Approach to Anaemia Flashcards
What are the 2 potential definitions of anaemia?
- Reduction in haemoglobin concentration below that which is optimum for that individual.
- Reduction in haemoglobin concentration below 95% range for the population.
‘Reduction in haemoglobin concentration below that which is optimum for that individual’ is a diagnosis of anaemia. Why is this difficult to clarify?
Because we often don’t know what someones normal Hb is
Hb of <120 in a female makes anaemia likely
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Hb <110 in a female, who is pregnant, makes anaemia likely
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Children from 6 months to 6 years can be diagnosed with anaemia if Hb …
<110 g/l
Children from 6 to 14 can be diagnosed with anaemia if Hb …
<120 g/l
What are the main tools of diagnosing anaemia?
History + exam
After history + exam, what other investigations can be done to diagnose anaemia?
- full blood count indices
- reticulocyte count
- blood film features
- haematinics (ferritin/B12/folate)
- bone marrow
- Specialised tests (hb electrophoresis etc)
What are the 2 main groups of anaemia?
- Decreased production.
2. Increased loss or destruction of red cells.
What are the 2 causes of a decreased production of RBC’s?
- Hypoproliferative – reduced AMOUNT of erythroipoiesis
2. Maturation abnormality – erythropoiesis present but ineffective
What 2 things can be classified as a maturation abnormality, resulting in decreased production of RBC’s?
- Cytoplasmic defects - impaired haemoglobinisation
2. Nuclear defects - impaired cell division
What are the 2 main causes of increased loss/destruction of RBC’s?
- Bleeding.
2. Haemolysis.
What is reticulocyte count a marker of?
Red cell production
What does it mean if reticulocytosis is seen?
That red cell production is increased
If someone has anaemia + a reticulocytosis (increased red cells), what does this mean?
- Bleeding
2. Haemolysis
How can bleeding and haemolysis be differentiated?
- If bleeding: red cells are gone.
* If haemolysing: increased products of red cell destruction are seen.
In haemolysis, what are the products of red cell destruction which are seen?
- Increased unconjugated serum bilirubin.
* Increased urinary urobilinogen.
In reticulocytosis, what happens to MACROPHAGE-RICH tissues?
‘Work hypertrophy.’
What does haemolysis result in?
Anaemia + jaundice, sometimes with splenomegaly.
Haem is broken down to porphyrin and Fe3+. The porphyrin is broken down to form bilirubin, what is this then made into?
Unconjugated, albumin bound bilirubin in the plasma
What is unconjugated, albumin bound bilirubin broken down to form?
Conjugated bilirubin in liver hepatocytes
If you suspect haemolytic anaemia, what should you look for evidence of?
Red cell breakdown products and a reticulocytosis
In an anaemic patient, reticulocyte count should be appropriately increased if what?
The bone marrow is functioning normally in response to erythropoietin to restore homeostasis.
By how much can normal marrow increase red cell production by?
3-4 fold
What is anaemia with a lesser reticulocyte response at least partly due to?
Impaired red cell production
What can MCV be classified as?
- Microcytic.
- Macrocytic.
- Normocytic.
What can film/MCH (mean corpuscular haemoglobin) be classified as?
- Hypochronic
* Normochromic
What is the commonest cause of hypochromic microcytic anaemia?
Iron deficiency
Iron deficiency anaemia is not a diagnosis so you must always investigate for a cause
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Apart from iron deficiency, suggest other, less common causes of microcytic anaemia.
- Thalassaemia.
- Some causes of anaemia of chronic disease – chronic inflammation, malignancy.
- Lead poisoning.
- Pyridoxine responsive anaemias.
- Sideroblastic anaemia.
B12 deficiency and folate deficiency cause a ______________ anaemia
Megaloblastic/macrocytic
Apart from B12 and folate deficiency, list other causes of macrocytic anaemia.
- Myelodysplasia.
- Myeloma.
- Aplastic anaemia.
- Reticulocytosis.
- Cold agglutinins (false).
Macrocytosis can occur without anaemia. Give examples of conditions.
- Alcohol.
- Liver disease.
- Hypothyroidism.
What causes normochromic normocytic anaemia?
- Acute blood loss.
* Early iron deficiency.
Why does acute blood loss cause normochromic normocytic anaemia?
If someone loses half their entire volume of blood very quickly, there body will not compensate fast
The blood results will appear normal initially as everything is reduced in proportion to each other
Hypoproliferation of bone marrow (absent erythropoiesis) results in what blood results?
Normochromic, normocytic anaemia
What would the reticulocyte count be in a normochromic normocytic anaemia?
Decreased reticulocyte count
Suggest causes of hypoproliferative normochromic normocytic anaemia.
- Chronic diseases – inflammatory, infective, malignant disorders.
- Anaemia of renal failure.
- Hypometabolic states – e.g. hypothyroidism.
- Marrow failure – e.g. aplasia or infiltration
What is renal anaemia an anaemia of?
Chronic disease
What should be given to patients with renal anaemia?
EPO (erythropoietin)
Outline the mechanism of normal renal anaemia.
- Kidneys detect reduced O2 carrying capacity of the blood
- When less O2 is delivered to the kidneys they secrete more EPO (erythropoietin) into the blood
- EPO stimulates erythropoiesis in bone marrow
- Additional circulating erythrocytes increases O2 carrying capacity of the blood
Why does renal anaemia occur?
EPO production goes down in most cases of renal failure
- EPO not being produced by the kidneys anymore
- Kidneys cannot stimulate erythropoeisis in bone marrow
- Less O2 carrying capacity of the blood
What – in terms of pathophysiology - is this?
A disease of multifactorial pathophysiology, with inflammation as a central process.
What is the second most common cause of anaemia worldwide, secondary to iron deficiency?
Anaemia of chronic disease
Anaemia of chronic disease is the 2nd most common cause of anaemia in the world
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Outline the mechanisms of anaemia of chronic disease (renal anaemia).
- Blunted epo response by kidney.
- Impaired iron availability to erythroid precursors.
- Inhibition of erythroid precursor proliferation and differentiation.
- Reduced red cell survival.
What is anaemia of chronic disease driven by?
Inflammatory cytokines, induced by
- Infection
- Malignancy
- Autoimmune disease dysregulation.
What are most chronic anaemias (>90%) primarily the result of?
Impaired red cell production (low retic).
What are a minority of chronic anaemias due to?
Increased red cell destruction (haemolysis) or acute bleeding (high retic).
Where is hepcidin produced?
Liver hepatocytes
Given an example of a situation where someone might have anaemia of chronic disease.
Rheumatoid arthritis anaemia of chronic disease with NSAID related GI blood loss.
How can iron deficiency and anaemia of chronic disease be distinguished?
Transferrin -
- Normal or high in iron deficiency
- Normal or low in anaemia of chronic disease
Ferritin -
- Reduced in iron deficiency
- Normal or increased in anaemia of chronic disease
MCV -
- Reduced or can be normal in iron deficiency
- Normal or can be reduced in anaemia of chronic disease
What are a minority of chronic anaemias due to?
Increased red cell destruction (haemolysis) or acute bleeding (high retic).
