Pathology Cheat Sheet
Globin, Immunity, Compatibility
Sickle cell, thalassaemia and immune haemolysis for NEET-PG: HbS valine substitution, hydroxyurea, autosplenectomy, HbA2, and warm vs cold AIHA disease.
MedNext Academy | 3 min read
Globin, Immunity, Compatibility
Sickle cell, thalassaemia and immune haemolysis for NEET-PG: HbS valine substitution, hydroxyurea, autosplenectomy, HbA2, and warm vs cold AIHA disease.
The genetics and pathology of sickle cell disease and thalassaemia, and the mechanisms of acquired immune haemolysis.
High-yield lines
- Sickle cell disease is caused by a point mutation replacing glutamic acid with valine at position 6 of the beta-globin chain, producing HbS.
- Deoxygenated HbS polymerises into fibres that distort red cells into sickle shapes, causing vaso-occlusion and haemolysis.
- Fetal haemoglobin does not polymerise with HbS, which is why hydroxyurea that raises HbF reduces crises.
- Repeated splenic infarction causes autosplenectomy, seen as Howell-Jolly bodies and risk from encapsulated organisms.
- Haemoglobin electrophoresis or HPLC is required to diagnose and distinguish sickle genotypes.
- Thalassaemias are quantitative defects in globin chain synthesis, alpha or beta, causing microcytic hypochromic anaemia.
- Beta-thalassaemia major causes severe anaemia, marrow expansion with crew-cut skull and chipmunk facies, and requires transfusion.
- Beta-thalassaemia shows raised HbF and HbA2 on electrophoresis.
- Warm autoimmune haemolytic anaemia is caused by IgG antibodies reacting at body temperature and produces spherocytes with extravascular splenic haemolysis.
- Cold agglutinin disease is caused by IgM antibodies reacting in the cold, fixing complement and often following Mycoplasma or EBV infection.
- Chronic lymphocytic leukaemia is the most common cause of secondary warm autoimmune haemolytic anaemia.
- The direct antiglobulin test is positive for IgG in warm and for complement C3 in cold autoimmune haemolysis.
Mapped competency codes
- PA16.3
- PA16.4
- PA16.7
Continue into the full chapter
This summary maps to PA16-hemolytic-anemia.
Frequently Asked Questions
What is the molecular defect in sickle cell disease?
A point mutation in the beta-globin gene replacing glutamic acid with valine at position 6, producing HbS that polymerises when deoxygenated.
How does hydroxyurea help in sickle cell disease?
It raises fetal haemoglobin, which does not polymerise with HbS, thereby reducing sickling and the frequency of vaso-occlusive crises.
How do warm and cold autoimmune haemolytic anaemia differ?
Warm type is caused by IgG antibodies active at body temperature producing spherocytes and splenic extravascular haemolysis, while cold type is caused by complement-fixing IgM active in the cold, often after Mycoplasma or EBV infection.
What electrophoresis findings suggest beta-thalassaemia?
Raised HbF and raised HbA2, reflecting reduced beta-globin chain production.
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