Haem: Haemolytic Anaemias Flashcards
What are the 2 types of haemolysis?
Intravascular - Within the circulation
Extravascular - Destruction by the reticular system/ spleen
What are the 2 ways haemolytic disorders can be classified?
Acquired
Inherited
What is the commonest cause of intravascular haemolytic anaemia?
Malaria - severe anaemia and haematurea
What are some other causes of intravascular haemolytic anaemia?
G6PD deficiency
Cold Ab haemolytic syndromes - IgM
MAHA - Damage to endothelium which causes damage to RBCs
Paroxysmal nocturnal haemaglobinuria - Genetic defect in GPI anchor
Give 2 examples of MAHA?
HUS in children whihc causes acute renal failure
TTP
What are the 3 types of disorders in hereditary haemolytic anaemia?
Membrane
RBC metabolism
Haemoglobin
What are some consequences of anaemia?
Increased RBC production and reticulocyte circulation
Increased folate demand
Susceptibility to Parvovirus B19 infection
Propensity to gallstones (cholelithiasis)
Iron overload
Osteoporosis
How does parvovirus affect anaemics?
Infect developing RBC and arrests their development.
Aplastic crisis - no RBC and no reticulocytes
Which gene is affected in Gilbert’s
UGT 1A1
How can you spot iron overload on histology
Blue stain with Prussian Blue/Perl’s stain
What are the clinical features of anaemia?
Pallor, jaundice, splenomegaly, pigmenturia, increased reticulocytes, polychromasia as RBCs take up eosinophilic and basophilic dyes giving a blue/purple appearance, hyperbilirubinaemia, Increased LDH, reduced haptoglobins, haemoglobinuria, haemosiderinurea
How does G6PD deficiency and PNH cause intravascular haemolysis?
Complement regulated proteins protect RBCs from complement in the plasma. These proteins are absent in these conditions.
What are the defects in RBC membranes in hereditary spherocytosis and elliptocytosis?
HS - Vertical interaction defects in the membranes (between bilayer and cytoskeleton0
HE - Horizontal interaction defects in the membrane
How is hereditary spherocytosis inherited?
Autosomal dominant
What are the features of hereditary spherocytosis?
Osmotic fragility - increased tendency to lyse
Lack area of central pallor
Biconcave shape
Hyperchromic cells
Smaller and more densely stained
Polychromatic cells - indicative of young cells
Reduced binding of the dye eosin-5-maleimide
What do you use to screen for hereditary spherocytosis?
Flow cytometry
How does hereditary elliptocytosis present?
Elliptical appearance
NO polychromasia
Blood count is normal
What is hereditary pyropoikilocytosis?
Homozygous state of hereditary elliptocytosis
How does hereditary pyropoikilocytosis present?
Fragmentation of RBCs
Poikilocytosis (different shapes)
How is G6PD deficiency inherited?
X linked recessive
Seen mainly in hemizygous males and homozygous males
What are the clinical presentations of G6PD deficiency?
Acute haemolytic anaemia
Neonatal jaundice
Impaired conjugation of bilirubin
What can you see on a blood film for acute haemolytic anaemia?
Contracted cells
Nucleated blood cells
Bite cells - cytoplasm removed
Hemi ghosts - Hb is contracted to one side of the cell
What can you see on the blood film of acute haemolytic anaemia in the steady state?
Heinz bodies - methylviolet stain
What are some agents that can provoke G6PD deficiency?
Anti malarials - Primaquine
Abx - Sulphonamides, Ciprofloxacin, Nitrofurantoin
Dapsone
Vit K
Mothballs
Fava beans
What is the most common defect in the glyocolytic pathway?
Pyruvate kinase deficiency (PK)
What does the blood film of PK deficiency look like?
Echinocytes (Burr cells)
RBCs shrink in size and resemble spherocytes
Number of echinocytes increases after splenectomy
What can lead poisoning lead to?
Pyrimidine 5’-nucleotidase deficiency
What does the blood film of Pyrimidine 5’-nucleotidase deficiency show?
Basophllic stippling/ inclusion in RBCs
Why would you do a direct antiglobulin test?
Detect immunoglobuline on RBCs - important in autoimmune haemolysis
Why would you look for urinary haemosiderin / hb
Looking for intravascular haemolysis
LDH will be raised and haptoglobulin will be reduced
Why would you look for osmotic fragility?
Membrane defect - Hereditary spherocytosis
Difference between G6PD def and PK def?
G6PD - episodic acute haemolysis and often on exposure to oxidants
PK - Chronic haemolysis
Why would you look for Hb separation A and F%
Hb disorders
Why would you look for Heinz body stain?
Oxidative haemolysis
Why would you look for Ham’s test/ flow cytometry of GPI linked proteins
PNH
Look at the sensitivity of RBCs to lysis via acidified serum - Ham’s test
Why would you look for thick and thin blood film
Malaria
You also need immunological dipstick test for malarial antigens
How do you manage haemolysis?
Folic acid
Avoid precipitators
RBC tranfuse/exchange
Immunisation against blood borne viruses
What are the indications for splenectomy?
PK deficiency Hereditary spherocytosis Severe elliptocytosis Pyropoikilocytosis Thalassemia Immune haemolytic anaemia
What is the biggest risk of splenectomy
Capsulated bacteria infections - Pneumococcus
How can you mitigate pneumoccocal infections in splenectomy
Prophylactic penicillin and immunisation
What are some specific indications for splenectomy
Transfusion dependance Growth delay Hypersplenism Physical limitation of Hb Between 3 and 10 years old
What is Hb Hammersmith?
severe unstable Hb that produced Heinz body haemolytic anaemia
What is the most important product of haemolytic anaemia?
Spherocytes
Are spherocytes DAT +ve or -ve?
DAT -ve
What is Waldenstrom’s macroglobulinaemia?
B cell clonal disorder
High levels of IgM
Feature s of hyperviscosity and vascular complications
What is paroxysmal cold Hb
Caused by viral infections
Donath-Landsteiner antibodies
