Anaemia 2 Flashcards
What are the essential components needed for normal RBC production? [8]
- erythropoietin
- iron
- B12
- folate
- minerals
- functioning bone marrow
- globin genes
- no increased loss/destruction of RBC (i.e. haemolytic anaemia)
Define haemoglobinopathies and describe the 2 different types [5]
- haemoglobinopathies are inherited conditions that result in a relative lack of normal globin chains due to:
-
thalassaemias
- absent genes
-
haemoglobin variants
- abnormal globin chains
- e.g. sickle cell disease
-
thalassaemias
What are the normal types of haemoglobin? [3]
- Foetus:
- HbF (α2, y2)
- Adult:
- HbA (α2, b2)
- HbA2 (α2, δ2)
Define thalassaemias [3]
- anaemia due to decreased synthesis of Hb globin chains
- results in ineffective erythropoiesis
- precipitation in mature cells leads to haemolysis
- results in ineffective erythropoiesis
What are the 2 types of thalassaemias? [2]
- alpha thalassemias (lack of α-globin genes)
- beta thalassemias (lack of β-globin genes)
Describe how alpha thalassemias clinically present from least severe (missing 1 gene) to most severe (missing 4 genes) [11]
-
missing 1 gene
- mild microcytosis
-
missing 2 genes
- microcytosis
- increased RBC count
- very mild (sometimes asymptomatic) anaemia
-
missing 3 genes
- HbH disease
- beta globins bind together instead of binding with alpha globulins due to excess beta chains
- blood transfusion required during periods of stress (e.g. infection)
- significant anaemia
- bizarre-shaped small RBCs
- HbH disease
-
missing 4 genes
- incompatible with life = hydrops foetalis
- this is due to the need of alpha chains in order to make fetal Hb
Define beta thalassaemia major and how is it inherited (genetic basis)? [2]
- missing both beta globin genes
- autosomal recessive
What are the consequences of beta thalassaemia major? [6]
- inability to make adult haemoglobin (HbA) resulting in significant dyserythropoiesis which leads to an expansion of the bone marrow and bone itself → characteristic frontal bossing
- patient is transfusion dependent from early life
- increased risk of iron overload (which reduces life expectancy), therefore iron chelators must be given
What is sickle cell disease? [1]
Autosomal recessive single amino acid substitution (point mutation) of beta globin chain on chromosome 11, position 6
What are the 2 types of sickle cell disease and what kind of substitution causes each type? [4]
- HbSS
- glutamine substituted for valine
- HbSC
- glutamine substituted for lysine
What are the clinical consequences of sickle cell anaemia in the blood? [4]
- reduced RBC survival → haemolysis
- vaso-occulsion → tissue hypoxia/infarction
Vaso-occulsion due to sickle cell anaemia can lead to multi-system disease. What are the effects on:
- brain [2]
- lungs [2]
- bones [2]
- spleen [1]
- kidneys [2]
- urogenital system [1]
- eyes [1]
- placenta [2]
- brain
- stroke
- moya moya
- lungs
- acute chest syndrome
- pulmonary hypertension
- bones
- dactilytis
- osteonecrosis
- spleen
- hyposplenism
- kidneys
- loss of urine concentration
- infarction
- urogenital system
- priapism (acute/chronic) → persistent, painful erection of the penis
- eyes
- vascular retinopathy
- placenta
- intrauterine growth restriction (IUGR)
- fetal loss
How do you treat sickle cell anaemia? [3]
-
prevent crises
- hydration, analgesia, early intervention
- prophylactic vaccination and antibiotics
- folic acid
-
prompt management of crises
- oxygen, fluids, analgesia, antibiotics, specialist care
- transfusion/red cell exchange
- (bone marrow transplantation)
Define haemolytic anaemia [3]
- anaemia related to reduced RBC lifespan
- no blood loss
- no haematinic deficiency
- (note: haematinic is a nutrient required for the formation of blood cells in the process of hematopoiesis)
What are the 3 underlying pathologies of congenital haemolytic anaemia? [3]
- abnormalities of RBC membrane
- hereditary spherocytosis
- haemoglobinopathies
- thalassaemia
- sickle cell anaemia
- abnormalities of RBC enzymes
- pyruvate kinase
- G6PD
What are the 2 types of abnormalities that can affect RBC enzymes and what are the clinical features of each? [8]
-
pyruvate kinase deficiency anaemia
- chronic/extravascular haemolytic anaemia
- ATP depletion
- autosomal recessive
-
glucose-6-phosphate dehydrogenase deficiency
- acute episodic intravascular haemolysis
- X-linked recessive
- acute haemolysis from oxidative stress
Describe the 3 types of acquired haemolytic anaemia [7]
-
autoimmune
- warm type (IgG)
- cold type (IgM)
-
isoimmune
- haemolytic disease of newborn (HDN)
-
non-immune
- fragmentation haemolysis
Describe cold type autoimmune haemolytic anaemia under the following headings:
- associated autoantibody? [2]
- pathology in the blood? [4]
- direct coombs test result? [1]
- causes? [2]
- treatment? [2]
-
associated autoantibody?
- IgM (+complement)
-
pathology in the blood?
- Blood cells stick together = agglutination
- Partially activate complement
- C3b receptors on macrophages bind to RBC
- RBCs not fully haemolysed
-
direct coombs test result?
- positive
-
causes?
- idiopathic
- secondary to infections (mycoplasma infections)
-
treatment?
- treat underlying cause
- keep warm
Describe warm type autoimmune haemolytic anaemia under the following headings:
- associated autoantibody? [2]
- pathology in the blood? [3]
- direct coombs test result? [1]
- causes? [4]
- treatment? [5]
-
associated autoantibody
- IgG (+/- complement)
-
pathology in the blood
- spherocytic, polychromatic RBC
- reticulocyte count raised
- Some IgG antibodies activate complement and lead to deposition of C3b on the red cell surface → enhancing phagocytosis by macrophages
-
direct coombs test result
- strongly positive
-
causes
- idiopathic
- secondary to systemic lupus erythematosus (SLE)
- lymphomas
- drug induced (Hapten, cephalosporins, immunosuppressants)
-
treatment
- steroids (prednisolone, 60-100mg p/d),
- blood transfusion,
- folic acid supplementation,
- immunosuppression,
- splenectomy may be necessary
