B5 - Haemolytic anaemia and haemoglobinopathies Flashcards
haemolytic anaemia
- Red cell destruction
○ Increased bilirubin (haem breakdown)
○ Increased LDH - lactate dehydrogenase which is liberated from red blood cells
○ Reduced haptoglobins (Hb-haptoglobin complex) - haptoglobin is consumed when binding with haemoglobin- Evidence of damaged red blood cells
○ Spherocytes
○ Fragmented red blood cells (schistocytes) - occurs in mechanical fragmentation in intravascular haemolysis - Evidence of increased RBC production
○ Reticulocytosis (polychromasia) - typically larger, purple immature cell
○ Nucleated red blood cells - a step in red blood cell maturation prior to reticulocyte (reticulocyte has nucleus extruded)
○ Occurs with normal bone marrow function
- Evidence of damaged red blood cells
clinical features of haemolytic anaemia
- Anaemia - tiredness, fatigue etc.
- Breathless/light headedness
- Jaundice: bilirubin in plasma
- Pigment gallstones (composed primarily of bilirubin) may occur
- Splenomegaly (common)
- Ankle ulcers, usually with people with sickle cell
- Expanded bone marrow - response to blood cell breakdown by increasing erythropoiesis
- Aplastic crises: parvovirus
- Megaloblastic anaemia: folate deficiency (used up)
hereditary causes of haemolytic anaemia
○ Membrane defect: hereditary spherocytosis
○ Enzyme defect: G6PD deficiency
○ Globin chain defect: haemoglobinopathies
acquired causes of haemolytic anaemia
○ Immune haemolytic anaemia ○ Fragmentation haemolysis - thrombotic thrombocytopenic purpura (TTP) ○ Oxidative haemolysis ○ Liver disease (spur cell anaemia) ○ Infections, renal disease, etc.
hereditary spherocytosis
§ Most common inherited haemolytic anaemia
§ Autosomal dominant with variable severity
§ Defect in structural RBC membrane protein
□ Spectrin, ankyrin, band 3
§ RBC less deformable and lose membrane when passing through spleen
□ Lose surface area
§ Red cells become spherical, rigid and then destroyed
§ Fluctuating anaemia and jaundice
§ Splenomegaly and pigment gall stones
hereditary spherocytosis lab features
□ Spherocytes on blood film
□ Polychromasia due to increased reticulocytes (bone marrow response)
□ Negative DAT (direct antiglobulin test)
® Test looking for evidence of immune haemolysis and the presence of antibodies that want to bind red blood cells and destroy them, would be positive in immune haemolysis)
□ Positive EMA (band-3) (probe looking for band 3 protein)
® Flow cytometric test
® Specialised assay that identifies target structures or proteins on cells by creating a fluorescent probe that finds a particular structure
® Eosin-5-malemide binds to band-3 protein
® Probe tends to be reduced or deficient because band-3 is lacking
® Gold standard
direct antiglobulin test
® Test looking for evidence of immune haemolysis and the presence of antibodies that want to bind red blood cells and destroy them, would be positive in immune haemolysis)
EMA (band-3) (probe looking for band 3 protein)
® Flow cytometric test
® Specialised assay that identifies target structures or proteins on cells by creating a fluorescent probe that finds a particular structure
® Eosin-5-malemide binds to band-3 protein
® Probe tends to be reduced or deficient because band-3 is lacking
® Gold standard
treatment for hereditary spherocytosis
□ Splenectomy - if the haemolysis is pronounced, severe cases
□ Folic acid, used to quickly so needs to be replenished otherwise they will have haemolytic and megaloblastic anaemia at the same time
□ Chlocystectomy: removal of the gall bladder to prevent bilirubin gall stones
○ Hereditary Elliptocytosis
§ Autosomal dominant § Milder than HS § Many asymptomatic § Mutations in spectrin § 10% have haemolysis § Elliptical red blood cells § Variants □ Hereditary pyro-poikilocytosis □ South east Asian ovalocytosis
G6PD deficiency
§ Glucose-6-phosphate dehydrogenase deficiency
§ Enzyme in the hexose monophosphate shunt which generated reducing power as NADPH
§ G6PD deficiency: most common red cell enzyme disorder worldwide
§ Gene-X linked chromosome: males more likely to be effected
§ G6PD deficiency
□ RBC susceptible to oxidative stress - causes haemolysis
□ When not subject to oxidative stress, they’ll be fine
□ Triggers of oxidant haemolysis: drugs, fava (broad) beans, infection, hypoxia
□ Intravascular haemolysis (self limiting)
□ Oxidised Hb removed
□ Blood film: bite or blister cells - looks like a bit has been taken out of them due to denatured haemoglobin being removed by macrophages
® Due to oxidative stress denatured haemoglobin (heinz bodies) are formed and macrophages remove them
□ Pooling to one side of the cell - hemighost cells
□ Treatment
® Remove/stop/treat offending agent
® Treat infection
® Transfuse if necessary - most people will not need this
□ Normal blood count between crises
2 enzyme defects leading to haemolytic anaemia
G6PD deficiency, pyruvate deficiency
G6PD deficiency blood film
□ Blood film: bite or blister cells - looks like a bit has been taken out of them due to denatured haemoglobin being removed by macrophages
® Due to oxidative stress denatured haemoglobin (heinz bodies) are formed and macrophages remove them
□ Pooling to one side of the cell - hemighost cells
triggers of oxidation in G6PD enzyme deficiency
drugs, fava (broad) beans, infection, hypoxia
G6PD inheritance
X-linked
