Haematology Flashcards
What are the causes of microcytic anaemia?
Thalassaemia, anaemia of chronic disease (CKD), iron deficiency anaemia, lead poisoning, sideroblastic anaemia
What are the causes of normocytic anaemia?
Acute blood loss, anaemia of chronic disease, aplastic anaemia, haemolytic anaemia, hypothyroidism
What are the causes of macrocytic anaemia?
Megaloblastic = B12 and folate deficiency
Normoblastic = alcohol, reticulocytosis, hypothyroidism, liver disease, azathioprine
What are the signs and symptoms of anaemia?
Tiredness, SOB, headcahes, dizziness, palpitations, pale skin, conjunctival pallor, tachycardia, raised respiratory rate
What investigations should you do in someone with suspected anaemia?
FBC, reticulocyte count, blood film, renal profile, LFTs, ferritin and haemtinics, intrinsic factor antibodies, TFTs, coeliac disease serology, myeloma screening, direct coombs test, bone marrow biopsy
What are the causes of iron deficiency anaemia?
Insufficient dietary iron, coeliac disease, pregnancy, bleeding, heavy periods
What signs are specifically associated with iron deficiency anaemia?
Pica, hair loss, koilonychia, angular cheilitis, atrophic glossitis, brittle hair and nails
What does the iron profile look like in someone with iron deficiency anaemia?
Low ferritin, total iron binding capacity is raised, transferrin low
What are the common side effects associated with oral iron replacement?
Constipation, black stools
What should be done in adults with new iron deficiency without a clear cause?
Colonoscopy and OGD
What are the causes of B12 deficiency anaemia?
Pernicious anaemia, insufficient B12 intake (veggies/vegans), PPI and metformin (reduce B12 absorption)
What is the pathophysiology of pernicious anaemia?
Parietal cells of the stomach produce intrinsic factor, intrinsic factor is essential for absorption of B12 in the distal ileum - autoantibodies target either parietal cells or intrinsic factor leading to lack of absorption of vitamin B12
What neurological symptoms are associated with B12 deficiency anaemia?
Peripheral neuropathy, loss of vibration sense, loss of proprioception, visual changes, mood and cognitive changes
How can you differentiate between megaloblastic and normoblastic macrocytic anaemia?
On blood film - megaloblastic anaemia will have hyper-segmented neutrophils
What is the management of B12 anaemia?
IM hydroxocobalamin
If no neuro symtpms - 3 times weekly for two weeks
If neuro symptoms - alternate days until there is no further improvement in symptoms
How do you manage pernicious anaemia?
2-3 monthly injections of B12 for life
Which do you have to treat first B12 deficiency or folate deficiency?
B12 before folate as it can cause subacute degeneration of the cord
What is haemolytic anaemia?
Destruction of RBC resulting in low haemoglobin concentration
What are the features of haemolytic anameia?
Anaemia, splenomegaly, jaundice
What are the investigations and results would you find in haemolytic anaemia?
FBC - normocytic anaemia
Blood film - schistocytes
Direct Coombs test - positive in autoimmune haemolytic anaemia
What is hereditary spherocytosis and what is the inheritance pattern?
Autosomal dominant
Most common inherited haemolytic anaemia
Sphere-shaped RBC that easily break down when passing through the spleen
What results would be found on FBC and blood film in someone with hereditary spherocytosis?
Raised reticulocyte count due to rapid turnover of RBC, spherocytes on blood film
Infection with what organism causes an aplastic crisis in spherocytosis?
Parvovirus
What is G6PD deficiency and what is the inheritance pattern?
X-linked recessive
Caused by a defect in the gene causing for G6PD an enzyme responsible for protecting the cells for oxidative damage
What triggers are there for haemolytic anaemia in those with G6PD deficiency?
Infections, drugs, fava beans, medications (ciprofloxacin, sulfonylurea, sulfasalazine)
What are the two types of autoimmune haemolytic anaemia and which is more common?
Warm and cold
Warm is more common
What is the management for autoimmune haemolytic anaemia?
Blood transfusions, prednisolone, rituximab, splenectomy
What is alloimmune haemolytic anaemia and what are some common causes?
Occurs due to foreign red blood cells or foreign antibodies
Transfusion reactions and haemolytic disease of the newborn
What is the inheritance pattern of sickle cell anaemia?
Autosomal recessive condition affecting the gene for beta globin on chromsome 11
What screening is done for sickle cell anaemia?
Tested on the newborn blood spot screening
Pregnant women at high risk are offered testing
What is a sickle cell crisis?
Including triggers and general management
Acute exacerbations that can occur in response to dehydration, infection, stress or cold weather
Management = keeping warm, good hydration and analgesia
What is a vaso-occlusive crisis?
Sickle shaped RBC clog capillaries causing distal ischaemia
Presents with pain and swelling in hands or feet
Can cause priapism in men which requires urgent aspiration
What is a splenic sequestration crisis?
Caused by RBC blocking blood flow within the spleen which leads to severe anaemia, splenomegaly and hypovolaemic shock
If recurrent - splenectomy can be done to prevent
What is an aplastic crisis?
Temporary absence of the creation of new RBC
Usually triggered by infection with parvovirus B19
Treated with blood transfusions
What is acute chest syndrome (in sickle cell disease)?
Vessels supplying the lungs become clogged with RBC
Presents with fever, SOB, chest pain, cough and hypoxia
CXR will show new pulmonary infiltrates
How is sickle cell anaemia definitively diagnosed?
Haemoglobin electrophoresis
What is the general management of sickle cell anaemia?
Antibiotic prophylaxis - usually penicillin V
Hydroxycarbamide - stimulates production of HbF
Crizanlizumab - prevents RBC from sticking to blood vessel wall and thereby reduced crises
What is the inheritance pattern of thalassemia?
All types of autosomal recessive
What is the pathophysiology of thalassaemia?
RBC are more fragile and break down easily causing a haemolytic anaemia due to defects in protein in haemoglobin
What type of anaemia is seen in thalassemia?
Microcytic anaemia that does not respond to iron (microytosis is disproportionate to the Hb drop)
Iron studies will often show iron overload
What investigations can be used to diagnose thalassaemia?
Haemoglobin electrophoresis, DNA testing, all women are offered thalassaemia testing during pregnancy
Which ethnicities are more commonly known to have thalassemia?
Asian, middle eastern or Mediterranean
Why does thalassemia result in iron overload and what is done to prevent this?
There is increased iron absorption in the GI tract or due to multiple blood transfusions
Limit blood transfusions where possible and iron chelation may be required
What is seen on a blood film of someone with alpha thalassaemia?
Heinz bodies in the RBCs
What is the difference between beta thalassaemia minor, intermedia and major?
Minor = carrier of abnormally functioning beta globin gene
Intermedia = two abnormal copies of beta globin gene or one defective and one deletion gene
Major = two deletion genes
What features are seen in thalassaemia major?
Bone marrow is under so much strain to produce extra RBC that is expands –> frontal bossing, enlarged maxilla, depressed nasal bridge and protruding upper teeth
What management is used in thalassaemia?
Blood transfusions + iron chelation with desferrioxamine, splenectomy, bone marrow transplant
What are the risk factors for lymphoma?
HIV, EBV, autoimmune conditions, family history, hepatitis
What is the presentation of lymphoma?
Lymphadenopathy (may be in the neck, axilla or inguinal region) - non-tender, firm or rubbery
In Hodgkin’s may experience lymph node pain after drinking alcohol
B symptoms - fever, weight loss, night sweats
May also have itching, fatigue, cough, SOB
What investigation is done in suspected lymphoma and what may you find?
Lymph node biopsy
In Hodgkin will find reed-sternberg cells
What are the different stages of lymphoma?
1 = confined to one node or group of nodes
2 = in more than one group of nodes but on the same side of the diaphragm
3 = affects nodes both above and below the diaphragm
4 = widespread involvement including non-lymphatic organs such as lungs/liver
A = absence of systemic symptoms, B = has B symptoms
What is the management of lymphoma?
Chemotherapy, radiotherapy, stem cell transplant
What is tumour lysis syndrome?
Usually triggered by introduction of chemotherapy
Occurs from the breakdown of tumour cells and subsequent release of chemicals
Present with AKI, high phosphate and high uric acid
What is used to treat tumour lysis syndrome?
IV fluids, allopurinol, rasburicase
What is the pathophysiology of multiple myeloma?
Affects the plasma cells in the bone marrow which leads to production of large quantities of specific paraprotein, affects multiple bone marrow areas in the body
What two conditions can progress to multiple myeloma?
MGUS, smouldering myeloma
Which antibody is most commonly produced in multiple myeloma?
IgG
What are the features of multiple myeloma?
Elevated calcium, renal failure, anaemia, bone lesions and bone pain
Why does anaemia occur in myeloma?
Cancerous plasma cells invade the bone marrow resulting in suppression of other blood lines leading to anaemia, leukopenia and thrombocytopenia
Why does myeloma result in bone disease?
Cytokines are released from the abnormal plasma cells –> increased osteoclast activity and suppressed osteoblast activity –> osteolytic lesions –> high calcium
Why does myeloma result in kidney disease?
Paraproteins are deposited in the kidneys, hypercalcaemia affects kidney function, dehydration, glomerulonephritis and medications that are used to treat the condition
Which investigations are done in myeloma?
Serum protein electrophoresis - detect paraproteinemia
Urine protein electrophoresis - detect Bence-Jones protein
Bone marrow biopsy - shows plasma cells
What is used to treat myeloma?
Chemotherapy and stem cell transplant can be used
Which type of leukaemia can result in transformation from a myeloproliferative disorder and is associated with Auer rods?
AML
Which leukaemia is most common in children and is associated with Downs syndrome?
ALL
Which type of leukaemia is associated with the Philadelphia chromosome?
CML
Which type of leukaemia is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells?
CLL
What is seen on a FBC in those with leukaemia?
Can result in a pancytopenia due to excessive production of a single type of white blood cells which suppresses all other cells lines - often will be isolated rise in WBC
What symptoms are associated with leukaemias?
Fatigue, fever, pallor, petechiae, bruising, abnormal bleeding, lymphadenopathy, hepatosplenomegaly
In those with suspected leukaemia what investigations should be done?
FBC within 48 hours
Blood film
Bone marrow biopsy
What is the philadelphia chromosome translocation?
t(9:22) - translocation between chromosome 9 and chromosome 22
How is leukaemia managed?
Chemotherapy and targeted therapies such as rituximab and tyrosine kinase inhibitors
Are blast cells seen in acute or chronic leukaemias?
Acute
What are the risks factors for VTE?
Immobility, recent surgery, long haul travel, pregnancy, oestrogen therapy, malignancy, polycythaemia, SLE, thrombophilia
What are some examples of thrombophilias?
Antiphospholipid syndrome, factor V leiden
What are the contraindications of LMWH?
Active bleeding or existing anticoagulation
What are the contraindications to anti-embolic stockings ?
Peripheral arterial disease
What is done if the well score indicates DVT is unlikely?
D-dimer is performed and if D-dimer is raised a USS of leg vein is done
What is done if well score demonstrates that DVT is likely?
Leg vein USS is performed immediately
What is the first line anticoagulant in VTE normally, in pregnancy and those with antiphospholipid syndrome?
Normally = DOAC
Antiphospholipid syndrome = warfarin
Pregnancy = LMWH
How long is anticoagulation continued for those with provoked and unprovoked DVT?
Provoked = 3 months
Cancer = 6 months
Unprovoked = long-term
What are the causes of thrombocytopenia?
B12/folate deficiency, liver failure, leukaemia, chemotherapy, medications (sodium valproate, methotrexate), ITP, TTP
What symptoms can occur when platelets drop below 50 and then below 10?
Nosebleeds, bleeding gums, heavy periods, easy bruising, haematuria, rectal bleeding
Platelets below 10 –> GI bleeding and intracranial haemorrhage
What is ITP, how does it present and how is it managed?
Antibodies are created against platelets leading to isolated low platelet count
Presents with bleeding and purpura
Managed with prednisolone or IV immunoglobulins
What is TTP, how does it present and how is it managed?
Condition where tiny thrombi develop throughout the small vessels using up platelets
Causes low platelets, purpura, tissue ischaemia and end organ damage
Managed with plasma exchange, steroids and rituximab
What is heparin induced thrombocytopenia, how does it present and how is it managed?
Development of antibodies against platelets in response to heparin
Presents 5-10 days after starting heparin with DVT and low platelets
Stop heparin and use alternative anticoagulant
What are some complications associated with multiple myeloma?
Infection, VTE, stroke, bone pain/fractures, peripheral neuropathy, spinal cord compression
What is the most common inherited cause of prolonged bleeding?
Von Willebrand disease
How is Von Willebrand disease managed?
Does not require daily treatment but needed in response to severe bleeding or in preparation for surgery
Includes desmopressin, tranexamic acid, von willebrand factor infusion
Which factors are deficient in Haemophilia A and B?
A = VIII
B = IX
What is the inheritance pattern of von willebrand disease?
Most commonly autosomal dominant
What is the inheritance pattern of haemophilia?
X-linked recessive
How does haemophilia present?
Spontaneous bleeding or severe bleeding in response to minor trauma
Spontaneous haemarthrosis in ankle, knee or elbow
How is haemophilia managed?
Affected clotting factor can be given by IV infusion given regularly or in response to bleeding
What are relative causes of polycythaemia?
Dehydration or stress
What are the secondary causes of polycythaemia?
COPD, altitude, OSA, excessive EPO e.g. uterine fibroids
Which gene is associated with myeloprolifertaive disorders?
JAK2
What are the FBC findings in someone with myelofibrosis?
Low Hb, high or low WBC, high or low platelet count
What are the FBC findings in someone with polycythaemia Vera?
High Hb, often associated with high WBC and platelets
What are the FBC findings associated with essential thrombocythaemia?
High platelet count
How are myeloprolifertaive disorders diagnosed?
Bone marrow biopsy
What clinical signs are seen in someone with polycythaemia?
Ruddy complexion, conjunctival plethora, splenomegaly, hypertension
What is the treatment for primary myelofibrosis?
No active treatment if mild
Manage any complications
Hydroxycarbamide chemotherapy
JAK2 inhibitors
Allogenic stem cell transplantation
What is the treatment for polycythaemia vera?
Venesection to keep Hb in normal range
Aspirin to reduce thrombus formation
Hydroxycarbamide chemotherapy
What is the treatment for essential thrombocythaemia?
Aspirin to reduce risk of thrombus formation
Hydroxycarbamide chemotherapy
What can myeloproliferative disorders develop into?
They can develop into acute myeloid leukaemia
What is myelodysplastic syndrome?
Form of cancer that results in inadequate production of blood cells –> anaemia, neutropenia and thrombocytopenia
What is the treatment for myelodysplastic syndrome?
Watchful waiting, supportive treatment with blood transfusions and platelet transfusions, EPO, allogenic stem cell transplant
What clotting abnormality will be present in von willebrand disease?
Prolonged APTT
normal INR
What features are seen in the bloods of someone with DIC?
Low platelets, prolonged clotting times and raised fibrin degradation products
What features indicate poor prognosis in lymphoma?
B symptoms, increasing age, advanced disease, male, lymphocyte depleted subtype
What is the classic symptom of polycythaemia rubra vera?
Itching following exposure to hot water/hot weather
What is the 1st line treatment for CML?
Tyrosine kinase inhibitors such as imatinib (87% effective)
How is superficial thrombophlebitis managed?
Oral NSAIDs and compression stockings
