HAEMOGLOBINOPATHIES

Haemolysis is cause by

1.membrane defect(ellipticocytosis,spherocytosis)

2.enzyme(G6PD)

3.Hemoglobin abnormality(thalassaemia,sickle cell anemia)

Abnormal Hemoglobin

-An inherited abnormality of globin chain production cause by a single point mutation resulting in amino acid substitution.

-αα excess -> denatures ->bcome Heinze body ->impair DNA synthesis & damage rbc membrane

-2 types:1.sstructural alterations-sickle cell anemia

                 2.defect in rate of synthesis of globin chains-thalassemia

THALASSEMIA

n  Reduced rate of synthesis of one or more of the globin chains: a or b

n  Imbalanced globin-chain synthesis

n  Defective Hb production

α-thalassemia is reduction in α globin chain.it have 4 classification:

Number of globin genes deleted	syndrome	c/f
4	Hydrops fetalis	Death in utero
3	Hemoglobin H disease	HbH (Hb-Bart’s-fetal-γ chain)
2	α-thalassemia	Normal HB, low MCH MCV
1	α-thalassemia	Slightly low

*not usually associated with anemia

a-thalassaemia trait

Pathophysiology α-thalassemia:

HbH

n  This Southeast Asian woman gave birth to an hydropic  stillborn fetus with Hb Bart’s, a 4-gene a–globin deletion.

n  She has hemoglobin H disease, a 3-gene a–globin deletion.

n  Blood smear on the left shows a microcytic, hypochromic anemia with poikilocytosis.

n  The right photo shows the golf-ball appearance elicited by methylene blue staining. The stained granules are denatured hemoglobin H.

n  b-thalassaemia trait (minor)

–        Symptomless

–        Low MCV and MCH but high RBC

–        Hb 10-15g/dl

–        Raised Hb A₂ >3.5%                                                                                                                 
Prenatal counselling; 25% risk of a thalassaemia major child if both parents are b-thalassaemia trait

Pathogenesis β-thalassemia

*blood smear cannot detect aggregations of α chains

*blood transfusions can corrected the anemia but give problem with iron overload.

n  Clinical feature                                                                                      

–        Severe anaemia at 3-6 months             -mongoloid facies,prominent malar bone

–        Hepatosplenomegaly                                                                              

–        Thalassaemic facies                

–        Iron overload

–        Recurrent infection

–        Osteoporosis – endocrine abnormalities and marrow expansion

Laboratory

-αβ globin chain  synthesis

-DNA analysis

-iron status

b-thalassaemia major

Treatment

-          Regular blood transfusions(maintain at 10 g/dl)

-          Chelation- the use of a chelator (as EDTA) to bind with a metal (as lead or iron) in the body to form a chelate so that the metal loses its toxic effect or physiological activity. Desferoxamine (Desferal)

-          Folate supplementation

-          Spenectomy (for hypersplenism)

-             Dramatic increase in transfusion requirements

-                 massive size that interferes with breathing and nutrition

-                 severe pain

-                 avoid before 5 years if at all possible

-                 immunize with pneumovax and menigovax pre-splenectomy

-                 post splenectomy will need penicillin prophylaxis for life

SICKLE CELL ANEMIA

Pathophysiology of sickle cell anemia 

Point mutation in Hb A chain: from glutamic acid to valine l/t HbA to HbS

n  Inherited sickle b-globin gene

n  Molecular

–        Substitution of valine for glutamic acid in position 6 of b chain

*Carrier state confer protection against malaria infection-defectives blood cell invaded by malaria parasites are more apt to be destroyed as they travel to spleen.

n  Pathology

–        Hb S – insoluble and form crystals when exposed to low oxygen tension

–        Deoxygenated HbS polymerizes into long fibres

–        Sickling red cells may block large vessel or microcirculation and causes infarction of organs

n  Hb S shift the oxygen dissociation curve to the right