Haemolytic Anaemia Flashcards
What is haemolytic anaemia?
Anaemia due to shortened red blood cell survival
Describe the normal RBC lifecycle?
2x10^11 RBC/day in the bone marrow
RBC circulate for approx 120 days without nuclei or cytoplasmic organelles
Removal senescent RBC by reticular endothelial system of the liver and spleen
What is haemolysis?
Shortened red cell survival
Compensation by bone marrow to increase production
Increased young cells in circulation = resticulocytosis
RBC production unable to keep up with decreased RBC lifespan = decreased Hb
What are the clinical findings of haemolysis?
- jaundice
- pallor
- fatigue
- splenomegaly
What are chronic clinical findings of haemolysis?
Gallstones - pigment
Leg ulcers
Folate deficiency (increased use)
What would be observed in a peripheral blood film in haemolysis?
Nucleated red blood cells
Thrombocytosis
Neutrophillia with left shift
Polychromatophilia
What would the bone marrow findings look like in someone with haemolysis?
Erythronium hyperplasia of bone marrow
- normoblastic reactions
- reversal of M:E ration
Reticulocytosis
- mild (2-10%) or moderate (10-60%)
What would lab investigations for haemolysis show?
Increased uncojugated bilirubin
Increased LDH (lactate dehydrogenase)
Decreased serum haptoglobin protein that binds free Hb
Increased urobilinogen
Increased urinary hemosiderin
What are the 3 classifications of haemolytic anaemia?
- Inheritance
- hereditary
- acquired - Site of RBC destruction
- intravascular
- extravascular - Origin of RBC damage
- intrinsic
- extrinsic (infection)
What are the causes of intrinsic haemolytic anaemia?
Membrane defects
Enzyme defects
(G6PD, PK)
Haemoglobin defects
What are causes of extrinsic haemolytic anaemia?
Immune-mediated
- autoimmune (drug induced)
- alloimmune (haemolytic)
Drug and chemicals
Infections
- malaria
Hyperspenism
Red cell fragmentation
- mechanical trauma
- microangiopathic HA
Explain the normal process of RBC destruction
-RBC broken into globin, iron and protoporphyrin in macrophage
-Extravascular process
- porophyrin converted to bilirubin and transported to liver as uncojugated bilirubin
- liver produces biribulin glucuronides
-in the gut they get processed and re absorbed in the kidney
Explain the abnormal process of RBC destruction.
- invascular process
- RBC under lysis
- haemoglobin remains in vasculature
- haemoglobin converted to methaealbumin or is reabsorbed by the kidney
- some haemoglobin found in urine (haemoglobinuria)
What membrane disorders can cause haemolytic anaemia?
Hereditary spherocytosis (defects in the verticals interactions)
-more common
Hereditary elliptocytosis (defects in the horizontal interactions)
- mutations in alpha and beta spectrum
What would be observed in a blood film for spherocytosis and elliptocytes?
Spherocytosis - sphere shape as unable to maintain the bioconcave shape. Cells become more susceptible to haemolysis.
Elliptocytes - tear drop cells, more like ovals.
What are the clinical features of hereditary spherocytosis?
- asymptomatic to server haemolysis
- neonatal jaundice
- splenomegaly (removes damaged red blood cells so spleen becomes enlarged)
- pigment gall stones (due to more bilirubin due to red blood cell degredation)
- reduced EMA binding to band 3 (a test used to detect condition)
- posative family history
- negative direct antibody test
How can defects in glucose 6 phosphate dehydrogenase cause oxidative haemolysis?
Oxidative stress occurs as no GSH (reduced glutathione) is made.
X LINKED - EFFECTS MALES MORE
Oxidation of Hb by oxidant radicals
- resulting in denatured Hb aggregates and forms Heinz bodies (bind to membrane)
Oxidised membrane proteins
- membrane proteins become phosphorylated
- reduced RBC deformability as they normally do to move through narrow blood vessels
Have protection against servere malaria
What is the role of the HMP shunt in anaerobic respiration?
- generates NADPH and reduced glutathione
- reduced glutathione (GSH) protects the cell from the oxidative stress
- REAUIRED GLUCOSE 6 PHOSPHATE DEHYDROGENASE
What would be observed in a blood film for oxidative haemolysis?
Bite cells
Blister cells
ghost cells
Heinz bodies
How does a pure age kinase deficiency cause haemolytic anaemia?
Autosomal recessive disorder
Low intracellular ATP concerntration
Less energy to maintain RBC shape and deformability
Less energy to regulate intracellular cation concentration via cation pumps (sodium and potassium pump)
Causes chronic non-spherocytic haemolytic anaemia
What would be observed in a blood film of someone with private kinase deficiency?
Prickle cells
What is thalassaemia?
A quantitative disorder
Caused by imbalance alpha and beta chain production
- Excess unpaired globin chains are unstable
Heterogeneous gp genetic disorders
And ineffective erythropoiesis (RBC production)
What are the 4 types of thalassaemias?
- hydrop foetalis
- beta thalassaemia major
- thalassaemia intermedia
- thalassaemia minor
What are the clinical features of BETA thalassaemia MAJOR?
- servere anaemia
- progressive hepatosplenomegaly
- bone marrow expansion - facial bone abnormalities
- mild jaundice
- iron overload
- intermittent infections, pallor
What is jaundice?
When the skin or whiteness of your eyes turn yellow
What is pallor?
Unhealthy pale appearance
What would be observed in the peripheral blood of someone with beta thalassaemia major?
Microcytic hypochromic with decreased MCV (mean cell volume) , MCH (mean cell haemoglobin) , MCHC
Target cells, nucleated rbc, tear drop cells
Reticulocytes > 2%
What is BETA thalassaemia trait MINOR?
- Asymptomatic
- often confused with Fe deficiency
- alpha-thal trait often by exclusion
- HbA2 increased in beta-thal trait
What are the different types or severities of ALPHA Thalassaemia?
Hb Bart’s hydrops syndrome
- deletion of all 4 globin genes
- incompatable
HbH disease
- deletion of 3/4 globin genes
- common in SE Asia
That trait (minor)
- normal or mild HA
- MCV and MCH low
What is thalassaemia intermedia?n
Disorder with clinical manifestation between major and minor
- transfusion independent
- diverse clinical phenotype
- varying symptoms
- bilirubin increased level
What is sickle cell disease?
All diseases as a result of inherited HbS
HbS is caused by a single nucleotide substitution (point mutation)
Valine instead of glutamic acid
Insoluble Hb tetramer when deoxygenated (polymerisation)
- HbSS is sicke cell anaemia (homozygous state)
- HbSA is sickle cell trait (heterozygous)
- HbS is beta thalassaemia
What is haemoglobin sickling?
As the red blood cells travels around the blood there is exposer to oxygenated and deoxygenated states that lead to membrane distortion of red blood cells.
What are the clinical features of sickle cell disease?
Painful crises
Aplastic crises
Infections due to hyposplenism
Acute sickling
- stroke
- chest syndrome
- splenic sequestration
Chronic sickling effects
- renal faliure
- avascular necrosis bone
What are the laboratory features of sickle cell disease?
Anaemia
Reticulocytosis
Increased NRBC
Raised bilirubin
Low creatinine
How can the diagnosis of sickle cell anaemia be confirmed in a lab?
Solubility test!
Expose blood to reducing agent
HbS precipitated
Positive in trait and disease
