Microcytic Anaemia Flashcards
What is the haemoglobin concentration in patients with anemia?
low haemoglobin concentration (<13.0g/dL for men and <11.6g/dL for women)
What are the symptoms of anaemia?
- Fatigue, headaches and faintness
- Breathlessness
- Angina
- Intermittent claudication (referring to impairment in walking, or pain, discomfort, numbness, or tiredness in the legs that occurs during walking or standing and is relieved by rest)
- Palpitations
What are the signs of anaemia?
General
- Pallor
- Tachycardia
- Systolic flow murmur
- Cardiac failure
Specific
- Koilonychia: spoon-shaped nails seen in longstanding iron deficiency anaemia
- Jaundice: found in haemolytic anaemia
- Bone deformities: found in thalassaemia major
- Leg ulcers: occur in association with sickle cell disease.
What are the investigations for anaemia?
Peripheral blood
- Red cell indices: Look at MCHC for AIH, MCHC will increase in AIH as volume has been pinched off but Hb levels the same
- WBC count
- Platelet count
- Reticulocytes
- Blood film
For decreased production
- Reticulocyte Count – to assess production!!
- Thalassemia Screen – via electrophoresis
- Folate / B12
- Iron Studies – the MOST important value you should look at is Ferritin Levels!
For increased loss
- FOB – for BGIT
- Urine Dipstick
- BR, Haptoglobin, LDH (if haemolysis is suspected; raised even if extravascular haemolysis!)
- Direct Coomb’s Test
Examination of the bone marrow is performed to further investigate abnormalities found in the peripheral blood.
What is the relevant history to take in a patient with anemia?
1) Elucidate symptoms of anemia 🡪 palpitations, chest pain, dyspnoea, pallor
2) Duration of Symptoms
If Acute 🡪 more likely to be increased LOSS
- Acute Bleed – Where is it?
- Haemolysis: Elucidate Scleral icterus
- Elucidate dark urine
If Chronic 🡪 more likely to be decreased PRODUCTION
3) Family hx of decreased production – eg: thalassemia
4) Drug history
5) Age
- Women think about menorrhagia
- Men – ulcer (esp if older), colorectal cancer
What are the causes of microcytic, hypochromic anemia (MCV<80)?
- Iron deficiency anemia
- Thalassemia
- Sideroblastic Anaemia
- Sickle Cell Anaemia
- Anemia of Chronic Disease
What are the causes of normochromic, normocytic anaemia?
- Acute Haemorrhage
- Anemia of Chronic Disease
- Renal Failure: hence reduced EPO
- Aplastic Anaemia
- Leukemia
- MDS
- Autoimmune rheumatic disease
What are the causes of macrocytic anemia?
Megaloblastic Anaemia: B12/folate deficiency
Non Megaloblastic Anaemia
- Increased reticulocytes: aemolytic anemia (e.g. Spherocytosis, G6PD, Sickle Cell Anaemia, AIHA, MAHA), haemorrhage
- liver disease
- alcohol
- drug therapy e.g. azathioprine
- Hypothyroid
What are the causes of iron deficiency anaemia?
- *Blood loss
- Blood loss is the MOST COMMON cause of Fe Deficiency!
- Always ask about duration of menses, Hx of Peptic ulcers, NSAID use, melena, blood in stools, haematemesis, hookworm infection!)
Increased demands such as growth and pregnancy
Decreased absorption (post-gastrectomy, Coeliac Disease, antacid use)
Poor intake (ask about dietary intake of red meats & supplementation)
What are the clinical features of iron deficiency?
- Brittle nails
- Spoon-shaped nails (koilonychia)
- Glossitis (we will see atrophy of the papillae of the tongue) 🡪 smooth, redbeefy tongue
- Angular stomatitis
- Brittle hair
- A syndrome of dysphagia and glossitis (Plummer–Vinson Syndrome or Paterson–Brown–Kelly syndrome 🡪 the same)
What are the investigations performed for iron deficiency anemia?
Blood count and blood film
- Microcytic, hypochromic
- There is poikilocytosis (variation in shape) 🡪 hypochromic elliptocytes
- There is anisocytosis (variation in size)
Pale area exceeds 1/3 of diameter.
Serum iron and iron-binding capacity
- Serum iron will fall significantly.
- TIBC rises
- Transferrine rises
Serum ferritin
- Serum ferritin should fall in classical iron deficiency.
OGD and colonoscopy (especially elderly patients): MUST NOT MISS colorectal cancer, diverticulitis / diverticular bleeding and cancer in the stomach.
What is the management of Fe deficiency anemia?
The correct management of iron deficiency is to find and treat the underlying cause, and to give iron to correct the anaemia and replace iron stores.
Best taken BEFORE FOOD – to maximally increase absorption
Recommended daily dose for iron deficiency adults is 150-200mg of elemental Fe. For children, 3mg/kg od/bd
- Ferrous gluconate: 250mg dose but, contains 30mg elemental iron
- Ferrous fumarate: 200mg dose, but contains 66mg elemental iron
Expect improvement (Hb increase >2g/dL after 4 weeks of treatment). Treat for 6 months beyond Hb normalization.
What are the drugs precent absorption of iron?
antacids, quinolones, tetracycline
What are the side effects of iron supplementation. How do you reduce the side effects?
Up to 50% will experience GI side effects e.g. abdominal discomfort, N&V, constipations. Side effects correlated with dose of elemental Fe ingested
Measures to reduce side effects: reduce elemental Fe dosage, start at a small dose, take supplements with meals; can give laxatives for constipation
What history do you need to ask in a patients with thalassemia?
Diagnosis: Who, What, Where, When How?
- Age of diagnosis
- Initial presentation
- Where & How it was diagnosed, how was patient diagnosed, investigations done, f/u status
[Treatment history ]
- Control (therapy, how often):
- -> age at 1st transfusion, age when chelation therapy was started
- -> how many transfusions required a year
- -> any increase in transfusion requirements
- -> Baseline Hb before and after transfusion, any symptomatic anaemia between transfusions
- Compliance
- Complications: transfusion reactions requiring pre- medications, leukocyte filter; anaphylaxis, infection, fluid overload (CCF), haemolysis, TRALI
What are the complications of thalassaemia/ anaemia?
- Symptomatic Anaemia
- Failure to thrive
- Haemolysis, jaundice
- SOB, heart failure from restrictive pericarditis
- Hypersplenism: easy Bruisability (thrombocytopenia); Often ill (leukocytopenia)
- Gallstones from haemolysis
What are the complications of iron overload (haematochromatosis) from chronic hypertransfusion?
Pituitary: Hypopituitarism (Hypothyroidism, Hypocortisolism, Hypogonadism)
- Pubertal Delay (no increase in LH/FSH in puberty)
- Short stature
Hypothyroidism (both Pri & Secondary, from deposition of Fe in thyroid Gland)
Hypoparathyroidism: hypocalcaemia (perioral numbness, paraesthesia)
Cardiomyopathy 🡪 heart failure & arrhythmias
- Sterile pericarditis
- Restrictive Cardiomyopathies 🡪 CCF
- Arrhythmias (both supraventricular and ventricular)
Chronic liver disease (cirrhosis, portal hypertension, splenomegaly)
Pancreas- Diabetes Mellitus: a mixture of T1 & T2
Increased RBC turnover – hyperuricaemia -> gouty arthropathy + jaundice + gallstones
Aplastic crisis from Parvovirus B19 infection – it is a blood-born infection!
What are the complications of chelation (required if ferritin > 1000)?
- Hearing loss (desferrioxamine)
- Vision loss (desferrioxamine)
- Infections (Yersinia, campylobacter)
What is the relevant family history to ask for in a patient with thalassemia ?
- Parent’s genetic status, do they know if they are carriers? Consanguinity?
- Any siblings affected? If so, on treatment?
- Any genetic counselling before?
- Family tree!
How would you perform a physical exam in a patient with thalassemia?
INSPECTION
- Dysmorphism: Thalassaemic facies (frontal bossing, maxillary) hypertrophy
- Growth: not well thrived / Short stature
- Bronzed skin
- Pallor
- Jaundice
- PCT, O2, IV line
ABDOMEN
- Desferal (Deferoxamine) scars (pigmented, round, no lipodystrophy)
- Surgical scars (open/laparoscopy)
- Hepatomegaly + splenomegaly from: Extramedullary Haematopoiesis, Fe Deposition within liver, Liver cirrhosis and Portal HTN
CHEST
- In CCF?
- Apex beat displaced?
- Flow murmur
OTHERS
- Signs of CLD
- Signs of hypothyroidism
- Screen visual acuity
- Tanner staging, if patient allows it.
Thal major vs Thal intermedia VS thal minor patients: transfusion dependence
Thal major patients require regular blood transfusions for severe haemolytic anaemia
- Usually once every 3-4 weeks
- Otherwise becomes very symptomatic
VS Thal intermedia patients who receive transfusions
- ONLY when they are symptomatic or when their Hb level is low
- Symptomatic thal but not requiring transfusion at least during first few years of life
- Patients can survive into second decade of life w/o chronic hypertransfusion therapy
- Subsequently, <6 transfusions per year (usually only needed during illness)
VS Thal minor patients do not require transfusions
Thal major vs Thal intermedia VS thal minor patients: transfusion dependence
Beta-thal major usually presents at 3 to 6 months during the switch from HbF to HbA
Beta-thal intermedia usually presents >18 months of age
Alpha-thal intermedia patients usually present at birth or soon after birth, as alpha chains are needed for both HbF, HbA and HbA2
What are the clinical features of chronic haemolytic anaemia?
- Pallor
- Jaundice (“lemon-yellow” jaundice of unconjugated hyperbilirubinaemia)
- Decreased effort tolerance (from anaemia) – fatigue, postural giddiness, SOB, chest pain, palpitations
- Decreased growth (due to increased caloric requirements of erythropoiesis, and endocrine effects of iron overload)
- Cardiac dilatation and failure if untreated (rarely untreated nowadays)
What are the clinical features of extramedullary haematopoeisis?
Skeletal changes secondary to expansion and invasion of erythroid bone marrow
- Frontal bossing
- Maxillary hypertrophy
- “Hair-on-end” Skulls radiographic appearance of skull bones due to widening of diploic spaces
Hepatomegaly
- Later in life, iron overload results in liver cirrhosis (small and non-palpable)
Splenomegaly
- Splenomegaly may result in hypersplenism – worsens anaemia or causes decrease in other cell lines 🡪 warranting splenectomy
- Look for scar of splenectomy – no palpable spleen
What are the investigations required for patients with thalassemia?
Full Blood Count:
- MCHC Anaemia w/ ↑ RCC & normal RDW
- Other cell lines may be affected by hypersplenism; leucopaenia, thrombocytopaenia
Peripheral Blood Film
- Microcytic hypochromic RBCs
- Target cells
- Evidence of intravascular haemolysis – fragments
HbH inclusion bodies on Brilliant Cresyl Blue stain
↑ Reticulocyte-count
- ↑ LDH – marker for cellular turnover
- ↓ Haptoglobin & Hemopexin: markers for INTRAVASCULAR haemolysis
Liver Function Test
- ↑ Unconjugated Br – Indirect bilirubin
- +/- Transaminitis – in CLD / cirrhosis 2’ to iron overload
Hb Electrophoresis – DIAGNOSTIC for Beta Thal
Genotyping
- DIAGNOSTIC for Alpha Thal (and Beta Thal, but not 1st line)
- Deletion mutation in alpha-thal – most commonly the Southeast Asian mutation in Singapore
- Point mutation in beta-thal
Serum Ferritin
- Assess need for Fe Chelation Therapy
- Sign of iron overload: serum ferritin will be increased
- Start iron chelation therapy when serum ferritin > 1000mcg/L
What are the Hb electrophoresis results in patients with beta thal?
↑ HbA2 % (to 3.5-7% from normal of <3%)
↑ HbF % (greater increase in beta-thal major than beta-thal-minor)
↓ HbA %
What are the Hb electrophoresis results in patients with alpha thal?
↓ HbA, ↓ HbA2, ↓ HbF
HbH band seen in HbH thalassaemia
Such findings can point to a myriad of diseases causing ↓Hb other than Alpha Thal.
Hence Dx of Alpha thal CANNOT be done via electrophoresis
How can transfusion reactions be reduced?
Can be reduced by methods such as using leucocyte filter during transfusion, or giving pre-transfusion medications e.g. hydrocortisone
If filter and meds not effective – transfuse washed cells (WBCs removed from packed cells) but more expensive, and need to do GXM for patient 2 days before each transfusion
What are the downsides of using Desferrioxamine/ Deferoxamine (Desferal) as an iron chelator?
☹ S/E: ototoxicity, ophthalmotoxicity, anaphylaxis
- Need to monitor vision and hearing
- Need to ask about hearing loss / BOV in Hx
☹ Problems with compliance as it has to be injected (Administered via slow subcutaneous infusion pumps at night)
What are the benefits and downsides of using Deferiprone as an iron chelator?
😊 Better in ↓ cardiomyopathy compared to desferrioxamine – consider starting when patients start to have bad Fe deposition in the heart
Not proven to be comparable to desferrioxamine as monotherapy – most patients are on combined therapy with both desferrioxamine and deferiprone
☹ Limitations: high cost; 0.5% risk of agranulocytosis – need to check FBC weekly for first year after starting
What do you need to monitor for if patients are started on iron chelation therapy?
- Serum ferritin – to monitor compliance + efficacy of Mx
- FBC if giving deferiprone
- Vision (Snellen & Ishihara) & Hearing Screening if giving desferrioxamine
- LFTs (for cirrhosis resulting from iron overload)
- MRI T2 star for heart and liver once yearly (monitor iron deposition)
What are the indications of splenectomy in patients with thalassaemia? What do they require before splenectomy?
Indication – ↑ in RBC transfusion requirement by ≥50 % over 1 year
Should receive vaccinations against encapsulated bacteria before splenectomy. In particular: H. influenzae, Strep pneumoniae, Neisseria meningitidis
Prophylactic penicillin (long-term therapy)
What endocrinopathies do you need to screen for in patients with thalassaemia?
Follow up investigations: Ca/Mg/PO4 (for hypoPTH), TFT, CBG, urine glucose, OGTT
- Screening for diabetes: early diagnosis and good control
- Screening for hypothyroidism
Yearly assessment of growth and pubertal status: bone age; if >14 years old, tests to screen hypothalamus-pituitary-gonadal axis e.g. testosterone/oestrogen, LH, FSH
Close monitoring of pubertal development and referral for appropriate endocrinological treatment for Hypogonadism
Sideroblastic anaemias are inherited or acquired disorders characterized by a refractory anaemia, a variable number of hypochromic cells in the peripheral blood, and ______________ in the bone marrow.
The presence of ______________ is the diagnostic feature of sideroblastic anaemia. There is accumulation of iron in the mitochondria of erythroblasts owing to disordered haem synthesis forming a __________________ that can be seen with Perls’ reaction.
Ineffective haem synthesis is responsible for the microcytic hypochromic cells.
excess iron and ring sideroblasts;
ring sideroblasts;
ring of iron granules around the nucleus
What are the causes of sideroblastic anaemia?
Primary cause: inherited as an X-linked disease transmitted by females.
Acquired causes include myelodysplasia (most common), myeloproliferative disorders, myeloid leukaemia, drugs (e.g. isoniazid), alcohol misuse and lead toxicity. It can also occur in other disorders such as rheumatoid arthritis, carcinomas, megaloblastic and haemolytic anaemias.
