Haematology Flashcards
Types of macrocytic anaemia
Megaloblastic and non-megaloblastic
Definition of macrocytic anaemia
Anaemia associated with a high MCV of erythrocytes (>100fl in adults)
Causes of megaloblastic macrocytic anaemia
Vitamin b12 deficiency
Folate deficiency
Drugs: methotrexate, hydroxyurea, azathioprine, zidovudine
Causes of non-megaloblastic macrocytic anaemia
Alcohol excess Liver disease Myelodysplasia Multiple myeloma Hypothyroidism Haemolysis (reticulocytosis) Drugs: tyrosine kinase inhibitors: imatinib, sunitinib
Causes of vitamin b12 deficiency
Decreased absorption:
- post gastrectomy
- pernicious anaemia
- terminal ilealresection or disease (crohns, bacterial overgrowth, pancreatic insufficiency, fish tapeworm, metformin, omeprazole)
Decreased intake (vegans)
Abnormal metabolism
- congenital tanscobalamin II deficiency
- inactivation of b12 by nitrous oxide
Causes of folate deficiency
Decreased intake
- alcoholics
- elderly
- anorexia
Increased demand
- pregnancy
- lactation
- malignancy
- chronic inflammation.
- chronic haemolysis
- exfoliative dermatitis
Decreased absorption
- jejunal disease (coeliac disease)
- tropical sprue
Drugs
- phenytoin
- trimethoprim
- methotrexate
Examination signs of anaemia
Pallor
Tachycardia
May be signs of cause: e.g. Malnutrition, jaundice, hypothyroid appearance
Signs of pernicious anaemia
Lemon-tinted skin (mild jaundice)
Glossitis (red sore tongue)
Angular stomatitis (cheilitis)
Weight loss
Signs of vitamin b12 deficiency
Peripheral neuropathy Ataxia Subacute combined degeneration of the spinal cord Optic atrophy Dementia
What is subacute combined degeneration of the spinal cord?
= degeneration of dorsal and lateral columns of the spinal cord causing loss of joint and position sense, ataxia and UMN weakness.
Partially or completely relieved by restoring vitamin b12 levels.
What is pernicious anaemia?
Autoimmune damage to gastric parietal cells causing atrophic gastritis and consequent decreased production of intrinsic factor needed for b12 absorption in the terminal ileum.
Pernicious anaemia can be associated with other autoimmune diseases (e.g. Vitiligo, hypothyroidism)
Management of pernicious anaemia
IM hydroxycobalamin (3x wkly for 2 weeks, then every 3 months for life)
Complications of pernicious anaemia
Increased risk of gastric cancer
Definition of aplastic anaemia
Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia)
Causes of aplastic anaemia
- Idiopathic (>40%) - may be due to destruction or suppression of the stem cell by autoimmune mechanisms
- Acquired
- Drugs (chloramphenicol, gold, alkylating agents, antiepileptics, sulphonamides, methotrexate, nifedipine)
- Chemicals (DDT, benzene)
- Radiation
- Viral infection (B19 parvovirus, HIV, EBV)
- paroxysmal nocturnal haemoglobinuria - Inherited
- Fanconi’s anaemia
- Dyskeratosis congenita (associated with reticulated hyperpigmented rash, nail dystrophy and mucosa leukoplakia)
What is Fanconi’s anaemia
Rare autosomal recessive or X-linked disorder, caused by an error in DNA repair.
Characterised by familial aplastic anaemia, short stature, abnormality of thumbs, café au lait spots, microcephaly, hypogonadism and renal tract defects.
History findings of aplastic anaemia
Slow (months) or rapid (days) onset
Anaemia: Tiredness, lethargy, dyspnoea
Thrombocytopaenia: Easy bruising, bleeding gums, epistaxis
Leukopaenia: Increased frequency and severity of infections
Examination findings of aplastic anaemia
Anaemia: Pale
Thrombocytopaenia: Petechiae, bruises
Leukopaenia: Multiple bacterial or fungal infections. No hepatomegaly, splenomegaly or lymphadenopathy
Management of aplastic anaemia
- Treat the underlying cause (e.g. drugs withdrawal)
- Supportive: blood & platelet transfusions, antibiotics for infections, consider antibiotic prophylaxis
- Patients with severe AA: allogeneic haematopoietic stem cell transplant (curative); immunosuppressive therapy (combined use of: anti-thymocyte globulin, cyclosporine, and corticosteroids, with or without GCSF) –> for patients who don’t have a sibling matched donor or who are >45 (increased chance of graft vs host)
Definition of haemolytic anaemia
Premature erythrocyte breakdown causing shortened erythrocyte life span (<120 days) and anaemia
Classification of causes of haemolytic anaemia
Hereditary - Membrane defects - Metabolic defects - Haemoglobinopathies Acquired - Autoimmune - Isoimmune - Drugs - Trauma - Infection - Paroxysmal noctural haemoglobinuria
Hereditary causes of haemolytic anaemia
Membrane defects - Hereditary spherocytosis - Elliptocytosis Metabolic defects - G6PD deficiency - Pyruvate kinase deficiencies Haemoglobinopathies - Sickle cell disease - Thalassaemia
Acquired causes of haemolytic anaemia
Autoimmune
- Warm or cold antibodies attach to erythrocytes causing intravascular haemolysis and extravascular haemolysis
Isoimmune
- Transfusion reaction
- Haemolytic disease of the newborn
Drugs
- Penicillin
- Quinine (through formation of drug-antibody-erythrocyte complexes)
Trauma
- Microangiopathic haemolytic anaemia caused by red cell fragmentation in abnormal microcirculation (e.g. haemolytic uraemic syndrome, DIC, malignant hypertension, pre-eclampsia)
- Artificial heart valves
Infection
- Malaria, sepsis
Paroxysmal nocturnal haemoglobinuria
- Increased complement-mediated lysis caused by decreased synthesis of protein cellular anchor of complement-degrading proteins
Examination findings of haemolytic anaemia
Pallor (anaemia), jaundice, hepatosplenomegaly
‘warm antibodies’
IgG agglutinate erythrocytes at 37°C
Associated with SLE, lymphomas or methyldopa
‘cold antibodies’
IgM agglutinate erythrocytes in at room temperature or colder.
Associated with infections (e.g. mcyoplasma, EBV) or lymphomas.
What is G-6PD deficiency?
(X-linked)
G-6PD is important in maintaining glutathione in reduced state. Deficiency results in susceptibility to oxidative stress (e.g. precipitated by sulphonamides, nitrofurantoin, dapsone, fava beans).
What is hereditary spherocytosis?
= autosomal dominant condition where decreased spectrin (structural membrane protein) causes decreased deformability of erythrocytes.
Investigations for haemolytic anaemia
- Blood: FBC (decreased Hb, increased reticulocytes, increased MCV, also increased unconjugated bilirubin, decreased haptoglobin), U&E, folate
- Blood film:
- Leucoerythroblastic picture
- Macrocytosis
- Nucleated erythrocytes
- Reticulocytes
- Polychromasia
Identifies specific abnormal cells, such as spherocytes, elliptocytes, sickle cells, fragmented erythrocytes, malarial parasites, erythrocyte Heinz bodies (denatured Hb, stained with methyl violet seen in G-6PD deficiency) - Urine: Increased urobilirubinogen. If there is haemoglobinuria and haemosiderinuria.
- Direct Coombs’ test: Identifies erythrocytes coated with antibodies (agglutinins) using antihuman globulin.
- Osmotic fragility test or Spectrin mutation analysis: to identify membrane abnormalities
- Ham’s test: Lysis of erythrocyte in acidified serum in paroxysmal nocturnal haemoglobinuria. More recently, red cells are analysed using monoclonal antibodies to the GPI-anchored proteins (CD55 and CD59) and flow cytometry.
- Hb electrophoresis or enzyme assays
- Bone marrow biopsy (rarely required): erythroid hyperplasia
Definition of microcytic anaemia
Anaemia associated with low MCV (<80 fl)
Causes of microcytic anaemia
- Iron-deficiency = commonest cause
- Blood loss (e.g. GI tract, urogenital tract, hookworm infection)
- Decreased absorption: small bowel disease, post-gastrectomy
- Increased demands: growth, pregnancy
- Decreased intake: vegans - Anaemia of chronic disease: often normocytic, but may be microcytic
- Thalassaemia
- Sideroblastic anaemia: Abnormality of haem synthesis. Can be inherited (X-linked), or secondary to alcohol, drugs (e.g. isoniazid, chloramphenicol), lead, myelodysplasia
What is anaemia of chronic disease?
Occurs in chronic inflammatory/autoimmune disease, chronic infections (e.g. TB/infective endocarditis), malignancy, chronic renal failure.
Serum ferritin is normal or increased.
It may be caused by decreased RBC survival, decreased erythropoietin response to the anaemia, decreased iron release from bone marrow to erythroblasts.
