HAEMOGLOBINOPATHIES for MBChB students.pptx

Heam disoders

1. HAEMOGLOBINOPATHIES MB.ChB YEAR 3

2. ABNORMAL HAEMOGLOBINS Disorders due to abnormal haemoglobins are caused by structural changes in the chains particularly the beta globin chains Clinically significant abnormal haemoglobulins include; --HbS --HbC --HbD --HbE

3. Properties of abnormal haemoglobulins Properties HbS disease HbC disease HbD disease HbE disease Abnormality Valine replaces glutamic acid in the 6 th amino acid position in the beta chain Lysine replaces glutamic acid in the 6 th amino acid position in the beta chain Lysine replaces glutamate in the 121st amino acid position in the beta chain Valine replaces glutamic acid in the 26 th amino acid position in the beta chain Geographical location Tropical Africa, parts of India, the Caribbean, Mediterranean region, Arabian peninsula West Africa North West India South East Asia and the Indian subcontinent Mode of inheritance Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive

4. Properties of abnormal haemoglobulins cont ’ Properties HbS disease HbC disease HbD disease HbE disease Clinical features Haemolytic anaemia, jaundice, fever, painful swelling of hands and feet .Pulmonary complications and kidney damage. Mild haemolytic anaemia and splenomegaly Very mild haemolytic anaemia Mild haemolytic anaemia Laboratory features Low haemoglobin, increased reticulocyte count. PBF shows marked Poikilocytosis with sickle cells, nucleated red cells and target cells. There is marked Polychromasia. PBF shows many target cells PBF shows target cells PBF shows microcytosis and hypochromia with target cells Confirmatory Diagnosis Hb electrophoresis Hb electrophoresis Hb electrophoresis Hb electrophoresis

5. SICKLE CELL DISEASE (SICKLE CELL ANAEMIA) Sickle cell disease is a group of haemoglobin disorders resulting from the inheritance of the sickle beta globin chain The sickle globin abnormality is caused by substitution of valine for glutamic acid in position six in the beta chain Mode of inheritance is autosomal recessive, homozygous sickle cell anaemia (Hb SS) being the most common severe syndrome. HbS is insoluble and forms crystals when exposed to low oxygen tension. Deoxygenated sickle haemoglobin polymerizes into long fibres. The red cells sickle and may block blood flow leading to infarcts of various organs HbAS is the carrier state and is wide spread. It is a benign condition with no anaemia and normal appearance of red blood cells in a peripheral film.

6. Clinical features of SCA Clinical features are of a severe haemolytic anaemia punctuated by crises The clinical expression of Hb SS is very variable, some patients having an almost normal life free of crises while others develop severe crises even as infants and may die in early childhood or as young adults Crises may be: Vaso –occlusive ( due to blockade of blood supply , can be painful or visceral) Aplastic (sudden fall in haemoglobin and reticulocyte levels) Haemolytic ( an increased rate of haemolysis and fall in haemoglobin level but rise in reticulocytosis and usually accompany painful crises)

7. Laboratory findings Haemoglobin is usually low Sickle cells and target cells usually seen in blood film Sickling test positive Hb electrophoresis shows no Hb A in Hb SS

8. Management Prophylactic -avoid those factors known to precipitate crises e.g. dehydration, anoxia, infections, cooling of the skin surface and stasis of the circulation Folic acid Good general nutrition and hygiene Manage crisis by rest, warmth and rehydration Blood transfusion when indicated Manage infection and/or pain appropriately if present

9. THALASSAEMIA SYNDROMES Thelassaemia genes are found in the Mediterranean Region, Middle East, India, Pakistan, S E Asia, Indonesia, Pacific Islands and Parts of North and West Africa These are inherited disorders caused by reduction in the rate of synthesis of alpha or Beta haemoglobin chains Alpha thalassaemias are caused by defective synthesis of alpha chains Beta thalassaemias are caused by defective synthesis of beta chains

10. Outcomes of thelassaemia Significant imbalance in the synthesis of alpha and beta chains leads to: I nadequate haemoglobin production. The MCV and MCH are low Accumulation of free uncombined globin chains in normoblasts and red cells causing destruction of red cell precursors in the bone marrow (ineffective erythropoiesis) and red cell destruction by the spleen.

11. ALPHA THELASSAEMIA A person normally inherits four alpha genes ( αα / αα ) for the production of alpha chains Alpha thelassaemia is commonly caused by deletion of alpha genes and less commonly by alpha gene inactivity following gene mutations Clinically important alpha thalassaemias include; Hb H ( thelassaemia intermedia ) caused by inactivity of three alpha genes, this presents with haemolytic anaemia Hb Barts hydrops syndrome ( Thelassaemia Major) all the four alpha genes are deleted. This is not compatible with life Asymptomatic alpha thelassaemia ( alpha trait , thelassaemia minor) where only one alpha gene is deleted ( α + ) or two alpha genes are deleted ( α o ) may present with mild microcytic anaemia

12. BETA THELASSAEMIA A person normally has two genes for the production of Beta globin chain ( β / β ) Commonest cause of beta thalassemia is gene mutations less commonly gene deletions Beta thelassaemia can be classified into major, intermedia and minor In major and intermedia severe anaemia becomes apparent at 3 to 6 months after birth Enlargement of liver and spleen and expansion of bones occurs Laboratory findings show microcytic hypochromic picture with target cells and normoblasts. Treatment in moderate to severe cases is blood transfusion

13. Summary: Thalassaemia syndrome abnormalities and clinical findings Abnormality Ppresentation Alpha thelassaemia major Homozygous (- -/- -) 0Hydrops fetalis Severe fatal anaemia incompatible with life Beta thelassaemia major Homozygous( β + /β + ) Homozygous( β o / β o ) Heterozygous β + /β o ) Severe heamolytic anaemia Transfusion dependent Hepatosplenomegally and expansion of bones Alpha t he lassaemia intermedia Deletion of three alpha genes (- +/- -) Hb H disease Moderately severe microcytic hypochromic anaemia with splenomegally Beta thelassaemia intermedia Homozygous B Thelassaemia Heterozygous B thelassaemia With enhanced HbF production Moderate to severe anaemia. Frequent transfusions are required Alpha thelassaemia minor α + ( - α / αα ) deletion of one alpha gene α o ( - - / αα ) deletion of two alpha genes Asymptomatic or mild anaemia Beta t helassaemia minor Beta thelassaemia trait Asymptomatic or mild anaemia