haemolytic anaemias Flashcards
haemolytic anaemia
anaemia due to reduced RBC survival
describe the normal RBC lifestyle
- RBC production (Iron, B12/Folate, Globin chains, Protoporphyrins)
- RBCs circulate for 120 days
- Removal of old RBCs (membrane changes are detected by macrophages)
Normal Red blood cell
- biconcave disc shape
- haemoglobin (carries o2)
- Metabolic pathways (ensuring RBC maintains structure and function)
what is haemolysis?
destruction of RBCs -> bone marrow compensates by increasing RBC production -> increased immature RBCs in the circulation (reticulecytosis, nucleated RBCs)
compensated haemolysis?
RBC production is able to compensate for the decrease in lifespan and so there is normal Hb levels
incompletely compensated haemolysis
RBC production is unable to keep up with the decreased Hb lifespan and so there is decreased Hb levels
clinical findings of haemolytic anaemia
- jaundice (excess bilirubin which is a breakdown of haemoglobin)
- pallor/fatigue
- splenomegaly (increased workload lead yo an enlarged spleen)
- dark urine: haemoglobinuria
chronic findings of haemolytic anaemia
- gallstones due to the accumulation of pigment (more bilirubin)
- leg ulcers (NO scavenging)
- Folate deficiency (using more folate to make RBCs)
laboratory findings of haemolytic anaemia
- Increased reticulocyte count
- Increased unconjugated bilirubin
- Increased LDH (lactate dehydrogenase)
- Low serum haptoglobin
- Increased urobilinogen
- Increased urinary haemosiderin
- Abnormal blood film
blood film of haemolytic anaemia
- reticulocytes
- polychromasia (high no of immature RBCs
- nucleated RBC
Spherocytosis
RBCs are sphere-shaped rather than bi-concave disk shaped as normal
Elliptocytosis
red blood cells are elliptical rather than the typical biconcave disc shape.
what are the 3 components of red cell membrane structure
Lipid bilayer
Integral proteins
Membrane skeleton
defects in vertical interaction proteins leads to
hereditary spherocytosis
- Spectrin
- Band 3
- Protein 4,2
- Ankyrin
defects in the horizontal interaction proteins leads to
hereditary elliptocytosis
- Protein 4.1
- Glycophorin C
- Spectrin
hereditary spherocytosis
inherited in autosomal dominant fashion
bone marrow makes the biconcave RBC as normal, but as it goes round the circulation the membrane is lost and the RBC becomes spherical
clinical features of hereditary spherocytosis
- Asymptomatic to severe haemolysis
- Neonatal jaundice
- Jaundice, splenomegaly, pigment gallstones
- Reduced eosin-5-maleimide (EMA) binding – binds to band 3
- Positive family history
- Negative direct antibody test
management of hereditary spherocytosis
Monitor
Folic acid
Transfusion
Splenectomy
Glucose-6-phosphate deficiency
- Red blood cells break down (hemolysis) when the body is exposed to certain foods, drugs, infections or stress
- Only has an effect when exposed to oxidant radicals: which denatures Hb forming aggregates & forms Heinz bodies
- Oxidised membrane proteins which reduces RBC deformability
G6PD deficiency
X-linked disorder
prevalence of G6PD deficiency
- Common in African, Asian, Mediterranean and Middle Eastern populations
- Mild in African (type A), more severe in Mediterraneans (type B)
Clinical features of G6PD deficiency
range from asymptomatic to acute episodes to chronic haemolysis
What can trigger symptoms of G6PD
Infections Fava/ broad beans Many drugs e.g.: Dapsone Nitrofurantoin Ciprofloxacin Primaquine
Blood film of G6PD
Bite cells
Blister cells & ghost cells
Heinz bodies (methylene blue)
pyruvate kinase deficiency
PK required to generate ATP
Essential for membrane cation pumps (deformability)
genetics of PKD
autosomal deficiency
Haemoglobinopathies
a group of recessively inherited genetic conditions affecting the haemoglobin component of blood. They are caused by a genetic change (mutation) in the haemoglobin
Structure of haemoglobin
Ferrous iron + Protoporphyrin = Haem
2a + 2B = Globin
Haem + Globin = Haemoglobin
Thalassaemias
Production increased/ decreased amount of a globin chain (structurally normal)
- excess unpaired globin chains are unstable
- RBCS damaged
- Ineffective erthropoeisis
- Haemolytic anaemia
Variant haemoglobins
Production of a structurally abnormal globin chain
two types of beta thalassaemia
Beta thalassemia trait: one gene on chromosome 16
Beta thalassemia major: two genes for betathalassemiaand no normal beta-chain gene (homozygous)
diagnosis of thalassaemia trait
Asymptomatic Microcytic hypochromic anaemia Low Hb, MCV, MCH Increased RBC Often confused with Fe deficiency HbA2 increased in b-thal trait –(diagnostic) a-thal trait often by exclusion globin chain synthesis (rarely done now) DNA studies (expensive)
beta thalassaemia trait
- need transfusion in the first day of life
- If don’t get a blood transfusion:
- Failure to thrive
- Progressive hepatosplenomegaly
- Bone marrow expansion – skeletal abnormalities
- Death in 1st 5 years of life from anaemia
side effect of blood transfusion
Iron overload
Endocrinopathies
Heart failure
Liver cirrhosis
sickle cell disease
- Point mutation in the β globin gene: glutamic acid → valine
- Insoluble haemoglobin tetramer when deoxygenated → polymerisation
- sickle shaped cells
clinical features of SCD
Painful crises Aplastic crises Infections Acute sickling: Chest syndrome Splenic sequestration Stroke Chronic sickling effects: Renal failure Avascular necrosis bone
Laboratory features of SCD
Anaemia Hb often 65-85 Reticulocytosis Increased NRBC Raised bilirubin Low creatinine
how to confirm diagnosis of SCD
Solubility test
Expose blood to reducing agent
Hb S precipitated
Positive in trait and disease
autoimmune haemolysis
Idiopathic Usually warm IgG, IgM Drug-mediated Cancer associated LPDs
Alloimmune haemolysis
Transplacental transfer: Haemolytic disease of the newborn: D, c, L ABO incompatability Transfusion related Acute haemolytic transfusion reaction ABO Delayed haemolytic transfusion reaction E.g Rh groups, Duffy
