Introduction to Anaemia Flashcards
What is the definition of anaemia?
- Haemoglobin (Hb) concentration falls below defined level (outside normal range)
- Units of Hb are g/L
What is the clinical consequence of anaemia?
•insufficient O2 delivery
What are the 3 causes of anaemia?
- Decreased Hb content
- Decreased red blood cells (RBCs)
- Altered Hb does not carry sufficient O2
Name the 5 red cell indices
- Haematocrit = % red cells after centrifugation ~ 40-45%
- RBC = number of red cells per litre ~ 4x1012/L
- MCV = mean cell volume (80-100fL)
- MCH = mean cell Hb
- MCHC = mean cell Hb concentration
Complete the table of the normal haemoglobin range
What are the symptoms of anaemia?
- Lethargy, fatigue
- Shortness of breath
- Palpitations
- Headache
- Worse symtoms if acute onset
- Acute bleed / haemolysis
What are the clinical signs of anaemia?
- Skin pallor
- Pale conjunctivae
- Tachypnoea
- Tachycardia
What clinical sign is this?
Koilonychia
- spoon shaped nails
- iron deficiency
What are the 2 types of inadequate synthesis and name some examples
•Deficiency in necessary components
Iron, B12, folic acid
•Bone Marrow Dysfunction / Infiltration
e.g., myelodysplasia or aplastic anaemia
What are the 2 problems of blood loss or consumption and name some examples
- Bleeding
- Haemolytic
Increased red cell destruction
Shortened RBC lifespan
What is the most common type of anaemia?
Iron deficiency anaemia
What are the 3 causes of iron deficiency anaemia and name some examples
- Bleeding (esp. occult)
- Nutritional deficiency
- Increased requirements
What tests are included in iron studies and what do they test for?
Serum Ferritin
- Storage form of iron
- Low = iron deficient (high = iron overload or reactive)
Serum Iron
•Labile in blood, so reflects recent intake of iron
Serum Transferrin
- Carrier molecule for iron from gut to stores
- Homeostatically goes up if iron is deficient
- Reflects total iron binding capacity (TIBC) of the blood•
% Transferrin Saturation
- Sensitive measure of iron status
- Reflects proportion of transferrin with iron bound
- Low TF saturation indicates iron deficiency
How would you confirm iron deficiency anaemia?
Complete the table
Complete the table with low, normal or high
What are the 3 catagories of RBC size and name some anaemias that would present with that MCV
Microcytic (small)
- Iron deficiency (iron contained within the haem molecule in Hb)
- Inherited disorders of haemoglobin (beta-thalassaemia trait)
Macrocytic (large)
- B12 and folate deficiency (needed for synthesis of nucleotides)
- Myelodysplasia (causes defective erythropoiesis)
Normocytic (normal)
- Anaemia of chronic disease
- Acute haemorrhage
- Renal failure (caused by low erythropoietin levels)
How is RBC size measured and what is the normal range?
Mean Corpuscular Volume
- This is the size of red blood cells (mean cell volume)
- Normally about 80-100fL
What 4 types of abnormalities can be seen on a blood film?
? haematinic deficiency
- microcytic/macrocytic
- hypochromic
- anisopoikilocytosis
? haemoglobinopathy
•sickled cells
? haemolysis
•polychromasia
? other abnormalities
- white cells
- platelets
- leukaemic cells
What is the lifespan of a red cell?
100 days
What are reticulocytes?
Reticulocytes represent newly produced RBCs ~1 day old
How can reticulocyte count be measured and what is the normal result?
- Can be calculated on a blood film using a stain to detect RNA
- Usually measured by flow cytometry based on size and colour
- Typically ~1% but can be >10% in haemolysis e.g., sickle cell disease
- Causes polychromasia on a blood film (large blue-ish red cells)
What do reticulocytes indicate?
Indicates the rate of production of RBCs by bone marrow
What do high / low reticulocytes indicate?
- Low during precursor deficiencies (e.g. iron)
- Low if bone marrow is infiltrated
- High in chronic bleeding
- High in haemolysis
What hormone drives RBC production and where is it produced?
Erythropoietin from kidney
What does this blood film show and what disease is it?
- Hypochromia
- Microcytosis
- Pencil Cells
- Target Cells
Iron deficiency anaemia
What history would you take from a patient with ?Iron deficiency anaemia?
- GI Symptoms
- Dyspepsia / Reflux
- Change in bowel habit (?melaena)
- Weight loss?
- Menstrual History ?menorrhagia
- Bowel history ?coeliac / Crohn’s disease
- Dietary history
- Travel History
- Ethnic Origin
- Family History
What causes megaloblastic anaemia?
Caused by deficiency of
- Vitamin B12
- Folate
What are the morphological features of megalobastic anaemia?
- Macrocytic red cells (MCV > 100)
- Hypersegmented neutrophils (more than 4 nuclear lobes)
What does this blood film show and what disease is it?
• Hypersegmented neutrophils (more than 4 nuclear lobes)
Megalobastic anaemia
How does pernicious anaemia work?
- Autoimmune – parietal cell loss
- Deficiency of intrinsic factor
- Cannot absorb B12 in terminal ileum where IF receptors are located
What would you check for in ?pernicious anaemia
Check for autoantibodies against intrinsic factor or gastric parietal cells
What is the treatment for pernicious anaemia?
Treat with B12 injections
Load initially with 5 doses alternate days, then every 3 months
What are the 3 causes of B12 deficiency and name some examples
Pernicious Anaemia
Dietary
•Strict vegans (B12 found in diary produce)
Malabsorption
- Coeliac disease and Crohn’s disease
- Post gastric / ileal surgery
What are the 5 causes of folate deficiency and name some examples
Dietary – common
Malabsorption
- Coeliac
- Crohn’s disease
Excess Utilisation
- Chronic haemolysis
- Pregnancy
Alcohol
Drugs
•Phenytoin
Methotrexate
What is the most common form of anaemia in hospital patients?
Anaemia of chronic disease
What are the 5 causes of anaemia of chronic disease?
- Chronic inflammation
- Chronic infection e.g. TB
- Auto-immune conditions e.g. rheumatoid arthritis
- Cancer
- Renal failure (also causes low EPO level)
What is the 3 ways that chronic disease causes anaemia?
- Poor utilisation of iron in the body
- Dysregulation of iron homeostasis
- Impaired proliferation of erythroid progenitors
How does poor utilisation of iron in the body cause anaemia of chronic disease?
- Iron is stuck in macrophages of the reticuloendothelial system
- There is poor mobilisation of the iron from the stores into the erythroblasts
How does dysregulation of iron homeostasis cause anaemia of chronic disease?
- Decreased transferrin
- Increased ferritin (acute phase reactant)
- Increased hepcidin
How does impaired proliferation of erythroid progenitors cause anaemia of chronic disease?
- Blunted response to EPO (erythropoietin)
- Iron is functionally unavailable
What’s the diagnosis?
Diagnosis – iron deficiency (or beta-thalassaemia trait)
What’s the diagnosis?
Diagnosis – megaloblastic anaemia due to B12 or folate deficiency
(or myelodysplasia)
How does sickle cell disease cause anaemia?
- Point mutation in the beta globin gene causing HbS (sickle Hb)
- Increased turnover of red cells = survival approx 20 days due to haemolysis
What is a sickle cell crisis?
- Triggered by low blood O2 level
- Vaso-occlusive due to sickling in the vessels
- Causes ischaemia leading to pain, necrosis and potential organ damage
What is the management of a sickle cell crisis?
Analgesics, hydration, transfusion
What is the genetic inheritance pattern of sickle cell disease and which geographical region does it originate from?
- Genetic, autosomal recessive
- Sub-Saharan Africa
Does sickle cell anaemia cause a shortened lifespan?
Yes
What disease is this?
Sickle cell anaemia
What disease is this?
Sickle cell anaemia
What are the differences between normal haemoglobin and sickled haemoglobin?
mutated sickle haemoglobin (HbS)
- forms long filamentous strands
- insoluble at low O2 tension
- RBCs become inflexible + spiky -> crisis
What is the difference between sickle cell anaemia and sickle cell trait?
Sickle cell trait - heterozygous,
- 50% HbS and 50% HbA
- much lower risk of sickling and crisis
- resistance to malaria infection
What is thalassaemia?
- Insufficient production of normal Hb
- Imbalance of alpha and beta chains
What is the genetic inheritance pattern for thallasaemia?
- Inherited autosomal recessive
- Either alpha or beta thalassaemia
What are the clinical features of thalassaemia?
- enlarged spleen, liver, and heart
- bones may be misshapen (frontal bossing)
What is the difference between beta-thal major and beta-thal minor?
Beta-thal major (homozygous) = disease - requires life-long transfusions
Beta-thal minor (heterozygous) = carrier (aka Beta-thal trait) - clinically healthy
What features would you see in a blood film for thalassaemia?
- Microcytic
- Hypochromic
What are the 3 types of bone marrow infiltration?
Leukaemia
Lymphoma
Myeloma
What are the symptoms of leukaemia?
- Non-specific symptoms
- Bone marrow failure
What are the symptoms of lymphoma?
- Lymphadenopathy
- Weight loss
What are the symptoms of myeloma?
- Anaemia
- Hypercalcaemia
- Renal Failure
- Bone lesions
What tests would you do for bone marrow infiltration?
Bone marrow sample obtained from iliac crest:
- aspirate film for morphology of cells
- trephine biopsy for histological section
When would you transfuse a patient for anaemia?
- Acute > chronic
- Be guided by symptoms rather than Hb level
- Can the patient make blood with haematinic therapy?
- If not, then transfuse for symptoms (usually if Hb <80g/L)
Name an example of an acute and a chronic haemorrhage
Actue - haematemesis (vomiting blood)
Chronic - melaena (darkened stools)
What is the management for long-term anaemia?
Treat the underlying cause:
- Iron supplementation (oral ferrous sulphate 3 months)
- Folic acid (oral folate for 3 months)
- B12 (load initially then injections every 3 months)
Erythropoietin (EPO) weekly sub-cut injections in patients receiving haemodialysis or with kidney failure
What are the negative side effects of long-term transfusion?
- Iron overload (iron deposition in organs)
- Allo-antibodies (to foreign red cells)
