Haematology Flashcards
Explain the synthesis of a red blood cells, including the synthesis of erythropoietin.
From bone marrow -> multipotent haemopoietic stem cells -> lymphoid stem cells / myeloid stem cells
Lymphoid stem cells -> T cell/ B cell/ NK cell
Myeloid stem cells -> granulocyte-monocyte/ erythroid/ megakaryocyte
Normal erythroid maturation
Myeloid -> proerythroblast -> erythroblast (squeeze cytoplasm out into sinusoid leaving nucleus behind which is then ingested by macrophage) -> erythrocytes
Process of production red cells is called erythropoiesis
Hypoxia/ anaemia -> kidneys -> erythropoietin increase -> increased bone marrow activity -> increased red cell production ->
Juxtatubular interstitial cells in kidneys synthesis 90% erythropoietin
Hepatocytes and interstitial cells synthesis 10%
What are the essential characteristics of a stem cell?
Ability to self-renew and produce mature progeny
Ability to divide into two cells with different characteristics, one is another stem cell and the other a cell capable of differentiating to mature progeny.
Describe the basic physiology of the red blood cells.
The erythrocytes survives around 120 days in the blood stream.
Main function is oxygen transport. Also transports some CO2.
Ultimately destroyed by phagocytise cells of the spleen; also liver (less)
Explain the synthesis of white blood cells.
The multipotent haemopoietic stem cell can also give ride to a myeloblast and a mono blast which in turn give rise to granulocytes and monocytes.
Cytokines such as G-CSF (granulocyte colony-stimulating factor), M-CSF (macrophage colony-stimulating factor), GM-CSF (granulocyte-macrophage colony-stimulating factor) and various interleukins are needed.
No need to remember:
Normal granulocyte maturation
Myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band form -> neutrophil
Describe the basic physiology of neutrophils.
The neutrophil granulocyte survives 7-10 hours in the circulation before migrating to tissues.
It’s main function is defence against infection; it phagocytosis and then kills micro-organisms
Diagram
Circulating neutrophils - flow through blood vessels (in middle)
Marginated neutrophils - are adherent to endothelium
Describe the physiology of the eosinophil.
Spends less time in circulation than neutrophil.
Main function is defence against parasitic infection.
Describe the physiology of the basophils.
Have a role in allergic responses
Describe the physiology of monocytes.
Spend several days in circulation.
Migrate to tissues where they develop into macrophages and other specialised cells that have a phagocytic and scavenging function.
Also store and release iron.
Describe the physiology of platelets.
Have a role in primary haemostasis.
Platelets contribute phospholipid which promotes blood coagulation.
Describe the physiology of lymphocytes.
Gives rise to T cells, B cells and natural killer (NK) cells.
Lymphocytes recirculate to lymph nodes and other tissues and then back to the blood stream.
Intravascular life span is very variable
Small lymphocyte = high nuclei: cytoplasmic ratio
Large granular lymphocyte = contain cytotoxic granules, e.g. NK cell, cytotoxic T cells
Explain the following terms:
- anisocytosis
- poikilocytosis
- microcytosis
- macrocytosis
- microcyte
- macrocyte
- microcytic
- normocytic
- macrocytic
Anisocytosis: red cells show more variation in size than normal
Poikilocytosis: red cells show more variation in shape than normal
Microcytosis: red cells are smaller than normal (e.g. smaller than nucleus of lymphocyte)
Macrocytosis: red cells are larger than normal
Microcyte: a red cell that is smaller than normal
Macrocyte: a red cell that is larger than normal
Can be of specific types:
-round macrocytes
-oval macrocytes - deficiency of Vit. B12/ folic acid
-polychromatic macrocytes - lots of young cells .e.g. recent haemorrhage
Microcytic: describes red cells that are smaller than normal or an anaemia with small red cells.
Normocytic: describes red cells that are of normal size or an anaemia with normal sized red cells
Macrocytic: describes red cells that are larger than normal or an anaemia with large red cells
Explain hypochromia.
Normal red cells that have about a third of the diameter pale.
This is a result of the disk shape of the red cell; the centre has less haemoglobin and is therefore paler
Hypochromia means that the cells have a larger area of central pallor than normal
This results from a lower haemoglobin content and concentration and a flatter cell
Red cells that show hypochromia are described as hypochromic
Hypochromia and microcytosis often go together.
Explain hyperchromia.
Hyperchromia means that cells lack central pallor.
This can occur because they are thicker than normal or because their shape is abnormal.
Cells showing hyperchromia can be described as hyperchromatic or hyperchromic.
Has many causes since many abnormal shaped cells lack the central thinner area. However there are only two important types: sphere types (round outline, shape of sphere) and irregularly contracted cells (dense, irregular, clumped)
Spherocytes
Cells that are approximately spherical in shape
Have a round, regular outline and lack central pallor
They result from the loss of cell membrane without the loss of equivalent amount of cytoplasm so cell is forced to round up.
Spherocytes are seen in hereditary spherocytosis but not all the cells are spherical
Irregularly contracted cells
Are irregular in outline but are smaller than normal cells and have lost their central pallor
They usually result from oxidant damage to the cell membrane and to the haemoglobin
Describe polychromatic, reticulocyes and reticulocytosis.
An increased blue tinge to the cytoplasm of a red cell. Indicates that the red cell is young.
Another way to detect young cells is to do reticulocyte stain
This exposed living red cells to new methylene blue, which precipitates as a network or reticulum
Detecting polychromatic or increased numbers of reticulocytes gives you similar information however identification of reticulocytes is more reliable so they can be counted.
Describe the different types of poikilocytes.
Spherocytes
Irregularly contracted cells
Sickle cells
Are sickle or crescent shaped/ boat shaped
They result from the polymerisation of haemoglobin S when it is present in a high concentration.
Target cells
Are cells with an accumulation of haemoglobin in the centre of the area of central pallor.
They occur in obstructive jaundice, liver disease, haemoglobinopathies and hyposplenism
Elliptocytes
Elliptical in shape
They occur in hereditary elliptocytosis and in iron deficiency
Fragments
Or schistocytes are small pieces of red cells
They indicate that a red cell has fragmented
Describe rouleaux, agglutinate and Howell-Jolly bodies.
Rouleaux
Are stacks of red cells
They’re resemble a pile of coins
They result from alterations in plasma proteins
Agglutinates
Agglutinates differ from rouleaux as they are irregular clumps rather than tidy stacks
They usually result from antibody on the surface of the cells
Howell-Jolly body
Nuclear remnant in a red cell
The commonest cause is lack of splenic function
Define the following terms:
- leucocytosis
- leukopenia
- neutrophilia
- neutropenia
- lymphocytosis
- eosinophilia
- thrombocytosis
- thrombocytopenia
- erythrocytosis
- reticulocytosis
- lymphopenia
- anaemia/polycythemia
- pancytopenia
Leucocytosis: too many white cells Leukopenia: too few white cells Neutrophilia: too many neutrophils Neutropenia: too few neutrophils Lymphocytosis: too many lymphocytes Eosinophilia: too many eosinophils Thrombocytosis: too many platelets Thrombocytopenia: too few platelets Erythrocytosis: too many red blood cells Reticylocytosis: too many reticulocytes Lymphopenia: too few lymphocytes Polycythaemia (slow growing blood cancer in which your bone marrow makes too many red blood cells) Pancytopenia: reduction of all lineages (RBCs, WBCs, platelets)
Describe atypical lymphocyte, left shift, toxic granulation and hypersegmented neutrophil.
Atypical lymphocyte
An abnormal lymphocyte
Often the term is used to describe abnormal cells present in infectious mononucleosis (glandular fever)
Atypical mononuclear cell is an alternative term
Left shift
There is an increase in non-segmented neutrophils or there are neutrophil precursors in the blood (infection/ inflammation)
Right shift = increase in segmented
Toxic granulation
Heavy granulation of neutrophils
Results from infection, inflammation and tissue necrosis (but is also a normal feature of pregnancy)
Hypersegmented neutrophil
There is an increase in the average number of neutrophil lobes or segments
Usually results from a lack of vitamin B12 or folic acid.
> or equal to 6 lobes
What is meant by a reference and a normal range?
What is normal affected by?
How is a reference range determined?
Reference range: range derived from a carefully defined reference population Normal range is more vague (usually 95% of healthy population will have test results falling within a normal range.
Affected by: Age Gender Ethnic origin Physiological status e..g pregnancy Altitude - pO2 decreases = hypoxia, kidney increases erythropoetin, haemoglobin increases Nutritional status Cigarette smoking, alcohol intake - WBC count and haemoglobin effected
Reference range determined by:
Samples are collected from healthy volunteers with defined characteristics
They are analysed using the same instrument and techniques that will be used for patient samples
The data are analysed by an appropriate statistical technique:
-data with a normal (Gaussian) distribution can be analysed by deterring the mean and standard deviation and taking mean +/- 2SD as the 95% range
-data with a different distribution must be analysed by an alternative method
Not all results outside the reference range are abnormal
Not all results within the normal range are normal
Want to know if normal for the individual/ patient
A health-related range may be more meaningful than a 95% range
Ideal and non-ideal tests
The less the overlap the more ideal, no overlap is best but little overlap is expected so best you can hope for in practice
State what those abbreviations are in a full blood count (FBC): WBC RBC Hb Hct PCV MCV MCH MCHC Platelet count
WBC - white blood cell count in a given volume of blood (x10^9/l)
RBC - red blood cell count in a given volume of blood (x10^12/l)
Hb - haemoglobin concentration (g/l)
Hct - haematocrit (l/l)
PCV - packed cell volume (% or l/l) (an older name for the Hct)
MCV - mean cell volume (fl)
MCH - mean cell haemoglobin (pg)
MCHC - mean cell haemoglobin concentration (g/) sometimes (g/dl)
Platelet count - the number of platelets in a given volume of blood (x10^9/l)
How are the WBC, RBC and platelet count measured?
How is Hb measured?
How is PCV/ Hct measured?
WBC, RBC, platelet count
Initially counted visually, using a microscope and a diluted sample of blood
Now counted in large automated instruments, by enumerating electronic instruments generated when cells flow between a light source and a sensor or when cells flow through an electrical field.
Hb
Initially measured in a spectrometer by converting haemoglobin to a stable form (cyanmethaemoglobin) and measuring light absorption at a specific wavelength
Now measured by an automated instrument but principle is the same.
PCV/ Hct
Initially measured by centrifuging a blood sample (hence PCV)
How much of the column is packed with RBC’s, RBC’s at bottom, WBC’s lighter so at top, platelets (buffy coat)
Describe MCV, MCH and MCHC.
MCV
Initially calculated by dividing the total volume of red cells in a sample by the number of red cells in a sample .i.e. dividing PCV by the RBC
Now determined in directing by light scattering or by interruption of an electrical field
Larger red blood cells = higher MCV
MCH
The amount of haemoglobin in a given volume of blood divided by the number of red cells in the same volume .i.e. the Hb divided by the RBC
MCHC
The amount of haemoglobin in a given volume of blood divided by the proportion of the sample represented by the red cells .i.e. the Hb divided by the Hct
MCHC is now measured electronically, most accurately on the basis of light scattering
Describe the difference between MCH and MCHC.
MCHC can be seen as the density of red blood cells
The MCH is the absolute amount of haemoglobin in an individual red cell
In microcytic and macrocytic anaemias, the MCH tends to parallel the MCV
The MCHC is the concentration of haemoglobin in a red cell
The MCHC is related to the shape of the cell
How do you interpret a blood count?
Is there leucocytosis or leukopenia? If so why?
Which cell line is abnormal?
Are there any clues in the clinical history? E.g. pneumonia
Is there thrombocytosis or thrombocytopenia? If so are there any clues in the blood count?
Are there any clues in the clinical history?
Interpret:
-WBC and differential (percentage of different types of cell)
-Hb
-MCV
-Platelet count
Describe polycythaemia, including its causes.
How do you evaluate polycythaemia.
Treatment?
Too many red cells in the circulation
The Hb, RBC and Hct/ PVC are all increased compared with normal subjects of the same age and gender (men>women, adults>children)
Pseudopolycythaemia = reduced plasma volume due to blood doping or overtransfusion (illegal blood transfusion by athletes)
True polycythaemia = increase in total volume of red cells in the circulation due to;
- appropriately increased erythropoietin - response to hypoxia
- inappropriate erythropoietin synthesis or use
- independent of erythropoietin
Evaluation:
Start with a clinical history and physical examination (splenomegaly, abdominal mass (sign of kidney) or cyanosis)
Next compare with an appropriate normal range
Is it genuine or apparent?
-a high Hb, RBC and PCV/Hct can result from a decrease in plasma volume, referred to as pseudopolycythaemia or apparent polycythaemia
-when the abnormalities result from an increase in the number of circulating red cells there is a true polycythaemia
Causes:
Blood doping in professional cyclists
Medical negligence (blood transfusion) -weight of patient needs too be considered
Appropriately raise levels of erythropoietin:
-altitude
-hypoxia (can be seen by cyanosis and clubbing of fingers)
Erythropoeitin inappropriately administered to haematologically normal subjects (cyclists)
Renal/ other tumour inappropriately secretes erythropoietin
Abnormal function of the bone marrow -inappropriately increased erythropoiesis that is independent of erythropoietin. This is an intrinsic bone marrow disorder called polycythaemia vera and is classified as a myeloproliferative neoplasm. Can lead to thick blood - hyperviscosity which can lead to vascular obstruction
Treatment
If there is no physiological need for a high haemoglobin, or if hyperviscosity is extreme, blood can be removed to thin the blood.
If there is intrinsic bone marrow disease, drugs can be used to reduce bone marrow production of red cells
How does clinical context help us with interpreting an FBC that shows polycythaemia?
A young healthy athlete - her very suspicious
A breathless cyanosis patient - probably due to hypoxia
An abdominal mass - it could be carcinoma of the kidney
Splenomegaly - a pointer to polycythaemia vera
Describe the term anaemia.
Anaemia is a reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of same age and gender
The RBC and Hct/PCV are usually also reduced
Occasionally it results from an increase in the volume of plasma rather than a decrease in the amount of haemoglobin. In a healthy person, anaemia resulting from this cannot persist because excess fluid in circulation is excreted so anaemia can be regarded as a decrease of absolute amount of haemoglobin in the circulation.
What are the mechanisms of anaemia and distinguish this from the term cause?
Mechanisms
- reduced production of red cells/ haemoglobin in the bone marrow
- loss of blood from the body
- reduced survival of red cells in the circulation
- pooling of red cells in a very large spleen so less in circulation
The mechanism of anaemia might be reduced synthesis of haemoglobin in the bone marrow
The cause of this could be either a condition causing reduced synthesis of haem (lack of iron) or one causing reduced synthesis of globin (inherited mutation - thalassemia)
How can we classify anaemia to figure out the cause?
By cell size
Microcytic (usually also hypochromic - cell smaller, reduced haemoglobin)
Normocytic (usually also normochromic - defect not in syntheiss of haemoglobin)
Macrocytic (usually also normochromic)
Explain microcytic anaemia.
Common causes:
Defect in haem synthesis
-iron deficiency e.g. iron trapped in macrophages in the stored form haemosiderin and is not mobilised for synthesis of haem
-anaemia of chronic disease - chronic infection e.g. rheumatoid arthritis, TB
Defect in globin synthesis (thalassaemia)
-defect in alpha chain synthesis (alpha thalassaemia)
-defect in B chain synthesis (B thalassameia)
Explain macrocytic anaemia.
Macrocytic anaemia usually results from abnormal haemopoiesis so that the red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally so red cells end up larger than normal
An alternative mechanism is premature release of cells from the bone marrow. Reticulocytes are larger so MCV increases
Common causes:
- Megaloblastic anaemia as a result of lack of vitamin B12 or folic acid
- Use of drugs interfering with DNA synthesis e.g. methotrexate used to treat leukemia
- Liver disease and ethanol toxicity
- Recent major blood loss with adequate iron stores (reticulocytes increased)
- Haemolytic anaemia (chronic macrocytosis) (reticulocytes increased)
What is the difference between macrocytic and megaloblastic?
A macrocytic anaemia is one in which average cell size is increased.
One cause of this is megaloblastic erythropoiesis. This refers specifically to the delay in maturation of the nucleus (defect in synthesis of DNA) while the cytoplasm continues to mature and the cell continues to grow.
A megaloblast is an abnormal bone marrow erythroblast.
It is larger than normal and shows nuclei-cytoplasmic dissociation (immature nucleus, not condensed)
It is possible to suspect megaloblastic anaemia from the peripheral blood features:
-oval macrocytes
-teardrop
-macrocytosis - high MCV
-anaemia
-neutrophils - hypersegmentation
But to be sure requires bone marrow examination
Explain normocytic anaemia.
Mechanisms:
- recent blood loss
- failure of production of red cells
- pooling of red cells in the spleen
Causes:
-peptic ulcer, oesophageal varices (enlarged/ swollen veins), trauma
-failure of production of red cells:
Early stages of iron deficiency or anaemia of chronic disease
Renal failure
Bone marrow failure (reduction of stem cells) or suppression
Bone marrow infiltration (cancer)
-hypersplenism e.g. portal cirrhosis, splenic sequestration (sickle cell anaemia)
Explain haemolytic anaemia.
Anaemia resulting from shortened survival of red cells in the circulation
Haemolysis can result from an intrinsic abnormality of the red cells.
Haemolysis can result from extrinsic factors acting on normal red cells.
Haemolytic anaemia can be classified as inherited or acquired:
Inherited haemolytic anaemia can result from abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cell
Acquired haemolytic anaemia usually results from extrinsic factors such as microorganisms, chemicals or drugs that damage the red cell. Extrinsic factors can interact with red cells that have an intrinsic abnormality
Can also be classified as intravascular or extravascular:
-intravascular haemolysis occurs if there is very acute damage to the red cell
-extravascular haemolysis occurs when defective red cells are removed by the spleen
Often haemolysis is partly intravascular and partly extravascular
When to suspect haemolytic anaemia:
Otherwise unexplained anaemia, which is normochromic and usually either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown e.g. lactate dehydrogenase high, increased bilirubin - if liver doesn’t cope - high unconjugated bilirubin (gallstones, jaundice)
Evidence of increased bone marrow activity - high reticulocyte count
Explain hereditary spherocytosis.
Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane
After entering the circulation the cells lose membrane in the spleen and thus become spherocytic due to tethering of cytoskeleton
Red cells become less flexible and are removed prematurely by the spleen - extravascular haemolysis
The bone marrow responds to haemolysis by an increased output of red cells leading to polychromatic and reticulocytosis
Haemolysis leads to increased bilirubin production, jaundice and gallstones
Spherocytes are also more prone to haemolysis when osmotic pressure is reduced
Treatment:
Only effective treatment is splenectomy, but this has its own risks so is only done in severe cases (spleen protects against malaria and bacteria)
A good diet is important so that secondary folic acid deficiency does not occur
Alternatively, one folic acid tablet can be taken daily
Explain glucose-6-phosphate dehydrogenase (G6PD) deficiency.
G6PD is an important enzyme in the pentose phosphate shunt
It is essential for the protection of the red cell from oxidant damage
Oxidants may be generated in the blood stream e.g. during infection, or may be exogenous causing haemolysis:
-extrinsic oxidants may be foodstuffs (e.g. broad beans), chemicals (e.g. naphthalene) or drugs (e.g. dapsone, primaquine)
The gene for G6PD is on the X chromosome so affected individuals are usually hemizygous males (but occasionally homozygous females)
G6PD deficiency usually causes intermittent, sever intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
These episodes of intravascular haemolysis are associated with the appearance of considerable numbers of irregularly contacted cells
Haemoglobin is denatured and forms round inclusions known as Heinz bodies, which can be detected by a specific test
Heinz bodies are removed by the spleen, leaving a defect in the cell
Acute haemolysis sometimes requires blood transfusion
Thereafter prevention is important - diet and drugs
Explain autoimmune haemolytic anaemia.
Autoimmune haemolytic anaemia results from production of autoantibodies directed at red cell antigens
The immunoglobulin bound to the red cell membrane is recognised by splenic macrophages which removes parts of the red cell membrane, leading to spherocytosis
Complement components can also be bound to the immunoglobulin molecule, and they are also recognised by receptors on splenic macrophages
The spherocytes are less flexible than normal red cells
The combination of cell rigidity and recognition of antibody and complement on the red cell surface by splenic macrophages leads to removal of cells from the circulation by the spleen (rigid so gets trapped in spleen)
Diagnosis is by:
Finding spherocytes and an increased reticulocyte count
Detecting immunoglobulin plus/minus complement on the red cell surface
Detecting antibodies (direct antiglobulin test - Coombs test) to red cell antigens or other autoantibodies in the plasma
Treatment is by:
Use of corticosteroids and other immunosuppressive agents
Splenectomy for severe cases
What is the treatment for microangiopathic anaemia?
Removing the cause e.g. treating severe hypertension or stopping a causative drug
Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition (thrombus, thrombocytopenia)
Describe haemoglobin.
Synthesis occurs during development of RBC and begins in pro-erythroblast
-65% erythroblast stage
-35% reticulocyte stage
Haem synthesised before nucleus removed
Structure of haemoglobin made up on haem (synthesised in mitochondria) and globin (synthesised in ribosomes)
1) Fe enters bound to transferrin (iron-binding blood plasma glycoproteins)
2) Transferrin is endocysed through vesicles
3) Iron enters the mitochondria to form haem
Haem synthesis is regulated by delta-ALA (excess haem —> negative feedback
Explain the structure and synthesis of haem.
Contained in proteins e.g. haemoglobin, myoglobin, cytochromes, peroxidases, catalase, tryptophan
Same in all types of Hb - globin differs
Combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
Iron usually in ferrous form (Fe2+)
Able to combine reversible with oxygen
Synthesised mainly in mitochondria which contains the enzyme ALAS
Regulation
Explain the synthesis and structure of globin.
Various types which combine with haem to form different haemoglobin molecules.
Eight functional globin chains, arranged in two clusters:
- b-cluster (b, g, f and e globin genes) on the short arm of chromosome 11
- a-cluster (a and z globin genes) on the short arm of chromosome 16
Globin gene expression and switching
Normal adult haemoglobin:
HbA>HbA2>HbF
Structure of globin
Primary
- a —> 141 aa
- non-a —> 146 aa
Secondary
-75% a and b chains - helical arrangement
Tertiary
- approximate sphere
- hydrophilic surface (charged polar side chains), hydrophobic core
- haem pocket
Explain the oxygen-haemoglobin dissociation curve.
O2 carrying capacity of Hb at different pO2
Sigmoid shape:
-binding on one molecule facilitates the second molecule binding (cooperativity)
-p50 = partial pressure of O2 at which Hb is half saturated with O2 (26.6 mmHg - HbA)
The normal position of curve depends on: Concentration of 2,3-DPG H+ ion concentration (pH) CO2 in red blood cells Structure of Hb
Right shift (easy oxygen delivery)
- high 2,3-DPG
- high H+
- high CO2
- HbS
Left shift (give up oxygen less readily)
- Low 2,3-DPG
- HbF
Define haemoglobinopathies.
Structural variants of haemoglobin or defects in globin chain synthesis (thalassaemia)
Define thalassaemia and describe its classification.
Genetic disorders characterised by a defect of globin chain synthesis
Most common inherited single gene disorder worldwide
(Worldwide distribution: malaria and thalassaemia overlap - protect malaria)
Classification
Globin type affected
-alpha
-beta
Clinical severity
-minor (trait) - asymptomatic but can pass gene
-intermedia - (in)dependent of transfusions (intermittent transfusions) non-dependent thalassaemia
-major - individuals need regular blood transfusions, transfusion dependent thalassaemia
Explain The general principle of beta (b) thalassaemia and inheritance.
Describe the laboratory diagnosis of Beta thalassaemia.
Deletion or mutation in b globin gene(s)
Reduced or absent production of b globin chains
Prevalence - mainly Mediterranean countries (Greece), Arabian Peninsula, Iran, Indian Subcontinent, Africa, South-east Asia
Autosomal inheritance
Laboratory diagnosis:
FBC- microcytic hypochromic indices, increased RBCs relative to Hb
Film - target ells, poikilocytosis but no anisocytosis
Hb EPS (electrophoresis)/ HPLC
-alpha - normal HbA2 and HbF, +/- HbH (harder to diagnose)
-beta - raised HbA2 and raise HbF
Globin chain synthesis/ DNA studies
-genetic analysis for B-thalassaemia mutations and Xmnl polymorphism (in B-thalassaemias) and a-thalassaemia genotype (in all cases)
Describe beta thalassaemia trait.
Describe beta thalassaemia major.
Also known as thalassaemia carrier
Carry a single abnormal copy of the beta globin gene
Usually asymptomatic
Mild anaemia
RBC’s are hypochromic microcytic
Have both normal HbA and abnormal beta thalassaemia haemoglobin
Thalassaemia major
Carry 2 abnormal copies of the beta globin gene
Severe anaemia, incompatible with life without regular blood transfusions
Clinical presentation usually after 4-6 months of life
Hypochromic sphere RBCs
Alpha chain precipitates
Pappenheimer bodies (iron deposits)
Clinical presentation:
Severe anaemia usually presenting after 4 months
Hepatosplenomegaly - RBCs enlarge
Blood film shows gross hypochromia, poikilocytosis and many NRBCs
Bone marrow - erythroid hyperplasia
Extra-medullary haematopoiesis
