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.
2
Q
What is APL syndrome associated with and what %
A
SLE, 20-30%
3
Q
What does APL syndrome cause (4)
A
APL cause CLOTS
- Coagulation defect
- Livedo reticularis
- Obstetric – recurrent miscarriages
- Thrombocytopenia (low platelets)
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.
5
Q
Epidemiology of APL syndrome
A
• More common in young females – accounts for 27% of females with >2 miscarriages
6
Q
RF of APL syndrome (3)
A
- History of SLE or autoimmune rheumatological disorders
- Other autoimmune diseases
- Autoimmune haematological disorders
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
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
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
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)
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)
12
Q
Drugs that cause aplastic anaemia (3)
A
Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)
13
Q
Chemicals that cause aplastic anaemia (2)
A
benzene, DDT
14
Q
Viruses that can cause aplastic anaemia (1)
A
Parvovirus B19
15
Q
Epidemiology of aplastic anaemia
A
- Annual incidence: 2-4/1,000,000
* Slightly more common in males
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
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
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
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
20
Q
What type of infection can cause DIC
A
Particularly gram -ve sepsis
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
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
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
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
25
Ix for DIC
```
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)
26
DDx for DIC (3)
1. Severe liver failure
2. Heparin-induced thrombocytopenia
3. Vitamin K deficiency
27
Which vitamin is folate
B9
28
What are the hallmarks of folate deficiency
Prolonged Diarrhoea and symptoms of Megaloblastic Anaemia
29
Causes of folate deficiency (5)
- 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
30
RF of folate deficiency (6)
- Low dietary folate intake
- Age >65
- Alcoholism
- Pregnant or lactating
- Prematurity
- Intestinal Malabsorptive Disorders (coeliac)
- Congenital defects in folate absorption and metabolism
31
Primary affected groups of folate deficiency (3)
- Young children
- Pregnant women
- Older people (>65 years old)
32
S/s of folate deficiency (12)
- 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
33
Ix for folate deficiency (3)
```
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
Define haemolytic anaemia and the 2 areas it occurs
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
What are the three hereditary ways you can have haemolytic anaemia
```
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
What are the five acquired ways you can get haemolytic anaemia
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
What are the 2 hereditary membrane defects that give you haemolytic anaemia
* Hereditary spherocytosis
| * Hereditary elliptocytosis
38
What are the 2 hereditary metabolic defects that give you haemolytic anaemia
• 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
Which 2 hereditary haemoglobinopathies give you haemolytic anaemia
Sickle cell
| Thalassaemia
40
Which drugs can cause haemolytic anaemia
* Penicillin – binding to RBC membranes
* Quinine – production of immune complexes
* NOTE: this is caused by the formation of a drug-antibody-erythrocyte complex
41
S/s of haemolytic anaemia (11)
* Jaundice
* Haematuria
* Dark urine
* Anaemia
* Can often be asymptomatic
* Race
* Recent travel
* Pallor
* Jaundice
* Hepatosplenomegaly
* Leg ulcers, due to poor blood flow
42
Ix for haemolytic anaemia (11)
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
Which test tests for AI haemolytic anaemia
Coomb's
44
What does the Coomb's test test for
AI haemolytic anaemia
45
Define Haemolytic Uraemic Syndrome (HUS) (and the two forms) and Thrombotic Thrombocytopenic Purpura (TTP)
• 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
What triad defines HUS
o Microangiopathic haemolytic anaemia (MAHA) – intravascular haemolysis and red cell fragmentation
o Acute renal failure
o Thrombocytopaenia
47
What is the difference between HUS and TTP (2)
• 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
Pathophysiology of HUS
* 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
Pathophysiology of HUS and TTP
* 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
Causes of HUS and TTP (infectious 4, drugs 4, others 5)
```
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
Epidemiology of HUS and TTP
* 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
S/s of HUS and TTP (3 GI, 10 general, 2 renal, 4 for TTP only)
• 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
Ix for HUS and TTP (FBC 3, U&Es 4, 12 others)
```
• FBC
o Normocytic anaemia
o High neutrophils
o Very low platelets
• U&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&S
• Renal Biopsy
o Can distinguish between D+ and D- HUS
```
54
How to differentiate between DIC and HUS/TTP
• Clotting
| o Normal APTT and fibrinogen levels in HUS and TTP (abnormality may indicate DIC)
55
Define haemophilia and the subtypes
• 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
Which haemophilias are X linked
A and B
57
Epidemiology of haemophilia
• Due to its X-linked recessive inheritance pattern, Haemophilia is mainly seen in MALES
58
S/s of haemophilia
* 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
Ix for haemophilia
* 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
Define ITP
• Syndrome characterised by immune destruction of platelets resulting in bruising or a bleeding tendency
61
Main difference between acute and chronic ITP
* Acute ITP is often seen after viral infection in children
| * Chronic ITP is more common in adults
62
Associations of ITP (7)
o Infections (e.g. malaria, EBV, HIV)
o Autoimmune diseases (e.g. SLE, thyroid disease)
o Malignancies
o Drugs (e.g. quinine)
63
Explain the pathophysiology of ITP
• Autoantibodies are generated, which bind to platelet membrane proteins (e.g. GlpIIb/IIIa) resulting in thrombocytopaenia
64
Epidemiology of ITP
• Acute ITP presenting CHILDREN aged 2-7 yrs
• Chronic ITP is seen in ADULTS
o 4 x more common in WOMEN
65
S/s of ITP
* 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
What do you need to exclude to diagnose ITP (3)
o Myelodysplasia
o Acute leukaemia
o Marrow infiltration
67
Ix for ITP (7)
• 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
2 main types of macrocytic anaemia
Megaloblastic and non
69
What defines macrocytic anaemia
a high MCV of erythrocytes (>100 fl in adults)
70
What does megaloblastic macrocytic anaemia specifically mean and what is it caused by
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
Causes of B12 deficiency (5)
* 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
Causes of folate deficiency (3 reduced intake, 4 increased demand, 2 reduced absorption, 1 disease, 1 drugs)
* 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
Which 5 drugs can cause megaloblastic anaemia
```
Phenytoin
• Methotrexate (dihydrofolate reductase inhibitor)
• Hydroxyurea
• Azathioprine
• Zidovudine
```
74
Non-megaloblastic causes of macrocytic anaemia (8)
```
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
Epidemiology of macrocytic anaemia
* More common in ELDERLY FEMALES
| * Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West
76
RF of macrocytic anaemia
FHx/Hx of AI disease
77
S/s of macrocytic anaemia (5 non-specific anaemic, 4 pernicious anaemia, 7 signs of B12 deficiency)
• 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
Ix for macrocytic anaemia (12)
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
Test for pernicious anaemia
Schillings test
80
Mx for macrocytic anaemia (think about the 3 main causes and the Mx for those)
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
Complications of macrocytic anaemia
* Pernicious anaemia --> increased risk of gastric cancer
| * Pregnancy - folate deficiency increases the risk of neural tube defects
82
Prognosis of macrocytic anaemia
• Majority are treatable if there are no complications
