Case 11 - Anaemia Flashcards
What is anaemia?
Decrease in the quantity of circulating red blood cells represented by a reduction in haemoglobin concentration (Hb), haematocrit (Hct), or RBC count.
- What determines if anaemia is microcytic, normocytic, and macrocytic?
- What are the normal values?
MCV - average volume of RBC
- 80–100 fL
- What is microcytic anaemia?
- What is the mechanism?
- RBC too small
- MCV: <80fL
- Insufficient haemoglobin production
- What is normocytic anaemia?
- What is the mechanism?
- RBC normal
- MCV: 80-100fL
- Decreased blood volume and/or decreased erythropoiesis
- What is macrocytic anaemia?
- What is the mechanism?
- RBC too big
- MCV: >100fL
- Insufficient cell production and/or maturation
What are the symptoms of anaemia
- Tiredness
- Shortness of breath
- Headaches
- Dizziness
- Fatigue
- Loss of appetite
- Muscle cramps
- Worsening of angina pectoris
- Weight loss
- Conjunctival pallor (also lips, nail beds)
- Koilonychia
- Brittle nails, hair loss
- What type of anaemia is iron deficiency?
- What are the causes?
- Microcytic
- Menorrhagia, pregnancy, low birth weight (neonates), cow’s milk (infants), GI bleeds (due to GI tract cancer, oesophagitis and gastritis), IBD,
What are the symptoms of iron deficiency?
- Signs and symptoms of anaemia
- Koilonychia: specific for IDA
- Sore or smooth tongue – glossitis
- Angular cheilitis
- Pica: specific for IDA
What are the investigations for iron deficiency anaemia?
- Decreased haemoglobin and MCH
- Decreased haematocrit
- Lower MCV – microcytic
- Lower mean corpuscular haemoglobin – hypochromic
- Increased red cell distribution width – differentiates IDA from anaemia of chronic disease and thalassemia where RDW is normal
- Decreased serum ferritin
- OGD: GI malignancy
What are the causes of microcytic anaemia?
TAILS -
- T: Thalassaemia
- A: Anaemia of chronic disease (later phase)
- I: Iron deficiency anaemia
- L: Lead poisoning
- S: Sideroblastic anaemia
What differentiates IDA from anaemia of chronic disease and thalassemia?
RDW -
- Increased in IDA
- Normal in anaemia of chronic disease and thalassemia
How to treat IDA?
- Dietary modification: increase consumption of iron rich diets
- Ferrous sulphate - 200mg, 3 TDS: 3-6 months (65 mg iron)
- Blood transfusion: severe anaemia
- Treat underlying cause:OCPs for menorrhagia
What are the SE for ferrous sulphate tablets?
- GI discomfort
- Nausea
- Constipation
- Black discolouration of stool
What confirms IDA?
Serrum ferritin <15 micrograms/L
What does IDA blood film show?
Small (microcytic) and pale (hypochromic) cells.
What is sideroblastic anaemia?
Iron trapping inside the mitochondria due to increasdi iron absorption or inefficient erythropoiesis.
When to consider sideroblastic anaemia?
Microcytic anaemia not responding to iron
What are the causes of sideroblastic anaemia?
- Congenital (rare and X-linked)
- Myeloproliferative/myelodysplastic disease – caused by bone marrow failure
- Chemotherapy, anti-TB drugs,
- Irradiation
- Alcohol use disorder
- Lead poisoning
What are the investigations of sideroblastic anaemia?
- Iron studies: ↑ferritin and iron and transferrin saturation
- Blood film: hypochromic, microcytic anaemia,
- Bone marrow staining - sideroblasts
How to treat sideroblastic anaemia?
- Treat the cause.
- Pyridoxine (vitamin B6) ± repeated blood transfusions for severe anaemia.
- What is thalassemia?
- What are the 2 different types?
- Faulty globin chain synthesis resulting in defective haemoglobin, which can lead to anaemia.
- Normal haemoglobin consists of 2 alpha and 2 beta globin chains, therefore Alpha and beta
- Which thalassemia is more common in Mediterranean descent?
- Which thalassemia is more common in Asian and African descent?
- Beta
- Alpha
- Which chromosome is affected in beta thalassemia?
- What are the 2 different types of beta thalassemia?
- Chromosome 11
- Beta thalassemia minor (trait): one defective allele: Heterozygous carrier state.
- Beta thalassemia major (Cooley’s anaemia): two defective alleles: Homozygous carrier state
What are the signs and symptoms of thalassemia?
- Skeletal deformities – high forehead, prominent zygomatic bones and maxilla
- Hepatosplenomegaly
- Growth retardation
- Jaundice
- Fatigue
What are the 4 different types of alpha thalassemia?
- All 4 genes are deleted, death is in utero (Bart’s hydrops fetalis)
- HbH occurs if 3 genes are deleted, with moderate anaemia and features of haemolysis.
- 2 genes deleted: asymptomatic carrier state
- 1 gene deleted: normal clinical state.
What are the investigations for thalassemia?
- Blood sample: Microcytic anaemia, low RBC count and high RDW
- Increased indirect bilirubin and reticulocytes
- Blood smear
- Confirmatory tests: Hb -electrophoresis, abnormal pattern
What is the treatment for thalassemia?
- Healthy diet + folate supplement
- Life-long erythrocyte transfusions: can lead to iron overload
- What iron overload lead to?
- What is the treatment?
- What are the SE of treatment?
- Cardiac iron overload, hypothyroidism, hypocalcaemia, and hypogonadism.
- Iron-chelators: desferasirox and desferrioxamine
- SE: deafness, retinal damage
What are the different causes of normocytic anaemia?
- Sickle cell anaemia
- Infections
- Blood loss
- Haemolytic anaemia
- Iron deficiency anaemia (early phase)
- Anaemia of chronic disease (early phase)
What are the signs of acute blood loss?
Clinical signs of hypovolaemic shock, e.g. pale and clammy, weak pulse, hypotensive, decreased level of consciousness
What are the causes of acute blood loss for women of child-bearing age?
Menorrhagia
What is anaemia of chronic disease?
- Anaemia due to chronic inflammation
What are the causes of anaemia of chronic disease?
- Inflammation: rheumatoid arthritis, lupus
- Malignancy: lung cancer, breast cancer
- Infection: TB
What investigations are done anaemia of chronic disease?
- FBC: normocytic anaemia (early phase), microcytic anaemia (late phase)
- Iron studies: elevated serum ferritin
What is the treatment for anaemia of chronic disease?
Treat underlying cause
What are the causes of macrocytic anaemia?
- Vitamin B12 deficiency
- Folate deficiency
- Fanconi anaemia
- Diamond-Black fan anaemia
- Haemolytic anaemia: elevated reticulocytes count (>2%)
What is the role of vitamin B12 (cobalamin)?
Essential role in enzymatic reactions responsible for red blood cell (RBC) formation
What are the causes of vitamin B12 deficiency anaemia?
- Pernicious anaemia
- Atrophic gastritis
- Surgical: ileal resection, gastric surgery
- B12 deficient diet (without fish, eggs, meat, milk)
- Pregnancy
- Coeliacs, Crohns
What are the symptoms of vitamin B12 deficiency anaemia?
- Symptoms of anaemia
- Neuropathy: peripheral (tingling and numbness, pins and needles, coldness),
- Pre-hepatic jaundice
- Glossitis – inflammation of tongue
- Stomatitis (angular cheilosis)
What autoantibodies cause pernicious anaemia?
- Intrinsic factor antibody
- Gastric parietal cell antibody
What investigations are done in vitamin B12 deficiency anaemia?
- Decreased Hb
- Raised MCV – macrocytic
- Decreased reticulocytes
- Serum B12 (↓),
- Intrinsic factor antibodies and anti-parietal cells antibodies
What is the treatment for vitamin B12 deficiency anaemia?
- IM supplementation of vitamin B12
- Prevent future vitamin B12 deficiency
Why might folate deficiency anaemia take 3 months to present?
The liver can store folate for up to three months
What are the causes of folate deficiency anaemia?
- Nutritional – poor diet (folate comes from leafy green vegetables, fruit), goats milk only
- Chronic alcohol intake,
- Coeliac disease, IBD, jejunal resection (folate is absorbed here)
- Pregnancy
- Drug related – methotrexate (folate antagonist), phenytoin, trimethoprim
What are the symptoms of folate deficiency anaemia?
- Signs of anaemia
- Glossitis
- Signs of B12 deficiency - but often only sensory peripheral neuropathy.
What can be seen in investigation for folate deficiency anaemia?
Raised MCV
What is the treatment for folate deficiency anaemia?
- Oral folate for 4 months
- Nutritional counselling to increase folate intake
- What is haemolytic anaemia?
- Why type of anaemia is it?
- Characterised by the breakdown of RBC
- Normocytic
What are the 2 key features of haemolytic anaemia?
- ↑(>2%) reticulocyte count
- Jaundice with unconjugated hyperbilirubinemia
What do the investigations show for haemolytic anaemia?
- Elevated indirect bilirubin
- Elevated Lactate dehydrogenase
- Elevated reticulocytosis
- Decreased haemoglobin
- Elevated WBC, LDH
- What is Coombs test?
- What do the results mean?
- Detects antibodies on RBCs surface (direct test) or in patient’s serum (indirect test).
- Autoimmune (positive Coombs test)
- Non-autoimmune anaemia (negative Coombs test).
What type of genetic disorder is thalassemia?
Autosomal recessive
What is hereditary spherocytosis?
Haemolytic anaemia
How does hereditary spherocytosis present?
Jaundice, anaemia, splenomegaly
What type of genetic disorder is hereditary spherocytosis?
Autosomal dominant
How to treat hereditary spherocytosis?
- Folic acid
- Then try splenectomy
What is sickle cell disease?
Autosomal recessive disease, from substitution of glu → val in the β-Hb chain
How many sickle cell anaemia alleles do sickle-cell anaemia patients carry?
- 2 alleles
- Homozygous
How many sickle cell anaemia alleles do sickle-cell trait patients carry?
- 1 allele
- Heterozygotes
What is the pathophysiology of sickle cell anaemia?
HbS polymerises when deoxygenated, forming sickle RBCs which are fragile and haemolyse, as well as block small vessels. Triggered by certain events.
What are the symptoms of sickle cell trait?
Asymptomatic
What are the symptoms of sickle cell disease?
Often present as complications (sickle cell crisis):
- Acute symptom of vaso-cclusive/painful crises
- Splenic sequestration crisis
- Aplastic crisis
What is splenic sequestration crisis in sickle cell anaemia?
- RBC blocking blood flow within the spleen
- Acute left upper quadrant pain
- Can lead to a severe anaemia and circulation collapse (hypovolaemic shock)
What is aplastic crisis in sickle cell anaemia?
- Temporary loss of new RBC creation
- Due to parvovirus B19
- Usually self-limiting <2wks
- Transfusion may be needed.
- What is vaso-cclusion/painful crisis?
- How does it present?
- Sickle shaped blood cells clogging capillaries resulting in ischaemia
- Episodes of severe deep bone pain
- Dactylitis: swollen dorsa of hands and feet
- Acute chest syndrome: chest pain, respiratory distress
- Stroke
- Infarctions of any organ
What investigations are done in sickle cell disease?
- FBC: ↑reticulocytes, ↑bilirubin
- Film: sickle cells
- Microcytic, low MCV: due to the very small diameter of the sickle shaped red blood cells.
- Hb electrophoresis: Confirms diagnosis and differentiates between disease and trait.
How to treat sickle cell disease?
- Keep patient warm, hydrated, well-nourished and rested.
- Hydroxycarbamide (hydroxyurea – turns on the production of foetal haemoglobin genes HbA and it should be above 15%)
- Bone marrow transplant may be curative but controversial.
What are other complications of sickle cell disease?
- Increased vulnerability to infection (pneumonia and meningitis)
- Lung: Pulmonary hypertension
- Heart: MI, HF, cardiomegaly
- Eye:retinal occlusion
- Kidney: glomerulonephritis
- Skeletal: osteoporosis
Which 2 enzyme defects can led to haemolytic anaemia?
- G6PD deficiency: X-linked recessive disease
- Pyruvate kinase deficiency: autosomal recessive disease
What are the different acquired haemolytic condition?
- Autoimmune haemolytic anaemia
- Wilsons disease: Copper deficiency
- Drugs, infections, toxins
What are the 2 types of autoimmune haemolytic anaemia?
Warm and cold depending on the thermal range across which the antibody is active.
- What is cold AIHA?
- What are the causes?
- IgM mediated, binds to RBCs at low temp
- Idiopathic or secondary to EBV infection, mycoplasma pneumonia, UC
What are the signs of cold AIHA?
- Pallor
- Fatigue
- Weakness
- Acrocyanosis – cyanosis of the extremities
What are the investigations of both AIHA?
- Lab tests signs of haemolysis
- Peripheral blood smear: spherocytes, polychromasia
- Coombs test: positive
How to treat cold AIHA?
- Mild disease: avoid cold exposure
- Moderate disease: immunosuppressive therapy with rituximab
- What is warm AIHA?
- What are the causes?
- IgG-mediated, binds to RBCs at body temperature (37deg)
- Lymphoproliferative disease (chronic lymphocytic leukaemia, lymphoma)
- Drugs – cephalosporins, penicillin’s
- Autoimmune disease – SLE, ovarian teratoma
What are the signs of warm AIHA?
- Often more severe and more acute than cold AIHA
- Signs of anaemia (pallor, fatigue, weight loss)
How to treat warm AIHA?
- Initially glucocorticoids
- If glucocorticoids unsuccessful then splenectomy
- How to test for SLE?
- When is it likely to develop?
- What is a frequent complication of SLE?
- Check for anti-DNA antibodies
- After AIHA
- Immune thrombocytopenia (ITP)
