Causes of Hemoglobinopathies Blood

• disorders Syndromes Diagnosis Treatment —

Hemoglobinopathies

• Oxygen is delivered to tissues by hemoglobin. Hemoglobin is present in erythrocytes in high con­centration and is responsible for the shape of the cell, viscosity of blood and cell deformability.
• Hemoglobinopathies are disorders of structure, func­tion or production of hemoglobin.
• Different hemoglobins are produced during embry­onic, fetal and adult life.
• The major adult hemoglobin HbA has the structure  a2b2
• Minor adult hemoglobin is HbA₂,a2d2
• HBF or fetal hemoglobin is —a2g2
• HbF predominates during gestation.
• During post natal life, only small amounts of HBF is present.
• At about 6 wks of gestation, the Hb is mainly embry­onic Hb.
• At 10 – 11 weeks, HbF becomes predominant. At 38 wks most of the Hb is HbA.
• During stress, as in hemolytic anaemias, bone mar­row transplant, chemotherapy, HbF increases.
• Hydroxyurea also increases HbF.

Classification of Hemoglobmopathies —

I. Structural hemoglobinopathies–

• 1. Sickle cell anaemia – HbS
• 2. Polycythemia, cyanosis
• 3. Hemolytic anaemia
• 4. Jaundice
• 5. Methemoglobinemia.

II. Thalassemia –

• Alpha thalassemia,
• Beta thalas­semia,
• Alpha-beta thalassaemia.

III. Thalassemic variants –

• HbE thalassemia
• – Hb Lepore

IV. HPFH –

• Hereditary persistence of fetal hemo­globin in adult life.

V. Acquired hemoglobinopathies

• 1. Methemoglobinemia
• 2. Sulfhemoglobinemia
• 3. Carboxyhemoglobinemia.

Diagnosis of Hemoglobmopathies — 

• is by haemoglobin electrophoresis and sickling tests.

The SICkLE CELL SYNDROMES —

SICkLE CELL

• These are hemoglobinopathies with abnormal hemo­globin HbS.
• The cells are sickle-shaped, non-pliable and there­fore cause vascular occlusion. The cells are easily destroyed leading to hemolytic anaemia. The cells are rigid and cause occlusion of capillaries and veins caus­ing tissue ischemia, pain, damage and infarction of organs.
• Sickle-cell anaemia is the homozygous state for HbS.

Clinical manifestations of Hemoglobmopathies —

• are anaemia, hemolysis, vascular occlusions, pain in limbs, renal failure, acute chest syndrome, chest pain, tachypnea, fever, cough, pulmonary embolization, cor-pulmonale.
• The most common clinical manifestation is recurrent acute pain, fever, and tachycardia called painful cri­ses. Repeated crises more than 3 per year require hospitalisation and have bad prognosis.

• The spleen may disappear within 3 years of life due to repeated microinfarction.
• The hand-foot syndrome is due to painful infarct in the digits.
• Sickle cell trait is asymptomatic, because HbS/A is 60/40.

THALASSEMIA SYNDROMES —

THALASSEMIA

• These are inherited disorders of alpha or beta globin synthesis. There is hypochromia and microcytosis.

Clinical manifestations of thalssemia syndromes —

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Clinical manifestations of thalssemia

• are deranged growth and development, anaemia, chipmunk facies with maxil­lary marrow hyperplasia, frontal bossing, thin long bones, growth retardation, hemolytic anaemia, hepatosplenomegaly, and congestive heart failure.
• Chronic transfusions with RBCs prolong life but iron overload occurs and death can occur in 3^rd decade.
• Alpha thalassemia syndromes may be asymptomatic or have hemolytic anaemia.
• Patients of beta thalassemia minor and beta thalas­semia trait are asymptomatic.
• Treatment consists of chronic blood and RBC transfu­sion, and splenectomy.
• Splenectomy is recommended if several transfusions are required in a year.
• Folic acid supplements and vaccination with pneumovax is done before splenectomy.
• Antenatal diagnosis is now widely available. PCR am­plification of fetal DNA is used for specific diagnosis.

Treatment of Hemoglobmopathies —

• of sickle cell syndrome is analgesics, antibiotics, morphine, oxygen therapy, blood trans­fusion.
• Hydroxyure a 10 mg/kg/day increases fetal hemoglo­bin and is helpful.
• Other drugs are azacytidine and decitabine.
• Bone marrow transplantation is curative in children. Gene therapy may provide the best treatment.

This is short description about Hemoglobinopathies.