Haem: Haemolytic Anaemias

Question 1

What are the 2 types of haemolysis?

Answer 1

Intravascular - Within the circulation

Extravascular - Destruction by the reticular system/ spleen

Question 2

What are the 2 ways haemolytic disorders can be classified?

Answer 2

Acquired

Inherited

Question 3

What is the commonest cause of intravascular haemolytic anaemia?

Answer 3

Malaria - severe anaemia and haematurea

Question 4

What are some other causes of intravascular haemolytic anaemia?

Answer 4

G6PD deficiency
Cold Ab haemolytic syndromes - IgM
MAHA - Damage to endothelium which causes damage to RBCs
Paroxysmal nocturnal haemaglobinuria - Genetic defect in GPI anchor

Question 5

Give 2 examples of MAHA?

Answer 5

HUS in children whihc causes acute renal failure

TTP

Question 6

What are the 3 types of disorders in hereditary haemolytic anaemia?

Answer 6

Membrane
RBC metabolism
Haemoglobin

Question 7

What are some consequences of anaemia?

Answer 7

Increased RBC production and reticulocyte circulation
Increased folate demand
Susceptibility to Parvovirus B19 infection
Propensity to gallstones (cholelithiasis)
Iron overload
Osteoporosis

Question 8

How does parvovirus affect anaemics?

Answer 8

Infect developing RBC and arrests their development.

Aplastic crisis - no RBC and no reticulocytes

Question 9

Which gene is affected in Gilbert’s

Answer 9

UGT 1A1

Question 10

How can you spot iron overload on histology

Answer 10

Blue stain with Prussian Blue/Perl’s stain

Question 11

What are the clinical features of anaemia?

Answer 11

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

Question 12

How does G6PD deficiency and PNH cause intravascular haemolysis?

Answer 12

Complement regulated proteins protect RBCs from complement in the plasma. These proteins are absent in these conditions.

Question 13

What are the defects in RBC membranes in hereditary spherocytosis and elliptocytosis?

Answer 13

HS - Vertical interaction defects in the membranes (between bilayer and cytoskeleton0

HE - Horizontal interaction defects in the membrane

Question 14

How is hereditary spherocytosis inherited?

Answer 14

Autosomal dominant

Question 15

What are the features of hereditary spherocytosis?

Answer 15

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

Question 16

What do you use to screen for hereditary spherocytosis?

Answer 16

Flow cytometry

Question 17

How does hereditary elliptocytosis present?

Answer 17

Elliptical appearance
NO polychromasia
Blood count is normal

Question 18

What is hereditary pyropoikilocytosis?

Answer 18

Homozygous state of hereditary elliptocytosis

Question 19

How does hereditary pyropoikilocytosis present?

Answer 19

Fragmentation of RBCs

Poikilocytosis (different shapes)

Question 20

How is G6PD deficiency inherited?

Answer 20

X linked recessive

Seen mainly in hemizygous males and homozygous males

Question 21

What are the clinical presentations of G6PD deficiency?

Answer 21

Acute haemolytic anaemia
Neonatal jaundice
Impaired conjugation of bilirubin

Question 22

What can you see on a blood film for acute haemolytic anaemia?

Answer 22

Contracted cells
Nucleated blood cells
Bite cells - cytoplasm removed
Hemi ghosts - Hb is contracted to one side of the cell

Question 23

What can you see on the blood film of acute haemolytic anaemia in the steady state?

Answer 23

Heinz bodies - methylviolet stain

Question 24

What are some agents that can provoke G6PD deficiency?

Answer 24

Anti malarials - Primaquine

Abx - Sulphonamides, Ciprofloxacin, Nitrofurantoin

Dapsone
Vit K
Mothballs

Fava beans

Question 25

What is the most common defect in the glyocolytic pathway?

Answer 25

Pyruvate kinase deficiency (PK)

Question 26

What does the blood film of PK deficiency look like?

Answer 26

Echinocytes (Burr cells) RBCs shrink in size and resemble spherocytes Number of echinocytes increases after splenectomy

Question 27

What can lead poisoning lead to?

Answer 27

Pyrimidine 5'-nucleotidase deficiency

Question 28

What does the blood film of Pyrimidine 5'-nucleotidase deficiency show?

Answer 28

Basophllic stippling/ inclusion in RBCs

Question 29

Why would you do a direct antiglobulin test?

Answer 29

Detect immunoglobuline on RBCs - important in autoimmune haemolysis

Question 30

Why would you look for urinary haemosiderin / hb

Answer 30

Looking for intravascular haemolysis | LDH will be raised and haptoglobulin will be reduced

Question 31

Why would you look for osmotic fragility?

Answer 31

Membrane defect - Hereditary spherocytosis

Question 32

Difference between G6PD def and PK def?

Answer 32

G6PD - episodic acute haemolysis and often on exposure to oxidants PK - Chronic haemolysis

Question 33

Why would you look for Hb separation A and F%

Answer 33

Hb disorders

Question 34

Why would you look for Heinz body stain?

Answer 34

Oxidative haemolysis

Question 35

Why would you look for Ham's test/ flow cytometry of GPI linked proteins

Answer 35

PNH | Look at the sensitivity of RBCs to lysis via acidified serum - Ham's test

Question 36

Why would you look for thick and thin blood film

Answer 36

Malaria | You also need immunological dipstick test for malarial antigens

Question 37

How do you manage haemolysis?

Answer 37

Folic acid Avoid precipitators RBC tranfuse/exchange Immunisation against blood borne viruses

Question 38

What are the indications for splenectomy?

Answer 38

``` PK deficiency Hereditary spherocytosis Severe elliptocytosis Pyropoikilocytosis Thalassemia Immune haemolytic anaemia ```

Question 39

What is the biggest risk of splenectomy

Answer 39

Capsulated bacteria infections - Pneumococcus

Question 40

How can you mitigate pneumoccocal infections in splenectomy

Answer 40

Prophylactic penicillin and immunisation

Question 41

What are some specific indications for splenectomy

Answer 41

``` Transfusion dependance Growth delay Hypersplenism Physical limitation of Hb Between 3 and 10 years old ```

Question 42

What is Hb Hammersmith?

Answer 42

severe unstable Hb that produced Heinz body haemolytic anaemia

Question 43

What is the most important product of haemolytic anaemia?

Answer 43

Spherocytes

Question 44

Are spherocytes DAT +ve or -ve?

Answer 44

DAT -ve

Question 45

What is Waldenstrom's macroglobulinaemia?

Answer 45

B cell clonal disorder High levels of IgM Feature s of hyperviscosity and vascular complications

Question 46

What is paroxysmal cold Hb

Answer 46

Caused by viral infections | Donath-Landsteiner antibodies