Haemolytic Anaemia

Question 1

How is sickle cell anaemia inherited?

Answer 1

autosomal recessive condition

Question 2

What is sickle cell anaemia?

Answer 2

synthesis of an abnormal haemoglobin chain termed HbS

Question 3

Which form of sickle cell offers some protection against malaria?

Answer 3

heterozygous

Question 4

Around what% of UK Afro-Caribbean’s are carriers of HbS

Answer 4

10%

HbS - Heterozygous

Question 5

When are heteroxygote carriers severly symptomatic (cikle cell)

Answer 5

When hypoxic

Question 6

In sickle cell symptoms in homozygotes don’t tend to develop until

Answer 6

4-6 months

when the abnormal HbSS molecules take over from fetal haemoglobin.

Question 7

Pathophysiology of sickle cell anaemia?

Answer 7

abnormal gene for beta-globin on chromosome 11
Polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains. This decreases the water solubility of deoxy-Hb
In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle

HbAS patients sickle at p02: 2.5 - 4 kPa

HbSS patients at p02: 5 - 6 kPa

sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction

Question 8

definitive diagnosis of sickle cell disease is

Answer 8

haemoglobin electrophoresis

Question 9

Name sickle cell crises?

Answer 9

thrombotic, 'painful crises'
sequestration
acute chest syndrome
aplastic
haemolytic

Question 10

Sickle cell anaemia is characterised by

Answer 10

periods of good health with intervening crises

Question 11

What are thrombotic crises precipitated by?

Answer 11

infection, dehydration, deoxygenation

Question 12

How are thrombotic crises diagnosed?

Answer 12

painful vaso-occlusive crises should be diagnosed clinically - there isn’t one test that can confirm them although tests may be done to exclude other complications

Question 13

What complications can you get in thromotic crises?

Answer 13

infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain

Question 14

What is a sequestration crises?

Answer 14

sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia

Question 15

Symptoms of acute chest syndrome?

Answer 15

dyspnoea, chest pain, pulmonary infiltrates, low pO2

Question 16

the most common cause of death after childhood is due to?

Answer 16

acute chest syndrome

Question 17

Aplastic crises is caused by what? What would you see investigations wise?

Answer 17

caused by infection with parvovirus

sudden fall in haemoglobin

Question 18

How common is Haemolytic crises? What would you see investigations wise?

Answer 18

rare

fall in haemoglobin due an increased rate of haemolysis

Question 19

What is the general management of sickle cell crises?

Answer 19

analgesia e.g. opiates
rehydrate
oxygen
consider antibiotics if evidence of infection
blood transfusion
exchange transfusion: e.g. if neurological complications

Question 20

What is the main stay of long term management of sickle cell anaemia?

Answer 20

hydroxyurea

Question 21

How does hydroxyurea work?

Answer 21

increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes

Question 22

NICE CKS suggest that sickle cell patients should receive which vaccine?

Answer 22

the pneumococcal polysaccharide vaccine every 5 years

Question 23

the majority of adults patients with sickle-cell will have an atrophied spleen due to repeated infarction

Answer 23

true

although you can get splenomegaly too

Question 24

What are the general classifications of haemolytic anaemias?

Answer 24

Hereditary causes
Acquired: immune causes
Acquired: non-immune causes

Question 25

Hereditary haemolytic anaemias can be subdivided into

Answer 25

membrane, metabolism or haemoglobin defects

Question 26

Hereditary causes of haemolytic anaemias?

Answer 26

membrane: hereditary spherocytosis/elliptocytosis metabolism: G6PD deficiency haemoglobinopathies: sickle cell, thalassaemia

Question 27

Acquired: immune causes of haemolytic anaemias?

Answer 27

autoimmune: warm/cold antibody type alloimmune: transfusion reaction, haemolytic disease newborn drug: methyldopa, penicillin

Question 28

Acquired: NON immune causes of haemolytic anaemias?

Answer 28

``` microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia prosthetic cardiac valves paroxysmal nocturnal haemoglobinuria infections: malaria drug: dapsone ```

Question 29

What is the most common hereditary haemolytic anaemia in people of northern European descent?

Answer 29

Hereditary spherocytosis

Question 30

What is the inheritance pattern if heriditary spherocytosis?

Answer 30

autosomal dominant

Question 31

What is hereditary spherocytosis?

Answer 31

defect of red blood cell cytoskeleton the normal biconcave disc shape is replaced by a sphere-shaped red blood cell red blood cell survival reduced as destroyed by the spleen

Question 32

How does hereditary spherocytosis present?

Answer 32

``` failure to thrive jaundice gallstones splenomegaly aplastic crisis degree of haemolysis variable MCHC elevated ```

Question 33

How do you diagnose hereditary spherocytosis?

Answer 33

patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests EMA binding test is diagnostic for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Question 34

How do you manage hereidtary spherocytosis?

Answer 34

acute haemolytic crisis: treatment is generally supportive, transfusion if necessary longer term treatment: folate replacement, splenectomy

Question 35

What would you see in hereditary spherocytosis on blood film?

Answer 35

Spherocytes (round, lack of central pallor)

Question 36

Lab investigations for hereditary spherocytosis?

Answer 36

spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes

Question 37

What is the typical history of heritary spherocytosis?

Answer 37

* Neonatal jaundice * Chronic symptoms although haemolytic crises may be precipitated by infection * Gallstones * Splenomegaly is common

Question 38

G6PD deficiency inheritance?

Answer 38

Male (X-linked recessive)

Question 39

G6PD deficiency ethnicity commonest in?

Answer 39

African + Mediterranean descent

Question 40

G6PD deficiency typical history?

Answer 40

• Neonatal jaundice • Infection/drugs precipitate haemolysis • Gallstones splenomegaly may be present

Question 41

G6PD deficiency on blood film?

Answer 41

Heinz bodies | Bite and blister cells may also be seen

Question 42

What is the diagnostic test for G6PD deficiency?

Answer 42

Measure enzyme activity of G6PD

Question 43

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect.

Answer 43

true

Question 44

What can precipitate a crisis in G6PD deficiency?

Answer 44

Many drugs can precipitate a crisis as well as infections and broad (fava) beans

Question 45

What protects RBCs from oxidative damage?

Answer 45

glutathine | (protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide

Question 46

What is important for converting oxidizied glutathine back to it's reduced form?

Answer 46

NADPH

Question 47

What does Glucose-6-phosphate dehydrogenase do?

Answer 47

G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH

Question 48

What is the pathophysiology of G6PD deficiency?

Answer 48

↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Question 49

After an acute episode in G6PD deifiency, when whould enzyme levels be checked? WHy?

Answer 49

levels should be checked around 3 months after an acute episode of hemolysis RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Question 50

Which drugs causing haemolysis in G6PD defiency?

Answer 50

anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

Question 51

Some drugs thought to be safe in G6PD defiency?

Answer 51

``` penicillins cephalosporins macrolides tetracyclines trimethoprim ```

Question 52

Autoimmune haemolytic anaemia (AIHA) may be divided in to?

Answer 52

'warm' and 'cold' types, according to at what temperature the antibodies best cause haemolysis.

Question 53

What causes Autoimmune haemolytic anaemia?

Answer 53

most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs

Question 54

AIHA is characterised by which test?

Answer 54

positive direct antiglobulin test (Coombs' test)

Question 55

In warm AIHA the antibody is usually what?

Answer 55

IgG

Question 56

In warm AIHA haemolysis occurs at which temp and which body sites?

Answer 56

body temperature and haemolysis tends to occur in extravascular sites, for example the spleen

Question 57

Management options for warm AIHA?

Answer 57

steroids, immunosuppression and splenectomy

Question 58

Causes of warm AIHA?

Answer 58

autoimmune disease: e.g. systemic lupus erythematosus* neoplasia: e.g. lymphoma, CLL drugs: e.g. methyldopa

Question 59

The antibody in cold AIHA is usually ? Haemolysis is mediated by?

Answer 59

IgM | Haemolysis is mediated by complement

Question 60

In cold AIHA haemolysis occurs at which temp? Which site does this usually occur?

Answer 60

4 deg C. | commonly intravascular.

Question 61

Patients respond better to steroids in cold vs warm AIHA

Answer 61

false | Patients respond less well to steroids

Question 62

What are the features of cold AIHA?

Answer 62

Features may include symptoms of Raynaud's and acrocynaosis.

Question 63

Causes of cold AIHA?

Answer 63

neoplasia: e.g. lymphoma infections: e.g. mycoplasma, EBV

Question 64

systemic lupus erythematosus can rarely be associated with a mixed-type autoimmune haemolytic anaemia

Answer 64

true