Haematolgy Flashcards
Differentiate the causes of megaloblastic and non-megaloblastic macrocytic anaemia
Megaloblastic: B12/folate deficiency (pregnancy, old age, veganism)
Non-megaloblastic: liver disease/ alcoholism/ multiple myeloma
Recall the 2 key symptoms and the 3 key signs of any anaemia
Symptoms: lethargy, breathlessness
Signs: pallor, tachycardia, breathlessness
Recall 3 signs of pernicious anaemia that might be present in addition to the normal signs of anaemia
Glossitis
Angular stomatitis
Mild jaundice
What signs of B12 deficiency may be present alongside an anaemia?
Peripheral neuropathy
Optic atrophy
Dementia
How are LFTs commonly deranged in macrocytic anaemia and why?
High bilirubin
Ineffective erythropoiesis, haemolysis
What blood tests are done to detect B12 and folate levels?
Serum cobalamin
Red cell folate
As well as macrocytic erythrocytes, what can be seen on a blood film in megaloblastic anaemia?
Hypersegmented neutrophils
What test is done to diagnose pernicious anaemia?
Schilling test
Recall the management of pernicious anaemia
IM hydroxycobalamin for life
What is the most likely cause of a microcytic anaemia?
Iron deficiency
Recall 4 causes of iron deficiency
GI blood loss
Small bowel disease
Vegan
Pregnancy
What size are the red cells in anaemia of chronic disease?
Microcytic
In what sort of anaemia may the patient develop brittle nails and hair?
Iron deficiency anaemia
What might an FBC show in microcytic anaemia?
Low Hb
Low MCV
High reticulocytes
Recall the iron, TIBC and ferritin seen in iron deficiency anaemia
Iron: low
TIBC: high
Ferritin: low
Does thalassaemia produce a microcytic or a macrocytic anaemia?
Microcytic
Systematically recall some causes of normacytic anaemia
Decreased production: vit B2/6 deficiency, ACD, aplastic anaemia
Increased destruction: haemolysis
Increased blood volume: fluids, pregnancy
Define aplastic anaemia
A pancytopaenia due to fewer haemotopoietic precursors
What symptoms and signs of aplastic anaemia will not be present in any other aetiology of anaemia?
Symptoms of thrombocytopaenia Purpura Easy bruising Epistaxis Petechiae Also multiple infections due to leukocytopaenia
What are the 2 different types of disseminated intravascular coagulation?
Acute overt
Chronic non-overt
Differentiate the pathophysiology of acute overt and chronic non-overt disseminated intravascular coagulation
Acute overt: bleeding –> depletion of platelets and clotting factors
Chronic non-overt: thromboembolism –> generalised activation of coagulation system
What sort of infection is most likely to cause disseminated intravascular coagulation?
Gram negative sepsis
Describe the pathophysiology of DIC
Endothelial damage –> tissue factor release
Tissue factor activates thrombin
Thrombin depletes clotting factors and platelets
Thrombin activates fibrinolysis
Fibrinolysis releases fibrin, which occludes the microvasculature
Which patients are particularly at risk of disseminated intravascular coagulation?
Pretty much all severely unwell patients will get
Differentiate the signs that are present in acute and chronic disseminated intravascular coagulation
Acute: purpura, petechiae, ecchymoses, epistaxis
Chronic: signs of DVT/ arterial thromboses
Describe the FBC of someone with disseminated intravascular coagulation
Low Hb and platelets
What should be tested for alongside FBC in the blood in suspected disseminated intravascular coagulation
APTT (will be high)
FDP (will also be high)
Recall the pathophysiology of haemachromatosis
GENETIC increase in iron absorption, iron accumulates in tissues, organs damaged
Recall some late symptoms of haemachromatosis
T2DM Bronzed skin Hepatomegaly Cirrhosis Hypogonadism Cardiac arrhythmias/ cardiomyopathy
Recall the results of haematinic investigations in haemachromatosis
Ferritin: high
Transferrin: low
[Transferrin]: high
TIBC: low
Systematically recall possible causes of haemolytic anaemia
- Hereditary
a) membrane defects - elliptocytosis, hereditary spherocytosis
b) haemaglobinopathies: thalassaemia, sickle-cell disease
c) metabolic defects: G6PD deficiency, PKU deficiency - Acquired
Infection: sepsis, malaria
Trauma
Drugs
Autoimmune
Recall 2 symptoms of haemolytic anaemia that are not present in other types of anaemia
Jaundice (due to increased red cell breakdown)
Haematuria (due to haemolysis)
Is haemolytic anaemia macrocytic or microcytic?
Macrocytic
Recall 3 abnormalities found on urinalysis in haemolytic anaemia
- High urobilinogen
- Haemaglobinuria
- Haemosiderinuria
What specific test is done for auti-immune haemolytic anaemia?
Direct Coomb’s test
What are the 2 categories of haemolytic uraemic syndrome
D+ (with diarrhoea, usually children)
D- (no prodromal illness)
Define haemolytic uraemic syndrome
Triad of microangiopathic haemolytic anaemia, thrombocytopaenia and acute renal failure
Explain the pathophysiology of HUS and TTP
Endothelial damage –> platelets aggregate
1a. Platelet aggregation –> thrombi formation –> promotion of intravascular haemolysis
1b. Platelet aggregation –> loads of vWF released –> small vessel thrombosis
Small vessel thrombi most likely to affect afferent glomerular arterioles which is why HUS + TTP –> renal failure
What is the difference between thrombotic thrombocytopaenic purpura and haemolytic uraemic syndrome
TTP has extra clinical manifestation of fever and CNS signs
Which pathogen is the most common cause of HUS and where it is usually found?
E Coli 0157
Contaminated water
Recall the symptoms of HUS
General sickness/ malaise
GI symptoms: bloody diarrhoea, severe colic
Renal symptoms: oligouria, haematuria
Describe the FBC results for someone with HUS and TTP
Normacytic anaemia
High neutrophils
VERY LOW platelets
What would an ABG show in HUS?
Lactic acidosis
What would a blood film show in HUS?
High reticulocytes and schistocytes
Recall 3 symptoms of haemophilia
- Haemarthroses
- Haematuria
- Deep bleeding
Recall 2 investigations that should be done in suspected haemophilia
Clotting factor assay
APTT
What is immune thrombocytopaenic purpura?
Immune destruction of platelets
What is the antibody that is implicated in immune thrombocytopaenic purpura?
Anti-GpIIb/ anti-GPIIIa
Recall the general signs/ symptoms of ITP
Easy bruising, epistaxis, visible purpura, menorrhagia
What will the result of a clotting screen be in ITP?
Normal
Why is it important to do a blood film in suspected ITP?
Need to rule out pseudothrombocytopaenia
What is the most common malignancy of childhood?
Acute lymphoblastic leukaemia
Systematically recall the symptoms of acute lymphoblastic leukaemia
Due to reduced synthesis of blood cells: anaemia, easy bruising, recurrent infections
Due to organ infiltration: tender bones, lymphadenopathy, meningism
Systematically recall the signs of acute lymphoblastic leukaemia
Due to bone marrow failure: bruising, pallor
Due to tissue infiltration: lymphadenopathy, hepatosplenomegaly, retinal haemorrhage + papilloedema, testicular swelling
What sort of anaemia results from acute lymphoblastic leukaemia?
Normacytic normachromic
Which enzyme is elevated in the blood in cancer patients?
LDH
Recall one blood test result that is a poor prognostic factor for acute lymphoblastic leukaemia
Uric acid high
Recall 4 appropriate investigations in suspected acute lymphoblastic leukaemia
- Bloods (FBC, U&Es, LDH)
- Blood film and BM aspirate
- Immunophenotyping
- CXR to look for mediastinal lymphadenopathy
Recall some signs of acute myeloblastic leukaemia that result from tissue infiltration, and aren’t seen in acute lymphoblastic leukaemia
Gum swelling/ bleeding
Skin rashes
CNS involvement: headache and diplopia
What is the expected white cell count in acute myeloblastic leukaemia?
Can be variable
In which demographic is acute myeloblastic leukaemia most common?
The elderly: incidence increases with age
Define chronic lymphocytic leukaemia
Progressive accumulation of functionally incompetent lymphocytes which have monoclonal origin
What causes lymphocytes to accumulate in CLL?
Failure of apoptosis
Which type of leukaemia is most likely to be asymptomatic?
CLL
Recall 2 signs of CLL on examination
Non-tender lymphadenopathy
Hepatosplenomegaly
Recall 2 findings on the blood film in CLL
Small lymphocytes
Smudge cells
With which other disease does CLL overlap?
Non-hodgkn’s lymphoma
What type of cell is hyperproliferating in CML?
Granulocyte precursors
What translocation occurs to produce the Philadelphia chromosome, and what sort of cancer does this predispose to?
Chromosomes 9 and 22
BCR-ABl fusion
Chronic myeloid leukaemia
In what sort of pateints is CML most likely to occur?
Men (4 x more common than in women)
Recall the 3 phases of CML
Stable chronic (4-6 years)
Accelerated (3-6 months)
Acute (blast transformation)
Recall a sign that is present in 90% of CML patients
Splenomegaly
What is the most likely aetiology of hypercobalaminaemia?
Haematological neoplastic cause
Define Hodgkin’s lymphoma
Neoplasm of lymphoid cells originating in the lymph nodes
How is Hodgkin’s lymphoma diagnosed?
Histopathologically, based on presence of REED-STENBERG cells
What are reed-stenberg cells and in which disease do they appear in the blood film?
Bi-nucleate lymphocytes
Hodgkin’s lymphoma
What is the main symptom of Hodgkin’s lymphoma?
Painless enlarging neck mass, that may become painful following alcohol consumption
How are the lymph nodes described in lymphoma?
Painless, firm and rubbery
What staging system is used to stage lymphoma?
Ann Arbor
What sign may be present on the skin of someone with hodgkin’s lymphoma/ non-hodgkin’s lymphoma
Hodgkin’s: excoriations
Non-Hodgkin’s: rashes eg. mycosis fungoides
In which types of cancer are ESR and CRP likely to be elevated?
Hodgkin’s/non-Hodgkin’s lymphomas
What % of Non-Hodgkin’s lymphomas involve B cells, T cells and NK cells?
85% B cells
15% T and NK cells
Recall one viral cause of non-Hodgkin’s lymphoma
EBV virus, causing Burkitt’s lymphoma
Recall 3 places where a mass may appear due to non-Hodgkin’s lymphoma
Neck
Groin
Axilla
Which type of lymphoma is most common?
Non-Hodgkin’s
Recall one common electrolyte imbalance in non-Hodgkin’s lymphoma
Hypercalcaemia
Recall one difference in the FBC between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
In Hodgkin’s = neutrophilia, in non-Hodgkin’s = neutropaenia
What is multiple myeloma a proliferation of?
Plasma cells
Recall 2 symptoms of multiple myeloma
Symptoms: bone pain, recurrent infection
Recall 3 signs of multiple myeloma
Heart problems (tachycardia, flow murmur, heart failure)
Carpal tunnel
Macroglossia
(why???)
What is a key finding on the blood film in multiple myeloma?
Rouleaux
= suggestive of high protein
Why is an X ray important to do in suspected multiple myeloma?
Osteolytic lesions will be seen
What is myelodysplasia?
A group of syndromes where the immature blood cells in the blood do not mature normally causing chronic pancytopaenia
Recall the 5 subgroups of myelodysplasia
Refractory anaemia
Refractory anaemia and ringed suderoblasts
Refractory anaemia with excess blasts
Refractory anaemia with excess blasts in transformation
Chronic myeloMONOCYTIC leukaemia
What is the most common cause of secondary myelodysplasia?
Chemotherapy/ radiotherapy
What are the symptoms of a myelodysplastic syndrome?
May be asymptomatic, or exhibit similar symptoms to any blood neoplasm due to loss of functional mature blood cells - anaemia, recurrent infections, easy bruising
Describe the epidemiology of myelofibrosis
Really rare
What is myelofibrosis?
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis
What is the main histopathological finding on the blood film of someone with myelofibrosis?
Increased number of abnormal megakaryocytes
What sign will always be present in myelofibrosis and why?
Splenomegaly, due to extramedullary haematopoiesis
Define polycythaemia
Higher than normal concentration of haemoglobin
Differentiate between relative polycythaemia and polycythaemia vera
Relative - normal MCV and decreased plasma volume
True - increased MCV
Differentiate the aetiology of primary and secondary polycythaemia
Primary: clonal proliferation of myeloid cells
Secondary: increased erythropoietin
Recall 5 symptoms of polycythaemia
Angina Chorea Gout Headache Visual changes
Recall 3 signs of polycythaemia
- Red complexion
- Conjunctional suffusion (redness)
- 75% have splenomegaly
What investigation is done to differentiate between polycythaemia vera and relative polycythaemia?
Isotope dilution
Describe the erythropoietin level in polycythaemia vera and relative polycythaemia
Polycythaemia vera: low
Relative polycythaemia: high
Differentiate sickle cell anaemia and sickle cell disease
SCA: homozygous HbS
SCD: heterozygous HbS and HbC OR HbS and Beta-thalassaemia
What is the gene mutation in HbS?
Glutamic acid replaced with valine at position 6 on beta globin gene
Recall 4 symptoms of sickle cell anaemia
- Pneumococcal infection due to autosplenectomy
- Abdominal and bone pain
- CNS symptoms: fits and strokes
- In children: dactylitis
Recall 2 signs of a sickle cell crisis
Acute chest syndrome
Priapism
Recall 2 abnormal erythrocytes seen on a blood film of someone with sickle cell disease
Target cells
Howel-Jolly bodies
Recall one medical treatment option for sickle cell
Hydroxyurea - induces HbF production
Which virus is especially dangerous to sickle cell patients and why?
Parvovirus B19
Aplastic crisis
What is the life expectancy of someone with sickle cell anaemia?
50
What is the inheritance pattern of thalassaemia?
Autosomal recessive
Recall the 4 types of alpha thalassaemia
Number of gene deletions: 4 = HbBarts: fatal in utero 3 = HbH (causes anaemia and splenomegaly) 2 = alpha 0, no anaemia 1 = alpha +, no anaemia
Recall the 3 types of beta thalassaemia
Major: homozygous
Intermedia: causes a microcytic anaemia, with fewer alpha chains and more gamma chains
Trait: heterozygous and asymptomatic
Systematically recall the symptoms of beta thalssaemia
Due to anaemia: pallor, malaise, dyspnoea
Due to increased red cell lysis: jaundice
Due to extramedullary erythropoiesis: splenomegaly
Frontal bossing
Is the anaemia caused by thalassaemia macro/microcytic?
Microcytic
Where is vitamin B12 absorbed following consumption?
Terminal ileum
What cofactor is required for Vit B12 absorption?
Intrinsic factor
What is the pathophysiology of pernicious anaemia?
Autoimmune condition directed against intrinsic factor - so Vit B12 can’t be absorbed
Why does metformin have a side effect of anaemia?
Impairs Vit B12 absorption
Recall the symptoms of B12 deficiency
Anaemia symptoms
Palpitations
Headache
Neurological symptoms - paraesthesia and visual disturbance
What would be seen on a blood film of someone with vit B12 deficiency?
Hypersegmented neutrophils
Which 2 antibodies are implicated in pernicious anaemia?
Anti-IF
Anti-parietal cell
What type of bleeding is exhibited in Von Willebrand disease?
Mucocutaneous
Differentiate the 3 different types of VWF disease
Type 1: depleted volume of well-functioning VWF
Type 2: adequate volume of ill-functioning VWF
Type 3: NO VWF
Recall 3 symptoms of VWF disease
Easy bruising
Epistaxis
Blood in stools/ urine