Haematology Flashcards
What is anaemia?
Decrease of haemoglobin in blood below reference level for age and sex of an individual
Can be due to low red cell mass or increased plasma volume
Due to reduced production of RBCs from bone marrow or increased loss or RBCs ie by spleen, liver, bone marrow and blood loss
How are the different types of anaemia classified?
Mean corpuscular volume (MCV) which is average volume of RBCs or size
What are the different types of anaemia?
Hypochromic (pale) microcytic - low MCV
Normochromic normocytic - normal MCV
Macrocytic - high MCV
What occurs to the body in anaemia?
Reduced O2 transport
Tissue hypoxia
Compensatory changes - increased tissue perfusion, increased O2 transfer to tissues, increased RBC production
Pathological consequences - myocardial fatty changes, fatty change in lever, aggravates angina and claudication, skin and nail atrophic changes, CNS cell death (cortex and basal ganglia)
What are the symptoms of anaemia?
Fatigue, headaches, faintness Dyspnoea Angina Anorexia Intermittent claudication Palpitations
What are the signs of anaemia?
May be absent even in severe anaemia Pallor Pale mucous membranes Tachycardia Systolic flow murmur Cardiac failure
How is anaemia diagnosed?
Test to determine whether bone marrow production issue - look at reticulocyte count (reticulocyte count low if is)
If removal then reticulocyte count will be high
Reduction in plasma volume will lead to falsely high haemoglobin seen in dehydration
What type of anaemia is anaemia of chronic disease?
Normocytic
But can be microcytic especially in rheumatoid arthritis and Crohn’s disease
What is anaemia of chronic disease?
Anaemia secondary to chronic disease, bone marrow also affected by chronic disease therefore anaemic
Second most common anaemia
Commonest anaemia in hospital patients
Occurs in individuals with - TB, Crohn’s disease, rheumatoid arthritis, SLE, malignant disease, CKD
These conditions can cause either a shortening of RBC cell life or reducing RBC production
Why does chronic disease cause anaemia?
Decreased release of iron from bone marrow to developing erythroblasts
Inadequate erythropoietin response to anaemia (cytokine which increases RBC production)
Decreased RBC survival
How does anaemia of chronic disease present?
Fatigue, headache, faintness Dyspnoea Angina is pre-existing coronary disease Anorexia Intermittent claudication Palpitations
How is anaemia of chronic disease diagnosed?
Serum iron and total iron-binding capacity low
Serum ferritin normal or raised due to inflammatory process
Serum soluble transferrin receptor level normal
Blood count and film - RBCs normal or microcytic and hypochromic as in RA and Crohn’s
How is anaemia of chronic disease treated?
Treat underlying chronic cause
Erythropoitein effective in raising haemoglobin level - used in anaemia of renal disease and inflammatory disease
Side effects - flu-like symptoms, hypertension, mild risk in platelet count and thromboembolism
What type of anaemia is folate deficiency anaemia?
Megaloblastic anaemia - inhibition of DNA synthesis, RBCs cannot progress onto mitosis causing continuing growth without division
What is folate deficiency anaemia?
Impairment of DNA synthesis resulting in delayed nuclear maturation resulting in large RBCs and decreased RBC production in bone marrow due to lack of green vegetables in diet
What can cause folate deficiency anaemia?
Poor intake - poverty, alcoholics, elderly
Increased demand - pregnancy, increased cell turnover (haemolysis, malignancy, inflammatory disease, renal dialysis)
Malabsorption - coeliac/Crohn’s disease
Antifolate drugs - methotrexate, trimethoprim
Name 5 risk factors for developing folate deficiency anaemia
Elderly Poverty Alcoholic Pregnant Crohn's or coeliac disease
How might folate deficiency anaemia present?
Asymptomatic
Symptoms of anaemia
Glossitis
No neuropathy
How is folate deficiency anaemia diagnosed?
Blood count and film - megaloblastic anaemia, RBCs macrocytic, peripheral film shows oval macrocytes with hypersegmented neutrophil polymorphs with 6/more lobes in nucleus
Serum and RBC folate low
GI investigation - small bowel biopsy to exclude GI disease
Serum bilirubin raised due to ineffective erythropoiesis - increased RBC breakdown
Erythrocyte folate level - indicated reduced body stores
How is folate deficiency anaemia treated?
Treat underlying cause
Folic acid tablets daily for 4 months - never without B12 as well as low B12 may precipitate or worsen subacute combined degeneration of spinal cord
What type of anaemia is haemolytic anaemia?
Normocytic or macrocytic
What is haemolytic anaemia?
Premature breakdown of RBCs before normal lifespan of 120 days
Macrocytic if many young RBCs (larger) due to excessive destruction of old RBCs
What can cause haemolytic anaemia?
Inherited - membranopathies, enzymopathies, haemoglobinopathies
Acquired - autoimmune, infections, secondary to systemic disease
What happens in haemolytic anaemia?
RBCs rapidly destroyed in circulation - haemoglobin released
Initially bound to haptoglobin but soon becomes saturated
Excess free plasma haemoglobin filtered by renal glomerulus and enters urine, small amounts reabsorbed by renal tubules
Haemoglobin broken down in renal tubular cells and deposited in cells as haemosiderin
Reticuloendothelial system also broken down
Shortened survival of RBCs - compensation of increase in RBC production in bone marrow - compensated haemolytic diseases
Bone marrow can increase output by 6-8 times by increasing proportion of cells committed to erythropoiesis and by expanding volume of active marrow
Larger than mature cells, macrocytic, stain with light blue tinge on peripheral blood film
How is haemolytic anaemia diagnosed?
High serum unconjugated bilirubin High urinary urobilinogen High faecal stercobilinogen Splenomegaly Bone marrow expansion Reticulocytosis - increased reticulocytes FBC - reduced Hb Blood film - schistocytes
What are the two different types of marcocytic anaemia?
Megaloblastic - presence of erythroblasts with delayed nuclear maturation because of delayed DNA synthesis - megaloblasts, large, no nuclei
Non-megaloblastic - erythroblasts normal
What can cause megaloblastic anaemia?
Vitamin B12 deficiency
Folate deficiency
What can cause non-megaloblastic anaemia?
Alcohol Liver disease Hypothyroidism Bone marrow failure Bone marrow infiltration Antimetabolite therapy Myeloma
What in microcytic anaemia?
Low MCV
Not enough iron, therefore not enough haemoglobin
Most common cause of anaemia
14% menstruating women
Develops when inadequate iron for haemoglobin synthesis
What can cause microcytic anaemia?
Blood loss - menorrhagia, GI bleed, hookworm
Poor diet - poverty
increased demand - growth, pregnancy
Malabsorption - poor intake, coeliac disease
Name 4 risk factors for developing microcytic anaemia
Undeveloped countries
High vegetable diet
Premature infants
Introduction of mixed feeding delayed - since breast milk contains low iron
How does less iron lead to microcytic anaemia?
Less iron for haem synthesis - decrease in haemoglobin so smaller RBCs leading to microcytic anaemia
How does microcytic anaemia present?
General anaemic symptoms
Brittle nails and hair
Spoon-shaped nails - koilonychia
Atrophy of papillae of tongue - atrophic glossitis
Angular stomatitis/cheilosis - ulceration of corners of mouth
What could be a differential diagnosis for microcytic anaemia?
Thalassaemia
Sideroblastic anaemia
Anaemia of chronic disease
How is microcytic anaemia diagnosed?
Blood count and film - microcytic and hypochromic (pale), poikilocytosis (variation in RBC shape) and anisocytosis
Serum ferritin - low, low amount of stored iron, could be normal in malignancy/infection
Serum iron - low, total iron binding capacity raised
Serum soluble transferrin receptors - number increases
Reticulocyte count low
Further investigations into cause
How is microcytic anaemia treated?
Treat cause
Oral iron - side effects nausea, abdominal discomfort, diarrhoea/constipation, black stools
Ferrous gluconate
Parenteral iron - IV or IM in extreme cases
What can cause normocytic anaemia?
Acute blood loss Anaemia of chronic disease Endocrine disorders such as hypopituitarism, hypothyroidism, hypoadrenalsim Renal failure Pregnancy
How does normocytic anaemia present?
Fatigue, headaches, faintness Dyspnoea Angina if pre-existing coronary disease Anorexia Palpitations Intermittent claudication
How is normocytic anaemia diagnosed?
Normal B12 and folate
Raised reticulocytes
Hb down
Blood film and count - RBCs normocytic
How is normocytic anaemia treated?
Treat underlying cause
Improve diet with plenty of vitamins
Erythropoietin injections
What type of anaemia is B12 deficiency anaemia?
Megaloblastic anaemia
What is B12 deficiency anaemia?
Pernicious anaemia is a type - caused by autoimmune destruction of parietal cells/intrinsic factor
Impairment of DNA synthesis resulting in delayed nuclear maturation resulting in large RBCs as well as decreased RBC production in bone marrow
Bone marrow most affected - most active in terms of division
Who is more at risk of pernicious anaemia?
Common in elderly over 60
More common in fair-haired, blue-eyed individuals
More common in those with blood group A
More common in women
Associated with other autoimmune diseases such as thyroid disease and Addison’s disease
What can cause B12 deficiency anaemia?
Diet - vegans Malabsorption - lack of intrinsic factor or terminal ileum removed Pernicious anaemia Atrophic gastritis Gastrectomy Crohn's Coeliac (Affect intrinsic factor production by parietal cells in stomach or affect absorption in ileum
Why does pernicious anaemia cause B12 deficiency?
Parietal cell antibodies present in serum
Intrinsic factor antibodies present in less patients but specific for diagnosis
Autoimmune gastritis affecting fundus with plasma cell and lymphoid infiltration
Parietal and chief cells replaced by mucin secreting cells
Achlorhydia (reduced HCl production) and absent secretion of intrinsic factor
How does B12 deficiency anaemia present?
Anaemia - insidious onset, progressively increasing symptoms
Lemon yellow skin - combination of pallor and mild jaundice by excess haemoglobin breakdown
Red sore tongue
Angular stomatitis/cheilosis
Neurological - symmetrical paraesthesia in fingers and toes, early loss of vibration sense and proprioception, progressive weakness and ataxia, paraplegia, dementia, psychiatric problems, hallucinations, delusions, optic atrophy, specific to pernicious anaemia
What could be a differential diagnosis for pernicious anaemia?
Folate deficiency
Need to differentiate from other causes of B12 deficiency anaemia
Any disease in terminal ileum/bacterial overgrowth in small bowel
Gastrectomy
How is pernicious anaemia diagnosed?
Blood count and film - macrocytic, oval macrocytes with hypersegmented neutrophil polymorphs with 6/more lobes in nuclei
Serum bilirubin raised - ineffective erythropoiesis resulting in increased RBC breakdown
Serum B12 low
Hb low
Reticulocyte low
Intrinsic antibodies - diagnostic but lower sensitivity
How is B12 deficiency anaemia treated?
If not pernicious - treat cause
If due to malabsorption - injections required of vitamin B12
Dietary - oral B12
Replenish B12 stores giving IM hydroxocobalamin
NOT FOLIC ACID
What is pernicious anaemia?
Autoimmune condition resulting in B12 deficiency and anaemia
What is sickle cell disease?
Disorder of quality
Abnormal molecule or variant haemoglobin
Autosomal recessive disorder causing production of abnormal beta-globin chains
Normocytic anaemia
Where is sickle cell disease most common?
Commonest in Africans but also in India, Middle East and Southern Europe
What are the risk factors of developing sickle cell disease?
African
Family history
How does one get sickle cell anaemia?
Sickle cell haemoglobin single based mutation of adenine to thymine producing a substitution of valine for glutamic acid at 6th codon of beta-haemoglobin chain
HbF normal so disease not present until HbF decreases to adult levels at about 6 months
Insoluble and polymerises when deoxygenated
Flexibility of cell decreased and become rigid and take up sickled appearance
Initially reversible but with repeated sickling, cells lose membrane flexibility and become irreversibly sickled
Dehydrated and dense and won’t return to normal when oxygenated
Shortened RBC survival resulting in haemolysis
Impaired passage of cells through microcirculation leading to obstruction of small vessels and tissue infarction and thus intense pain
Will feel well despite being anaemic as HbS releases O2 more readily to tissue than normal
How does sickle cell disease present?
Vaso-occlusive crisis - acute pain in hands and feet due to vaso-occlusion of small vessels and avascular necrosis of bone marrow in children, pain in long bones due to avascular necrosis of bone marrow in adults, CNS infarction in children leading to stroke, seizures, cognitive defects, attacks vary in frequency
Acute chest syndrome - vaso-occlusive crisis of pulmonary vasculature, pulmonary hypertension and chronic lung disease, infection, fat embolism from necrotic bone marrow/pulmonary infarction, SOB, chest pain, hypoxia
Pulmonary hypertension - greater than 25mmHg, damage from repeated crises and repeated thromboembolism and intravascular haemolysis, increases risk of hypoxaemia and worsening sickle cell crisis
Anaemia - splenic sequestration (acute painful enlargement of spleen and acute fall in Hb, fibrotic, non-functioning spleen), bone marrow aplasia
Long term problems with growth and development (low weight, short, delayed sexual maturation), bones (chronic infarcts from vaso-occlusive crises, avascular necrosis of hips, shoulders, compression of vertebrae and shortening of bones in hands and feet
Osteomyelitis
Infections
Cardiomegaly, arrhythmias, iron overload cardiomyopathy, MI
TIA, fits, cerebral infarction, coma
Chronic hepatomegaly, liver dysfunction due to trapped sickle cells
Chronic tublointersitial nephritis
Retinopathy, vitreous haemorrhage, retinal detachments
What problems can sickle cell disease cause in pregnancy?
Impaired placental blood flow resulting in spontaneous abortion
How is sickle cell disease diagnosed?
Blood count - Hb 60-80g/L, raised reticulocyte count
Sickled erythrocytes on blood film
Sickle solubility test positive
Hb electrophoresis - confirms diagnosis, shows 80-95% HbS, absent HbA, aim for diagnosis at birth to prompt pneumococcal prophylaxis
How is sickle cell disease treated?
Precipitating factors eg infection, cold, dehydration avoided or treated quickly
Folic acid to all haemolysis patients
Acute painful attacks - IV fluids, analgesia (morphine, codeine, paracetamol, NSAIDs), O2 and antiboitics
Anaemia - blood transfusion for acute chest syndrome, acute anaemia due to acute splenic sequestration, aplastic crisis, stroke, HF
Oral hydroxycarbamide - increases HbF concentration
Stem cell transplant
What are the 3 main causes of microcytic anaemia?
Iron deficiency
Chronic illness
Thalassaemia
What are the 3 main causes of normocytic anaemia?
Combined
Acute blood loss
Chronic disease
What are the 3 main causes of macrocytic anaemia?
Vitamin B12 deficiency (pernicious anaemia)/folate deficiency
Hypothyroidism
Liver disease
What is a DVT?
Formation of one or two blood clots in one of the bodies larger veins - tends to be in lower limbs
Inappropriate coagulation
Fibrin rich clot - requires anticoagulants
How common are DVTs?
25,000 people die of DVT and PE per year in UK
50% preventable, premature mortality
More than RTA, AIDS, and breast cancer combined
What are the main risk factors for DVT and PE?
Surgery, immobility and leg fracture - on thromboprophylaxis
OC pill, HRT, pregnancy
Long haul flights/travel
Inherited thrombophilia - genetic predisposition
What are the circumstantial causes of DVT?
Surgery Immobilisation Oestrogens Malignancy Long haul flights Pregnancy
What are the genetic causes of DVT?
Higher risk in Caucasian population Factor V Leiden PT20120A Antithrombin deficiency Protein C deficiency Protein S deficiency Plasminogen deficiency Thrombophilia
What are the acquired causes of DVT?
Anti-phospholipid syndrome
Lupus anticoagulant
Hyperhomocysteinaemia
Varicose veins
What are the main symptoms of a DVT?
Pain particularly when walking
Swelling in ankles
Unilateral
Redness
What are the main signs of DVT?
Tenderness
Swelling
Warmth
Discolouration
How are DVTs diagnosed?
Clinical not sufficient
D-dimer - normal excludes it, positive doesn’t confirm diagnosis, blood test, also raised in infection, pregnancy ect, used to determine who to give ultrasound to
Ultrasound compression test - identify vein, push with ultrasound probe and squashes = empty, if not = full, likely to be with clot
Coagulation screen
FBC - including platelets
Wells score
How do you treat a DVT?
Low molecular weight heparin s/c od for min 5 days, weight adjusted dose
Oral wafarin INR 2-3 for 3 months
Direct oral anticoagulatns for 3 months
Compression stockings - prevents swelling and symptomatic relief
Treat underlying cause - malignancy, thrombophilia
Spontaneous DVT more likely to recur than provoked
NOACS
How do you prevent a DVT?
Mechanical - hydration, early mobilisation, compression stockings, foot pumps, leg elevation
Chemical - LMW heparin once daily injections, small dose so will not cause bleeding during surgery
Thromboprophylaxis
What is a pulmonary embolism?
Blockage of an artery in lungs by a substance that has moved elsewhere
Often a piece of/a thrombus
What are the signs of a pulmonary embolism?
Hypotension, cyanosis, severe dyspnoea, right heart strain/failure
What are the symptoms of a PE?
Sudden, sharp, pleuritic chest pain Dyspnoea - sudden Signs/symptoms of DVT Risk factors No other diagnosis more likely Coughing up blood Fainting
What are the signs of a PE?
Tachycardia Tachypnoea Pleural rub Anxiety Cor pulmonae (RHF) Cyanosis Raised JVP Pleural effusion Hypoxic
How do you diagnose a PE?
Chest x-ray usually normal - no signs of pneumonia
ECG - sinus tachycardic
Blood gases - T1 respiratory failure, decreased O2 and CO2
D-dimer
Ventilation/perfusion scan
CTPA spiral CT with contrast
What could be a differential diagnosis for a PE?
Chest infection
How do you treat a PE?
Same as DVT Ensure normal Hb, platelets, renal function and baseline clotting LMW heparin s/c od weight adjusted DOAC Oral warfarin 6 months Treat cause IVC filter Admit to ITU
How is PE prevented?
Same as DVT
What is the main complication of a PE?
Sudden death
What are the main differences in the signs and symptoms of arterial and venous thrombosis?
Venous - warm limb, pulse, pain, redness, cramps, tenderness
Arterial - cold, decreased/no pulse, pain in affected area due to hypoxia, pallor, paraesthesia, claudication
What are the 6 main signs of acute limb ischaemia?
6Ps Perishingly cold Paraesthesia Pallor Pain Pulselessness Paralysis
What is Virchow’s triad?
Triad of three things that can cause blood clotting
Stasis - lack of movement
Hypercoagulability
Vessel wall injury
What is the difference in the treatment of arterial and venous thrombosis?
Arterial thrombosis - treatment with drugs that target platelets
Venous thrombosis - treatment with drugs that target fibrin
What is leukaemia?
Rapidly proliferating immature blast blood cells in bone marrow that are non-functional
Neoplasm within bone marrow
Generally unwell - systemic B symptoms
Generalised cytopenia - infection bleeding - progenitors can’t mature, too many blasts
What are the 4 different types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What is ALL?
Most common between 2-4 years
Malignancy of immature lymphoid cells
Affects B/T lymphocytes, arrests maturation and promotes uncontrolled proliferation of immature blast cells/lymphoid cells
Majority B cell precursors
Increased proliferation of immature lymphoblast cells in bone marrow - if all B cells children, if all T cells adults
Commonest cancer in childhood
Combination of genetic susceptibility and environmental trigger
Ionising radiation during pregnancy and Down’s syndrome associated
CNS involvement common
What is AML?
Neoplastic proliferation of blast cells derived from marrow myeloid elements
Progresses rapidly with death in 2 months if untreated
Commonest acute leukaemia of adults
Associated with radiation and Down’s syndrome
What is CML?
Uncontrolled clonal proliferation of myeloid cells
Disease of adults
40-60 most common age
Slight male predominance
More than 80% have Phiadelphia chromosome which forms a fusion gene - stimulates cell division
What is CLL?
Commonest leukaemia
Occurs later in life
Accumulation of mature B cells that have escaped programmed cell death and undergone cell-cycle arrest
Mutations, trisomies and deletions influence risk
Pneumonia triggering event sometimes
What is the pathophysiology of leukaemia?
Divide rapidly but serve no function so wasting energy making useless cells and so less energy available to make functional cells
Due to rapid replication cells take up a lot of space in bone marrow meaning little space and less food for other cells to grow
Bone marrow makes fewer functioning cells and so fewer functioning cells in blood giving symptoms of leukaemia
No longer space in bone marrow, leukaemia cells present into blood too
Can occur at any age but type depends on age
What is the pathophysiology of CLL?
Many stable for years and may regress
Death often due to complication of infection
May transform into aggressive lymphoma - Richter’s syndrome
How does ALL present?
Marrow failure
- Anaemia low Hb, SOB, fatigue, angina, claudication, pallor, cardiac flow murmur
- Infection low WCC
- Bleeding low platelets
- Bone marrow infiltration = bone pain
- Liver/spleen infilatration = hepatosplenomeglay
- Node infiltration = lymphadenopathy
- CNS infiltration = headache, cranial nerve palsies
- Mediastinum infiltration resulting in mediastinal masses with SVC obstruction
How does AML present?
Marrow failure
- Anaemia
- Infection
- Bleeding
- Hepatomegaly and splenomegaly due to infiltration
Gum hypertrophy
DIC occurs in subtype of AML where release of thromboplastin
How does CML present?
Symptomatic anaemia Abdominal discomfort - splenomegaly Weight loss Tiredness Pallor Fever and sweats in absence of infection Features of gout due to purine breakdown Bleeding due to platelets dysfunction
