Haemolytic Anaemia Flashcards
Thalassaemias covered in Microcytic Anaemia deck
How is sickle cell anaemia inherited?
autosomal recessive condition
What is sickle cell anaemia?
synthesis of an abnormal haemoglobin chain termed HbS
Which form of sickle cell offers some protection against malaria?
heterozygous
Around what% of UK Afro-Caribbean’s are carriers of HbS
10%
HbS - Heterozygous
When are heteroxygote carriers severly symptomatic (cikle cell)
When hypoxic
In sickle cell symptoms in homozygotes don’t tend to develop until
4-6 months
when the abnormal HbSS molecules take over from fetal haemoglobin.
Pathophysiology of sickle cell anaemia?
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
definitive diagnosis of sickle cell disease is
haemoglobin electrophoresis
Name sickle cell crises?
thrombotic, 'painful crises' sequestration acute chest syndrome aplastic haemolytic
Sickle cell anaemia is characterised by
periods of good health with intervening crises
What are thrombotic crises precipitated by?
infection, dehydration, deoxygenation
How are thrombotic crises diagnosed?
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
What complications can you get in thromotic crises?
infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain
What is a sequestration crises?
sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
Symptoms of acute chest syndrome?
dyspnoea, chest pain, pulmonary infiltrates, low pO2
the most common cause of death after childhood is due to?
acute chest syndrome
Aplastic crises is caused by what? What would you see investigations wise?
caused by infection with parvovirus
sudden fall in haemoglobin
How common is Haemolytic crises? What would you see investigations wise?
rare
fall in haemoglobin due an increased rate of haemolysis
What is the general management of sickle cell crises?
analgesia e.g. opiates
rehydrate
oxygen
consider antibiotics if evidence of infection
blood transfusion
exchange transfusion: e.g. if neurological complications
What is the main stay of long term management of sickle cell anaemia?
hydroxyurea
How does hydroxyurea work?
increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
NICE CKS suggest that sickle cell patients should receive which vaccine?
the pneumococcal polysaccharide vaccine every 5 years
the majority of adults patients with sickle-cell will have an atrophied spleen due to repeated infarction
true
although you can get splenomegaly too
What are the general classifications of haemolytic anaemias?
Hereditary causes
Acquired: immune causes
Acquired: non-immune causes
Hereditary haemolytic anaemias can be subdivided into
membrane, metabolism or haemoglobin defects
Hereditary causes of haemolytic anaemias?
membrane: hereditary spherocytosis/elliptocytosis
metabolism: G6PD deficiency
haemoglobinopathies: sickle cell, thalassaemia
Acquired: immune causes of haemolytic anaemias?
autoimmune: warm/cold antibody type
alloimmune: transfusion reaction, haemolytic disease newborn
drug: methyldopa, penicillin
Acquired: NON immune causes of haemolytic anaemias?
microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia prosthetic cardiac valves paroxysmal nocturnal haemoglobinuria infections: malaria drug: dapsone
What is the most common hereditary haemolytic anaemia in people of northern European descent?
Hereditary spherocytosis
What is the inheritance pattern if heriditary spherocytosis?
autosomal dominant
What is hereditary spherocytosis?
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
How does hereditary spherocytosis present?
failure to thrive jaundice gallstones splenomegaly aplastic crisis degree of haemolysis variable MCHC elevated
How do you diagnose hereditary spherocytosis?
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
How do you manage hereidtary spherocytosis?
acute haemolytic crisis: treatment is generally supportive, transfusion if necessary
longer term treatment: folate replacement, splenectomy
What would you see in hereditary spherocytosis on blood film?
Spherocytes (round, lack of central pallor)
Lab investigations for hereditary spherocytosis?
spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes
What is the typical history of heritary spherocytosis?
- Neonatal jaundice
- Chronic symptoms although haemolytic crises may be precipitated by infection
- Gallstones
- Splenomegaly is common
G6PD deficiency inheritance?
Male (X-linked recessive)
G6PD deficiency ethnicity commonest in?
African + Mediterranean descent
G6PD deficiency typical history?
• Neonatal jaundice
• Infection/drugs precipitate haemolysis
• Gallstones
splenomegaly may be present
G6PD deficiency on blood film?
Heinz bodies
Bite and blister cells may also be seen
What is the diagnostic test for G6PD deficiency?
Measure enzyme activity of G6PD
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect.
true
What can precipitate a crisis in G6PD deficiency?
Many drugs can precipitate a crisis as well as infections and broad (fava) beans
What protects RBCs from oxidative damage?
glutathine
(protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide
What is important for converting oxidizied glutathine back to it’s reduced form?
NADPH
What does Glucose-6-phosphate dehydrogenase do?
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
What is the pathophysiology of G6PD deficiency?
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
After an acute episode in G6PD deifiency, when whould enzyme levels be checked? WHy?
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
Which drugs causing haemolysis in G6PD defiency?
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
Some drugs thought to be safe in G6PD defiency?
penicillins cephalosporins macrolides tetracyclines trimethoprim
Autoimmune haemolytic anaemia (AIHA) may be divided in to?
‘warm’ and ‘cold’ types, according to at what temperature the antibodies best cause haemolysis.
What causes Autoimmune haemolytic anaemia?
most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs
AIHA is characterised by which test?
positive direct antiglobulin test (Coombs’ test)
In warm AIHA the antibody is usually what?
IgG
In warm AIHA haemolysis occurs at which temp and which body sites?
body temperature and haemolysis tends to occur in extravascular sites, for example the spleen
Management options for warm AIHA?
steroids, immunosuppression and splenectomy
Causes of warm AIHA?
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
The antibody in cold AIHA is usually ? Haemolysis is mediated by?
IgM
Haemolysis is mediated by complement
In cold AIHA haemolysis occurs at which temp? Which site does this usually occur?
4 deg C.
commonly intravascular.
Patients respond better to steroids in cold vs warm AIHA
false
Patients respond less well to steroids
What are the features of cold AIHA?
Features may include symptoms of Raynaud’s and acrocynaosis.
Causes of cold AIHA?
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
systemic lupus erythematosus can rarely be associated with a mixed-type autoimmune haemolytic anaemia
true
