Haematology Flashcards
give 3 causes of microcytic anaemia
iron-deficiency anaemia.
thalassaemia.
sideroblastic anaemia.
give 3 causes of normocytic anaemia
acute blood loss; anaemia of chronic disease; bone marrow failure; renal failure; hypothyroidism; haemolysis; pregnancy
give 3 general symptoms of anaemia
fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia
give 3 general signs of anaemia
pallor, tachycardia, systolic flow murmurs, enlarged heart
give a physiological cause of anaemia
pregnancy (normocytic)
give 3 causes of iron-deficiency anaemia
blood loss, poor diet, malabsorption, hookworm
describe what is seen on a peripheral blood film in iron-deficiency anaemia
microcytic hypochromic RBCs, varying in size and shape (anisocytosis and poikilocytosis)
give 3 specific features of iron deficiency anaemia
koilonychias, angular chelitis and glossitis
spoon nails, inflammation in corner of mouth, inflammation of tongue
In iron deficiency anaemia, what will happen to the iron, ferritin and total iron binding capacity (TIBC)?
iron and ferritin are decreased.
TIBC is increased.
how would you treat iron deficiency anaemia? how long would this treatment be given?
oral ferrous sulphate - given until anaemia resolved + further 3/12
what are some side effects of ferrous sulphate?
nausea, abdominal discomfort, diarrhoea/constipation, black stools
what diagnostic tests would you perform if you suspected anaemia?
blood count and film.
ferritin, B12 etc.
how would you treat anaemia of chronic disease?
treat underlying disease.
give Epo.
what is sideroblastic anaemia?
microcytic hypochromic.
inherited or acquired disorder - body has enough iron but can’t incorporate it into Hb.
how would you diagnose sideroblastic anaemia?
bone marrow sample - presence of sideroblasts - RBCs being produced with a ring of excess iron around the nucleus.
how would you treat sideroblastic anaemia?
Pyridoxine (vit B6).
repeated RBC transfusion (+iron chelation!)
give 3 causes of sideroblastic anaemia.
inherited; myeloid leukaemia; drugs (isoniazid); alcohol misuse; lead toxicity.
what causes pernicious anaemia?
autoimmune disease - antibodies against parietal cells and intrinsic factor, so these are destroyed leading to achlorydia and B12 malabsorption
how does B12/folate deficiency lead to anaemia?
B12 and folate needed for DNA synthesis - developing red cells can’t divide, they are stuck as large immature cells (megaloblastic) which then become macrocytic RBCs
what specific sign characterises pernicious anaemia?
mild jaundice due to haemolysis - pallor + jaundice = lemon tinge to skin
what specific tests would you perform if you suspected pernicious anaemia?
FBC, blood film and:
parietal cell antibodies, intrinsic factor antibodies
how would you treat pernicious anaemia?
IM injection of hydroxycobalamin
give some causes of folate deficiency
poor diet.
increased demand - pregnancy or increased cell turnover.
malabsorption.
drugs, alcohol.
how would you treat folate-deficiency anaemia?
oral folic acid + B12
give some acquired causes of haemolytic anaemia
Drug-induced, autoimmune haemolytic anaemia (AIHA), hep B and C, haemolytic-uraemic syndrome (HUS), TTP, DIC, malaria
give some hereditary causes of haemolytic anaemia
G6PD deficiency, pyruvate kinase deficiency, hereditary spherocytosis, sickle cell disease, thalassaemia
what is aplastic anaemia?
anaemia due to bone marrow failure - pancytopenia with hypoplastic marrow - marrow stops making all cells
give some causes of aplastic anaemia
autoimmune, drugs, irradiation, inherited
give 2 specific features of aplastic anaemia
bruising with minimal trauma.
blood blisters in mouth.
what test would you perform in aplastic anaemia? what would it show?
bone marrow biopsy - hypocellular aplastic bone marrow with increased fatty spaces
how would you treat aplastic anaemia?
allogenic marrow transplant.
or immunosuppression - ciclosporin.
what is sickle cell anaemia?
autosomal recessive disorder causing production of abnormal beta globin chains.
HbSS/HbAS instead of HbA (HbAS is carrier state)
being a carrier of sickle cell protects you against what disease?
falciparum malaria
what is the pathogenesis of sickle cell anaemia?
HbS polymerizes when deoxygenated causing RBCs to sickle - rigid, fragile cells that occlude small vessels and have short lifespan (haemolyse).
describe the clinical features of vaso-occlusive crises seen in sickle-cell anaemia
severe pain due to effect on marrow of microvascular occlusion. acutely painful hands and feet.
what is splenic sequestration?
a type of sickle-cell crisis:
vaso-occlusion produces acute painful enlargement of spleen.
pooling of RBCs in spleen = hypovolaemia = circulatory collapse and death.
immediate transfusion needed.
give 3 long-term complications of sickle-cell disease
poor growth, bone problems, infections, leg ulcers, neurological complication, gallstones, retinal disease, lung fibrosis, pulmonary hypertension
what tests would you perform in a case of sickle cell disease? what would you see?
FBC.
blood film - sickle cells and target cells (pale centre).
sickle solubility test - HbSS/HbAS instead of HbA
Hb electrophoresis - distinguishes HbSS and HbAS.
how would you treat sickle cell disease?
hydroxycarbamide.
prophylactic abx/immunisations.
bone marrow transplant.
describe the genetics of beta thalassaemia
mutations in beta-globin genes (chromosome 11) leading to decreased/no beta chain production
how does beta thalassaemia cause anaemia?
unmatched globins and excessive alpha chains precipitate - increased haemolysis and ineffective erythropoiesis.
what are the features of minor beta thalassaemia?
symptomless carrier state. mild anaemia. hypochromic and microcytic.
what are the features of medium beta thalassaemia?
moderate anaemia with splenomegaly, gallstones, leg ulcers etc. doesn’t require transfusions.
what are the features of major beta thalassaemia?
severe anaemia - needs regular transfusions.
presents in 1st year - abnormalities in both beta globin genes.
characteristic head shape and hepatosplenomegaly.
how would you treat beta thalassaemia?
folate supplements.
regular blood transfusions - desferrioxamine (iron-chelator) to prevent iron overload.
bone marrow transplant = cure.
what are the genetics of alpha thalassaemia?
gene deletions (not point mutations as in beta) in alpha globin chain genes on chromosome 16
describe the features of a 4+ gene deletion alpha thalassaemia
no alpha chains synthesised.
infants = stillborn, or die very quickly.
describe the features of a 3 gene deletion alpha thalassaemia
moderate anaemia and splenomegaly, jaundice, leg ulcers
describe the features of a 2 gene deletion alpha thalassaemia
microcytosis ± mild anaemia
how many alpha globin gene deletions may a patient have and still appear clinically normal?
1
what is glucose-6-phosphate dehydrogenase (G6PD) deficiency?
X linked haemolytic condition caused by mutation in the G6PD gene
what does G6PD do?
enzyme of the hexose monophosphate pathway - needed for generating reduce glutathione which protects RBC membrane from damage
does G6PD deficiency affect mainly men or women?
men
give some precipitants of G6PD deficiency crises
henna.
favism (ingesting fava beans).
drugs, infections.
what are the features of an acute G6PD deficiency haemolytic episode?
anaemia, fever, jaundice, dark urine.
bite and blister cells on blood film.
what is polycythaemia?
an increase in Hb, PCV - packed cell volume (haematocrit) - or RCC (red cell count)
PCV = % by volume of RBCs in blood
what is the difference between relative and absolute polycythaemia?
relative = low plasma volume, but no change in cell numbers. absolute = increase in RBC mass.
who gets relative polycythaemia?
middle aged obese males, smokers, high alcohol intake, hypertension
what causes primary polycythaemia?
polycythaemia rubra vera - malignant proliferation of a clone from one pluripotent marrow stem cell
what causes secondary polycythaemia?
due to hypoxia - high altitudes, chronic lung disease, heavy smoking
what gene mutation causes polycythaemia rubra vera?
JAK2
In polycythaemia rubra vera, what is there an excess proliferation of?
red cells, white cells and platelets - hyperviscosity/hypervolaemia.
give 3 symptoms of polycythaemia
headache, dizziness, tinnitus, visual disturbance, itching after warm bath, burning in fingers and toes.
give 3 things you might find on examination in polycythaemia
facial plethora (red, turgid face), splenomegaly (only in PRV), gout, arterial/venous thrombosis
why do polycythaemia patients get gout?
increased urate from RBC turnover
what will the marrow of a patient with polycythaemia rubra vera show?
hypercellularity with erythroid hyperplasia
how would you treat polycythaemia rubra vera?
venesection, hydroxycarbamide, low dose aspirin
how would you treat secondary polycythaemia?
treat primary cause.
oxygen therapy + smoking cessation.
list 4 risk factors of DVT
increasing age, pregnancy, synthetic oestrogens (pill, HRT), trauma, surgery, past DVT, cancer, obesity, immobility, thrombophilia
what other disease may a DVT present as?
pulmonary embolism
describe the clinical features of a DVT
warm, tender calf, with erythema. fever. pitting oedema.
what investigations would you do on a patient with a suspected DVT?
D-dimer - -ve result excludes DVT, +ve doesn’t mean it is DVT.
doppler US.
give 4 features included in the Wells score
active cancer, immobility, major surgery in last 4 weeks, local tenderness, swollen leg, pitting oedema, collateral superficial veins
how would you manage a patient with a DVT?
LMWH or fondaparinux - short term anticoagulation.
warfarin or NOAC - long term anticoagulation.
compression stockings.
mobilise, stop the pill.
what steps can be taken to prevent DVT?
stop the pill.
early mobilisation.
compression stockings/leg elevation.
LMWH/fondaparinux.
how does fondaparinux work as an anticoagulant?
factor Xa inhibitor - prevents the final coagulation pathway from continuing, preventing formation of fibrin clot.
how do heparins work as anticoagulants?
activate antithrombin, which inactivates factor Xa.
LMWHs also act to inhibit factor Xa directly.
how would you stop bleeding in an over-anticoagulated patient?
IV vitamin K - warfarin ‘antidote’
protamine = heparin antidote
what is disseminated intravascular coagulation?
massive activation of clotting cascade leads to lots of fibrin deposition within vessels.
using up all your platelets and coagulation factors forming these intravascular clots - so get bleeding elsewhere.
give 2 causes of DIC?
sepsis. major trauma/burns. advanced cancer. obstetric complications. acute promyelocytic leukaemia.
what are the clinical features of DIC?
profuse bleeding where there shouldn’t be any - from venepuncture sites, from nose/mouth
what results would you find on investigation of a patient with DIC?
low platelets, prolonged prothrombin time, very low fibrinogen, increased D dimer
other than treating the underlying cause, how would you manage a patient with DIC?
maintain blood volume and tissue perfusion - replacement platelets FFP (fresh frozen plasma) and cryoprecipitates
what is immune/idiopathic thrombocytopenia purpura (ITP)?
antiplatelet autoantibodies lead to immune destruction of platelets - low platelet count
what are the main features of ITP?
easy bruising + purpura - rash of purple spots on skin due to internal bleeding.
isolated thrombocytopenia - low platelets, but everything else is normal.
how would you treat ITP?
prednisolone.
splenectomy or chemo
what is thrombotic thrombycytopenia purpura (TTP)?
deficiency of protease that breaks down vWF - widespread platelet adhesion/aggregation leading to microvascular thrombosis + thrombocytopenia.
what is thrombocytopenia?
lack of platelets
give some causes of TTP
congenital
sporadic
autoantibody mediated - pregnancy, SLE, infection
how might a patient with TTP present?
purpura, fever, fluctuating cerebral dysfunction, haemolytic anaemia
how would you treat a patient with TTP?
plasma exchange.
steroids/monoclonal antibodies.
what is haemophilia A?
X-linked recessive inherited factor VIII deficiency
how would a patient with haemophilia A present?
early in life/after surgery or trauma.
bleeds into joints and muscles - arthropathy and haematomas.
how would you diagnose and treat haemophilia A?
factor VIII assay
IV recombinant factor VIII
what is haemophilia B? how is it treated?
factor IX deficiency - same clinical behaviour as haemophilia A.
treat with factor IX.
what is von Willebrand’s disease?
deficiency of vWF - leads to platelet dysfunction
what clinical signs indicate a platelet disorder (e.g. von Willebrand’s disease)?
bruising, epistaxis, menorrhagia, excessive bleeding after tooth extraction
how would you treat von Willebrand’s disease?
desmopressin for mild bleeds.
vWF-containing factor VIII concentrate.
what cell lines are affected in acute lymphoblastic leukaemia (ALL)?
lymphoblasts - B/T cell precursors
which leukaemia most commonly affects children?
ALL - acute lymphoblastic leukaemia
name a trigger of ALL
ionising radiation during pregnancy
which of the leukaemias is associated with Downs syndrome?
ALL - acute lymphoblastic leukaemia
give some clinical features of ALL
marrow failure - anaemia, infections, bleeding.
hepatosplenomegaly, lymphadenopathy, CNS involvement, bone pain.
what infections are commonly seen in ALL patients?
CMV, measles, candidiasis, Pneumocystis pneumonia (PCP)
what investigations would you carry out on an ALL patient? what would the results show?
peripheral blood film and bone marrow aspirate - blast cells.
CXR/CT scan for lymphadenopathy.
LP for CNS involvement.
how would you treat ALL?
allopurinol. prophylactic abx, antifungals, antivirals.
Chemo - vincristine, prednisolone + daunorubicin.
bone marrow transplant.
what cell lines are affected in acute myeloid leukaemia (AML)?
blast cells
what may trigger AML?
long-term chemotherapy
radiation
what is the typical age of onset of AML?
around 65
give some clinical features of AML
DIC, hepatosplenomegaly, gum hypertrophy, bleeding, infections, skin involvement
how would you diagnose AML?
bone marrow biopsy - Auer rods are characteristic
how would you treat AML?
chemo - daunorubicin and cytarabine.
bone marrow transplant.
ciclosporin ± methotrexate after transplant.
what cell lines are affected in chronic myeloid leukaemia (CML)?
myeloid
what are the genetics behind CML?
Philadelphia chromosome - translocation between chromosomes 9 and 22 - t(9;22).
affects tyrosine kinase activity.
describe the clinical features of CML
chronic and insidious.
weight loss, fatigue, fever, sweats.
gout, bleeding, splenomegaly, bruising, abdo discomfort.
which of the leukaemias doesn’t cause recurrent infections?
CML - chronic myeloid leukaemia
what investigations would you do in CML? what results would you expect?
FBC - WCC raised. Hb low.
bone marrow aspiration - hypercellular.
cytogenetic analysis - Ph chromosome.
how would you treat CML?
Chemo: IMATINIB - tyrosine kinase inhibitor.
stem cell transplant.
what cell lines are affected in chronic lymphocytic leukaemia?
mature B cells - they have escaped programmed cell death.
who does CLL affect? what is the prognosis like?
it’s an incurable disease of older people - but some show no/slow progression - have a near normal life expectancy.
(others show active progression so have a worse prognosis).
what can trigger CLL?
pneumonia
give some clinical features of CLL
fever, painless lymphadenopathy (rubbery nodes), weight loss, anorexia, hepatospenomegaly, LUQ pain.
what would a FBC show in CLL?
raised WCC, especially lymphocytes.
low Hb/neutrophils/platelets.
how would you treat CLL?
chemo: fludarabine + cyclophosphamide + rituximab.
radiotherapy.
stem cell transplants.
what histological feature differentiates Hodgkin’s lymphoma from NHL?
presence of Reed-Sternberg cells (mirror-image nuclei)
what are lymphomas?
neoplastic transformations of B and T cells which accumulate in lymph nodes - lymphadenopathy
give 3 risk factors for Hodgkin’s lymphoma
affected sibling; EBV; SLE; post-transplant; obesity; Westernization
at what ages are the 2 peaks of incidence of Hodgkin’s lymphoma?
young adults and the elderly
describe the lymphadenopathy seen in Hodgkin’s lymphoma. give 2 possible sites.
enlarged, painless, rubbery superficial lymphadenopathy.
cervical, axillary, inguinal.
give 3 systemic features of Hodgkin’s lymphoma
fever; drenching night sweats; weight loss; pruritus; fatigue; anorexia
list some differential diagnoses of Hodgkin’s lymphoma
any cause of lymphadenopathy - infections, secondary carcinoma, leukaemia, systemic diseases (e.g. SLE, rheumatoid arthritis, sarcoidosis)
what investigations would you carry out in Hodgkin’s lymphoma? what results would you expect?
lymph node biopsy - histology for Reed Sternberg cells.
FBC - low Hb, raised ESR.
describe the staging of Hodgkin’s lymphoma
Ann Arbor system:
I = single region
II = 2+ nodal areas involved on one side of diaphragm
III = involvement on both sides of diaphragm
IV = spread beyond nodes
then divided into A and B - B if systemic symptoms are present.
how would you treat Hodgkin’s lymphoma?
ABVD chemo + radiotherapy - curative.
give 3 causes of Non-Hodgkin’s lymphoma (NHL)
immunodeficiency - drugs, HIV.
HLTV-1; H pylori; toxins; congenital.
what AIDS defining illness is associated with NHL?
Burkitt’s lymphoma - jaw lymphadenopathy
give some clinical features of NHL
painless peripheral lymph node enlargement. systemic symptoms the same as for Hodkin’s - weight loss, fever, sweats.
bone marrow failure, bleeding.
what investigations would you do in NHL? what would you expect to see?
bloods - normocytic anaemia, raised WCC, neutropenia, thrombocytopenia.
raised ESR/LDH. raised urate.
Lymph node biopsy + bone marrow aspirate.
what staging system is used for non-Hodgkin’s lymphoma?
Ann Arbor system
how would you treat low grade NHL?
radiotherapy.
chlorambucil, interferon or rituximab.
how would you treat high grade NHL?
RCHOP - rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin prednisolone.
what cell line is affected by myeloma?
plasma cells - malignant clonal expansion - produce excessive amounts of one type of Ig
what are the diagnostic criteria for myeloma?
1) monoclonal protein band on serum/urine electrophoresis
2) increased plasma cells on bone marrow biopsy
3) evidence of end organ damage (hypercalcaemia, renal failure, anaemia)
describe the clinical features of myeloma
bone pain, osteolytic lesions, pathological fractures, anaemia, bleeding, recurrent bacterial infection. renal impairment.
what investigations would be carried out in myeloma? what would you see?
blood film - Rouleaux formation (RBCs stack on top of each other).
urine - Bence Jones protein.
X ray - punched out lesions e.g. pepper pot skull.
how would you treat myeloma?
bone pain - bisphosphonates and analgesia - avoid NSAIDs (kidneys).
fluids, abx, correct anaemia.
Chemo - melphalan + prenisolone ± thalidomide.
give 3 complications of myeloma
hypercalcaemia of malignancy.
spinal cord compression.
hyperviscosity.
acute renal failure.
how is malaria transmitted?
protozoa that is transmitted by bite of infected female Anopheles mosquito
what are the 4 species of plasmodium that cause malaria?
P vivax, P ovale, P malariae, P falciparum
give 3 general clinical features of malaria
fever, malaise, headache, vomiting, diarrhoea, rigors, sweats
give 3 features of Vivax/ovale malaria
anaemia, tender hepatosplenomegaly, mild illness
give 3 features of Malariae malaria
relatively mild, more chronic, glomeulonephritis/nephrotic syndrome
give 3 features of Falciparum malaria
anaemia, jaundice, hepatosplenomegaly, cerebral malaria (fits, confusion, coma), metabolic acidosis, pulmonary oedema, hypoglycaemia, diarrhoea, DIC
what investigation would you perform to diagnose malaria? what does this tell you?
thick and thin blood smears
thick - diagnoses malaria
thin - quantifies % of infected RBCs, identifies species
what must you take into account, before treating a malaria patient?
whether they’ve taken any prophylaxis - which type? likely their malaria is resistant, so don’t treat them with this!
how would you treat falciparum malaria?
uncomplicated - oral riamet or quinine ± doxycycline.
complicated - IV artesunate or quinine.
how would you treat non-falciparum malaria?
oral chloroquine
what drugs can be used as prophylaxis for malaria?
mefloquine, atovaquant, proguanil, chloroquine, doxycycline.
list 3 causes of macrocytic anaemia
B12/folate deficiency.
haemolytic anaemias.
alcoholism, liver disease, hypothyroidism.
what must you assess before giving anticoagulation therapy? how would you assess this?
bleeding risk. HAS-BLED. Hypertension. Abnormal liver/renal function. Stroke. Bleeding. Labile INR. Elderly. Drugs/alcohol.
give a main advantage and disadvantage of NOACs
adv - no need for regular INR monitoring - easier for patient.
dis - don’t have an antidote, so patient at risk of massive haemorrhage if injured etc.
which leukaemia commonly affects the elderly?
CML
if you see blast cells on a blood film, what does this suggest?
an acute leukaemia
if Auer rods are seen on a blood film, which leukaemia is this?
AML
if smudge cells are seen on a blood film, which leukaemia is this?
CLL
what are the signs of end-organ damage seen in myeloma?
CRAB. Calcium - hypercalcaemia (bones). Renal failure Anaemia Bone lytic lesions e.g. pepperpot skull.
give an example of an iron chelator.
how do these drugs work?
desferrioxamine.
binds free iron in bloodstream and enhance its elimination in urine.
list some triggers of sickle cell crisis
cold, dehydration, infection, hypoxia.
