L9 - haemolytic anaemias and haemoglobinopathies Flashcards
What is a haemolytic anaemia?
An anaemia that results from the abnormal breakdown (haemolysis) of RBC’s in the blood vessels or spleen
What is the normal life span of a RBC?
120 days
The bone marrow can compensate for haemolysis up to a point, what is the average life span that is deemed a haemolytic anaemia because the bone marrow can’t keep up producing new sells to compensate for the dying ones?
20–30 days
Symptoms of haemolytic anaemia are the same as other forms, i.e. shortness of breath, fatigue etc. However what symptoms do we see in haemolytic anaemias because of the haemolysis that goes on that we don’t see in other ones?
Jaundice - due to excess bilirubin (breakdown product of haem in RBC’s) NOTE - This also means that because of this patients are at increased risk of gallstones
Splenomegaly - overworking red pulp
Haemolytic anaemias are classified into acquired and inherited types. Give two examples of each class
Acquired - Microangiopathic haemolytic anaemia(MAHA)/autoimmune haemolytic anaemia/exposure to oxidants/severe burns/snake venom causing enzyme damage
Inherited - pyruvate kinase deficiency/G6PDH deficiency/hereditary spherocytosis/sickle cell disease
What is the underlying cause of a microangiopathic haemolytic anaemia?
RBC’s are damaged by trauma, most commonly moving through compromised vessels.
What would we seen on a blood film that would confirm a suspected haemolytic anaemia that is resulting from mechanical damage to cells
Schistocytes (fragments of RBC’s) - NOTE - this can also occur as a result of defective heart valves
What is the underlying mechanism behind autoimmune haemolytic anaemia?
What is the test for this?
The patients generates autoantibodies which bind to the RBC membrane, the spleen then recognises these as abnormal and removes them
Test is direct coombs test - uses an antibody to the antibodies
Note - there are two kinds - Warm (responds under warm lab conditions) - IgG mediated
and cold (IgM mediated)
Now we know the specific symptoms of a haemolytic anaemia, what are the specific signs?
- Increased reticulocyte count
- Raised bilirubin
- Raised LDH - lactate dehydrogenase (red cells rich in enzyme)
What is a hemoglobinopathy and what are the major ones?
An genetic defect in one or more of the globin chains that make up haemoglobin
- Alpha thalassemia
- Beta thalassemia
- Sickle cell disease
What happens in an alpha thalassemia?
Deletion or loss of function of one or more of the FOUR alpha thalassemia genes. Results in reduced or absent expression of the alpha globin chain, this results in aggregates of the B chain in excess -> damage to membrane -> mechanical damage kills them
NOTE - so the haemoglobin production is defective AND they are killed more easily
Is thalassemia microcytic, normocytic or macrocytic?
microcytic
distinguish between alpha thalassemia trait and haemoglobin H disease
In alpha thalassaemia trait, two of the four genes are affected you would see mild anaemia and microcytic, hypochromic cells
In haemoglobin H disease three of the genes are affected, we now see an increase in severity of anaemia and target cells and Heinz bodies in the blood film NOTE - these patients will have skeleyal abnormalities because extramedullary haemopoiesis occurs to compensate for defective RBC’s in the bone marrow
B-thalassemia trait (or minor) is symptomatically and signs identical to alpha thalassemia trait. Distinguish between B thalassaemia intermedia and major
Both would have severe anaemic symptoms and look similarly under the microscope - target cells, Heinz bodies, hypochromic, microcytic.
Clinically though intermedia is not transfusion dependent whereas major is (i.e. REGULAR blood transfusions, many will have to have some)
Iron overload is a major cause of premature death in thalassemia patients, explain
Patients absorb excess iron in their diet to compensate for ineffective haemopoiesis and also in severe cases have repeated blood transfusions which as we know is a risk factor for major iron build up
What are the specific treatments for thalassaemia
Iron chelation (removal) agents Folic acid transfusion of RBC's Holistic care stem cell transplants Antenatal screening
What is sickle cell disease?
Inheritance of the sickle beta globin gene resulting in the formation of sickle cells under oxygen deprivation and anaemia
Patients with a heterozygous mutant of HbS have a protection against malaria because of their malformed RBC’s, T/F?
T
Patients with sickle cell disease are at increased risk of three types of anaemia - vaso-occlusive, due to occlusion of small capillaries, aplastic anaemia (where a region of bone marrow is damaged) and haemolytic anaemia. Give some possible consequences of sickle cell disease
anaemia
jaundice (haemolytic anaemia)
hyposplenism due to spleen infarction
End organ problems -e.g. neurological problems, kidney failure etc.
Acute and chronic pain
What are the suggested treatments for sickle cell disease?
Folic acid
Penicillin and vaccinations when hyposplenism ensues
Hydroxycarbamide
Red cell transfusion
Hereditary spherocytosis is inherited in an autosomal dominant fashion, mutations in the 4 genes of the cytoskeleton cause it, what are these?
Spectrin/ankyrin/band 3/protein4.2
The spherical shape of RBC’s in hereditary spherocytosis means they are easily sheared in the spleen thus causing a haemolytic anaemia. What bodies are seen in the blood of these patients?
Howell-Jolly bodies
How can a G6PDH deficiency lead to a haemolytic anaemia?
this is an inborn error of metabolism, it is the rate limiting enzyme of the pentose phosphate pathway. It supplies the reducing energy for NADPH which in turn protects against oxidative stress by maintaining glutathione levels. This is the only source of glutathione in RBC’s-> thus patients with the disease can suffer haemolytic anaemia in times of oxidative stress e.g. exposur eto certain chemicals
how can a pyruvate kinase deficiency lead to a haemolytic anaemia?
Necessary for glycolysis -> RBC’s have no mitochondria so their only pathway for metabolism is inhibited -> water moves in an the cells haemolyse
What is the cause of 95% of myeloproliferative neoplasms?
A mutation in JAK2 kinase causing overproliferation of a certain type of cell
What is disseminated intravascular coagulation (DIC)?
A condition in which blood clots form throughout the body blocking small blood vessels
Give some laboratory findings common to all haemolytic anaemias
increased reticulocyte count (marrow tries to compensate)/raised bilirubin/raised LDH (RBC’s rich in this too)
What are the three crises that patients with sickle cell disease can experience?
vaso-occlusive due to occlusion of small capillaries causing end organ problems
haemolytic (because the sickle cells have a shorter half-life)
aplastic
Sickle cell disease patients only have some of their RBC’s sickled?
Sickeld blood cells cause problems in times of oxygen deprivation, the shape is due to a mutated beta globin gene
Describe the symptoms of someone with beta thalassemia major/ Haemoglobin H disease (severe thalassaemia)
hepatomegaly, splenomegaly, anaemic symptoms, skeletal abnormalities, potentially jaundiced as its a haemolytic aanaemia as well. In beta symptoms will be come apparent about 6 months after birth as this is when the beta gene begins to be expressed
