Haematology 5 - Haemolytic anaemias

Question 1

Recall some causes of intravascular vs extravascular haemolytic anaemias

Answer 1

Intravascular:

• Malaria (black water fever)
• G6PDD
• MAHA (due to HUS/TTP/PNH)
• ABO haemolysis

Extravascular:

• Autoimmune
• hereditary spherocytosis

Question 2

Which infection are patients with haemolytic anaemias more susceptibile to?

Answer 2

Parvovirus B19

Question 3

What is hepatic siderosis indicative of?

Answer 3

haemolytic anaemia

Question 4

What laboratory results can you expect in haemolytic anaemia?

Answer 4

anaemia, reticulocytosis, polychromasia

↑­ BR, ­↑ LDH, ↓ haptoglobins, haemoglobinuria, haemosiderinuria

Question 5

What is the inheritance pattern of hereditary spherocytosis?

Answer 5

Autosomal dominant

Question 6

Recall the pathophysiology of hereditary spherocytosis

Answer 6

Spectrin or ankyrin deficiency → problems in RBC cytoskeleton

Extravascular haemolysis

Question 7

How can hereditary spherocytosis be diagnosed?

Answer 7

osmotic fragility test: ↑ sensitivity to lysis in hypotonic saline

Di-binding test (eosin-5-maleimide / EMA)→ ↓ binding

pathology slide = lack of central pallor

Question 8

What is the difference in clinical features of hereditary elliptocytosis in a heterozygote vs a homozygote?

Answer 8

Heterozygote: no polychromasia
Homozygote: Severe haemolytic anaemia (pyropoikilocytosis)

Question 9

Recall the pathophysiology of hereditary elliptocytosis

Answer 9

spectrin mutation

Question 10

In which parts of the world is G6PDD most common?

Answer 10

Where malaria is endemic

Question 11

What is the inheritance pattern of G6PDD?

Answer 11

X linked recessive

Question 12

What is the normal physiological role of G6PD?

Answer 12

catalyses 1st step in pentose phosphate pathway (to generate NADPH)

Question 13

What is the main symptom of G6PDD in neonates?

Answer 13

Neonatal jaundice (otherwise asymptomatic)

Question 14

Recall 3 triggers for a crisis in G6PDD

Answer 14

Acute haemolysis - triggered by:

haemoglobunirua

Anti-malarials (Primaquine)

Antibiotics (sulphonamides, ciprofloxacin, nitrofurantoin)

Other (Dapsone, Vitamin K)

Fava beans and mothballs

Infections

Question 15

Recall features of G6PD deficiency on blood film

Answer 15

Bite cells, hemi-ghosts, nucleated RBCs, Heinz bodies (methyl violet stain)

Question 16

What is the typical appearance of erythrocytes in Pyruvate Kinase Deficiency?

Answer 16

echinocytes (hedgehog) and spherocytes on slide

Question 17

What is the typical appearance of erythrocytes in Pyruvate Kinase Deficiency?

Answer 17

basophilic inclusions on slide

Question 18

What is the first investigation to do in haemolytic anaemia?

Answer 18

DAT/ Coombs test

Positive = autoimmune haemolysis

Question 19

What does a positive urinary haemosiderin test show?

Answer 19

Intravascular haemolysis

Question 20

What is the osmotic fragility test used to detect?

Answer 20

Hereditary spherocytosis

Question 21

What is homozygous hereditary elliptocytosis also known as?

Answer 21

Pyropoikilocytosis

Question 22

What do Heinz bodies indicate?

Answer 22

denatured haemoglobin - G6PDD

Question 23

Differentiate the class of immunoglobin involved in warm vs cold AIHA

Answer 23

Warm: IgG
Cold: IgM

Question 24

Recall the causes of warm vs cold AIHA

Answer 24

warm - mainly primary idiopathic, lymphoma, CLL, SLE, methyldopa

cold - primary idiopathic, lymphoma, infections: EBV, mycoplasma

Question 25

What is paroxysmal cold haemoglobinuria (PCH)?

Answer 25

Hb in urine usually caused by viral infection Donath-Landsteiner Abs stick to RBCs in cold -\> complement mediated haemolysis on rewardming

Question 26

What is paroxysmal nocturnal haemoglobinuria?

Answer 26

Acquired loss of protective surface markers on RBCs leading to complement-mediated lysis and nocturnal intravascular haemolysis

Question 27

Recall 2 symptoms of paroxysmal nocturnal haemoglobinuria

Answer 27

Morning haemoglobinuria Throbosis (+Budd Chiari syndrome - hepatic v thrombosis)

Question 28

Recall 2 ways that paroxysmal nocturnal haemoglobinuria can be diagnosed?

Answer 28

1. Altered GPI (surface proteins on RBC) on immunophenotyping 2. Ham's test (in vitro acid-induced lysis)

Question 29

What is the pathophysiology of autoimmune TTP?

Answer 29

Antibodies against ADAMST13 --\> long strands of VWF These VWF strands act like cheese wire in blood vessels

Question 30

Which monoclonal Abs can be used in trreating PNH?

Answer 30

eculizumab - prevents complement binding RBCs

Question 31

What is the Ham’s test / Flow cytometry of GPI-linked proteins used to show?

Answer 31

Paroxysmal nocturnal haemoglobinuria

Question 32

Recall the causes of MAHA

Answer 32

HUS, TTP, DIC, pre-eclampsia, eclampsiaa

Question 33

What is the classic pentad of symptoms in TTP?

Answer 33

MAHA Fever Renal impairment Neurological abnormalities Thrombocytopaenia

Question 34

Recall the pathophysiolgy of autoimmune MAHA

Answer 34

Abs against ADAMTS13 -\> long strands vWF which act like cheese wire in the blood vessels, cutting up RBCs

Question 35

Recall the pathophysiology of HUS

Answer 35

E coli - toxin damages endothelial cells, forms fibrin mesh and damages RBCs -\> impaired renal function + MAHA

Question 36

Recall the clinical features of HUS

Answer 36

diarrhoea, renal failure, no neuro problems, children and elderly