Haematology Flashcards
What is anaemia?
Low concentration of haemoglobin in blood due to reduced number of red blood cells
What are the specific Hb cut-offs for anaemia in males and females?
Males: Hb less than 130 g/l
Females: Hb less than 120 g/l
Pregnant females: Hb less than 110 g/l
What are the two main categories of aetiology for anaemia?
Reduced production of red blood cells (ineffective erythropoiesis), causing reduced reticulocytes
Increased destruction of red blood cells (haemolysis, bleeding), causing increased reticulocytes
List clinical features of anaemia
Tiredness, fatigue Breathlessness Pallor Headache Palpitations Syncope
What investigations would you do for anaemia?
FBC - red cells, white cells, platelets, reticulocytes
Mean cell volume (distinguish between microcytic and macrocytic)
Blood film
Bone marrow aspirate
What is microcytic anaemia?
Reduced Hb production that results in small, hypochromic cells
Defined by reduced MCV
List aetiology for microcytic anaemia
Haem deficiency: iron deficiency, anaemia of chronic disease, defective porphyrin synthesis
Globin deficiency: thalassaemia
Sideroblastic anaemia
What is macrocytic anaemia?
Delayed nuclear maturation of erythroblasts due to defective DNA [megaloblastic macrocytic]
Normoblastic bone marrow [non-megaloblastic macrocytic]
Defined by raised MCV
List aetiology for macrocytic anaemia
Megaloblastic: B12/folate deficiency, enzyme deficiency, myelofibrosis
List aetiology for normocytic anaemia (normal MCV)
Acute blood loss Anaemia of chronic disease Bone marrow failure (esp if leukopenia/thrombocytopenia) Renal failure Hypothyroidism Pregnancy
List aetiology/risk factors for iron-deficiency anaemia
Dietary insufficiency
Menorrhagia
Malabsorption (Coeliac)
GI bleeding
List clinical features of iron-deficiency anaemia
Spoon-shaped nails (koilonychia) Glossitis Angular cheilitis Brittle hair Features of microcytic anaemia
What investigations would you do for iron-deficiency anaemia?
FBC
Blood film: hypochromic microcytic cells, anisocytosis (varied shape), poikilocytosis (varied size)
Reduced ferritin, iron, MCV
Endoscopy if suspected GI bleeding
Outline management of iron-deficiency anaemia
Treat causes
Oral ferrous sulphate
IV iron if intolerant
List aetiology/risk factors for anaemia of chronic disease
Chronic infection (TB, osteomyelitis) Vasculitis Rheumatoid arthritis IBD SLE Polymyalgia rheumatica Malignancy
What investigations would you do for anaemia chronic disease?
Normal/raised ferritin Reduced serum iron Increased hepcidin (inhibits iron absorption)
Outline management of anaemia of chronic disease
Treat underlying cause
EPO injections stimulate RBC production
What is sideroblastic anaemia?
Refractory anaemia usually unresponsive to iron therapy
List aetiology/risk factors for sideroblastic anaemia
Inherited X-linked disease Myelodysplasia Myeloproliferative disease Myeloid leukaemia Drugs, alcohol
What investigations would you do for sideroblastic anaemia?
Blood film: hypochromic cells, ring sideroblasts
Increased iron absorption + loading +- haemosiderosis
Outline management of sideroblastic anaemia
Treat cause
Pyroxidine (B6 supplement)
Transfuse if severe
Describe MCV, serum iron, serum ferritin and serum transferrin in iron deficiency anaemia
Reduced MCV
Reduced iron
Reduced ferritin
Increased transferrin
Describe MCV, serum iron, serum ferritin and serum transferrin in anaemia of chronic disease
Variable MCV
Reduced iron
Normal/increased ferritin
Normal transferrin
What is pernicious anaemia?
B12 deficiency caused by autoimmune destruction of gastric parietal cells, causing reduced absorption of B12
List clinical features of pernicious anaemia
Symptoms of anaemia Lemon-yellow skin Polyneuropathy Dementia Psychosis Subacute cord degeneration (posterolateral) Paraesthesiae
What investigations would you do for pernicious anaemia?
Blood film: hypersegmented polymorphs, oval macrocytes
Reduced B12
Anti- parietal cell/intrinsic factor antibodies
Outline management of pernicious anaemia
Treat other causes (diet, malabsorption)
Oral B12 supplements
IM hydroxycobalamin
Where is B12 absorbed?
Ileum
Where is folate absorbed?
Duodenum
Jejunum
List aetiology/risk factors for folate deficiency
Poor diet
Increased demand (pregnancy, haemodialysis, malignancy)
Alcohol excess
Anti-folate agents (phenytoin, methotrexate, anti-epileptics, trimethoprim)
What investigations would you do for folate deficiency?
Blood film: megaloblastic
Reduced folate
GI biopsy
Outline management of folate deficiency
Folic acid
Treat causes
List aetiology of macrocytic non-megaloblastic anaemia
Pregnancy Alcohol Reticulocytosis (e.g. compensated haemolysis) Cirrhosis Hypothyroidism Aplastic anaemia Drugs (hydroxycarbamide, azathioprine)
What is aplastic anaemia?
Stem cell disorder leading to pancytopenia and hypocellular marrow
List aetiology/risk factors for aplastic anaemia
Autoimmunity Idiopathic Infection Inherited (Fanconi anaemia) Drugs (chloramphenicol, gold, penicillamine, anticonvulsants) Chemicals (toluene, glue, benzene) Viruses
What investigations would you do for aplastic anaemia?
FBC: pancytopenia
Marrow aspirate: fatty infiltrates
Outline management of aplastic anaemia
Treat low blood count - transfusion
Antibiotics if infection
Allogenic marrow transplant if under 50 yo
Immunosuppression (ciclosporin)
What is haemolysis?
Premature destruction of red blood cells before their lifespan (before 120 days)
What are the two different types/classifications of haemolysis?
Intravascular (occurs in circulation with spillage of abnormal RBC products)
Extravascular (occurs in reticuloendothelial system (liver, spleen, marrow) with excess normal RBC products)
What abnormal products are produced in intravascular haemolysis?
Free haemoglobin Methaemalbuminaemia Haemoglobinuria Haemosiderinuria Urobilogenuria
List aetiology/risk factors for haemolysis
Inherited (spherocytosis, thalassaemia, sickle-cell, G6P deficiency)
Acquired (autoimmunity, alloimmunity, infection, drugs (penicillin, quinine)
List clinical features of haemolysis
Jaundice Hepatosplenomegaly Gallstones Leg ulcers Dark urine
What investigations would you do for haemolysis?
FBC, reticulocytes Bilirubin LDH Urinary urobilogen Blood film Direct antiglobulin Coomb's test Indirect antiglobulin Coomb's test
What would you typically see on a blood film in haemolysis?
Increased reticulocytes - polychromasia, macrocytosis
Schistocytes/sickle cell/abnormal cells/eliptocytes/Heinz bodies
What is the direct antiglobulin Coomb’s test?
Test for autoimmune haemolytic anaemia
Identifies red cells coated/bound with antibody/Complement; +ve agglutination indicates immune cause of haemolysis
What is the indirect antiblobulin Coomb’s test?
Detects antibody produced against free/unbound RBC
Used in prenatal testing and before blood transfusions
What type of haemolysis occurs in autoimmune haemolytic anaemia?
Extravascular - antibody produced against RBC in reticuloendothelial system
What is the difference between “warm” and “cold” autoimmune haemolysis?
Warm: IgG binds to RBC better at 37’C
Cold: IgM binds to RBC better at low temperature
List clinical features of autoimmune haemolysis
Anaemia symptoms Jaundice Splenomegaly Infection Worse symptoms in cold/hot
Outline management of autoimmune haemolysis
Warm: prednisolone, azathioprine, splenectomy
Cold: keep warm, chlorambucil, rituximab
Blood transfusion may be considered in both
What is microangiopathic haemolytic anaemia?
Mechanical disruption of RBC’s in circulation (essentially a type of intravascular haemolysis)
List aetiology/risk factors for microangiopathic haemolytic anaemia
Haemolytic uraemic syndrome (E coli 0157)
Thrombotic thrombocytopenic purpura
DIC
Pre-eclampsia
Outline management of microangiopathic haemolytic anaemia
Treat cause
Blood transfusion
Plasmapharesis
What is hereditary spherocytosis?
Autosomal dominant defect of RBC membrane, causing functional impairment of RBC’s, including inability to pass through spleen (extravascular haemolysis)
List clinical features of hereditary spherocytosis
Jaundice at birth Anaemia symptoms Splenomegaly Leg ulcers Pigment stones
What investigations would you do for hereditary spherocytosis?
-ve direct Coomb’s test
Fragile RBC’s, spherocytes on blood film
Outline management of hereditary spherocytosis
Splenectomy
Prophylactic penicillin
What is glucose-6-phosphate deficiency?
X-linked G6P deficiency affects RBC production and destruction
List aetiology/risk factors for G6P deficiency
Africans, Mediterraneans, Eastern Europeans
Reduced glutathione (causes oxidative crisis)
Broad beans
What investigations would you do for G6P deficiency?
Blood film: bite cells, blister cells, Heinz bodies
Outline management of G6P deficiency
Blood transfusion Avoid precipitants (sulfonamides, aspirin, henna)
What are all the types of blood transfusion that can be given?
Whole blood (rare)
Red cells (for anaemia, blood loss)
Platelets
FFP (clotting factors)
Which antibody mediates an acute transfusion reaction?
IgM within 24 hours
List aetiology/risk factors for acute transfusion reaction
ABO incompatibility Rhesus reaction Anaphylaxis Contamination HLA reactions
List clinical features of acute transfusion reactions
Agitation Fever Hypotension Flushing Pain DIC Breathlessness
Outline management of an acute transfusion reaction
Stop transfusion, check identity + origin of recipient and sample IV fluids Treat complications, maintain ABCDE Antibiotics if contamination Paracetamol Chlorphenamine if anaphylaxis
Which antibody mediates delayed transfusion reaction?
IgG beyond 24 hours
List aetiology/risk factors for delayed transfusion reactions
Alloimmunisation by previoui transfusion/pregnancy
Infection
Iron overload
Graft vs host disease
What molecular units make up all the different types of haemoglobin in a foetus and in adults?
HbF: alpha2-gamma2 HbA: alpha2-beta2 HbA2: alpha2-delta2 HbH: beta4 Barts: gamma4
What is thalassaemia?
Defective synthesis of one globin (alpha, beta) chain causes reduced Hb production and ineffective erythropoiesis
What is the pathophysiology of alpha-thalassaemia?
Deletion of one or both alpha-globin genes on c16
State the configuration of alpha-thalassaemia if one alpha-globin gene is deleted, the type of Hb produced and its clinical sequelae
αα/α-
“alpha-thalassaemia silent”
HbA produced
Mild naaemia
State the configuration of alpha-thalassaemia if two alpha-globin gene is deleted, the type of Hb produced and its clinical sequelae
α-/α- or αα/–
“alpha-thalassaemia trait”
HbA produced
Mild anaemia
State the configuration of alpha-thalassaemia if three alpha-globin gene is deleted, the type of Hb produced and its clinical sequelae
α-/–
“alpha-thalassaemia HbH disease”
HbH disease (either HbH or Barts Hb produced)
Mod-sev anaemia
State the configuration of alpha-thalassaemia if four alpha-globin gene is deleted, the type of Hb produced and its clinical sequelae
4 alpha-globin gene deletions (//-//)
“alpha-thalassaemia major”
Hb Barts produced
Severe anaemia, hydrops fetalis
List clinical features of alpha-thalassaemia
Anaemia Hepatosplenomegaly Jaundice Growth retardation Hb Barts: oedema, cardiac failure, skeletal abnromality, death in utero
What investigations would you do for alpha-thalassaemia?
Blood film: HbH bodies (red cell inclusions), Mexican hat cells, target cells
Outline management of alpha-thalassaemia
Treat significant anaemia
Blood transfusions
Splenectomy
What is the pathophysiology of beta-thalassaemia?
Point mutation of one or both B-globin genes on c11
Excess chains combine with other chains, resulting in more HbA2/HbF
State the configuration of beta-thalassaemia if one beta-globin gene is mutated and its clinical sequelae
ββ+/ββ
“beta-thalassaemia minor”
Asymptomatic/mild anaemia
State the configuration of beta-thalassaemia if two beta-globin gene is mutated and its clinical sequelae
ββ+/β+β+
“beta-thalassaemia intermedia”
Moderate anaemia, splenomegaly, leg ulcers, infection
State the configuration of beta-thalassaemia if all beta-globin gene is mutated and its clinical sequelae
β+/β+
“beta-thalassaemia major”
Severe anaemia, failure to thrive, splenomegaly, bone deformity
What investigations would you do for beta-thalassaemia?
Blood film: hypochromic microcytic cells, nucleated RBC’s, lots of HbF compared to little/no HbA
Outline management of beta-thalassaemia
Fitness, healthy diet
Folic acid supplements
Regular transfusions for B-thalassaemia major
Iron-chelator if overload (desferrioxamine)
Splenectomy