Session 5 Heamolytic anemias and issues with Heamopoeisis Flashcards
what is thalassemia ?
outline the disease
pair of a globulin genes on chromosome 16
B globin genes on chromosome 11
if you are deficient in a production have B thal
deficient in B product then you have a thal
be aware of ethnincity - S asian and middle east ect are more prevalent in thal disease
get hypochromic microcytic red cells
The relative excess of the other globin chain (eg in ß-thal get insoluble aggregates of
alpha chains) contributes to the defective nature of the red cell as the aggregates get
oxidised and damage the red cell membrane
• Most of the maturing erythroblasts are destroyed within the bone marrow and there
is excessive destruction of mature red cells in the spleen
• So… as well as defective Hb production this is a form of
haemolytic anaemia also as the red cells are destroyed
The peripheral blood erythrocytes are hypochromic and microcytic and show anisopoikilocytosis with frequent target cells and circulating nucleated red blood cells
outline the variations of a thal
Silent carrier state
Deletion of a single α-globin gene.
It is asymptomatic,
without anaemia
α-Thalassemia trait
Deletion of two α-globin genes.
It may affect both genes of one chromosome or one gene of each chromosome
There is minimal or no anaemia and no physical signs; findings are identical to those of β-thalassemia minor
(microcytosis and hypochromia)
Hemoglobin H (HbH) disease
Deletion of three α-globin genes.
Tetramers of β-globin, called HbH, are formed
There is moderately severe anaemia, resembling β-thalassemia intermedia (microcytic,hypochromic anaemia with target cells and Heinz bodies in the blood film)
Hydrops fetalis
Deletion of all four α-globin genes
Not viable with life
outline the various B thals
chromosome 11 - often gene mutations, rather than deletions
β0=total absence of production
β+= reduction of globin production
β-Thalassaemia major
Severe transfusion-dependent anaemia that first becomes manifest 6 to 9
months after birth as synthesis switches from HbF to HbA
Homozygous
Either type βo or β (βo/βo or β+/β+)
β-Thalassaemia minor or β-thalassemia trait
Usually asymptomatic with a mild anemia (very microcytic and hypochromic)
Heterozygous
One normal gene (βo/β or β+/β)
what are the consequences and treatments of Thalasamiea ?
• Extramedullary haemopoiesis is an attempt to compensate but results in
splenomegaly, hepatomegaly and expansion of haemopoiesis into the bone cortex
..this impairs growth and causes classical skeletal abnormalities
• Reduced oxygen delivery leads to stimulation of EPO which further contributes to
the drive to make more defective red cells
- Iron overload is major cause of premature death and occurs due to:
- Excessive absorption of dietary iron due to ineffective haematopoiesis
- Repeated blood transfusions required to treat the anaemia
- Transfusions of red cells from childhood
- Iron chelation
- Folic acid
- Immunisation
• Reduced Life expectancy
draw a diagram showing the problems of B thal
check against session 5 lec 1
outline sickle cell disease
Inheritance of the sickle ß-globin chain
- A point mutation causes substitution of valine for glutamic acid in position 6 in the ßchain
- HbSS = homozygous sickle cell anaemia, is most common cause of severe sickling syndrome
- HbS carrier state causes a mild asymptomatic anaemia and is found in up to 30% of W African people as it confers protection against malaria
Symptoms of anaemia usually mild ie the anaemia is well tolerated
• Problems come in low oxygen state / repeated cycles of deoxygenation when the deoxygenated HbS forms polymers and the red cells form a sickle shape
• Irreversibly sickled red cells are less
deformable and can cause occlusion in
small blood vessels – ‘sticky’ - thrombosis
what is the clincal pattern of sickle cell
(what are the conditons?)
3 problems
- Vaso-occlusive
Painful bone crises
Organ – chest, spleen - Aplastic (often triggered by parvovirus infection) - no production
- Haemolytic
net result of these is end organ damage due to chronic or acute thrombosis and oxygen deprivation
outline heamolytic anaemia
may want to draw large mind map and check against lecture
- Results from the abnormal breakdown of red blood cells (=haemolysis) :
- within blood vessels (intravascular haemolysis)
- or in the spleen or wider RES (extravascular haemolysis)
Results in:
• Symptoms of anaemia – severity worse if Hb very low or if a sudden fall in Hb rather
than in chronic disease
• Accumulation of bilirubin leading to jaundice and associated risk of complications
such as pigment gallstones.
• Overworking of the red pulp leading to splenomegaly
can be inherited - defects in glycolysis - pyruvate kinase deficiny, Pentose P pathways - G6PDH deficney, membrane protien - spehro/eliptocytosis
heamglobin defect - sickle cell
acquired - microangiopathic anemia - MAHA
DIC
autoimmune antibody
damage -
• In this condition autoantibodies (an Immunoglobulin protein produced by
person’s own B lymphocytes) bind to the red cell membrane proteins
• Broadly classified as
• warm autoimmune haemolytic anaemia (IgG, maximally active at 370C)
• cold autoimmune haemolytic anaemia (IgM, maximally active at 4
0C)
• Causes can be infections (eg chest infections in children causing the cold form)
or cancers of the lymphoid system (eg B cell lymphoma)
• The spleen recognises the red cell as ‘abnormal’ and removes it
oxidant damage
severe burns
what are key factors in the blood sample for a heamolytic anemia
• Some key laboratory features:
- increased reticulocytes (as the marrow tries to compensate)
- raised bilirubin (from breakdown of Haem)
- raised LDH (as red cells rich in this enzyme)
what are the main myeloproliferative disorders ?
Essential thrombocytopenia
Polcythemia Vera
Myleofibrosis
Chronic Myeloid Leukaemia
• All of these disorders involve dysregulation at the multipotent haematopoietic stem cell
what is a common mutation in MPD’s
mutation in one copy
of the Janus kinase 2 gene (JAK2)
- a cytoplasmic tyrosine kinase on chromosome 9,
which causes increased proliferation and survival of haematopoietic precursors
Oultine the disease Polycythemia vera
too many red cells
Diagnostic criteria = High haematocrit OR raised red cell mass
• JAK2 V617F mutation is present
Clinical features: • Significant cause of arterial thrombosis • Venous thrombosis • Haemorrhage into skin or GI tract • Pruritis • Splenic discomfort , splenomegaly • Gout
treat with venesection to reduced heamtocrit
Aspirin to thin blood
manage the CVS risk factors
compare PV to polyctheamia
• Polycythaemia = an increase in circulating red cell concentration typified by a persistently raised haematocrit (Hct).
- This increase can be:
- Relative = normal red cell mass with ↓ plasma volume (dehydration) or
- Absolute = ↑ red cell mass:
- Primary = polycythaemia vera
- Secondary – driven by erythropoietin EPO production
- Physiologically appropriate – in response to tissue hypoxia
- Physiologically inappropriate
classify the causes of secondary polycythemia
draw a table and check
check against session 5 lecture 2
what is essential thrombocytopenia ?
too many platelets
jak2 mutation
management -
• Any cardiovascular risk factors should be aggressively
managed
• Aspirin
• return the platelet count into the normal range with drug
such as hydroxycarbomide
look to exclude reactive causes such as infecitons, inflammation, cancer, burns/trauma - if so treat condition first and it will go away
