Flashcards in 1.4 Red cell disorders 1 Deck (38):
Reduction of Hb due to quantitative or qualitative impairment in red cell production
What is the normal Hb in adult male and females?
What are the clinical features of haemolytic anaemia?
Gallstones (pigment from Hb)
What are spherocytes?
red cells that are ball shaped instead of biconcave
What are poikilocytes?
What is polychromasia?
What is reticulocytosis?
Increase in reticulocytes (immature RBCs)
What is thalassaemia?
Imbalance in the globin chains of Hb
What is haemoglobinopathy?
Structural abnormalities in globin molecule due to point mutations
What is the normal Hb structure?
Tetramer of two alpha and two beta chains, each of which has a heme molecule to which an Fe is attached
What is haemoglobin F?
Hb in foetus which has 2 alpha and 2 gamma chains (rather than beta like in adults HbA)
What is haemaglobin A2?
2 alpha and 2 delta chains
Which chromosomes encode the Hb genes and which ones encode which?
Chromosome 11: beta cluster, delta and 2 fetal gamma genes
Chromosom 16: alpha cluster
How does Hb change from foetus to adult?
Hb F consists of alpha chains and gamma chains which predominate until the time of birth. After birth the gamma chains will be replaced by beta chains
What tests can you use for Hb samples?
Alkaline gel electrophoresis
Acid gel electrophoresis
High performance liquid chromatography
What are the clinical features of beta thalassaemia major?
Hair on end appearance on x-ray (skull)
Enlarged liver and spleen
Expansion of flat bones of face and skull
What are the lab features of beta thalassaemia major?
hypo-chromic microcytic Anaemia
target cells, NRBCs
Marrow: red cell hyperplasia, increased iron
Most of Hb is HbF (A1 replaced by F)
What is the treatment for beta thalassaemia major?
Long term transfusions
Iron chelation therapy (desferrioxamine SC or Deferasirox oral)
Allogenic marrow transplant
MRI imaging of liver and heart for iron content
What is Beta thalassaemia intermedia?
Clinical syndrome which has traits of major but wil less severe clinical outcomes. Due to different genotypes such as HbE/B
What causes beta thalassaemia minor?
Single gene defect
What are the traits of beta thalassamia minor?
hypochromic, microcytic blood film with high RBC count
Raised HbA2 on electrophoresis
Usually picked up on routine tests - asymptomatic just have to think about it for genetic counselling
What are the results of alpha thalassaemia?
4 genes: hydrops foetalis
3 genes: HbH disease, thalassaemia intermedia
1-2 genes: hypochromic, microcytic blood film and HbH bodies on incubation with dye
What causes sickle cell anaemia?
Substitution of Valine for glutamic acid in the 6th position of the beta chain (single base change)
How do you diagnose sickle cell anaemia?
Hb electrophoresis and DNA analysis
What are the clinical features of sickle cell anaemia?
Pain due to vaso-occlusion (from adhesion)
Infection: pneumonia, osteomyelitis, septic arthritis, parvovirus B19
Respiratory: acute chest syndrome, pulmonary hypertension
CNS: stroke, haematuria
Renal: haematuria, proliferative glomerulopathy, nephrotic syndrome, renal failure
What is hereditary spherocytosis?
a genetic defect in the proteins involved in the interaction between the membrane skeleton and phopholipid bilayer of the RBC memrane
What is hereditary spherocytosis?
a genetic defect in the proteins involved in the interaction between the membrane skeleton and phopholipid bilayer of the RBC membrane
abnormalities in the ankyrin and spectrin proteins
What is the molecular defect in hereditary spherocytosis?
usually due to dominant mutations in ANK1 (ankyrin) or spectrin (SPTP)
What are the clinical features of hereditary spherocytosis?
(will depend on age)
What is used to diagnose hereditary spherocytosis?
Anaemia with spherocytosis
Increased osmotic fragility
positive cryohaemolysis test
What is the treatment for hereditary spherocytosis?
often not required but can be splenectomy
cholecystectomy for gallstones
What is the pathophysiology of G-6PD deficiency?
Defective production of NADPH
Lower levels of reduced glutathione (GSH)
Methaemoglobin forms (cant carry oxygen)
What is the clinical presentation of G-6PD deficiency?
Chronic haemolytic anaemia
Favism (precipitate haemolytic crisis)
Primaquin sensitivity (malaria drug)
Acute intravascular haemolysis due to drugs
What will you see on a blood film with G-6PD deficiency?
Bite or blister cells - denatured Hb removed laving a pitted out pocket
What drugs should G-6PD deficient people avoid?
Anti-malarial, anti-diabetic and antibiotics
What happens in pyruvate kinase deficiency?
reduction in ATP in RBCs leading to the cells becoming rigid. This causes splenic trapping and a right shift in the Hb dissociation curve due to the build up of 2,3 BPG
What are the clinical features or pyruvate kinase deficiency?
Haemolytic anaemia and jaundice in the newborn