RBC 2: acquired anaemia Flashcards

1
Q

What is anaemia?

A
  • Hb below normal for age and sex
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2
Q

What is included in the normal range for blood Hg?

A
  • Subjects without disease
  • Normal distribution
  • Mean +/- 2 standard deviations
  • Excludes 5% of “normals”
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3
Q

Which factors influence the ‘normal range’?

A
  • Haem varies with age
  • Sex: men have higher haem
  • Ethnic origin: can effect the mean cell volume
  • Time of day sample taken
  • Time to analysis
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4
Q

What are the normal references for Hg?

A
  • Male 12-70 (140-180)
  • Male >70 (116-156)
  • Female 12-70 (120-160)
  • Female >70 (108-143)
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5
Q

What are the general features (of anaemia) due to reduced oxygen delivery to tissues?

A
  • Tiredness/pallor
  • Breathlessness
  • Swelling of ankles
  • Dizziness
  • Chest pain
  • (Depend on age and Hb level)
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6
Q

What are the anaemia features relating to underlying cause?

A
  • Evidence of bleeding
    • Menorrhagia
    • Dyspepsia, PR bleeding
  • Symptoms of malabsorption
    • Diarrhoea
    • Weight loss
  • Jaundice
  • Splenomegaly/Lymphadenopathy - may be chronic/acute
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7
Q

What are the anaemia pathophysiologies?

A

Issues with: Bone marrow, Red cells, Destruction loss

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8
Q

What are red cell indices and what can they show us?

A
  • Automated measure of red cell size and haemoglobin content
  • MCV = Mean cell volume (cell size)

MCH = Mean cell haemoglobin

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9
Q

How can anaemia be morphologically described?

A
  1. Hypochromic microcytic (small and pale red cells)
  2. Normochromic normocytic (normal red cells)
  3. Macrocytic (big flabby red cells)
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10
Q

What does this FBC show?

A
  • Initial tests show hypochromic microcytic
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11
Q

What can haem lab provide for the clinician?

A

will advise on further appropriate investigations

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12
Q

If hypochromic microcytic what lab tests do we order next?

If Normochromic Normocytic what labs next?

If macrocytic what labs order next?

A

Serum ferritin

Reticulocyte count [tells us if marrow is functioning correctly - may be sickle cell]

B12/folate, Bone marrow [BM prob may be myelodysplasia]

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13
Q

hypochromic microcytic

What causes low serum ferritin?

What causes normal/increased ferritin?

A

Low: iron deficiency

Normal/high: Thalassaemia, Secondary Anaemia

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14
Q

How much total body iron?

How is balance maintained?

How is iron recycled?

Where is iron predominantly stored?

A

4g

Dietary intake balanced by loss

Recycled through breakdown of haem

Predominantly stored in liver

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15
Q

In which form is iron most readily absorbed?

A

Haem iron is easily absorbed (meat), so more difficult for veggies/vegans

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16
Q

How do we get rid of iron?

A

Absorbed iron - bound to mucosal ferritin and sloughed off. Transported across the basement membrane by protein ferroportin, then bound to transferrin protein in plasma

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17
Q

Which hormone controls ferroportin? And what does this affect?

A

Hepcidin

Hepcidin inhibits iron transport by binding to the iron export channel ferroportin

18
Q

Please explain in brief the iron metabolism

A
  1. Iron absorbed in duodenum - Fe2+ > Fe3+
  2. Transported from enterocytes and macrophages by ferroportin
  3. Transported in plasma bound to transferrin
  4. Stored in cells as ferritin
  5. Hepcidin synthesised in hepatocytes in response to inflammation (also renal failure and ↑iron levels)– blocks ferroportin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells
19
Q

Commonest cause of anaemia?

A

Iron deficiency anaemia (hypochromic microcytic)

20
Q

hypochromic microcytic

What on history and examination would point to a cause of iron deficiency anaemia?

A
  • History
    • Dyspepsia GI bleeding
    • Other bleeding, eg menorrhagia
    • Diet (NB children and elderly)
    • Increased requirement - pregnancy
  • Examination
    • Signs of iron deficiency
    • Abdominal and rectal
21
Q

hypochromic microcytic

Features on examination pointing towards iron deficiency anaemia?

A
  • Atrophic tongue (although most anaemics complain of this)
  • Koilonychia is uncommon to see
22
Q

hypochromic microcytic

Common causes of iron deficiency anaemia?

A
  • GI blood loss
  • Menorrhagia
  • Malabsorption
    • gastrectomy
    • coeliac disease
23
Q

hypochromic microcytic

How do we manage iron defiency anaemia?

A
  • Correct the deficiency -
    • Oral iron usually sufficient
    • IV iron if intolerant of oral
    • Blood transfusion rarely indicated
  • Correct the cause -
    • Diet
    • Ulcer therapy
    • Gynae interventions
    • Surgery
24
Q

Normochromic Normocytic

Causes of increased reticulocyte?

Causes of normal/low reticulocyte?

A

Increased - Acute blood loss, haemolysis

Normal, low - Secondary anaemia, hypoplasia

25
Q

Normochromic normocytic

What are features of haemolytic anaemia?

A
  • Accelerated red cell destruction (Hb)
  • Compensation by bone marrow (Retics)
26
Q

normochromic normocytic

Where can haemolysis occur?

A
  • Intravascularly
  • Extravascularly: red cells burst in vasculature, abnormal
27
Q

normochromic normocytic

What are the congenital haemolytic anaemia?

Commonest acquired haemolytic anaemia?

Which intravascular haem anaemia?

A
  • Congenital eg.
    • Hereditary spherocytosis (HS)
    • Enzyme deficiency (G6PD deficiency)
    • Haemoglobinopathy (HbSS)
  • Acquired
    • Auto-immune haemolytic anaemia (Extravascular) - MOST COMMON
    • Mechanical eg.artificial valve (intravascular)
    • Severe infection/DIC (Intravascular)
    • PET/HUS/TTP (intravascular)
28
Q

normochromic normocytic

How is acquired haemolytic anaemia divided?

A
  • Immune (extravascular)
  • Non-immune (intravascular)
29
Q

normochromic normocytic

What is the DAGT test and what is the role?

A

Direct antiglobulin test

  • Detects antibody or complement on red cell membrane
  • Reagent contains either
    • anti-human IgG
    • anti-complement
  • Reagent binds to Ab (or complement) on red cell surface and causes agglutination in vitro
  • Implies immune basis for haemolysis
30
Q

normochromic normocytic

If DAGT is positive/negative - what does this mean?

A

Positive: immune mediated

Negative: Non-immune mediated

31
Q

normochromic normocytic

So it is immune haemolysis

What causes:

Warm auto-antibody?

Cold auto-antibody?

Alloantibody?

A
  • Warm auto-antibody: Auto-immune, Drugs, CLL
  • Cold auto-antibody: CHAD, infections, lymphoma
  • Alloantibody: Transfusion reaction
32
Q

normochromic normocytic

What to do to check if patient is haemolysing?

A
  • FBC, reticulocyte count, blood film
  • Serum bilirubin (direct/indirect), LDH
  • Serum haptoglobin – protein that mops up haem, so low levels hap
33
Q

normochromic normocytic

How to find mechanism behind haemolysis?

A
  • History and examination
  • Blood film
  • Direct Antiglobulin Test (Coombs’ test)
  • Urine for haemosiderin/urobilinogen
34
Q

normochromic normocytic

Management of haemolytic anaemia?

A
  • Support marrow function
    • Folic acid
  • Correct cause
    • Immunosuppression if autoimmune
      • Steroids
      • Treat trigger eg.CLL, Lymphoma
    • Remove site of red cell destruction
      • Splenectomy
    • Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
  • Consider transfusion
35
Q

normochromic normocytic

Reticulocytes normal/low ??

A

Secondary Anaemia

  • “Anaemia of chronic disease”
  • 70% normochromic normocytic
    • 30% hypochromic microcytic
  • Defective iron utilisation
    • Increased hepcidin in inflammation
    • Ferritin often elevated
  • Identifiable underlying disease
    • infection, inflammation, malignancy
36
Q

Macrocytic Anaemia

What to do if macrocytic anaemia?

A

B12 / Folate Assay

37
Q

Macrocytic Anaemia

What results can arrise from B12/Folate test?

A
  • Megaloblastic: B12/folate deficiency
  • Non-megaloblastic: Myelodysplasia, Marrow infiltration, Drugs
38
Q

Macrocytic Anaemia

Causes of megaloblastic anaemia?

A
  • B12/Folate Deficiency
    • Anaemia
    • Neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)
  • B12 deficiency - causes
    • Pernicious anaemia
    • Gastric/ileal disease
  • Folate deficiency -causes
    • Dietary
    • Increased requirements (haemolysis)
    • GI pathology (eg.coeliac disease)
39
Q

Macrocytic Anaemia

Megaloblastic anaemia

Pernicous anaemia - what are the causes etc?

A
  • Commonest cause of B12 deficiency in western populations
  • Autoimmune disease
  • Antibodies against
    • intrinsic factor (diagnostic)
    • gastric parietal cells (less specific)
  • Malabsorption of dietary B12
  • Symptoms/signs take 1-2 years to develop
40
Q

Macrocytic Anaemia

Treatment for megaloblastic anaemia?

A
  • Replace vitamin
  • B12 deficiency
    • –B12 intramuscular injection
    • –Loading dose then 3 monthly maintenance
  • Folate deficiency
    • Oral folate replacement
    • Ensure B12 normal if neuropathic symptoms
41
Q

Macrocytic anaemia

Other causes?

A
  • Drugs: methotrexate, antiretrovirals
  • Disordered liver function
  • Alcohol
  • Hypothyroidism
  • Myelodysplasia