Haematology 1s - Haemolytic anaemias

Question 1

Most common cause of intravascular haemolysis globally

Answer 1

Malaria

Question 2

Causes of extravascular haemolysis

Answer 2

Autoimmune, alloimmune and hereditary spherocytosis

Question 3

Hereditary spherocytosis inheritance

Answer 3

AD

Question 4

g6pd deficiency intravascular or extravascular?

Answer 4

Intravascular

Question 5

Consequences of haemolytic anaemia

Answer 5

Anaemia, raised reticulocyte count, increased folate demand, susceptibility to parvovirus B19 infection, propensity to gallstones, iron overload risks, osteoporosis, hepatic siderosis

Question 6

What does parvovirus b19 do to cells?

Answer 6

It infects erythroid cells and stops their maturation, this is normally not an issue in people with normal RBC lifespan but if impaired span –> dangerously low Hb and aplastic crisis

Question 7

What feature increases the risk of gallstones in haemolytic anaemia?

Answer 7

Coinheritance of Gilbert’s syndrome (UGT - UDP glucuronyl transferase 1A1)

Question 8

Clinical features of haemolytic anaemia

Answer 8

Splenomegaly, pallor, jaundice, pigmenturia

Question 9

Lab features of HA

Answer 9

Raised bilirubin, raised LDH, anaemia, reticulocytosis, polychromasia, reduced haptoglobins, haemoglobinuria, haemosiderinuria

Question 10

Which type of HA is LDH particualrly raised in?

Answer 10

Intravascular haemolysis

Question 11

Stain for haemosiderin

Answer 11

Prussian blue or Perl’s

Question 12

The defect in the RBC membrane in Hereditary spherocytosis

Answer 12

Vertical interaction, beta spectrin and ankyrin-1 deficiency

Question 13

The defect in the RBC membrane in Hereditary elliptocytosis

Answer 13

Horizontal interaction, alpha and beta spectrin and protein 4.1 - spectrin mutation

Question 14

The molecule lacking in paroxysmal nocturnal haemoglobinuria

Answer 14

GPI

Question 15

Investiations used in hereditary spherocytosis

Answer 15

Osmotic fragility test or Dye-binding test/Eosin-5-maleimide (used more often than OFT)

Question 16

Hereditary elliptocytosis inheritance

Answer 16

AD but you can be heterozygous (not v dangerous) or homozygous which is dangerous (pyropoikilocytosis)

Question 17

Haemolytic anaemias arise from disorders of 3 main domains:

Answer 17

Red cell membrane, red cell metabolism and haemaglobin

Question 18

Finding on blood film in hereditary spherocytes

Answer 18

Lack of central pallor and many polychromatic cells to show that there are lots of reticulocytes

Question 19

G6PD deficiency in heritance

Answer 19

X-linked but it affects males or homozygous females

Question 20

Which pathway is G6PD involved in?

Answer 20

Pentose phosphate pathway (to generate NADPH and prevent oxidative stress to RBC)

Question 21

G6PD triggers

Answer 21

Drugs: anti-malarials, sulphonamides, dapsone, vitamin K, ciprofloxacin, nitrofurantoin
Fava beans and mothballs , infections

Question 22

G6PD deficiency blood film

Answer 22

Heinz bodies, bite cells, nucleated RBCs, hemi-ghosts

Question 23

In the steady state, what does the blood film of someone with G6PD deficiency look like?

Answer 23

NORMAL, abnomral blood film only seen when undergoing acute haemolytic crisis

Question 24

How can Heinz bodies be visualised?

Answer 24

Need a methyl violet stain

Question 25

Name some other RBC metabolic disorders

Answer 25

Pyruvate kinase deficiency, pyrimidine 5'-nucleotidase deficiency

Question 26

Blood film features of Pyruvate kinase deficiency

Answer 26

Echinocytes and spherocytes

Question 27

First line investigations in haemolytic anaemia

Answer 27

``` DAT (autoimmune haemolysis) Urinary haemoglobin/haemosiderin - intravascular haemolysis Osmotic fragility/Eosin-5-maleimide - HS G6PD +/- PK activity Haemaglobin separation (thalassaemias) Heinz body stains (methyl violet) G6PDD Ham's test/flow cytometry of GPI proteins PNH Thick and thin blood films - Malaria ```

Question 28

Criteria for splenectomy

Answer 28

Transfusion dependence, growth delay, physical limitation (Hb<8g/dL), hypersplenism, 3-10 yrs

Question 29

What are heinz bodies?

Answer 29

Denatured haemaglobin

Question 30

Warm vs cold HA

Answer 30

Warm = IgG: Lymphoproliferative disease, SLE, Penicillin, spherocytes on blood film Cold = IgG: Mycoplasma, EBV, Lymphoma, Raynaud's

Question 31

Management of warm vs cold aIHA

Answer 31

Warm: steroids, splenectomy, immunosuppression Cold: treat underlying, avoid cold, chlorambucil (Chemo)

Question 32

Donath-Landsteiner antibodies

Answer 32

Paroxysmal cold haemaglobinuria

Question 33

Paroxysmal cold haemaglobinuria causes

Answer 33

Viral infection e.g. VZV, Measles, syphilis

Question 34

Type of haemolysis in PCH

Answer 34

Acquired, autoimmune haemolytic anaemia caused by complement mediated haemolysis

Question 35

Type of haemolysis in PNH

Answer 35

Acquired, non-immune haemolytic anaemia

Question 36

Cause of PNH

Answer 36

Acquired loss of GPI markers on RBCs --> chronic intravascular haemolysis especially at night

Question 37

triad of sx of PNH

Answer 37

Morning haemaglobinuria, intravascular haemolysis and thrombosis

Question 38

Monoclonal antibody in PNH

Answer 38

Eculizumab

Question 39

Casues of MAHA

Answer 39

HUS, TTP, DIC, Pre-eclampsia

Question 40

TTP cause

Answer 40

Autoantibodies against ADAMTS13 --> vWF multimers

Question 41

Pentad in TTP

Answer 41

MAHA, renal failure, thrombocytopenia, fever, neurological sx