Anaemia Flashcards
Anaemia
Reduced total red cell mass
What is the normal response to anaemia
Reticulocytosis
Reticulocytosis
The increase of production of immature red blood cells
When is a blood film described as polychromatic
When there are too many reticulocytes
Why do reticulocytes stain blue/purple
Still have remnants of RNA
Symptoms of anaemia (5)
Breathlessness
Fatigue
Headaches
Palpitations
Faintness
Investigations for anaemia (3)
FBC
blood film
Reticulocyte count
What does haematocrit measure
Ratio of the whole blood that is red cells
Microcytic anaemia
Anaemia caused by deficient haemoglobin synthesis
Causes of Microcytic anaemia
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
What are the 3 general causes of iron deficiency
Insufficient intake
Loosing too much
Not absorbing enough
What can cause you to not absorb enough iron
Coeliac disease
What happens to % saturation of transferrin in hereditary haemochromatosis
Increases
Where is iron mostly stored in the body
Liver
Renal anaemia
Anaemia of chronic disease due to failure of erythropoietin production
Why do we get anaemia of chronic disease
Protective mechanism to reduce the supply of iron to pathogens
Pathophysiology of anaemia of chronic disease (5)
- inflammatory cytokines result in increased transcription of ferritin mRNA
- ferritin synthesis increases
- inflammatory cytokines also causes an increase plasma hepcidin
- blocks ferroportin-mediated release of iron
- impaired iron supply to marrow erythroblasts
Clinical features of long standing iron deficiency (6)
- brittle nails
- koilonychia
- atrophy of tongue papillae
- angular stomatitis
- brittle hair
- dysphasia and glottitis
Transferrin levels in iron deficiency anaemia
Normal or increased
% transferrin saturation in iron deficiency anaemia
Reduced
MCV in iron deficiency anaemia
Reduced
Serum iron in Anaemia of chronic disease
Reduced
Transferrin levels in Anaemia of chronic disease
Normal or reduced
% transferrin saturation in Anaemia of chronic disease
Reduced
Ferritin levels in Anaemia of chronic disease
Normal or increased
MCV in Anaemia of chronic disease
Normal (or can be reduced)
When is oral iron recommended to be taken
30 mins before a meal or 2 hours before other drugs
What should you avoid taking with oral iron
Calcium, antacids, caffeine and high fibre foods
Side effects of oral iron
Constipation, N+V , abdominal pains and dark stools
When is IV iron recommended
ONLY if oral is unsuccessful
Megaloblastic anaemia
Presence of erythroblasts in the bone marrow with delayed nuclear maturation because of defective DNA synthesis
What are the main 2 causes of megaloblastic anaemia
Folate and B12 deficiency
Causes of B12 deficiency (7)
- low intake
- pernicious anaemia
- PPI and H2 antagonists
- bypass surgery
- chronic pancreatitis
- coeliac disease
- chronic
Causes of folate deficiency (6)
- low intake
- coeliac
- chrons
- anticonvulsants
- pregnancy
- malignancy
Megaloblasts
Abnormally large red cell precursor with an immature nucleus
Where are megaloblasts normally found
Bone marrow
State 2 biochemical reactions in which folate and B12 are needed
DNA synthesis and nuclear maturation
DNA modification and gene activity
Where is B12 absorbed
Ileum
Where is folate absorbed
Duodenum and jejunum
What extra complications can B12 deficiency cause
Neurological
Blood film findings for megaloblastic anaemia (2)
Macrovalocytes
Hypersegmented neutrophils
What auto-antibodies might you check for in megaloblastic anaemia (2)
Anti gastric parietal cell
Anti intrinsic factor
Management of pernicious anaemia
B12 injections for life
Management of folate deficiency anaemia
Folic acid tablets
State 4 causes of non-megaloblastic macrocytosis
- alcohol
- liver disease
- hypothyroidism
- marrow failure
What happens in spurious macrocytosis
The volume of mature red cells are normal but MCV is measured as high as
State 2 causes of spurious macrocytosis
Reticulocytosis in response to acute blood loss or haemolysis
Cold-agglutinins
What is thalassaemia
Disorder which causes reduced globin chain synthesis
What kind of inheritance is seen in thalassaemia
Autosomal recessive
Alpha thalassaemia
Defects in alpha globin chains
Beta thalassaemia
Defects in beta globin chains
What causes alpha thalassaemia
Deletion of one or both alpha genes on chromosome 16
What causes a patient to have A thalassaemia trait
Missing one or two alpha genes
Clinical presentation of someone with a thalassaemia trait
Microcytic hypochromic red cells with mild anaemia
How do you differentiate between iron deficiency anaemia and a thalassaemia trait
Low ferritin in iron deficiency anaemia
What causes HbH disease
Only one alpha gene left
What is a consequence of HbH disease
Excess b chains form tetrameres
Where is HbH disease mostly found
SE Asia
State 2 key signs of HbH disease
Jaundice and splenomegaly
What causes Hb Bart’s hydrops fetalis
No functional alpha genes
Consequence of Hb Bart’s hydrops fetalis
No alpha chains so tetrameres of Hb Bart’s and HbH are produced
Clinical features of Hb Bart’s hydrops fetalis (5)
- profound anaemia
- cardiac failure
- growth retardation
- severe hepatosplenomegaly
- skeletal and cardio abnormalities
What causes beta thalassaemia
Point mutation on chromosome 11
Thalassaemia intermedia
Beta genes are present but there’s a mutation
Thalassaemia major
Beta globin genes are missing
When do patients with b thalassaemia major tend to present
6-24 months
Presentation of a patient with b thalassaemia major (4)
- pallor
- failure to thrive
- hepatosplenomegaly
- skeletal changes
Management of b thalassaemia major
Regular transfusion
What kind of anaemia does thalassaemia present with
Microcytic hypochromic
Hb analysis findings of a patient with b thalassaemia major
Mainly HbF , NO HbA
What is diagnostic for b thalassaemia trait
Raised HbA2
How do we quantify haemoglobin present in the body (2)
- electrophoresis
- high performance liquid chromatography
Complication of managing thalassaemia
Iron overload
Haemolysis
Premature red cell destruction
Signs of G6PD deficiency on a blood film
Heinz bodies
Sign of membrane damage on a blood film
Spherocytes
What do Sickle syndromes affect
The structure of haemoglobin
What kind of mutation is seen is sickle syndromes
Point mutation on codon 6 of the b globin gene
What is the consequence of the mutation in sickle syndromes
Glutamine is substituted to valine producing bS
What happens if a patient with sickle syndrome becomes hypoxic
Red blood cells become distorted damaging their membrane
Describe haemoglobin in sickle cell trait
One normal and one abnormal b gene
Is someone sickle cell trait usually symptomatic or asymptomatic
Asymptomatic
When may a patient with sickle cell trait present
Severe hypoxia : high altitude, under anaesthesia
Blood film in a patient with sickle cell trait
Normal
What is the proportion of HbS in sickle cell trait
<50%
Genetic presentation of sickle cell anaemia
2 abnormal b genes
Proportion of HbS in patients with sickle cell anaemia
> 80%
What group of patients are more likely to have sickle cell anaemia
Patients with an Afro-Caribbean family background
Sickle cell crisis
Acute pain due to vaso-occlusion of the small vessels
What do people with sickle cell have an increased risk of
Infection
What is given long term management of sickle cell anaemia (4)
Folic acid supplements
Hydroxycarbamide
Regular transfusion
Prophylactic penicillin
How do we manage a sickle crisis (6)
Opiate analgesia
Hydration
Rest
Oxygen
Antibiotics if sign of infection
Red cell transfusion
Lung complication of sickle cell
Acute chest syndrome
What causes acute chest syndrome (3)
Infection
Fat embolism
Pulmonary infarction
Clinical presentation of acute chest syndrome
SOB, chest pain, pyrexia, hypoxia and consolidation on CXR
Haemolysis
Premature red cell destruction
What are the 5 general causes of haemolysis
Immune
Mechanical red cell destruction
Membrane defects
Abnormal red cell metabolism
Abnormal haemoglobin
Cold antibodies
IgM
Warm antibodies
IgG
Warm autoimmune causes of haemolysis
Idiopathic
SLE
lymphoproliferatice disorders
Drugs
infection
Name a drug that can cause haemolysis
Penicillin
Cold immune causes of haemolysis
Idiopathic
EBV
Lymphoproliferative disorders
State 2 alloimmune causes of haemolysis
Haemolytic transfusion reaction
Haemolytic disease of the newborn
Name some causes of mechanical red cell destruction
Disseminated intravascular coagulation
TTP
Leaking heart valve
Haemolytic uraemia syndrome
Burns
Infections
State membrane defect causes of haemolysis
Zieves syndrome
Vitamin E deficiency
Hereditary spherocytosis
What makes red cells more vulnerable to damage
Biconcave
Can’t generate new proteins as no nucleus
Limited metabolic reserve as no mitochondria
Haemolytic anaemia
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production causes a fall in haemoglobin
State 3 consequences of haemolysis
- reticulocytosis by bone marrow
- bone marrow erythroid hyperplasia
- excess red cell break down products
What are the 2 main classifications of haemolysis
Intravascular and extravascular
What happens to red blood cells in extravascular haemolysis
Red cells are taken up by reticuloendothelial system
Are products normal or abnormal in extravascular haemolysis
Normal but generated in access
Are products of intravascular haemolysis normal or abnormal
Abnormal
Consequence of extravascular haemolysis
Hyperplasia at the site of destruction (splenohepatomegaly)
What happens to red cells in intravascular haemolysis
Red cells destroyed within the circulation spilling their contents
Clinical sign of haemoglobinurea
Pink urine that turns black on standing
Causes of intravascular haemolysis (4)
Incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria
PNH, PCH
Reticulocyte count in haemolysis
Raised
Serum unconjugated bilirubin result in haemolysis
Raised
Serum hepatoglobins in haemolysis
Low
Urinary urobilinogen in haemolysis
Raised
What do spherocytes on blood film suggest
Membrane damage
What do red cell fragments suggest on blood film
Mechanical damage
What do Heinz bodies suggest on blood film
Oxidative stress due to G6PD deficiency
Coombs test result in haemolysis
Positive
