Anaemia I Flashcards

(37 cards)

1
Q

Define anaemia.

A

Hb level below normal.

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2
Q

What are ‘normal’ Hb levels affected by?

A

Age

Sex

Pregnancy

Altitude

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3
Q

Effects of anaemia

A

A slightly depressed Hb level may be asymptomatic (Hb 70-100 g/L)

More severe or impaired cardiorespiratory system

  • Tiredness
  • Palpitations
  • Short of breath
  • Angina
  • Cardiac failure
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4
Q

What determines the Hb level?

A

The Hb level is a balance between:

  • Production of RBC in bone marrow, which needs:
    • Normal blood forming cells
    • Haematinics and hormones (EPO)
    • Absence of inhibitors (inflammatory cytokines)
  • Shortened time of RBC in circulation
    • Blood loss from circulation: haemorrhage
    • Shortened RBC life span: haemolysis

A change in level of Hb can either be a failure of production or increased breadown or loss.

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5
Q

Reticulocyte count

A
  • Measure of recently produced RBC (1-2 days old)
  • Measure of marrow erythropoietic activity.
    • Increased = healthy marrow response to anaemia
    • Reduced/low-normal = ?marrow (production) pathology
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6
Q

Haematinics

A

Iron studies

B12 and folate

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7
Q

Tests for haemolysis

A

Bilirubin, haptoglobin, LDH

Measure of increased RBC breakdown.

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8
Q

Bone marrow aspirate and trephine

A

Assesses marrow activity, function +/- presence of abnormal cells

Aspirate

  • Cellular details
  • Iron stores

Trephine

  • Overall view of BM structure
  • Better assessment of cellularity
  • Patchy abnormalities e.g. lymphoma
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9
Q

Classification of anaemias

A

**Decreased production **(synthetic failure) vs. **increased destruction/loss **(bleeding, haemolysis…)

or

**MCV **(mean corpuscular volume of RBC)

  • Microcytic = ‘too small’
  • Normocytic = ‘just right’
  • Macrocytic = ‘too big’
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10
Q

Microcytic anaemic causes

A
  • Iron deficiency
  • Anaemia of chronic disease (ACD)
  • Thalassaemias/haemoglobinopathies
  • Others
    • Congenital sideroblastic anaemia (rare)
    • Lead poisoning
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11
Q

Microcytic anaemia common features

A

Failure of adequate Hb incorporation into RBC.

Iron deficiency: lack of iron for haem.

ACD: block of iron transfer into RBC

Thalassaemia/haemoglobinopathies: problem with production of globin chain for Hb molecule.

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12
Q

Anaemic of chronic disease

A
  • May be microcytic of normocytic.
  • Also may be hypochromic or normochromic.

Irons stores fail to incorporate iron into RBC.

  • BM resistant to EPO
  • Inadequate production of EPO in response to anaemia

Not helped by iron therapy (can have mixed Fe deficiency and ACD).

Treat underlying cause + EPO *may *help.

Iron findings

  • Transferrin low: production inhibited in inflammation, acute phase response.
  • Serum ferritin high: increased body iron stores, increased in inflammation (acute phase)
  • BM iron increased: increased iron in macrophages.

Causes

  • infection
  • Inflammatory disorders: rheumatoid, SLE etc
  • Malignancy
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13
Q

Iron studies in iron deficiency

A

Never look at serum iron.

Ferritin reduced = iron deficiency

_Ferritin _normal/low-normal = ?iron defiency

  • Acute phase response
  • Look at transferrin saturation (if reduced - iron deficiency is likely)
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14
Q

Causes of iron deficiency

A

Blood loss

  • Iron deficiency in an adult Australian is bowel cancer until proven otherwise

Dietary

  • Vegetarians/vegans
  • Infants (cow milk protein/lactose intolerance), adolescents
  • Pregnancy (increased requirement)
  • Menorrhagia/increased requirement
  • Elderly

Malabsorption

  • Coeliac disease
  • Crohn’s
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15
Q

Causes of macrocytic anaemia

A

Magaloblastic

  • B12, folate, medication (folate depletion - e.g. MTX), BM disorders.

Non-megaloblastic

  • Increased reticulocyte count e.g. acute bleed or haemolysis
  • Normal reticulocyte count
    • Liver disease/alcohol
    • Hypothyroidism
    • Bone marrow disorders

Spurious

  • E.g. Myeloma
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16
Q

Blood film findings in megaloblasic anaemia

A
  • Single/pancytopenia
  • Macrocytosis +/- oval macrocytes
  • Hypersegmented neutrophils
17
Q

Vitamin B12 deficiency causes

A

Dietary

  • Rarely except strict vegans

Malabsorption

  • Lack of instrinsic factor
    • Pernicious anaemia
    • Gastrectomy
  • Intrinsic factor present
    • Terminal Ileal disease (IBD) or resection

Metabolic causes (rare)

18
Q

Effects of B12 deficiency

A

Dividing cells and neurological

  • Megaloblastic anaemia
  • Gastrointestinal effects
  • Neurological
    • Peripheral neuropathy
    • Subacute combined degeneration of cord
    • Other (delirium screen)
19
Q

Haemoglobinopathies

A

Thalassaemia

Haemoglobin variants

20
Q

Thalassaemia

A

Decreased rate of production of one of the globin chains, causing an ‘imbalance’ and therefore red cell changes.

Alpha thalassaemia: decreased production of alpha globin chains

Beta thalassaemia: decreased production of beta globin chains

21
Q

Haemoglobin variants

A

Production of Hb with an abnormal globin chain e.g. HbS

Most common is sickle cell disease

Amino acid substitution in globin chain.

22
Q

Alpha thalassaemia

A

Number of alpha genes deleted

  • One or two: alpha thal trait (asymptomatic)
  • Three: Hb H disease (mild to moderate disease)
  • Four: hydrops fetalis (incompatible with life)
23
Q

Homozygous alpha thalassaemia

A

Hydrops fetalis

4 alpha globin genes deleted.

Cannot make HbF, HbA or HbA2

Severe anaemia

Fatal pre-term

24
Q

Beta thalassaemias

A

Decreased production of beta globin chain

Homozygous: severe disease

Heterozygous: asympotmatic, microcytic RBC

25
Homozygous beta thalassaemia
Marked decrease in HbA (decreased beta globin chains, excess alpha globin chains). Symptoms from age 3-6 months (HbF) Severe anaemia plus: * Erythroid hyperplasia ++ and bony malformations * Hepatosplenomegaly * Iron overload * Cardiomyopathy, endocrine disorders etc. **Transfusion dependent for life**
26
Haemoglobin E
Substitution one amino acid in beta globin chain. Common in South East Asia. _HbE homozygous and heterozygous_ * Asymptomatic * Low MCV and blood film changes only _Double heterozygote HbE + beta thal_ * Severe disease (like beta thal major)
27
Haemoglobin S
Substitution one amino acid in beta globin chain. HbS less soluble and precipitates in hypoxia (sickling) _Heterozygous HbS (_sickle cell trait) * Asymptomatic with normal FBC and film _Homozygous HbS_ (sickle cell anaemia) * Severe disease * Anaemia, sickle cell crises with pain and vascular occlusion by sickling cells
28
Bone marrow failure syndromes
_Aplasia:_ decrease in haemopoietic cells _Dysplasia:_ BM cells abnormal _Bone marrow infiltration:_ BM replacement
29
Anaemia due to aplasia
_General BM failure_ * Aplastic anaemia * Pancytopenia - low Hb, WBC and platelets _Specific to RBC_ * Pure red cell aplasia - parvovirus, autoimmune
30
Bone marrow dysplasia
Bone marro wnromal or increased cellularity but cells look abnormal and are dysfunction. _Primary myelodysplastic syndromes_ * Acquired bone marrow genetic change * Often high MCV and low WBC and/or platelets _Secondary_ * Medication, pyridoxine deficiency, heavy metal poisoning
31
Erythropoiesis in a dysplastic BM
_Disturbed erythropoiesis_ * Increased RBC precursors * Abnormal morphology * Decreased RBC production (ineffective)
32
Haemolytic anaemia
Anaemia due to shortened RBC life span. Two sites of haemolysis * Extravascular (in reticuloendothelial cells) * Intravascular
33
Evidence of haemolysis
1. Morphological evidence of red cell damage * Spherocytes * RBC fragmentation 2. Biochemical evidence of red cell breakdown * Increased *unconjugated bilirubin *(jaundiced) * Decreased haptoglobin (rapid test) * Increased LDH (non-specific) 3. Increased rate of RBC production * Increased polychromasia (bluish RBC) * Increased reticulocyte count
34
Causes of haemolytic anaemia
1. _Congenital_ 2. _Acquired_ *also classified as* * _Extrinsic_ (change in blood or blood vessels) * Autoimmune haemolytic anaemia * Drugs * DIC, mechanical valve * _RBC membrane_ * _​_Hereditary spherocytosis * _RBC cytoplasm_ * ​G6PD deficiency
35
Investigation of haemolysis
1. *Is this patient haemolysing?* * ​​FBC and blood film * Reticulcyte count * Bilirubin, urobilinogen * Haptoglobin * LDH 2. *What is the cause? Is it immune mediated (AIHA)?* * *​​*Clinical * RBC morphology from film * Spherocytes * Fragments * Specific features e.g. sickle cell * DAT (direct antiglobin test) * Other special tests
36
Direct antiglobin test
Detects antibody on RBC Add anti-human Ig to RBC If antibody on RBC then added anti human Ig cross links RBC causing agglutination (DAT positive)
37
Autoimmune hamolytic anaemia
Autoantibodies to own RBC Increased haemolysis with spherocytes and polychromasia DAT positive.