Haemolytic Anaemia Flashcards
What is haemolytic anaemia?
Anaemia due to shortened RBC survival
What organ produces erythropoietin?
Kidneys produce erythroopooietin
What do RBC lose?
Lose their nucleus
What do RBC acquire as they get older and so what happens to them?
• As they get older, they aquire changes in membrane so are removed via spleen and liver
What components do RBC have?
- Hb
- Membrane
- Enzymes that keep them running
What compensates with increased RBC production?
Bone marrow compensates with increased RBC production
What is reticulocytosis?
Its an increased number of young cells in circulation
What is compensated haemolysis?
Its RBC production which is able to compensate for decreased RBC life span
What is incompletely compensated haemolysis?
Its RBC production which is unable to keep up with the decreased RBC life span
What are the clinical findingd of haemolytic anaemia?
- Jaundice
- Pallor/fatigue
- Splenomegaly
- Dark urine
- Aplastic-anaemia, reticulocytopenia with parvovirus infection
What is the spleen the site for?
The site for removal of abnormal cells so swells during anaemia
Why do we have dark urine in haemolytic anaemia?
Dark urine because the bilirubin comes out quickly in urine
What does the parvovirus infection cause in haemolytic anaemia?
Causes red cheeks and rash and turns off RBC production for 10 days
What are chronic clinical findings of haemolytic anaemia?
• Gallstones - pigment
• Leg ulcers (NO scavenging)
• Folate deficiency
-Increased use as RBCs are being made quickly
What are lab findings of haemolytic anaemia?
• Increased reticulocyte count • Increased unconjugated bilirubin • Increased LDH (lactate dehydrogenase) ○ Non-specific, not just in anaemia • Low serum haptoglobin ○ Protein that binds free haemoglobin • Increased urobilinogen • Increased urinary haemosiderin • Abnormal blood film
What does the blood film for haemolytic anaemia have present?
- Reticulocytes
- Polychromasia
- Nucleated RBCs
- Poikilocytes
What are the 3 factors we use to classify haemolytic anaemia?
- Inheritance
- Inherited
- Acquired - Site of RBC destruction
- Intravascular
- Extravascular - Origin of RBC damage
- Intrinsic
- Extrinsic
Inheritance of what can cause haemolytic anaemia?
• Autoimmune haemolysis
○ Can make antibodies against cells
• Membrane disorders
○ Spherocytosis
○ Elliptocytosis
• Enzyme disorders
○ G6PD deficiency
○ Pyruvate kinase deficiency
• Hb disorders
○ Sickle cell anaemia
○ThalassaemiasWhat is the structure of a normal red blood cell?
○ Lipid bilayer
○ Integral proteins that anchor the membrane onto the cytoskeleton
§ Keep it stable
○ Membrane skeleton
What membrane disorders contribute to haemolytic anaemia?
○Defects in vertical interaction(spherocytosis)
○Defects in horizontal interaction(Eliptocytosis)
Defect in vertical interaction(Hereditary spherocytosis)
○ Autosomal dominant ○ Spectrin ○ Band 3 ○ Protein 4.2 ○ Ankyrin
Defects in horizontal interaction(Hereditary elliptocytosis)
○ Protein 4.1
○ Glycophorin C
○ Spectrin – HPP
What is the most common hereditary haemolytic anaemia?
Hereditary spherocytosis
What fashion is hereditary spherocytosis inherited in?
Inherited in autosomal dominant fashion
What happens to RBC in hereditary spherocytosis?
- Defects in proteins involved in vertical interactions between the membrane skeleton and the lipid bilayer
- Decreased membrane deformability
What does the bone marrow make in hereditary spherocytosis?
Bone marrow makes biconcave RBC, but as membrane is lost, the RBC become spherical
What are the 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 hostory
- Negative direct antibody test
What is the management plan for hereditary spherocytosis?
• Monitor • Folic acid • Transfusion • Splenectomy -The RBCs then have a remainder of the nucleus as seen on blood film because usually spleen responsible for removing nucleus
What are the inherited enzymopathies involved in haemolytic anaemia?
- G6P deficiency
* Pyruvate kinase deficiency
What type of disorder is G6P deficiency?
X-linked disorder
What do clinical features range from in G6P deficiency?
• Clinical features range from asymptomatic to acute episodes to chronic haemolysis
What is the role of the HMP shunt?
-Generates reduced glutathione
What does the HMP shunt do?
Protects the cell from oxidative stress
What are the effects of oxidative stress?
○ Oxidation of Hb by oxidant radicals
○ Resulting denatured Hb aggregates & forms Heinz bodies – bind to membrane
○ Oxidised membrane proteins – reduced RBC deformability
Features of G6P deficiency
○ Haemolysis
○ Film:
§ Bite cells
§ Blister cells & ghost cells
§ Heinz bodies (methylene blue)
○ Reduced G6PD activity on enzyme assay
§May be falsely normal if reticulocytosisWhat is pyruvate kinase required for?
Required to generate ATP
What fashion is pyruvate kinase inherited in?
Autosomal recessive
What does pyruvate kinase deficiency cause?
Causes chronic anaemia
What can chronica anaemia be improved with?
Improves with splenectomy
What can go wrong with haemoglobin structures?
- Quantitative
2. Qualitative
What happens in thalassemias?
○ Imbalanced alpha and beta chain production
○ Excess unpaired globin chains are unstable
What do we always need for Hb?
Always need 2 alpha chains and 2 other like chains
What does excess unpaired globin chains do?
○ Precipitate and damage RBC and their precursors
What does excess unpaired globin chains lead to?
Lead to ineffective erythropoiesis in bone marrow
What fashion in beta thalassaemia inherited in?
Autosomal recessive
What is the 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)
What happens if patient suffering from beta thalassaemia isn’t transfused?
• If not transfused:
○ Failure to thrive
○ Progressive hepatosplenomegaly
○ Bone marrow expansion – skeletal abnormalities
○Death in 1st 5 years of life from anaemia
What are side effects of transfusion?
○ Iron overload
§ Endocrinopathies
§ Heart failure
§ Liver cirrhosis
What mutation causes sickle cell disease?
Point mutation in the β globin gene: glutamic acid → valine
What causes the sickle shape to form in SCD?
Insoluble haemoglobin tetramer when deoxygenated leads to polymerisation leading to sickle shaped cells
What are the clinical features of SCD?
○ Painful crises ○ Aplastic crises ○ Infections ○ Acute sickling: § Chest syndrome § Splenic sequestration Stroke
What are chronic sickling effects of SCD?
○ Renal failure
○ Avascular necrosis bone
What are the features of SCD in the lab?
○ Anaemia § Hb often 65-85 ○ Reticulocytosis ○ Increased NRBC ○ Raised bilirubin ○ Low creatinine
Autoimmune haemolysis
Idiopathic
Alloimmune haemolysis
- Transplacental transfer
- Transfusion related
Non-immune acquired haemolysis
- Paroxysmal nocturnal haemoglobinuria
- Fragmentation haemolysis
- Severe burns
- Infections
