Haematology Flashcards
What is seen on a blood film in hypospenism (coeliac disease)
target cells, Howell-Jolly bodies, Pappenheimer bodies, siderotic granules, acanthocytes
Blood film in iron deficiency anaemia
target cells, ‘pencil’ poikkilocytes
Blood film in myelofibrosis
‘tear-drop’ poikilocytes
Blood film in intravascular haemolysis
schistocytes
Causes of microcytic anaemia
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning (rare)
Sideroblastic anaemia (rare)
Causes of normocytic anaemia
AAAHH
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism
Causes of macrocytic anaemia
Megoblastic = Vit B12 deficiency, folate deficiency
Normoblastic = alcohol, liver disease, hypothyroidism, haemolysis, azathioprine
What is anaemia
Decrease of haemoglobin in blood below reference level for age and sex of individual
Presentation of anaemia
- Fatigue
- Headaches
- Faintness
- Dyspnoea, tachypnoeic
- Anorexia
- Palpitations, tachycardia
- Pallor, Conjunctival pallor
- Systolic flow murmur
Investigations for anaemia
- Bloods Hb, MCV, B12, folate, ferritin
- Blood film
- OGD/colonoscopy = GI cause
- Bone marrow biopsy
Complications of anaemia
- Reduced O2 transport
- Tissue hypoxia
- Compensatory changes
o Increased tissue perfusion
o Increased O2 transfer to tissues
o Increased RBC production - Myocardial fatty change
- Fatty change in liver
- Aggravates angina and claudication
- Skin and nail atrophic changes
- CNS cell death
Risk factors for iron deficiency anaemia
- Menstruating women
- Undeveloped countries
- High vegetable diet
- Premature infants
- Introduction of mixed feeding delayed = breast milk contains low iron
- Crohn’s or coeliac
Causes of iron deficiency anaemia
- Blood loss (adults)
- Dietary insufficiency (children)
- Poor iron absorption
- Increased requirements during pregnancy
Features of iron deficiency anaemia
- Brittle nails and hair
- Hair loss
- Pica = dietary cravings for abnormal things (dirt)
- Spoon-shaped nails = koilonychia
- Atrophy of papillae of tongue
- Angular stomatitis = ulceration of corners of mouth
- Post-cricoid webs
Management of iron deficiency anaemia
- Oral iron = ferrous sulphate 3 times daily
- IV/IM Iron infusion (cosmofer)
Side effects of oral iron
nausea, abdo discomfort, diarrhoea, black stools
What is thalassaemia
Autosomal recessive genetic defect in protein chains that make up haemoglobin
- Red blood cells more fragile and break down more easily
- Spleen acts as sieve to filter blood and remove older blood cells
- Spleen collects all destroyed red blood cells
Presentation of thalassaemia
- Microcytic anaemia (low MCV)
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences (cheek bones)
- Failure to thrive (thalassaemia major)
Investigations for thalassaemia
- FBC = microcytic anaemia
- Haemoglobin electrophoresis = globin abnormalities
- DNA testing
- Pregnant women offered screening
Management of thalassaemia
- Monitor serum ferritin levels, FBC
- Alpha thalassaemia
o Blood transfusions
o Splenectomy
o Bone marrow transplant (curative) - Beta Thalassaemia minor no active treatment
- Beta thalassaemia intermedia Occasional blood transfusions
- Beta thalassaemia major
o Regular transfusions
o Iron chelation
o Splenectomy
o Bone marrow transplant
Complications of iron overload
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain
Risk factors for pernicious anaemia
- Fair-haired, blue eyes
- Blood group A
- Thyroid and Addison’s disease
Causes of pernicious anaemia
- Autoimmune = antibodies against parietal cells or intrinsic factor
- B12 deficiency = diet or malabsorption
Presentation of pernicious anaemia
- Mild jaundice
- Red sore tongue and ulceration of corners of mouth
- Peripheral neuropathy = numbness or paraesthesia
- Loss of vibration sense or proprioception
- Visual changes
- cognitive changes
- Progressive weakness and ataxia
- Paraplegia
- Dementia, psychiatric problems, hallucinations, delusions, optic atrophy
Investigations of pernicious anaemia
- Intrinsic factor antibody
- Gastric parietal cell antibody
- Blood count and film = macrocytic
- Raised serum bilirubin
- Low serum B12 and Hb and reticulocyte count
- Schilling test = assess B12 absorption
Management of pernicious anaemia
- Diet = oral replacement with cyanocobalamin
- IM hydroxycobalamin 3 times per week for 2 weeks
Risk factors for folate deficiency
- Poverty
- Alcoholic
- Pregnant
- Crohn’s or coeliac disease
- Elderly
- Antifolate drugs = methotrexate and trimethoprim
Presentation of folate deficiency
- May be asymptomatic
- Glossitis (sore red tongue)
Management of folate deficiency
- Treat underlying cause
- Give folic acid tablets daily for 4 months with B12
Causes of haemolytic anaemia
- Inherited
o Hereditary spherocytosis
o Hereditary elliptocytosis
o Thalassaemia
o Sickle cell anaemia
o G6PD deficiency - Acquired
o Autoimmune haemolytic anaemia
o Paroxysmal nocturnal haemoglobinuria
o Microangiopathic haemolytic anaemia
Presentation of haemolytic anaemia
- Splenomegaly
- Jaundice
Investigations of haemolytic anaemia
- FBC = normocytic anaemia
- Blood film = schistocytes
- Direct Coombs test positive = autoimmune haemolytic anaemia
- High serum unconjugated bilirubin
- High urinary urobilinogen
- High faecal sterocobilinogen
Epidemiology of G6PD
- Mediterranean, Middle Eastern and Africa
- X-linked recessive (Male only)
Triggers of G6PD
- Medications
o Anti-malarials: primaquine
o Ciproflaxacin
o Sulph-group drugs = sulphonamides, sulphasalazine, sulfonylureas
o Trimethoprim - Infections
- Broad/fava beans
Presentation of G6PD
- Neonatal jaundice + intermittent jaundice
- Anaemia
- Intravascular haemolysis
- Gallstones
- Splenomegaly
Investigations of G6PD
- Blood film = Heinz bodies, bite and blister cells
- G6PD enzymes assay (measure enzyme activity)
What is sickle cell anaemia
Autosomal recessive disorder causing production of abnormal beta globin chains
Presentation of sickle cell anaemia
- Asymptomatic until crises
- Sickling precipitated by infection, dehydration, cold, acidosis and hypoxia
- Pulmonary hypertension
- Anaemia
Investigations of sickle cell anaemia
- Genetic testing
- Newborn screen heel prick test
- Sickle solubility test positive
- Hb electrophoresis and blood films show sickled cells
- FBC = low Hb and raised reticulocyte count
- Painful attack = IV fluids, analgesia, O2, Abx
Management of sickle cell anaemia
- Avoid dehydration and other triggers of crises
- Folic acid
- Abx prophylaxis with penicillin V
- Hydroxycarbamide = stimulation production of fetal Hb
- Blood transfusion
- Bone marrow transplant
Complications of sickle cell anaemia
- Increased risk of infection
- Stroke/ MI/ cardiomyopathy
- Avascular necrosis = large joints of hip
- Pulmonary hypertension
- Painful and persistent penile erection
- CKD
- Liver dysfunction
- Aplastic crises reduced reticulocyte count
- Sequestration crises increased reticulocyte count
- Acute chest syndrome = Dyspnoea, chest pain, pulmonary infiltrates on CXR, low pO2
Risk factors for DVT
- Increased age
- Pregnancy
- Synthetic oestrogen (OCP)
- Trauma
- Recent Surgery (within last 3 months)
- Past DVT
- Obesity
- Immobility
- Leg fracture/plaster of Paris
- Long haul flights
- Malignancy
- Thrombophilia = antiphospholipid syndrome
Presentation of DVT
- Asymptomatic
- Unilateral calf/leg swelling and pain
- Affected calf often warmer, redder
- Tenderness
- Dilated superficial veins
- Oedema
Investigations for DVT
- Wells score (2 points or more DVT is likely)
- Plasma D-dimer = normal excludes DVT but not diagnostic
- Compression doppler ultrasound = cannot squash diagnoses DVT
o If investigations cannot be done within 4 hrs start on treatment dose DOAC
Management of DVT
- DOAC (apixaban or rivaroxaban) for 3-6 months
- Low molecular weight Heparin = SC dalteparin (min 5 days)
- Oral warfarin with target INR of 2.5 for 6 months after
- Compression stockings
- Inferior vena cava filters = Reduce risk of pulmonary emboli
Prevention of DVT
- Early mobilisation post-op
- Compression stockings/foot pumps
- Thrombophylaxis for both low risk and high risk
- Hydration
Risk factors for leukaemia
- Down’s syndrome
- Kleinfelter’s syndrome
- Noonan syndrome
- Fanconi’s anaemia
Red flags for leukaemia
- Any features in 0-24 y/o should prompt urgent FBC
- Pallor
- Persistent fatigue
- Unexplained fever
- Unexplained persistent infections
- Generalised lymphadenopathy
- Persistent or unexplained bone pain
- Unexplained bruising
- Unexplained bleeding
Investigations for leukaemia
- FBC
- Blood film
- Lactate dehydrogenase raised
- Bone marrow biopsy
- CXR = infection or mediastinal lymphadenopathy
- Lymph node biopsy = lymphoma
- Lumbar puncture = CNS involvement
- CT/MRI/PET scans = staging
Features of Acute Lymphoblastic leukaemia
Childhood (2-4yo)
Down’s syndrome
Blood film = blast cells
Features of acute myeloid leukaemia
Common in adults
Transformation from myeloproliferative disorder
Blood film = auer rods
Neutropenia with high WCC
Thrombocytopenia
Features of chronic myeloid leukaemia
Philadelphia chromosome
Chronic, accelerated, blast phases
Gout
Blood film = left shift and basophilia
Features of chronic lymphocytic leukaemia
Commonest in adults (>55)
Blood film = smear/smudge cells
Warm autoimmune haemolytic anaemia
High-grade lymphoma = Richter’s transformation
Risk factors for Hodgkin’s lymphoma
- EBV, HIV
- Autoimmune = RA, SLE, sarcoidosis
- Family history
- Male > female
- Bimodal age distribution = 20 and 75
Presentation of Hodgkin’s lymphoma
- B symptoms = fever, weight loss, night sweats, pruritus, loss of appetite
- Fatigue
- Cough
- Shortness of breath
- Recurrent infections
- Painless cervical lymphadenopathy = ‘rubbery’
- Sometimes alcohol-induced lymph node pain
- Hepatosplenomegaly
Investigations of Hodgkin’s lymphoma
- Normocytic anaemia
- Lactate dehydrogenase raised
- Lymph node biopsy = Reed-Sternberg cells (owl’s eye appearance)
- CT/MRI/PET = staging
- High ESR or Low Hb = worse prognosis
Staging od Hodgkin’s lymphoma
Ann Arbor
- I = confined to single lymph node region
- II = involvement of 2+ nodal areas on same side of diaphragm
- III = Involvement of nodes on both sides of diaphragm
- IV = spread beyond lymph nodes liver/bone marrow
- A = no systemic symptoms other than itching
- B = fever, weight loss, night sweats
Complications of chemotherapy
leukaemia and infertility
Complications of radiotherapy
risk of cancer, damage to tissues, hypothyroidism
Risk factors for non-hodgkin’s lymphoma
- Burkitt’s lymphoma = EBV
- MALT lymphoma = H. pylori infection
- Diffuse large B cell lymphoma = Over 65
- Family history
- HIV
- Hep B/C
- Pesticides exposure = trichloroethylene
Presentation of myeloma
- Calcium raised Constipation, Nausea, Anorexia, Confusion
- Renal failure Thirst, Amyloidosis
- Anaemia Tiredness and malaise
- Bone lytic lesions Back/bone pain +/- fractures
- Bleeding and bruising
- Carpal tunnel syndrome
Investigations for myeloma
- FBC = low WCC, raised Ca, raised ALP, raised ESP, raised plasma viscosity
- Blood film = rouleaux formation
- Urine Bence-Jones protein test
- Serum free Light chain assay
- Serum immunoglobulins
- Serum protein electrophoresis
- Bone marrow biopsy
- Plain XR = punched out lesions, lytic lesions, raindrop skull
Diagnostic crtieria for myeloma
- 1 major and 1 minor or 3 minor
- Major
o Plasmacytoma
o 30% plasma cells in bone marrow sample
o Elevated levels of M protein in blood or urine - Minor
o 10-30% plasma cells in bone marrow sample
o Minor elevations in level of M protein in blood or urine
o Osteolytic lesions
o Low levels of antibodies in blood
Complications of myeloma
- Recurrent bacterial Infection
- Peripheral neuropathy
- Spinal cord compression
- Hyperviscosity
Inheritance of Von Willebrand’s
Autosomal dominant
Presentation of von willebrand’s disease
Epistaxis
Menorrhagia
Haemoarthoses
Muscle haematomas
Investigations for von willebrand’s disease
Prolonged bleeding time
APTT may be prolonged
Factor VIII levels moderately reduced
Defective platelet aggregation with ristocetin
Management of von willebrand’s disease
Tranexamic acid for mild bleeding
Desmopressin
Factor VIII concentratin
Causes of thrombocytopenia
- Decrease in production
o Congenital thrombocytopenia
o Infiltration of bone marrow
o Low B12/folate
o Reduced thrombopoietin
o Medication = methotrexate and chemotherapy
o Toxins = alcohol
o Infections = viral or TB
o Aplastic anaemia
o Myelodysplasia - Increase in destruction
o Autoimmune
o Hypersplenism
o Drug related immune destruction
o Disseminated intravascular coagulopathy
o TTP
Causes of immune thrombocytopenia purpura
- Primary (acute)
o Muco-cutaneous bleeding
o History of recent viral infection = chickenpox/measles
o May follow immunisation
o Sudden self-limiting purpura = red/purple spots in skin caused by bleeding underneath - Secondary (chronic)
o Chronic lymphocytic leukaemia, solid tumours, after viral infections (HIV/Hep C)
o Platelet autoantibodies
Presentation of ITP
- Easy bruising
- Epitaxis = nose bleed
- Menorrhagia = heavy menstruation
- Gum bleeding
- Major haemorrhage (rare)
- Purpura = red/purple spots on skin caused by bleeding underneath
- Splenomegaly (rare)
Investigations of ITP
- Bone marrow examination = thrombocytopenia with increased or normal megakaryocytes in marrow
- Platelet autoantibodies (60-70%)
Management of ITP
- Prednisolone + IV immunoglobin = raises platelet count more rapidly
- Splenectomy + oral/IV azathioprine
Causes of thrombotic thrombocytopenic purpura
- Idiopathic
- Autoimmune = SLE
- Cancer
- Pregnancy
- Drug associated = quinine, ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- Post-infection = urinary, GI
- HIV
Presentation of TTP
- Florid purpura
- Fever
- Fluctuating neuro signs (due to microemboli)
- Haemolytic anaemia with red cell fragmentation
o Often accompanied by acute kidney injury - Thrombocytopenia
Investigations of TTP
- Coagulation screen is normal
- Lactate dehydrogenase is raised as result of haemolysis
Management of TTP
- Plasma exchange
- IV methylprednisolone
- IV rituximab
Causes of disseminated intravascular coagulation
- Massive activation of coagulation cascade
- Initiating factors are
o Extensive damage to vascular endothelium exposing tissue factor
o Enhance expression of tissue factor by monocytes in response to cytokines - Sepsis
- Major trauma and tissue destruction
- Advanced cancer
- Obstetric complications
- Pancreatitis
Presentation of DIC
- Acutely ill and shocked
- Bleeding may occur from mouth, nose and venepuncture sites
- Widespread ecchymoses = discolouration of skin due to bleeding caused by bruising
- Confusion
- Bruising
- Thrombotic event = skin, brain, kidney
Investigations of DIC
- Severe thrombocytopenia
- Decreased fibrinogen
- Elevated FDPs
o D-dimer
o Intense fibrinolytic activity that is stimulated by presence of fibrin in circulation - Blood film = fragmented RBCs
- Prolonged Prothrombin time, activated partial thromboplastin time and thrombin time
Management of DIC
- Treat underlying condition
- Replace platelets if low via transfusion
- Fresh frozen plasma to replace the coagulation factors
- Cryoprecipitate to replace fibrinogen and some coagulation factors
- Red cell transfusion in patients who are bleeding
Presentation of polycythaemia vera
- Asymptomatic
- Headaches
- Itching (worse after hot bath/when patient warm)
- Tiredness
- Dizziness
- Tinnitus
- Visual disturbance
- Erythromelagia = burning sensation in fingers and toes
- Gout = due to increased turnover
- Intermittent claudication
- Plethoric complexion = congested or swollen with blood in facial skin
- Hypertension
- Angina
- Hepatosplenomegaly
Investigations of polycythaemia vera
- FBC = raised WCC, platelets, Hb
- Genetic screen = Presence of JAK2 mutation
- Bone marrow biopsy = Prominent erythroid, granulocytic and megakaryocytic proliferation
- Serum erythropoietin low
Management of polycythaemia vera
- Treatment aims to maintain normal blood count
- Venesection = Removal of 400-500ml of blood weekly
- Chemotherapy = Not tolerate venesection/ poorly controlled features
- Low dose aspirin
- Radioactive phosphorus = over 70
- Allopurinol = block uric acid production reduce gout
Complications of polycythaemia vera
- Thrombosis
- Haemorrhage
Blood transfusion complications
- Non-haemolytic febrile reaction
o Fever + chills
o Mx: slow or stop transfusion, paracetamol, monitor - Minor allergic reaction
o Pruritus, urticaria
o Mx: temporarily stop transfusion, antihistamine, monitor - Anaphylaxis
o Hypotension, dyspnoea, wheezing, angioedema
o Mx: stop transfusion, IM adrenaline, ABCDE support - Acute haemolytic reaction
o Fever, abdominal pain, hypotension, chest pain, agitation
o Mx: stop transfusion, generous fluid resuscitation, send blood for direct Coombs test and repeat typing and cross-matching
o Complications: disseminated intravascular coagulation, renal failure - Transfusion-associated circulatory overload (TACO)
o Pulmonary oedema, hypertension
o Mx: slow or stop transfusion, consider IV furosemide and O2 - Transfusion-related acute lung injury (TRALI)
o Hypoxia, pulmonary infiltrates on CXR, fever, hypotension
o Within 6 hours of transfusion
o Stop transfusion, O2 and supportive care - Infective
o Transmission of vCJD
