with hepatomegaly and splenomegaly Some patients may also suffer hydrops fetalis syndrome in utero

68 electrophoresis Hb H disease can be identified by electrophoresis

69 Hydrops fetalis ( erythroblastosis fetalis): Swollen dead fetus

70 Usually these infants die in utero or shortly after birth
An excess of Bart hemoglobin (γ4), which is unable to carry oxygen effectively, is indicated Infants born have massive total body edema with high output congestive heart failure due to the severe anemia massive hepatomegaly due to heart failure and extramedullary hematopoiesis

71  - Thalassemia         Hydrops fetalis Chromosome 16
 - thalassemia trait (+/- anemia) Silent carrier HbH β4 disease Hb Bart γ4 (severe anemia) Hydrops fetalis (lethal in utero)


73 Beta Thalassemia Inherited disorder (handed to children from parents equally) A gene from each parent Carrying beta thalassemia HB disorder (minor beta thalassemia) 2 genes of Beta thalassemia life long disorder (major beta thalassemia)

74 Symbolism Beta Thalassemia
Greek letter used to designate globin chain:

75 Symbolism Beta Thalassemia
+: Indicates diminished, but some production of globin chain by gene: +

76 Symbolism Beta Thalassemia
0 :Indicates no production of globin chain by gene: 0

77 Classification & Terminology Beta Thalassemia
Normal / Minor /0 /+ Intermedia 0/+ Major 0/0 +/+

78 Beta Thalassemia Minor
Carrying beta thalassemia beta thalassemia gene + normal HB A gene

79 Measure RBC size (MCV). Analyse the types of HB. (A+A2)
Testing Measure RBC size (MCV). Analyse the types of HB. (A+A2)

80 Protection from Malaria Protection from heart attacks But……………………?
Advantages Protection from Malaria Protection from heart attacks But……………………?

81 Passing beta thalassemia minor
The child may carry beta tahassemia The child may not carry any HB variant

82 Beta thalassemia major
2 defected Beta genes no beta chains synthesis alpha chains precipitate premature death of RBCs. Complications Enlargement…

83 Treatment Regular Blood transfusion ……4 weeks. Blood testing
Live through 20s ……remove iron (desferrioxamine) pump Bone marrow transplantation Disadvantages Expensive , tiresome , not available for every one

84 The need of the hour (prevention)
Screening and Counseling Carrier testing Inform carriers Both carriers counsellor Prenatal diagnosis (unborn baby) if affected terminate or continue with planning Neonatal diagnosis (after birth) if early diagnosed Save the child

85 Telling a partner to have a blood test
When ? Before marriage Before pregnancy As soon as the pregnancy started Easy….. because ?

86 Passing Beta thalassemia major
Child may carry beta thalassemia major Child may not carry any HB variant Child may carry beta thalassemia trait

87 Facts Beta thalassemia major one of the commonest inherited disorder
1 of 50 human beings carry beta thalassemia (100 million carriers) children are born with beta thalassemia major Carriers are particularly common among people originate from Mediterranean , ME and east of Asia and not common among people from northern Europe.

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