haemoglobinopathies

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HAEMOGLOBINOPATHIES

• S.P CHUWA

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• Describe condition where the HAEMOGLOBIN is
  ABNORMAL.
• Are group of GENETIC disorder of globin sythesis.
• Heterozygous for hemoglobinopathies may be mild
  affected but the HOMOZYGOTES may SEVERELY
  AFFECTED.

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• HAEMOGLOBINOPATHIES are inherited specific
  biochemical disorders within polypeptide chain of
  GLOBIN fraction
• NOTEHaemoglobin consist of four molecules each
  has HEAM and a PROTEIN or GLOBIN chain.

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• The position of amino acid in the globin chain
  determines the type of haemoglobin produced.
• The type of globin chain is genetically
  determined.
• Defective Genes lead to the formation of ABNORMAL
  haemoglobin.

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SICKLE CELL ANAEMIA

• Is found mostly in people with African Origin.
• The defective gene produce abnormal haemoglobin
  (beta chain) to Hbs
• In sickle cell anaemias (HbSS or SCA) abnormal
  gene here have inherited from both parents where
  Sickle Cell Trait (HbAS) only ONE abnormal gene
  have been inherited.
• In SCD valine is replaced by glutamin at position
  6 chromosome 11.

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• Sickle cell have increased FRAGILITY and SHORTNED
  LIFE SPAN of 17 days,which results in CHRONIC
  HAEMOLYTIC ANAEMIA.
• HAEMOLYTIC ANAEMIA causes episodes of ISCHAEMIA
  and PAIN known as SICKLE CELL CRISIS.
• Sickling crisis may occur whenever oxygen
  concentration is low.

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PRECIPITATING FACTORS

• For sickle crisis that affects oxygen uptake
  includes
• i.psychological stress
• ii.Smoking-induced smoking
• iii.Extreme change in Temperature
• iv.Strenuous physical activities
• v.Fatique
• vi.Respiratory disease

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cont

• VII.Infection
• VIII.Pregnancy
• When to LOW OXYGEN TENSION,Hbs contracts demaging
  the cell and causing it to SICKLE shape.
• Demaged cells Block capillaries Results into
  INFARCTION,leads to pain,affecting particularly
  bones,joints, and abdominal organs.

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• The spleen may also be demaged which affects the
  ability to fight INFECTION.
• EMBOLI may be thrown into the circulation which
  may cause STROKE and threaten LIFE.
• MATERNAL AND FETAL EFFECTS OF SICKLE CELL ANAEMIA

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• Increase incidence of
• 1.Abortion
• 2.Prematurity
• 3.Intrauterine growth restriction
• 4.Foetal loss
• 5.Preeclampsia

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cont

• 6.Post partum hemorrhage
• 7.Infection
• 8.Maternal death due to
• A.Pulmonary Infarction
• B.Congestive Heart Failure.
• C.Emboli
• Increased distruction of RBCS leads to
  HAEMOLYSIS,ANAEMIA and JAUNDICE.

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• II.FOETAL
• A.Preterm birth
• B.Small for gestation age
• C.Neonatal jaundice
• D.Intrauterine fetal death

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Diagnosis Of Sickle Cell Anaemia

• 1.Refractory hypochromic anaemia
• 2.Identification by SICKLING TEST
• 3.Persistent reticulocytosis
• 4.Hb Electrophoresis.
• MANAGEMENT OF SICKLE CELL ANAEMIA.
• 1.Premarital counselling
• 2.Careful antenatal supervision

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• 3.Prophylact folic acid
• 4.Prophylactic Iron supplement
• 5.Administraction of effective ANALGESIA
• 6.Maintain good fluid intake to prevent
  DEHYDRATION.
• 7.Antibiotic therapy if infection is suspected
• 8.Social,psychological and physical support.

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• Prophylactic antibiotics should be given because
  in sickle cell there is a risk of infection due
  to Haemophilus influenza and Naisseria
  meningitidis penicillins are antibiotic of
  choice eg Penicillin V. Hydroxy urea is used as
  disease modifying drug increase level of HBF and
  hydration reduce polymerazation of HBS and reduce
  crisis.It should be stopped 3 monthes before
  conception its teratogenic.

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DURING LABOUR

• 1.As in all cases of anaemia
• 2.Continuous oxygen therapy
• 3.Epidural anaesthesia
• 4.Adequate I/V fluid to avoid dehydration and
  acidosis
• 5.Routine broad spectrum antibiotic prophylactic
  to prevent infection in peuperium.

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• Preferred method of delivery is vaginally
  caesarian section is for obstetric indication.
• Women should also be given thromboprophylaxis
  (LMWH) during pregnancy and peuperium
• Cord blood should sent for hemoglobinopathy
  screen.

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• Contraceptive Barrier method.COC has risk of
  thromboembolism,intrauterine contraceptive device
  has a risk of infection,progesterone only
  contraceptive pills can be used or LNG-IUS IE
  levonogestrol intrauterine system is safe and
  effective.

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THALLASEMIA

• Is more common in those from mediterranean
  and far East
• The basic defect is reduced rate of globin
  chain sythesis,leads to ineffective erythropoesis
  and increase haemolysis result to inadequate
  haemoglobin content.

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• . The major syndromes are of two groupsthe alpha
  or beta thalassemia depending on whether the
  alpha or the beta globin chain synthesis of the
  adult hemoglobin is depressed. a and ß
  thalassemia exist in both the homozygous (major)
  and heterozygous (minor) states. Overall
  incidence during pregnancy is 1 in 300 to 500.

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• Alpha thalassemia is distributed amongst South
  East Asia and China. Alpha thalassemia major is
  incompatible with life. a-peptide chain
  production is controlled by four genes, located
  on chromosome 16 (two on each
• copy). Depending upon the degree of deficient
  a-peptide chain synthesis, four clinical types of
  syndromes have

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• Mutation of one gene-silent carrier no clinical
  signs and labaratory defect found- silent disease
• Mutation in two genes-pregnancy tolerated alpha
  thalassemia minor pregnancy is tolerated
• Mutation in three genes-they develop hemolytic
  anaemia in pregnancy

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• D. Mutation in all four genesa-thalassemia
  major. There is no a globin chain, hemoglobin
  Bart (four ? chains) and hemoglobin H (four ß
  chains) are formed. The fetus dies either in
  utero or soon after birth. This is an important
• cause of non-immune fetal hydrops and perinatal
  death

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• Parental diagnosis All forms of a-thalassemia
  can be diagnosed by CVS or amniocentesis.
• Treatment Alpha thalassemia minorThe
  reproductive performance in a-thalassemia minor
  is usually normal.
• They require oral iron and folate supplementation
  during pregnancy. If the hemoglobin is low, blood
  transfusion is indicated. Parenteral iron therapy
  should never be given.

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• Beta thalassemia This entity is predominantly
  distributed along the Mediterranean coast, South
  East Asia.
• Normal adult hemoglobin (HbA) is composed of two
  a and two ß peptide chains (a2 ß2). ß chain
  production is directed by two genes, one on each
  copy chromosome 11. More than 150 point mutations
  in the ß-globin gene have been identified. With
  ß-thalassemia, ß chain production is decreased
  and excess of a-chains precipitate to cause red
  cell membrane damage.

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• Beta thalassemia major (Cooley anemia)When
  mutation affect both the genes. There is red cell
  destruction as there is no ß chain production.
  Erythropoiesis is ineffective. Such an infant
  needs repeated blood transfusionto survive.

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• Beta thalassemia major (Cooley anemia)When
  mutation affect both the genes. There is red cell
  destruction as there is no ß chain production.
  Erythropoiesis is ineffective. Such an infant
  needs repeated blood transfusionto survive.

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• There is progressive hepatosplenomegaly,
  impaired growth, anemia, congestive cardiac
  failure and intercurrent infection. Chance of
  survival beyond teens is uncommon. They are often
  sterile. Problem of iron overload is observed
  beyond the first decade of life. Iron chelation
  therapy with desferrioxamine and blood
  transfusion can improve the outcome.

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• The red cell indices show a low HB and MCHC
  level.
• DIAGNOSIS
• By eletrophoresis
• TREATMENT
• Oral folic acid
• Iron when there is proved iron defiency.

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• The red cell indices show a low HB and MCHC
  level.
• DIAGNOSIS
• By eletrophoresis
• TREATMENT
• Oral folic acid
• Iron when there is proved iron defiency.