Haematology - Haemolytic Anaemias

Question 1

Recall some causes of intravascular vs extravascular haemolytic anaemias

Answer 1

EXTRAvascular = hereditary spherocytosis 
INTRAvascualr = everything else (malaria, G6PDD, MAHA, PNH ETC)

Question 2

Which infection are patients with haemolytic anaemias more susceptibile to?

Answer 2

Parvovirus B19
often develop gallstones

Question 3

What is the expected LDH level in haemolytic anaemia?

Answer 3

High

Question 4

What is the inheritance pattern of hereditary spherocytosis?

Answer 4

Autosomal dominant

Question 5

How can hereditary spherocytosis be diagnosed (2)?

Answer 5

eosin-5 -maleimide (EMA) binding test

osmotic fragility test = increased susceptibility to lysis in hypotonic saline

Question 6

In which parts of the world is G6PDD most common?

Answer 6

Where malaria is endemic

Question 7

What is the inheritance pattern of G6PDD?

Answer 7

X linked recessive

Question 8

What is the normal physiological role of G6PD?

Answer 8

NADPH generation

Question 9

What is the main symptom of G6PDD in neonates?

Answer 9

Jaundice

Question 10

Recall 4 triggers for a crisis in G6PDD

Answer 10

Moth balls
Fava beans
Anti-malarials
Antibiotics (sulphonamides, cipro

Question 11

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

Answer 11

echinocytes ‘hedgehog’ appearnce

Question 12

What is the first investigation to do in haemolytic anaemia?

Answer 12

DAT/ Coombs test
Need to exclude autoimmune haemolysis

Question 13

What does a positive urinary haemosiderin test show?

Answer 13

Intravascular haemolysis

Question 14

What is homozygous hereditary elliptocytosis also known as?

Answer 14

Pyropoikilocytosis

Question 15

Differentiate the class of immunoglobin involved in warm vs cold AIHA

Answer 15

Warm: IgG = EXTRAvascular haemolsysis - most common
Cold: IgM = INTRAvascular haemolysis

Question 16

What abnormal shape of RBC may be seen on blood film in warm AIHA?

Answer 16

Spherocytes

Question 17

Recall and compare the management of warm vs cold AIHA

Answer 17

Warm: steroids, splenectomy, immunosuppression
Cold: treat underlying condition (lymphoma/EBV), avoid the cold, chlorambucil

Question 18

What is paroxysmal cold haemoglobinuria?

Answer 18

Hb in the urine, usually preceded by exposure to cold temperature and viral- infection

Question 19

Which antibodies are the cause of paroxysmal cold haemoglobinuria?

Answer 19

Donath-Landsteiner antibodies

Question 20

What is paroxysmal nocturnal haemoglobinuria?

Answer 20

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

Question 21

Recall 2 symptoms of paroxysmal nocturnal haemoglobinuria

Answer 21

Morning haemoglobinuria
Throbosis

Question 22

Recall 2 ways that paroxysmal nocturnal haemoglobinuria can be diagnosed?

Answer 22

1. Altered GPI (surface proteins on RBC)
2. Ham’s test

Question 23

What is the pathophysiology of autoimmune Thrombotic thrombocytopenia purpura

Answer 23

mutation in ADAMST13 –> long strands of VWF (deficienct in VWF cleaving proteaste)

These VWF strands act like cheese wire in blood vessels

Question 24

What is the classic pentad of symptoms in TTP?

Answer 24

MAHA
Fever
Renal impairment
Neurological abnormalities
Thrombocytopaenia

Question 25

what's a finding of extravascular HA

Answer 25

splenomegaly

Question 26

state 2 inherited conditions w membrane defects

Answer 26

hereditary spherocytosis hereditary eliptocytosis

Question 27

state 2 inherited enzyme defects

Answer 27

G6PDD pyruvate kinase def

Question 28

state 2 inherited haemoglobiopathies

Answer 28

SCD thalassemia

Question 29

what is the membrane abnormality in hereditary spherocytosis

Answer 29

spectrin or ankyrin deficiency (membrane proteins)

Question 30

2 histological findings of G6PDD

Answer 30

``` bite cells Heinz bodies (blue deposits, oxide Hb) ```

Question 31

echinocytes and spherocytes seen in what condition

Answer 31

pyruvate kinase deficiency echinocytes = hedgehog appearance

Question 32

what stain for G6PDD

Answer 32

heinz body stains (methyl violet)

Question 33

what causes HUS

Answer 33

e coli

Question 34

what is the inheritance of hereditary eliptocytosis? what protein is affected

Answer 34

AD spectrin

Question 35

4 consequences of haemolysis broadly

Answer 35

anaemia erythroid hyperplasia (increased RBC production and reticulocyte circulation) increased folate demand susceptibility to parvovirus B19, galstones etc

Question 36

what does a positive DAT test indicate

Answer 36

autoimmune haemoytic anaemia

Question 37

what cell do you see in MAHA

Answer 37

schistocytes (fragmented RBC)

Question 38

5 causes of MAHA

Answer 38

HUS TTP DIC Pre-eclampsia ADENOCARCINOMA

Question 39

define MAHA

Answer 39

mechanical RBC destruction (as forced through fibrin/platelet mesh in damaged cels)

Question 40

treatment of paroxsymal nocurnal heamoglobinuria

Answer 40

Eculizumab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein and thereby reduces complement-mediated cell lysis

Question 41

treatment of TTP

Answer 41

PLASMA EXCHANGE

Question 42

triad of HUS

Answer 42

MAHA, thrombovytopaenia, AKI

Question 43

5 bllod findings common to HUS and TTP

Answer 43

Hb down Platelets down (bleeding, petechiae, haematemeis, melena) DAT/Coombs -ve (not autoimmune) schistocytes on blood smear signs of haemlosys = bilirubin up, reticulocytes up, LDH up

Question 44

thrombi are found where in HUS vs TTP

Answer 44

HUS - thrombi confined to kidney TTP - cicrulation inclduing CNS

Question 45

does HUS of TTP usually affect children

Answer 45

HUS - children mre (e coli from kids touchign animlas etc) TTP - more adults (ADAMTS13 mutation)

Question 46

does HUS typically have neuro sequelae

Answer 46

NO HUS = renal failure TTP= neuro (headache, sezire, redcued GCS, coma)