Haematology 1 Flashcards
What is haematopoiesis?
It is the process through which all blood cells are derived
What are the components of the haematopoietic system? (5)
Bone marrow Spleen Liver Lymph nodes Thymus
Where does haematopoiesis occur in:
Children?
Adults?
C: bone marrow of nearly all bones
A: axial skeleton (skull, spine, ribs) and proximal parts of the long bones
What type of cell starts the haematopoietic process?
Pluripotent stem cell
can self-renew and differentiate
What is the main function of this cell line?
Red blood cells
Transport oxygen from lungs to tissues
What is the main function of this cell line?
Neutrophils (3)
Chemotaxis
Phagocytosis
Killing phagocytosed cells
What is the main function of this cell line?
Eosinophils (3)
Neutrophil functions
Antibody-dependent damage to parasites
Immediate hypersensitivity
What is the main function of this cell line?
Basophils (2)
Immediate hypersensitivity
Modulate inflammatory response via proteases and heparin
What is the main function of this cell line?
Monocytes & macrophages (5)
Chemotaxis Phagocytosis Killing of microorganisms Antigen presentation Release of IL-1 & TNF
What is the main function of this cell line?
Platelets
Primary haemostasis (adhere to subendothelial connective tissue)
What is the main function of this cell line?
Lymphocytes
Immune response
Haemopoietic growth factors
What is anaemia?
It is a reduction in haemoglobin level below reference range for age and sex of individual
What dictates the symptoms and signs of anaemia?
The rate at which anaemia develops
Outline the symptoms of anaemia (6)
Lassitude (lack of energy) Fatigue Dyspnoea on exertion (hard to breathe) Palpitations Headache Chest pain
Outline the signs of anaemia (5)
Pallor Tachycardia Wide pulse pressures (wide difference between top and bottom number) Systolic flow murmurs Congestive cardiac failure
What are the potential mechanisms in the development of anaemia? (5)
- Blood loss
- Decreased red cell lifespan (haemolytic)
- Congenital (sickle cell anaemia)
- Acquired (malaria, drugs)
- Impairment of red cell formation
- Insufficient erythropoiesis
- Ineffective erythropoiesis
- Pooling and destruction in spleen
- Increased plasm volume (pregnancy)
Name the 3 ways anaemia can be classified by morphology
Microcytic
Normocytic
Macrocytic
What may cause microcytic anaemia? (2)
Iron deficiency
Thalassaemia
What may cause normocytic anaemia? (3)
Acute blood loss
Anaemia of chronic disease
Chronic renal failure
What may cause macrocytic anaemia? (4)
Alcoholism
Folate deficiency
Vitamin B12 deficiency
Drugs
What is the most common cause of anaemia worldwide?
Iron deficiency anaemia
Why does the body tightly control absorption of iron?
Because excess iron is potentially toxic
What are the 3 mechanisms from which iron deficiency anaemia (IDA) can develop?
- Poor dietary intake (e.g. vegetarians, vegans)
- Malabsorption (duodenum in coeliac disease or jejunum in Crohn’s disease)
- Increased loss (commonly menorrhagia (menstrual) or GI)
(e. g. IBS, peptic ulceration, malignancy, hookworm)
Outline classic presentation of IDA (6)
Koilonychia (spoon nails)
Angular cheilitis
Atrophic glossitis (smooth, painful tongue)
Recurrent oral ulceration
Burning mouth
Oesophageal web (Plummer-Vinson/Patterson-Brown Kelly syndrome)
[Mild deficiency is typically asymptomatic]
Which demographics are more likely to have IDA? (2)
Men
Post-menopausal women
(unexplained)
What investigations are involved when diagnosing IDA? (2)
Blood film
Iron studies
What is the treatment for IDA? (4)
Address underlying cause Oral supplementation (ferrous sulphate 200mg x 3/day for 3 months) Parenteral (taking medication in a way other than via the GI tract) available (fever, arthropathy (joint disease), anaphylaxis) Blood transfusion (only in severe compromise)
What conditions are associated with normocytic anaemia? (4)
Chronic inflammatory/connective tissue conditions (rheumatoid arthritis)
Chronic infections (tuberculosis)
Chronic renal disease (due to reduction in erythropoietin)
Malignancies (bone marrow infiltration)
What are the 2 divisions of macrocytic anaemia?
- Megaloblastic erythropoiesis (abnormal red cell development due to disordered DNA synthesis)
- Normoblastic erythropoiesis (normal red cell maturation)
(to do with production of RBC)
Why is folate essential for the human body?
How does the body obtain folate?
It is essential for DNA synthesis
Derived from many food sources (esp green leafy veg)
What are the causes of megaloblastic anaemia (folate)? (5)
- Inadequate intake (elderly, alcoholism)
- Malabsorption (coeliac disease, crohn’s disease, resection)
- Increased requirement (pregnancy, haemolytic anaemias, myelofibrosis)
- Increased loss (dialysis, liver disease, congestive heart failure)
- Drugs (methotrexate, phenytoin, trimethoprim)
Why is vitamin B12 required by the body?
How do humans obtain B12?
Required in number of enzymatic reactions - deficiency impacts DNA synthesis
Found only in foods of animal origin
What are the causes of vitamin B12 deficiency? (5)
- Inadequate intake
- Inadequate secretion of intrinsic factor (pernicious anaemia, gastrectomy)
- Inadequate release from food (gastritis, PPI, EtOH abuse)
- Diversion of dietary B12 (bacterial overgrowth, small intestinal structures)
- Malabsorption (Crohn’s disease, ileal resection)
Outline the clinical features of folate and B12 deficiency (4)
Generic symptoms and signs of anaemia
Occasionally mild jaundice
Glossitis
Oral ulceration
What are the further clinical features of B12 deficiency exclusively? (3)
Peripheral neuropathy (loss of proprioception and vibration sense)
Demyelination with subacute combined degeneration of spinal cord
Dementia
What investigations are done for folate/B12 deficiency?
Blood film
Serum folate and B12 (low B12 can lead to low folate - always test together)
What is the treatment for folate/B12 anaemia? (3)
Address underlying cause
Oral supplementation (never folate only if B12 level not known)
Parenteral vitamin B12 (IM) required in pernicious anaemia
What are the potential causes of normoblastic anaemia? (4)
Alcohol excess
Liver dysfunction
Hypothyroidism
Drugs (methotrexate, azathioprine)
What are the 3 different defects that can cause congenital haemolytic anaemia?
- Membrane defects
- number of proteins are essential to maintain membrane integrity; any mutation can lead to increased fragility and haemolysis. - Enzyme defects
- Globin defects
What is the most common congenital haemolytic anaemia condition?
Hereditary spherocytosis (RBC shaped like spheres)
Give an example of an enzyme defect that can result in congenital haemolytic anaemia?
How does it lead to anaemia?
Glucose-6-phosphate dehydrogenase (G6DP) Deficiency
This is involved in glucose metabolism
Deficiency results in increased sensitivity to oxidative stress
What are the 2 types of acquired haemolytic anaemia?
Immune
Non-immune
How is phagocytosis triggered in immune acquired haemolytic anaemia?
IgG coated red blood cells interact with macrophages resulting in phagocytosis
Name an example of an autoimmune process that may be included in acquired immune haemolytic anaemia? (5)
Idiopathic Secondary to infection drugs SLE haematological malignancies
How may acquired haemolytic anaemia be cause by alloimmune results?
Transfusion and production of antibodies to transfused red cell
What may cause acquired non-immune haemolytic anaemia? (4)
Trauma
Burns
Infection (e.g. malaria)
Drugs (dapsone - often used for skin conditions like dermatitis)
Clinical features of haemolytic anaemia vary greatly depending on cause. What are the common features? (4)
Pallor
Jaundice (due to elevated bilirubin)
Splenomegaly
Expansion of erythropoiesis leading to bone deformities (frontal bossing) and pathological fractures
What does normal Hb comprise of?
2 alpha chains
2 beta chains
Each globin group is associated with a haem group (protoporphyrin ring and iron)
What happens to Hb between O2 bound and unbound states?
It undergoes a conformational change
Does Hb always have the same affinity for oxygen?
No - it’s affinity alters (loads oxygen in high oxygen tension environments and releases oxygen in low oxygen environments)
What are the 2 main groups of thalassaemia and what does this indicate?
a-thalassaemia (alpha chain defect)
b-thalassaemia (beta chain defect)
What is the consequence of the excess chains in thalassaemia?
Excess chains precipitate in precursor red cells, this leads to premature death.
Precipitated chains also result in oxidative damage to the cell membrane leading to haemolysis
Severity of thalassaemia depends on what?
The degree of globin chain imbalance
How is thalassaemia diagnosed?
It is made by using Hb electrophoresis
Which type of thalassaemia is most common is SE Asia (thailand, indonesia) and west africa?
What is the prevalence of this?
Alpha thalassaemia
20-30%
How many alpha-globin genes are there on 2 chromosomes?
4
Name the 4 traits/diseases of alpha thalassaemia?
a+ thalassaemia trait (deletion of 1 gene) - asymptomatic with normal Hb and reduced MCV
a0 thalassaemia trait (deletion of 2 genes on 1 chromosome) - slight reduction Hb and reduced MCV
Hb H disease (deletion of 3 genes) - chronic haemolytic anaemia (transfusion independent)
Hb Bart’s hydrops fetalis syndrome (deletion of all 4 genes) - intrauterine or neonatal death
What causes a+ thalassaemia and what are the consequences of this?
Deletion of 1 gene
Asymptomatic with normal Hb
Reduced MCV
What causes a0 thalassaemia and what are the consequences of this?
Deletion of 2 genes on 1 chromosome
Slight reduction Hb
Reduced MCV
What causes Hb H disease (a-thalassaemia) and what are the consequences of this?
Deletion of 3 genes
Chronic haemolytic anaemia
transfusion independent
What causes Hb Barts hydrops fetalis syndrome (a-thalassaemia) and what are the consequences of this?
Deletion of all 4 genes
Intrauterine or neonatal death
Which type of thalassaemia is more common in Southern Europe (especially Greece)?
What percentage of the world population are beta-thalassaemia carriers?
Beta-thalassaemia
~1.5% are carriers
Which type of thalassaemia is usually due to mutation rather than deletion?
Beta thalassaemia
Outline the 2 types of beta-thalassaemia
Heterozygous b-thalassaemia trait - asymptomatic
Homozygous b-thal - moderate to marked anaemia developing within first 2 years (may be transfusion dependent)
Name the 4 clinical classifications of thalassaemia
Thalassaemia minima
Thalassaemia Minor
Thalassaemia intermedia
Thalassaemia major
When does Thalassaemia minima occur?
When there is a mutation presence but there isn’t clinical consequence
What are the consequences of thalassaemia minor?
Microcytosis
Hypochromic red cells
What are the consequences of thalassaemia intermedia?
Microcytic hypochromic anaemia
Extramedullary haematopoiesis with splenomegaly
What are the consequences of thalassaemia major?
Microcytic hypochromic anaemia
Extramedullary haematopoiesis with splenomegaly
Severe anaemia and transfusion dependent
Describe the clinical presentation of thalassaemia (4)
Typically those of anaemia unless severe
Untreated = growth retardation, splenomegaly, bony deformities (due to marrow expansion due to trying to compensate for chronic anaemia)
Oral: enlargement of maxilla (chipmunk facies), migration and spacing of upper anterior teeth
Iron overload - due to transfusion leading to iron accumulation in myocardium (cardiac failure), liver (cirrhosis), pancreas (DM) and salivary glands
What is the most common structural variant of Hb? What causes this variation?
HbS
Due to mutation in B-globin gene. Interaction of sickle B-globin chains with normal a-globin chains
What does HbS variant result in?
Deformation of cell into sickle shape
Where is HbS most prevalent?
Tropical Africa, middle east and southern india
Areas in which falciparum malaria is endemic
What percentage of Hb is HbS in heterozygous sickle cell trait (carrier)?
20-40%
usually asymptomatic
What percentage of Hb is HbS in sickle cell anaemia (homozygous)?
100%
What are the clinical manifestations of sickle cell anaemia?
Chronic haemolytic anaemia Hyposplenism (due to infarcts = increased risk of infection) Splenic sequestration Acute chest syndrome CVA/TIA Bone infarction and subsequent infections Chronic leg ulcers Haematuria and chronic renal disease
Sickling = shortened erythrocyte survival, microcirculation obstruction
How is sickle cell anaemia diagnosed?
Hb electrophoresis
How is sickle-cell anaemia managed? (3)
Transfusion when necessary
Pneumococcal, haemophilus influenzae type B (Hib) and meningitis vaccinations (increased susceptibility due to hyposplenism)
Prophylactic penicillin
Describe a typical crises with sickle cell anaemia
Acute vaso-occlusive painful episodes
Precipitated by infection, dehydration, hypoxia
Oral and IV fluids
Analgesics (opiates)
What can lead to an immunological reaction between a blood donor and recipient?
Variation in surface constituents - e.g. different blood group systems
So compatibility and cross-matching is essential
H antigen is attached to cell membrane - what affect does A, B or O allele have on the H antigen?
A and B modify H antigen
O = no modification
What are the 6 possible ABO genotypes?
AA AB AO BB BO OO
What are the 4 ABO phenotypes? - so what blood can they receive?
A (receive A or O)
AB (receive A, B or O)
B (r B or O)
O (r O)
What are the 2 genetic loci that encodes for Rh?
RHD and RHCE
2 genetic loci on one chromosome
Which antigen is most clinically relevant?
D antigen
What may happen if a person if RhD-neg received RhD-pos blood transfusion?
They are at a significant risk of developing anti-D antibodies after transfusion
Why do pregnant women have the Rh status tested?
Because if a mother is RhD-neg, the foetus may be RhD-pos and placental transfer may lead to an adverse reaction.
Pregnant mothers are given antenatal anti-D prophylaxis if necessary
How can immune-mediated transfusion reactions be classified?
Acute reactions (within 24 hrs, include acute haemolytic, febrile non-haemolytic, allergic and transfusion-related acute lung injury)
Delayed reactions (occur days to weeks after, include delayed haemolytic transfusion reactions, transfusion-associated graft vs host (GVHD) disease and post-transfusion purpura)
Immune-mediated transfusion reactions have what mortality rate?
10%
Immune-mediated transfusion reactions - what are the clinical features? (9)
Fever Agitation/anxiety Rigor Rash Flushing and sweating Chest/abdominal pain Profound hypotension Bleeding Diarrhoea
Immune-mediated transfusion reactions - what is the management for this? (7)
- Stop transfusion
- Check patient identity against donor blood product unit
- Replace giving set
- Paracetamol
- IV fluids
- If suspect anaphylaxis IM Adrenaline
- Contact haematology
What is the dental relevance of anaemia?
People may present with oral features suggestive of anaemia
Alternatively anaemia may complicate treatment - if no explanation, may be sensible to delay treatment
What oral features may you see that could indicate haematinic deficiencies (ie iron, vitB12, folate)? (4)
Angular cheilitis
Glossitis
Oral ulceration
Peripheral neuropathies
What oral features may you see in sickle cell anaemia? (4)
Oral pain possibly due to infarction
Osteomyelitis
Trigeminal neuropathy (due to osteomyelitis)
Hypomineralised dentition
What radiographic features may you see if a pt has anaemia? (3)
Dense lamina dura
Hypercementosis (cementum is thickened)
Radio-opacities due to previous infarcts
What treatment issues can be caused by anaemia?
- Bleeding:
If bone marrow infiltration, may be failure of other cell lines (e.g. platelets) with increased risk of bleeding.
Liver disease may result in anaemia as well as increased risk of bleeding due to impact on clotting factors synthesis - Anaesthesia
Avoid prilocaine (methemoglobinemia - increased methemoglobin in blood)
Thalassaemia and sickle cell anaemia can complicate procedures performed under general anaesthesia
