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Y3 Haem > APL syndrome - Macrocytic anaemia > Flashcards

APL syndrome - Macrocytic anaemia Flashcards

1
Q

What is APL syndrome characterised by (5)

A

• Characterised by the presence of antiphospholipid antibodies (APL) in the plasma, venous and arterial thromboses, recurrent foetal loss and thrombocytopenia.

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2
Q

What is APL syndrome associated with and what %

A

SLE, 20-30%

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3
Q

What does APL syndrome cause (4)

A

APL cause CLOTS

  • Coagulation defect
  • Livedo reticularis
  • Obstetric – recurrent miscarriages
  • Thrombocytopenia (low platelets)
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4
Q

Explain the aetiology of APL syndrome

A
  • Usually occurs as a primary disease but 20-30% are associated with SLE.
  • APL are directed against plasma proteins bound to anionic phospholipids e.g. beta 2-GP-I
  • APL may develop in susceptible individuals e.g. SLE patients, following exposure to infectious agents.
  • Once APL is present, a ‘second hit’ is required for the development of the syndrome.
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5
Q

Epidemiology of APL syndrome

A

• More common in young females – accounts for 27% of females with >2 miscarriages

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6
Q

RF of APL syndrome (3)

A
  • History of SLE or autoimmune rheumatological disorders
  • Other autoimmune diseases
  • Autoimmune haematological disorders
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7
Q

S/s of APL syndrome

A
  • Recurrent miscarriages
  • History of arterial thromboses – stroke
  • History of venous thromboses – DVT, PE
  • Headaches, migraines
  • Chorea
  • Epilepsy
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8
Q

S/s of APL syndrome (15, think of signs of the things commonly caused by/causing APL syndrome)

A
  • Livedo reticularis - image
  • Signs of SLE – malar flush, discoid lesions, photosensitivity
  • Signs of valvular heart disease
  • Thrombopenia features: petechial signs or mucosal bleeding
  • Recurrent miscarriages
  • History of arterial thromboses – stroke
  • History of venous thromboses – DVT, PE
  • Headaches, migraines
  • Chorea
  • Epilepsy
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9
Q

Ix for APL syndrome (8)

A

Bloods:
• FBC (decreased platelets)
• Clotting Screen (increased APTT),
• U&Es (increased creatine and urea, antiphospholipid nephropathy)

ELISA Testing for:
• Anticardiolipin and Anti-β2-GPI antibodies

Lupus Anti-coagulant Assays
• Clotting assays showing effects of APL on the phospholipid dependent factors in coagulation cascade

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10
Q

Define aplastic anaemia

A
  • Rare stem cell disorder characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia)
  • Leads to pancytopenia and hypoplastic marrow (marrow stops making cells)
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11
Q

Causes of aplastic anaemia (5 acquired causes, 2 inherited)

A

Idiopathic (> 40%)
- May be due to destruction or suppression of stem cells via autoimmune mechanisms

Acquired

  • Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)
  • Chemicals (e.g. benzene, DDT)
  • Radiation
  • Viral infection (e.g. parvovirus B19)
  • Paroxysmal nocturnal haemoglobinuria (PNH)

Inherited

  • Fanconi’s anaemia
  • Dyskeratosis congenita (rare, progression bone marrow failure syndrome)
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12
Q

Drugs that cause aplastic anaemia (3)

A

Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)

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13
Q

Chemicals that cause aplastic anaemia (2)

A

benzene, DDT

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14
Q

Viruses that can cause aplastic anaemia (1)

A

Parvovirus B19

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15
Q

Epidemiology of aplastic anaemia

A
  • Annual incidence: 2-4/1,000,000

* Slightly more common in males

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16
Q

S/s of aplastic anaemia

A

• Can be both slow-onset (months) or rapid-onset (days)
• Anaemia Symptoms:
o Tiredness
o Lethargy
o Dyspnoea
o Pallor
• Thrombocytopaenia Symptoms:
o Easy bruising
o Bleeding gums
o Epistaxis
o Petechiae
• Leukopaenia Symptoms:
o Increased frequency and severity of infections
o Multiple bacterial and fungal infections
o No hepatomegaly, splenomegaly or lymphadenopathy

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17
Q

Ix for aplastic anaemia

A 
•	Bloods
o	FBC
•	Low Hb
•	Low platelets 
•	Low WCC
•	Normal MCV 
•	Low or absent reticulocytes 
•	Blood Film
o	Exclude leukaemia (check for abnormal circulating white blood cells)
•	Bone Marrow Trephine Biopsy
•	Fanconi's Anaemia
o	Check for presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents
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18
Q

Define DIC and explain the two forms

A

• A disorder of the clotting cascade that can complicate a serious illness.
o DIC can occur in TWO forms:
• Acute overt form where there is bleeding and depletion of platelets and clotting factors
• Chronic non-overt form where thromboembolism is accompanied by generalised activation of the coagulation system

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19
Q

What can cause DIC (10)

A

• Infection - particularly GRAM-NEGATIVE sepsis
• Obstetric Complications
o Missed miscarriage (when the foetus dies but the body doesn’t realise it and the placenta continues to release hormones)
o Severe pre-eclampsia
o Placental abruption (separation of the placenta from the wall of the uterus during pregnancy)
o Amniotic emboli
• Malignancy
o Acute promyelocytic leukaemia - ACUTE DIC
o Lung, breast and GI malignancy - CHRONIC DIC
• Severe trauma or surgery
• Others: haemolytic transfusion reaction, burns, severe liver disease, aortic aneurysms, haemangiomas

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20
Q

What type of infection can cause DIC

A

Particularly gram -ve sepsis

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21
Q

What obstetric complications can cause DIC (4)

A

o Missed miscarriage (when the foetus dies but the body doesn’t realise it and the placenta continues to release hormones)
o Severe pre-eclampsia
o Placental abruption (separation of the placenta from the wall of the uterus during pregnancy)
o Amniotic emboli

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22
Q

Which malignancies can cause DIC and what forms do they cause (4)

A

o Acute promyelocytic leukaemia - ACUTE DIC

o Lung, breast and GI malignancy - CHRONIC DIC

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23
Q

Explain the pathophysiology of acute and chronic DIC

A

o Acute DIC
• Endothelial damage and the release of granulocyte/macrophage procoagulant substances (e.g. tissue factor) lead to activation of coagulation
• This leads to explosive thrombin generation, which depletes clotting factors and platelets, whilst also activating the fibrinolytic system
• This leads to bleeding in the subcutaneous tissues, skin and mucous membranes
• Occlusion of blood vessels by fibrin in the microcirculation leads to microangiopathic haemolytic anaemia and ischaemic organ damage
o Chronic DIC
• IDENTICAL process to acute DI
• Happens at a slower rate with time for compensatory responses
• The compensatory responses diminish the likelihood of bleeding but give rise to hypercoagulable states and thrombosis can occur

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24
Q

S/s of DIC (15)

A 
•	The patients will tend to be severely unwell with symptoms of the underlying disease 
•	Confusion 
•	Dyspnoea
•	Evidence of bleeding
•	Fever 
•	Evidence of shock (hypotension, tachycardia)
•	Acute DIC
o	Petechiae, purpura, ecchymoses 
o	Epistaxis 
o	Mucosal bleeding 
o	Overt haemorrhage 
o	Signs of end organ damage 
o	Respiratory distress 
o	Oliguria due to renal failure
•	Chronic DIC
o	Signs of deep vein and arterial thrombosis or embolism
o	Superficial venous thrombosis
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25
Q

Ix for DIC

A 
Bloods: FBC
•	Decreased platelets
•	Decreased Hb 
•	Increased APTT/PT
•	Decreased fibrinogen
•	Increased D-dimer 
•	Increased fibrin degradation product

Peripheral Blood Film:
• Schistocytes (red blood cell fragments)

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26
Q

DDx for DIC (3)

A
  1. Severe liver failure
  2. Heparin-induced thrombocytopenia
  3. Vitamin K deficiency
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27
Q

Which vitamin is folate

A

B9

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28
Q

What are the hallmarks of folate deficiency

A

Prolonged Diarrhoea and symptoms of Megaloblastic Anaemia

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29
Q

Causes of folate deficiency (5)

A
  • Malabsorption (i.e. coeliac disease, extensive intestinal resection)
  • Drugs and Toxins (i.e. alcohol, anti-convulsant, methotrexate, trimethoprim)
  • Increased Demand (i.e. during pregnancy, lactation)
  • Increased loss of folate (i.e. chronic dialysis, states of increase cell turnover like chronic haemolytic disease)
  • Dietary Insufficiency
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30
Q

RF of folate deficiency (6)

A
  • Low dietary folate intake
  • Age >65
  • Alcoholism
  • Pregnant or lactating
  • Prematurity
  • Intestinal Malabsorptive Disorders (coeliac)
  • Congenital defects in folate absorption and metabolism
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31
Q

Primary affected groups of folate deficiency (3)

A
  • Young children
  • Pregnant women
  • Older people (>65 years old)
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32
Q

S/s of folate deficiency (12)

A
  • Headache
  • Loss of appetite and weight loss
  • Fatigue
  • Shortness of breath
  • Dizziness
  • Pallor
  • Tachycardia
  • Tachypnoea
  • Heart murmur
  • Signs of heart failure: displaced apex beat, gallop rhythm, elevated JVP

Signs of Chronic Alcohol Abuse
Signs of haemolytic anaemia

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33
Q

Ix for folate deficiency (3)

A 
Peripheral Blood Smear:
•	Macrocytosis 
•	Anisocytosis (variable size of RBC’s)
•	Poikilocytosis (variable shape of RBC’s)
•	Hyper segmented neutrophils

Full Blood Count:
• Decreased Hb
• Increased MCV and MCH

Reticulocyte Count: decreased corrected reticulocyte count

34
Q

Define haemolytic anaemia and the 2 areas it occurs

A

Haemolytic anaemia describes the premature erythrocyte breakdown causing shortened erythrocyte life span (< 120 days) with anaemia.
• Occurs in the circulation to damaged RBCs (intravascular) or in the reticuloendothelial system i.e. macrophages of liver, spleen and bone marrow remove defective RBCs (extravascular)

35
Q

What are the three hereditary ways you can have haemolytic anaemia

A 
o	Membrane Defects 
•	Hereditary spherocytosis 
•	Hereditary elliptocytosis 
o	Metabolic Defects
•	G6PD deficiency – G6PD is part of the pentose shunt pathway which is designed to protect against oxidants found in drugs, chemicals etc
X-linked
Most common enzyme effect
Must avoid oxidants – broad beans, mothballs, henna 
•	Pyruvate kinase deficiency – pyruvate kinase is required at the last stage of glycolysis so deficiency causes RBCs with decreased ATP
o	Haemoglobinopathies
•	Sickle cell disease 
•	Thalassemia
36
Q

What are the five acquired ways you can get haemolytic anaemia

A

o Autoimmune
• Antibodies attach to erythrocytes causing intravascular and extravascular haemolysis e.g. AIHA – autoimmune antibodies causing mainly extravascular haemolysis and spherocytosis.
o Isoimmune
• Transfusion reaction
• Haemolytic disease of the newborn
o Drugs – cause formation of RBC autoantibodies from…
• Penicillin – binding to RBC membranes
• Quinine – production of immune complexes
• NOTE: this is caused by the formation of a drug-antibody-erythrocyte complex
o Trauma
• Microangiopathic haemolytic anaemia (caused by RBC fragmentation in abnormal microcirculation – intravascular)
 E.g. haemolytic uraemic syndrome, DIC, malignant hypertension
o Infection
• Malaria
• Sepsis

37
Q

What are the 2 hereditary membrane defects that give you haemolytic anaemia

A
  • Hereditary spherocytosis

* Hereditary elliptocytosis

38
Q

What are the 2 hereditary metabolic defects that give you haemolytic anaemia

A

• G6PD deficiency – G6PD is part of the pentose shunt pathway which is designed to protect against oxidants found in drugs, chemicals etc
X-linked
Most common enzyme effect
Must avoid oxidants – broad beans, mothballs, henna
• Pyruvate kinase deficiency – pyruvate kinase is required at the last stage of glycolysis so deficiency causes RBCs with decreased ATP

39
Q

Which 2 hereditary haemoglobinopathies give you haemolytic anaemia

A

Sickle cell

Thalassaemia

40
Q

Which drugs can cause haemolytic anaemia

A
  • Penicillin – binding to RBC membranes
  • Quinine – production of immune complexes
  • NOTE: this is caused by the formation of a drug-antibody-erythrocyte complex
41
Q

S/s of haemolytic anaemia (11)

A
  • Jaundice
  • Haematuria
  • Dark urine
  • Anaemia
  • Can often be asymptomatic
  • Race
  • Recent travel
  • Pallor
  • Jaundice
  • Hepatosplenomegaly
  • Leg ulcers, due to poor blood flow
42
Q

Ix for haemolytic anaemia (11)

A

o FBC:
• Low Hb
• High reticulocytes
• High MCV
• High unconjugated bilirubin
• Low haptoglobin (a protein that binds to free Hb released by red blood cells)
o U&Es
• Increased creatinine and
• Increased urea in: Thrombotic Thrombocytopenic Purpura or Haemolytic Uraemic Syndrome
o Folate
• Blood Film
o Leucoerythroblastic picture
o Macrocytosis
o Nucleated erythrocytes or reticulocytes
o Polychromasia
o May identify specific abnormal cells pointing to the diagnosis such as:
• Hypochromic microcytic anaemia - thalassemia
• Spherocytes – hereditary spherocytosis or AIHA
• Elliptocytes – hereditary elliptocytosis
• Sickle cells – sickle cell anaemia
• Schistocytes - MAHA
• Malarial parasites
• Heinz bodies (‘bite cells’) – G6PD deficiency
• Urine
o High urobilinogen
o Haemoglobinuria
o Haemosiderinuria
• Direct Coombs’ Test
o Tests for autoimmune haemolytic anaemia
o Identifies erythrocytes coated with antibodies
• Osmotic fragility test or Spectrin mutation analysis
o Identifies membrane abnormalities

43
Q

Which test tests for AI haemolytic anaemia

A

Coomb’s

44
Q

What does the Coomb’s test test for

A

AI haemolytic anaemia

45
Q

Define Haemolytic Uraemic Syndrome (HUS) (and the two forms) and Thrombotic Thrombocytopenic Purpura (TTP)

A

• DEFINITION: triad of:
o Microangiopathic haemolytic anaemia (MAHA) – intravascular haemolysis and red cell fragmentation
o Acute renal failure
o Thrombocytopaenia
• There are TWO forms of HUS:
o D+ = diarrhoea-associated – prodrome of diarrhoea
o D- = no prodromal illness identified
• HUS overlaps with TTP (thrombotic thrombocytopenia purpura), which has additional features of:
o Fever
o Fluctuating CNS signs
o Many consider TTP and HUS as a spectrum of disease
o All with TTP have HUS, along with the additional features

46
Q

What triad defines HUS

A

o Microangiopathic haemolytic anaemia (MAHA) – intravascular haemolysis and red cell fragmentation
o Acute renal failure
o Thrombocytopaenia

47
Q

What is the difference between HUS and TTP (2)

A

• HUS overlaps with TTP (thrombotic thrombocytopenia purpura), which has additional features of:
o Fever
o Fluctuating CNS signs
o Many consider TTP and HUS as a spectrum of disease
o All with TTP have HUS, along with the additional features

48
Q

Pathophysiology of HUS

A
  • In HUS, a toxin causes endothelial damage which leads to platelet activation.
  • Endothelial injury results in platelet aggregation and the release of unusually large vWF multimers and activation of platelets and the clotting cascade
  • There is also fibrin deposition in small vessels, leading to microthrombi
  • Damaged RBCs clog up vessels. The glomerular-afferent arteriole and capillaries are particularly vulnerable - they undergo fibrinoid necrosis
  • This leads to renal ischaemia and acute renal failure
  • The thrombi also promote intravascular haemolysis
49
Q

Pathophysiology of HUS and TTP

A
  • In HUS, a toxin causes endothelial damage which leads to platelet activation.
  • Endothelial injury results in platelet aggregation and the release of unusually large vWF multimers and activation of platelets and the clotting cascade
  • There is also fibrin deposition in small vessels, leading to microthrombi
  • Damaged RBCs clog up vessels. The glomerular-afferent arteriole and capillaries are particularly vulnerable - they undergo fibrinoid necrosis
  • This leads to renal ischaemia and acute renal failure
  • The thrombi also promote intravascular haemolysis

• In TTP, there is deficiency of a protease that normally cleaves vWf – which causes build up of the large multimers of vWf – this leads to platelet aggregation and fibrin deposition.

50
Q

Causes of HUS and TTP (infectious 4, drugs 4, others 5)

A 
o	Infection 
•	Escherichia coli O157 – causes 90% of cases. Produces a verotoxin that attacks endothelial cells – usually in young children due to eating undercooked meat.
•	Shigella
•	Neuraminidase-producing infections 
•	HIV 
o	Drugs
•	COCP
•	Ciclosporin 
•	Mitomicin
•	5-fluorouracil
o	Others:
•	Malignant hypertension 
•	Malignancy
•	Pregnancy 
•	SLE 
•	Scleroderma
51
Q

Epidemiology of HUS and TTP

A
  • UNCOMMON
  • D+ HUS often affects YOUNG CHILDREN
  • It is the most common cause of acute renal failure in children
  • TTP mainly affects ADULT FEMALES
52
Q

S/s of HUS and TTP (3 GI, 10 general, 2 renal, 4 for TTP only)

A

• GI
o Severe abdominal colic
o Watery diarrhoea that becomes bloodstained
Abdo tenderness

•	General
o	Malaise 
o	Fatigue 
o	Nausea 
o	Fever < 38 degrees (D+)
o	Pallor 
o	Slight jaundice (due to haemolysis) 
o	Bruising 
o	Generalised oedema 
o	Hypertension 
o	Retinopathy

• Renal
o Oliguria or anuria
o Haematuria

•	CNS Signs
o	Occurs in TTP
o	Weakness 
o	Reduced vision 
o	Fits 
o	Reduced consciousness
53
Q

Ix for HUS and TTP (FBC 3, U&Es 4, 12 others)

A 
•	FBC
o	Normocytic anaemia 
o	High neutrophils 
o	Very low platelets 
•	U&amp;Es
o	High urea 
o	High creatinine
o	High K+ 
o	Low Na+ 
•	Clotting
o	Normal APTT and fibrinogen levels (abnormality may indicate DIC)
•	LFTs
o	High unconjugated bilirubin 
o	High LDH from haemolysis 
•	Blood cultures
•	ABG
o	Low pH 
o	Low bicarbonate 
o	Low PaCO2
o	Normal anion gap 
•	Blood Film
o	Schistocytes 
o	High reticulocytes and spherocytes 
•	Urine
o	1+ g protein/24 hrs
o	Haematuria
•	Stool Samples
o	MC&amp;S
•	Renal Biopsy
o	Can distinguish between D+ and D- HUS
54
Q

How to differentiate between DIC and HUS/TTP

A

• Clotting

o Normal APTT and fibrinogen levels in HUS and TTP (abnormality may indicate DIC)

55
Q

Define haemophilia and the subtypes

A

• Bleeding diatheses resulting from an inherited deficiency of a clotting factor

o THREE subtypes:
• Haemophilia A: MOST COMMON - deficiency in factor 8
• Haemophilia B: deficiency in factor 9
• Haemophilia C: RARE - deficiency in factor 11

• Note: acquired haemophilia is a form caused by suddenly appearing autoantibodies that interfere with factor 8.

56
Q

Which haemophilias are X linked

A

A and B

57
Q

Epidemiology of haemophilia

A

• Due to its X-linked recessive inheritance pattern, Haemophilia is mainly seen in MALES

58
Q

S/s of haemophilia

A
  • Symptoms usually begin in early childhood, or after surgery/trauma
  • Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
  • Painful bleeding into muscles causing haematomas – high pressure can lead to nerve palsies and compartment syndrome
  • Haematuria
  • Excessive bruising or bleeding after surgery or trauma
  • FEMALE carriers are usually asymptomatic, but may experience excessive bleeding after trauma
  • Generally speaking, bleeding in haemophilia is DEEP (into muscles and joints)
  • Multiple bruises
  • Muscle haematomas
  • Haemarthroses
  • Joint deformity
  • Nerve palsies (due to nerve compression by haematomas)
  • Signs of iron deficiency anaemia
59
Q

Ix for haemophilia

A
  • Clotting screen (high APTT)
  • Coagulation factor assays (low factor 8, 9 or 11 (depending on type of haemophilia))
  • Other investigations may be performed if there are complications (e.g. arthroscopy)
60
Q

Define ITP

A

• Syndrome characterised by immune destruction of platelets resulting in bruising or a bleeding tendency

61
Q

Main difference between acute and chronic ITP

A
  • Acute ITP is often seen after viral infection in children

* Chronic ITP is more common in adults

62
Q

Associations of ITP (7)

A

o Infections (e.g. malaria, EBV, HIV)
o Autoimmune diseases (e.g. SLE, thyroid disease)
o Malignancies
o Drugs (e.g. quinine)

63
Q

Explain the pathophysiology of ITP

A

• Autoantibodies are generated, which bind to platelet membrane proteins (e.g. GlpIIb/IIIa) resulting in thrombocytopaenia

64
Q

Epidemiology of ITP

A

• Acute ITP presenting CHILDREN aged 2-7 yrs
• Chronic ITP is seen in ADULTS
o 4 x more common in WOMEN

65
Q

S/s of ITP

A
  • Easy bruising
  • Mucosal bleeding
  • Menorrhagia
  • Epistaxis
  • Visible petechiae and bruises
  • Signs of other illness (e.g. infections, wasting, splenomegaly) would suggest that other causes
66
Q

What do you need to exclude to diagnose ITP (3)

A

o Myelodysplasia
o Acute leukaemia
o Marrow infiltration

67
Q

Ix for ITP (7)

A

• Bloods
o FBC - low platelets
o Clotting screen - normal PT, APTT and fibrinogen
o Autoantibodies (e.g. antiplatelet antibody)
• Blood Film
o To rule out pseudothrombocytopaenia (which is caused by platelets clumping together and giving falsely low counts)
• Bone Marrow biopsy/aspiration
o To exclude other pathology

68
Q

2 main types of macrocytic anaemia

A

Megaloblastic and non

69
Q

What defines macrocytic anaemia

A

a high MCV of erythrocytes (>100 fl in adults)

70
Q

What does megaloblastic macrocytic anaemia specifically mean and what is it caused by

A

specifically refers to a delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow - unusually large, structurally abnormal, immature red cells
o Oval macrocyctes
o Caused by deficiency of B12 or folate required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation

71
Q

Causes of B12 deficiency (5)

A
  • Reduced absorption (e.g. post-gastrectomy, pernicious anaemia – autoimmune condition causing severe lack of IF, terminal ileal/small bowel resection or disease)
  • Reduced intake (vegans)
  • Abnormal metabolism (congenital transcobalamin II deficiency)
72
Q

Causes of folate deficiency (3 reduced intake, 4 increased demand, 2 reduced absorption, 1 disease, 1 drugs)

A
  • Reduced intake (alcoholics, elderly, anorexia)
  • Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
  • Reduced absorption (coeliac, tropical sprue)
  • Jejunal disease (e.g. coeliac disease)
  • Drugs (e.g. phenytoin
73
Q

Which 5 drugs can cause megaloblastic anaemia

A 
Phenytoin
•	Methotrexate (dihydrofolate reductase inhibitor) 
•	Hydroxyurea 
•	Azathioprine 
•	Zidovudine
74
Q

Non-megaloblastic causes of macrocytic anaemia (8)

A 
o	Alcohol excess or Liver disease – ROUND macrocytes
o	Myelodysplasia
o	Multiple myeloma
o	Hypothyroidism 
o	Aplastic anaemia
o	Haemolysis (shift to immature red cell form - reticulocytosis) 
o	Drugs (e.g. tyrosine kinase inhibitor)
o	Pregnancy
75
Q

Epidemiology of macrocytic anaemia

A
  • More common in ELDERLY FEMALES

* Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West

76
Q

RF of macrocytic anaemia

A

FHx/Hx of AI disease

77
Q

S/s of macrocytic anaemia (5 non-specific anaemic, 4 pernicious anaemia, 7 signs of B12 deficiency)

A

• Non-specific symptoms of anaemia:
o Tiredness
o Lethargy
o Dyspnoea

•	Signs of Anaemia
o	Pallor 
o	Tachycardia  
•	Signs of Pernicious Anaemia
o	Mild jaundice 
o	Glossitis 
o	Angular stomatitis 
o	Weight loss 
•	Signs of B12 Deficiency
o	Peripheral neuropathy 
o	Ataxia 
o	Subacute combined degeneration of the spinal cord 
o	Optic atrophy 
o	Dementia 
o	Positive Babinski’s, absent ankle reflex, increase knee reflex
78
Q

Ix for macrocytic anaemia (12)

A

Bloods
• FBC: increased MCV, PANCYTOPENIA
• LFTs: increased bilirubin (due to ineffective erythropoiesis or haemolysis)
• Serum Vitamin B12, Red Cell Folate, Anti-parietal cell AND anti-intrinsic factor antibodies
• Serum protein electrophoresis – looking for dense band in Myeloma
• Other: TFT

Blood film
• Large erythrocytes
• Megaloblastic: Megaloblasts, Hyper segmented Neutrophil Nuclei (>5 lobes)

Schilling Test: Method of testing for pernicious anaemia
• B12 will only be absorbed when given with intrinsic factor

Other:
• Bone Marrow Biopsy (megaloblast, myelodysplastic changes)
• Investigations for the cause

79
Q

Test for pernicious anaemia

A

Schillings test

80
Q

Mx for macrocytic anaemia (think about the 3 main causes and the Mx for those)

A

o IM hydroxycobalamin for life
o If no neurological defect
 IM hydroxycobalamin 1mg 3x/week for 2 weeks then 1mg/3 months
o If neurological defect present
 1mg every other day until no further improvement then 1mg/2 months
• B12 deficiency
o Dietary supplements – PO cyanocobalamin
• Folate Deficiency
o Oral folic acid
o If B12 deficiency is present, it must be treated before the folic acid deficiency as B12 is needed for folate to enter cells
• In pregnancy, prophylactic folate is given from conception until 12 weeks to prevent spina bifida
§

81
Q

Complications of macrocytic anaemia

A
  • Pernicious anaemia –> increased risk of gastric cancer

* Pregnancy - folate deficiency increases the risk of neural tube defects

82
Q

Prognosis of macrocytic anaemia

A

• Majority are treatable if there are no complications

Y3 Haem (3 decks)

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