1. Anaemia Flashcards
Causes of anaemia.
a) Microcytic - ferritin low/high?
b) Normocytic - reticulocytes low/high?
c) Macrocytic - megaloblastic or not?
a) Iron-deficiency: ferritin low, raised TIBC
- Thalassaemia: ferritin high/ normal
b) - Increased loss + compensation- acute haemorrhage, haemolysis (eg SCD): raised reticulocyte count (>2)
- Impaired production: chronic disease, bone marrow failure (eg leukaemia, aplastic anaemia, myeloma)
c) - Megaloblastic: B12 or folate deficiency
- Non-megaloblastic: hypothyroid, alcohol
Macrocytic anaemia
a) Megaloblastic vs non-megaloblastic causes
b) How and where is B12 absorbed
c) Causes of B12 deficiency: main one (80%) and others
d) Causes of folate deficiency
e) Management of B12 and/or folate deficiency
- note: if they co-exist - how MUST you proceed?
f) Referral: to whom and for why?
a) - Megaloblastic: B12 or folate deficiency
- Non-megaloblastic: alcoholism, liver disease, hypothyroidism
b) Absorbed in the terminal ileum; requires intrinsic factor (IF) to be absorbed, which is produced in gastric parietal cells
c) - Pernicious anaemia (autoimmune destruction of gastric parietal cells; pernicious = insidious progression)
- Other: gastric causes (gastrectomy, gastritis, long-term PPI or H2RA use); intestinal causes (terminal ileal disease - Crohn’s, ileal resection), inadequate intake (eg vegan diet), HIV infection
d) Dietary inadequacy, malabsorption, drug-induced (e.g. anticonvulsants, alcohol)
e) - Screen for underlying conditions (eg. coeliac, IBD, malignancy) as appropriate
- B12 (cobalamin) injections: every other day for 2/52 or until improvement; then every 3/12
- Folic acid 5 mg daily for 4/12; or until term in pregnancy
- If B12/folate deficiency coexist- you must treat B12 deficiency first or risk worsening it and inducing subacute combined degeneration of the cord
f) Haem: suspected malignancy, pregnant, neurological symptoms
- GI: malabsorption (not pernicious anaemia), suspected malignancy, pernicious anaemia + gastric symptoms
- Dietitian: if dietary advice needed
Subacute combined degeneration of the spinal cord.
a) Cause
b) Pattern of neurological damage
c) Clinical features
d) Management
a) B12 deficiency
b) Diffuse, multifocal pattern of axonal loss and demyelination most severe in the cervical and thoracic spinal cord. The disease predominantly affects the posterior columns followed by the anterolateral and anterior tracts
c) Dysaesthesia, disturbance of position sense, and spastic paraparesis or tetraparesis.
d) B12 injection
Aplastic anaemia.
a) Define
b) Causes
c) Presentation
d) Investigations (findings vs. main differential)
e) Management
a) Pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate or marrow fibrosis
b) - Congenital (rare): Fanconi anaemia
- Acquired: Idiopathic (70-80%), sickle cell aplastic crisis, infection (eg EBV, HIV, hepatitis), drug-induced (eg chloramphenicol, sulfonamides, NSAIDs, phenytoin), graft vs. host disease, pregnancy
c) Symptoms of anaemia (fatigue, SOB, weakness, pallor), thromboyctopenia (bleeding, bruising) and possibly infections (less common)
d) FBC, blood film,
- Bone marrow aspirate: hypocellular marrow with no abnormal cells (vs. blast cells in ALL; Auer rods in AML)
e) - Non-severe: immunosuppression (cyclosporin) and supportive care (eg blood transfusions, infection prophylaxis)
- Severe: HSCT / bone marrow transplant
Sickle cell disease.
a) Genetics
b) Presentation - age, symptoms, signs
c) Investigations
d) To confirm diagnosis
e) Management - conservative, medical, surgical
a) Autosomal recessive condition on Ch 11; homozygous have SCD, heterozygous have sickle cell trait
b) - Usually on newborn heel prick test
- Symptoms present around 3-6 months when HbF starts falling;
- Symptoms of haemolytic anaemia (pallor, jaundice, fatigue, FTT, weakness, recurrent infections)
- Signs: splenomegaly, jaundice
c) - FBC: normocytic anaemia, raised reticulocytes
- Blood film: sickled erythrocytes, features of hyposplenism.
d) Haemoglobin electrophoresis:
- no HbA, 80-95% HbSS, and 2-20% HbF.
e) i) - Carry national haemoglobinopathy card
- Avoid smoking (acute chest) and alcohol (dehydration)
- Increased monitoring in pregnancy
- Increased care pre/post-operatively
- Advice for travel (avoid dehydration, stay active)
- Regular abdominal palpation for splenic enlargement (?sequestration)
ii) Penicillin V prophylaxis (against pneumococcus)
- Vaccinations, including pneumococcus
- Transfusion therapy (+ iron chelation if required)
- Hydroxyurea (increases HbF)
- May require splenectomy
Sickle cell crises.
a) Prevention advice
b) Types of vaso-occulsive crises, with presentation and management
c) Other sickle cell crises
a) - Avoiding situations that can precipitate crises (eg, cold, dehydration, and exhaustion)
- Avoid smoking (acute chest) and alcohol (dehydration)
b) 1. Bone /joint pain with avascular necrosis of marrow: treat with analgesia +/- transfusion/hydroxyurea
2. Acute chest syndrome: mimics pneumonia; treat with oxygen, ventilation and transfusions
3. Stroke/TIA/etc.
4. Priapism: conservative (analgesia, bladder emptying, warm baths), if fail: intra-cavernous adrenaline
c) - Aplastic crisis: sudden reduction in erythropoeisis, requires transfusion (often secondary to parvovirus B19)
- Sequestration crisis: sudden enlargement of spleen, with reduction in Hb and circulatory collapse; requires transfusion +/- splenectomy
Pernicious anaemia.
a) Cause
b) Clinical features
a) Autoantibodies directed against parietal cells; risk factors - female, other autoimmune conditions
b) B12 deficiency - macrocytic anaemia,
Thalassaemia.
a) Normal Hb in foetuses and adults
b) Genetics and pathogenesis
c) Variants and presentation
d) Clinical signs
e) Investigations and findings
f) To confirm diagnosis
g) Management
a) Foetus: HbF (2 alpha, 2 gamma chains)
Adults: HbA (2 alpha, 2 beta), HbA2 (2 alpha, 2 delta)
b) - Auto recessive haemoglobinopathy, resulting in deficiencies of either the alpha or beta chains of Hb.
c) - Alpha or beta-thalassaemia trait: usually asymptomatic, microcytic anaemia
- Alpha-thalassaemia: may be asymptomatic, may have anaemia/hepatosplenomegaly and bone changes
- Alpha-thal major: hydrops fetalis (usually die in utero)
- Beta-thal intermedia: presents from 6 months, anaemic, bone changes, variable transfusion dependence
- Beta-thal major: presents from 6 months, severe haemolytic anaemia, splenomegaly, bone changes, chronic transfusion dependency
- Note: may co-exist with SCD
d) - Pallor +/- jaundice (esp if severe haemolysis)
- Hepatosplenomegaly.
- Bony deformities: frontal bossing, prominent facial bones, and dental malocclusion.
e) - FBC/haematinics - microcytic anaemia, raised/normal ferritin, raised serum iron level
- LFTs - raised bilirubin
- Skull XR - ‘hair on end’ appearance
f) Haemoglobin electrophoresis:
- Normal HbA2 is between 1.5 and 3.0%
- HbA2 >3.5 % is diagnostic
g) - Asymptomatic: monitor
- Carry national haemoglobinopathy card
- Symptomatic: blood transfusions
- Avoid iron overload - low dietary iron and may need iron chelation (eg Desferrioxamine)
- Hydroxyurea - increase expression of HbF
- Pregnancy: counselling, antenatal testing, increased monitoring, folic acid, etc.
Iron-deficiency anaemia (IDA): aetiology
a) Pathogenesis
b) 4 primary mechanisms and main causes
a) Inadequate iron substrate for RBC production
b) 1. Excessive blood loss:
- Menorrhagia (most common cause in pre-menopausal women)
- GI bleed (most common cause in men and post-menopausal women) - PUD/NSAIDs, GI malignancy, liver disease/varices, IBD, haemorrhoids
- Hookworm/schistosomiasis (tropical countries),
- Obstetric/gynaecological - APH, PPH, endometrial Ca
- Urological malignancy (renal, bladder)
- Bleeding disorders: anticoagulation, recurrent epistaxis, haemarthrosis, etc.
- Malabsorption:
- Coeliac, IBD, etc. (usually accompanied by folate/B12 deficiency)
- Drugs - tetracyclines - Inadequate intake
- dietary (more common in children) - Increased requirement
- pregnancy
- rapid growth (puberty)
IDA: assessment and investigations
a) Red flags in the history
b) Examination
c) Confirming IDA
d) Appearance on blood film
e) Further investigations
f) 2-week wait criteria
a) - UGI malignancy - dysphagia, vomiting, melaena/ haematemesis, weight loss, dyspepsia, epigastric pain/mass
- LGI malignancy - change bowel habit, rectal bleed, weight loss, abdominal mass
- Endometrial Ca - PMB
- Urological Ca - flank pain/mass, painless haematuria with risk factors
b) - Obs - HR, BP, SpO2
- General appearance - pallor, jaundice, bruising, petechiae
- Face - conjunctival pallor, yellow sclera, mouth - ulcers, angular cheillitis, glossitis
- Chest - murmur (flow), focal signs (?malignancy)
- Abdomen - masses, organomegaly, stigmata of LD
- PR / PV - masses, bleeding
c) - FBC: microcytic anaemia (low MCV, low Hb), low ferritin (caveat: may be raised in acute-phase reactions)
d) Hypochromic, anisocytosis (variation in size between red blood cells) and poikilocytosis (abnormally shaped red blood cells) - pencil cells
e) In women - cervical smear, hysteroscopy (if PMB)
- In all adults - consider upper and lower GI endoscopy
- If endoscopy normal - consider h. pylori studies
f) - Men/non-menstruating women of any age with unexplained iron-deficiency anaemia - refer to Gastro
- Women with PMB - refer to gynae
Anaemia: clinical features
a) General (mild-moderate)
b) Severe anaemia
c) Signs of overt…?
d) In children
a) Fatigue, pallor, SOBOE, pruritis, hair loss, palpitations, sore tongue (glossitis), angular cheillitis, koilonychia
b) SOB at rest, angina, syncope, heart failure
c) Blood loss: PR bleed, melaena, haematemesis, haematuria, menorrhagia/ PMB, epistaxis, bruising, etc.
d) FTT
Haemolytic anaemia
a) Classic triad
b) Causes
c) Triggers in G6PD
d) Investigations
e) Haemolysis long-term increases the risk of developing what hepatobiliary disease?
a) Anaemia (pallor), jaundice and splenomegaly
b) - Genetic: SCD, G6PD, thalassaemia, spherocytosis
- Acquired: Sepsis/DIC, ABO incompatibility/Rhesus reaction
c) Fava beans, certain drugs, infections
d) - FBC, haematinics, CRP/ESR, LFTs, septic screen, D-dimer, clotting (DIC)
- Blood film
- Hb electrophoresis: SCD, thalassaemia
- Direct Coombs’ test (immune-mediated haemolysis)
e) Gallstones (black pigment gallstones)
Management of IDA.
a) When to start Rx?
b) What Rx? Take how?
c) Side effects of Rx (all GI)
d) Monitoring response to Rx - initial check-up
e) If good response - monitoring?
f) If inadequate response - actions?
g) When should parenteral iron be considered?
h) Dietary advice
a) As soon as IDA is found (before results of investigations)
b) Ferrous salts (eg ferrous sulfate 200mg 2-3x per day)
- If taking thyroxine also, allow 2-hour interval as iron alters thyroxine absorption
- Vitamin C aids absorption - take iron with glass of OJ
(Note: Iron more easily absorbed in the ferrous state rather than the ferric state)
c) Constipation, black stools, diarrhoea, heartburn, nausea, abdominal/epigastric pain
d) FBC at 2-4 weeks -
e) If good response at 2-4 weeks, check again at 2-4 months for normalisation of Hb;
- Once normal continue iron for 3 months;
- Re-check every 3 months for 1 year (if ever it drops, restart Rx)
f) - Check compliance
- If poor compliance due to side effects, consider co-prescription (eg laxative for constipation) or alternative formulation
- If still no better/ poor tolerance - refer for specialist assessment
g) - Failure of oral supplementation
- Unable to take/ tolerate oral meds
- Malabsorption
h) Dark green vegetables, red meat, apricots, prunes, raisins and iron-fortified bread
Anaemia of chronic disease.
a) Pathogenesis
b) Causes (4 main ones)
c) Confirming diagnosis + supporting tests
d) Management
a) Impaired RBC production (erythropoeisis) - hence low reticulocyte count
b) - Chronic infection
- Chronic inflammation (autoimmune / connective tissue disease)
- Malignancy
- CKD
c) - FBC - normocytic (or microcytic) anaemia with low TIBC and normal/raised ferritin; reticulocytes low; iron usually low
- ESR often raised
d) - Treat underlying condition
- Other measures: EPO, transfusion, iron replacement (if low)
Direct and indirect Coombs’ tests: explained
Direct Coombs’ test/ direct antiglobulin test (DAT):
- Test for antibodies against RBCs, causing haemolytic anaemia. Positive in…
1. Alloimmune destruction (eg. ABO incompatibility, haemolytic disease of the newborn)
2. Autoimmune destruction (eg. idiopathic, SLE, glandular fever)
3. Drug-induced destruction (eg. methyldopa, penicillin)
Indirect Coombs’ test / indirect antiglobulin test (IAT):
- Test for very low concentrations of antibodies present in the serum, and used in the following instances…
1. Pre-transfusion - compatibility and cross-matching
2. Antenatally - to screen mother for Rhesus antibodies
