GP - Anaemia Flashcards

1
Q

What is aplastic anaemia?

A

Characterised by:

  1. Pancytopenia (reduced RBC, WBC and platelets)
  2. Hypoplastic bone marrow (few blood cells vs aplastic which is no cells)

Peak incidence = 30-yrs old

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2
Q

What are the features of aplastic aneamia?

A

Features:

  • Normochromic, normocytic anaemia
  • Leukopenia (lymphocytes relatively spared)
  • Thrombocytopenia
  • Can be the presenting features of acute lymphoblastic or myeloid leukaemia
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3
Q

What can cause aplastic anaemia?

A
  • Idiopathic
  • Infections: parvovirus, hepatitis
  • Congenital: Fanconi anaemia, dyskeratosis congenita (DKC)
  • Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
  • Toxins: benzene
  • Radiation
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4
Q

What are some ‘Red-flag’ questions for suspected anaemia?

A
  • Indigestion or vomiting - upper GI cancer can present with anaemia + these symptoms
  • Blood loss anywhere - urine, on wiping front/back passage, in stool, in sperm, vaginal bleeding, haematemesis, haemoptysis
  • Diet - diet low in red-meat / vegetarian / vegan can cause iron-deficiency anaemia
  • Change in bowels (loose/constipated) - a symptom of bowel cancer can be anaemia
  • Medications - NSAIDs can increase risk of peptic ulcer and GI inflammation –> causing anaemia
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5
Q

What are the normal ranges for haemoglobin in men and women?

A
  • Men = 130 - 180 g/L
  • Women = 115 - 165 g/L
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6
Q

What are some causes of Microcytic Anaemia?

A

Causes of Microcytic anaemia (< 80 fL):

  1. Iron-deficiency anaemia
  2. Thalassaemia
    • In beta-thalassaemia minor, the microcytosis is disproportionate to the anaemia
  3. Congenital sideroblastic anaemia
  4. Anaemia of chronic disease
    • more commonly a normocytic, normochromic picture
  5. Lead poisoning
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7
Q

What are the main categories of anaemia?

A
  • Microcytic = < 80 fL
  • Normocytic = 80-100 fL
  • Macrocytic = > 100 fL
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8
Q

New onset microcytic anaemia in a pt > 60-yrs requires investigation for what?

A

2WW referral to invetigate for colorectal cancer

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9
Q

What are some causes of normocytic anaemia?

A
  1. Anaemia of chronic disease
    • Can be microcytic but more commonly normocytic
  2. Chronic kidney disease (CKD) - deficiency of erythropoietin
  3. Aplastic anaemia (pancytopenia)
  4. Haemolytic anaemia (↑ reticulocytes)
  5. Acute blood loss
    • Hb doesn’t drop immediately in blood loss as the concentration of Hb doesn’t actually fall
  6. Sickle Cell anemia
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10
Q

What are some causes of macrocytic anaemia?

A

Megaloblastic bone marrow:

  1. Vitamin B12 deficiency
  2. Folate deficiency

Normoblastic bone marrow:

  1. alcohol
  2. liver disease
  3. hypothyroidism
  4. reticulocytosis (increased immature RBCs)
  5. myelodysplasia (cancers in which immature blood cells don’t mature)
  6. pregnancy
  7. drugs: cytotoxics
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11
Q

What is Megaloblastic anaemia?

A

Anaemia (of macrocytic classification) which results from inhibition of DNA synthesis during RBC production

  • DNA synthesis impairment –> cell cycle can’t progress from G2 growth stage to mitosis –> results in continued cell growth without division (macrocytosis)
  • Often due vitamin deficiency:
    • Vitamin B-12 deficiency
    • Folate deficiency
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12
Q

What are some causes of hereditary haemolytic anaemia?

A

RBC membrane defects:

  • hereditary spherocytosis
  • hereditary elliptocytosis

Metabolism defect:

  • G6PD deficiency

Haemoglobin defects:

  • Sickle cell anaemia
  • Thalassaemia
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13
Q

What are some causes of Acquired haemolytic anaemia?

A

Immune causes:

  • Autoimmune - warm / cold antibody type
  • Alloimmune - tranfusion reaction, haemolytic disease of newborn
  • Drugs - methyldopa, penicillin

Non-immune causes:

  • Microangiopathic haemolytic anaemia (MAHA) - TTP / HUS, DIC, malignancy, pre-eclampsia
    • Microangiopathy - refers to microvascular disease
  • Prosthetic cardiac valves
  • Paroxysmal nocturnal haemoglobinuria (PNH)
  • Malaria
  • Drugs - Dapsone (Abx often used for; leprosy, dermatitis herpetiformis, pneumocystis jirovecii pneumonia)
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14
Q

What is Fanconi anaemia?

A

Autosomal recessive - impaired response to DNA damage

Features:

  • aplastic anaemia
  • increased risk of acute myeloid leukaemia
    • ~80% develop bone marrow failure by 20-yrs
  • skeletal abnormalities e.g. short stature
  • skin hyperpigmentation e.g. cafe au lait spots
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15
Q

What is pernicious anamia?

A

Pernicious anaemia is a type of B-12 deficiency anaemia, resulting from an autoimmune condition against gastric parietal cells or intrinsic factor → ↓ B-12 absorption

Epidemiology:

  • F > M
  • Commoner in middle age - old age
  • Increased risk of gastric carcinoma

Associated with other autoimmune conditions:

  • Thyroid disease
  • Addisons
  • RA
  • Vitiligo
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16
Q

What are the features of pernicious anaemia?

A

Gen​eral:

  • Lethargy & weakness
  • SoB
  • Paraesthesia
  • Glossitis (inflammed tongue)
  • Mild jaundice
  • Diarrhoea
  • Premature grey hair
  • Fever (low-grade)
  • Neurological: mild cognitive impairment, ataxia, muscle weakness
  • Signs: retinal haemorrhages, mild splenomegaly, retrobulbar neuritis (posterior optic nerve inflammation)
17
Q

What are the causes of B12 deficiency?

A
  1. Poor intake
    • Vegan diet
  2. Malabsorption of B12
    • Pernicious anaemia (most common!)
    • Gastrectomy (no or reduced intrinsic factor from gastric mucosa)
    • Terminal ileum disease (Crohn’s) / Resection
    • Coeliac disease
  3. Losses
    • Cancer
18
Q

What are the causes of folate deficiency?

A
  1. Poor Intake:
    • old age
    • poverty
    • alcohol excess (though beer is a good source!)
    • anorexia
  2. Malabsorption:
    • coeliac disease (more common to experience folate than B12 deficiency)
    • tropical sprue (tropical malabsorption disease with inflammation of lining of small intestine)
  3. Excess utilization:
    • pregnancy, lacatation, prematurity
    • chronic haemolytic anaemia, malignant and inflammatory diseases
    • dialysis
  4. Drugs:
    • Methotrexate
    • Anticonvulsants
19
Q

What are the causes of iron deficiency anaemia?

A

Poor dietary iron intake:

  • Diet low in red meat or low in dark greens if vegetarian / vegan

Malabsorption:

  • Coeliac disease
  • Colorectal cancer
  • Bowel ressection
  • IBD

Excessive blood loss:

  • Menorrhagia (most common cause of iron-deficiency in pre-menopausal women)
  • GI bleed:
    • peptic ulcer
    • mallory weiss tear
    • oesophageal varices
    • diverticulitis
    • colorectal cancer
    • haemorrhoidal bleeding
  • Parasitic (hookworm, Africa)
  • Haematuria
  • Medication (blood thinners)
  • Pregnancy (↑ demands)
20
Q

How do you treat iron deficiency anaemia?

A

Treat underlying cause!!

Oral ferrous sulfate:

  • Continue take iron medication for 3-months after iron-deficiency has been corrected (normal Hb) to replenish iron stores
  • Side-effects:
    • nausea
    • abdo pain
    • constipation
    • diarrhoea
    • dark stools
21
Q

What are the signs of iron deficiency anaemia?

A
  1. Brittle hair + nails
  2. Atrophic glossitis (bald/smooth tongue, tender, due to atrophy of lingual papillae)
  3. Angular stomatitis
  4. Koilonychia
22
Q

How is B12 deficient anaemia managed?

A

If no neurological involvement:

  • 1 mg of IM hydroxocobalamin (B12) 3 times per week for 2-weeks –> then once every 3-months

If pt is also deficient in folic acid:

  • Treat B12 deficiency 1st!! –> this is to avoid precipitating subacute combined degeneration of the spinal cord (Lichtheim’s disease) - which can be caused by B12 deficiency
23
Q

What are the counselling points of iron replacement therapy?

A
  1. Black poo!
  2. If you experience side-effects –> can be reduced by changing preparation
    • SEs: nausea, abdo pain, diarrhoea, constipation
  3. Avoid taking with food (reduces absorption) unless it is causing nausea
  4. Avoid taking with:
    • tea
    • coffee
    • milk
    • eggs
  5. But can take with OJ (acid helps absorption)
  6. Will take a few months before benefit is felt
24
Q

When should iron replacement be used with caution/ not be given?

A
  • May exacerbate symptoms of;
    • IBD
    • diverticular disease
    • intestinal strictures
  • Can reduce absorption of;
    • Levothyroxine
    • Bisphosphonates
  • Stop 7 days before colonoscopy (black sticky stools makes hard to visualise)
25
Q

What is Coomb’s test?

aka direct antiglobulin test

A

Coombs’ Test:

Direct Coombs’ test (direct antiglobulin test):

  • Tests a sample of red blood cells, and identifies RBCs coated with antibody/complement
  • Positive result (agglutination) = ususally indicates an immune cause of anaemia e.g.
    • Autoimmune haemolytic anaemia (AIHA) - cold / warm subtypes
    • Alloimmune - tranfusion reaction, haemolytic disease of newborn
    • Drug induced haemolysis - methyldopa, penicillin

Indirect Coombs’ test:

  • Test is done on a sample of blood serum
  • Detect antibodies in the serum that could bind to certain red blood cells, leading to problems if blood mixing occurs (e.g. pregnancy)
  • Uses:
    • Pre-transfusion testing e.g. blood types / cross-matching
    • Pre-natal antibody screen (IgG antibodies that can cross placenta)
26
Q

What is Autoimmune haemolytic anaemia (AIHA)?

A

Autoimmune heamolytic anaemia (AIHA) is characterised by a positive direct antiglobulin test (i.e. Direct Coombs’ test positive)

  • Cause = often idiopathic - can be secondary to lymphoproliferative disorder, infection or drugs
  • AIHA divided into 2 types - depending on the temp the antibodies best cause haemolysis:
    • Warm
    • Cold
27
Q

What are the features of Warm AIHA?

A

Warm AIHA:

  • Antibody (usually IgG antibody) causes haemolysis best at body temp
  • Haemolysis tends to occur in extravascular sites e.g. spleen
  • Management:
    • Steroids
    • Immunosuppression
    • Splenectomy
  • Causes:
    • autoimmune disease e.g. SLE
    • neoplasia e.g. lymphoma, CLL
    • drugs e.g. methyldopa
28
Q

What is hereditary spherocytosis?

A

Hereditary spherocytosis = cause of inherited haemolytic anaemia - due to RBC membrane defect (bi-concave disc shape replaced with sphere-shape)

  • Is the most common form of inherited haemolytic anaemia in the US and northern Europe
  • Autosomal dominant
  • RBC survival reduced (destroyed be spleen) –> haemolytic anaemia

Features:

  • Failure to thrive
  • Pallor
  • Neonatal jaundice
  • Splenomegaly
  • Gallstones
  • Aplastic crisis (precipitated by parvovirus infection) - body doesn’t make enough RBCs to replace those lost to haemolysis (reticulocytopenia)
  • Variable degree of haemolysis
  • MCHC elevated (mean corpuscular haemoglobin)

Treatment:

  • Folic acid replacement
  • Splenectomy

Diagnosis:

  • British journal of haematology recommend diagnosis if following picture:
    • FHx of hereditary spherocytosis
    • Typical clinical features
    • Spherocytes on blood film
    • Raised MCHC
    • Increased reticulocytes
  • If unsure –> EMA binding tests for specific binding
29
Q

What are the features of Cold AIHA?

A

Cold AIHA:

  • Antibody (usually IgM antibody) causes haemolysis best at ~ 4 degrees C
  • Haemolysis is mediated by complement
  • Commonly occurs at intravascular sites
  • Features:
    • May have Raynaud’s symptoms
    • May have acrocyanosis (persistent, painless, symmetric cyanosis of the hands + feet or face) - due to vasospasm of small vessels in response to cold
  • Management:
    • Pts respond less well to steroids
  • Causes:
    • neoplasia e.g. lymphoma
    • infections e.g. mycoplasma,
30
Q

What are the main signs of anaemia?

A
  • Fatigue / weakness
  • Pale or yellowish skin
  • Irregular heartbeats
  • SoB – worse if underlying respiratory or cardiac disease
  • Dizziness or light-headedness
  • Chest pain – worse if underlying arterial disease
  • Cold hands and feet
  • Headache