Haem Flashcards
What are Auer rods seen on bone marrow biopsy or blood film pathognomonic of?
AML
What translocation is most likely present in CML?
t(9;22) Bcr-Abl translocation –> forms unregulated tyrosine kinase which causes excessive proliferation and reduction in apoptosis.
What type of leukaemia does high levels of neutroph and platelets indicate?
CML –> as these are mature myeloid derived cells.
What mutation is implicated in the majority of cases of polycythaemia vera>
JAK2 mutation
What is polycythaemia vera?
Malignancy of RBCs
What investigations are indicated in tumour lysis syndrome?
1) ECG
2) U&Es
3) Calcium
4) Uric acid
What investigation will confirm a diagnosis of aplastic anaemia?
Bone marrow biopsy
What is aplastic anaemia?
When the bone marrow fails to produce blood cells of all lineages –> pancytopenia.
What is Richter transformation?
This is when CLL transforms into a rare type of non-Hodgkin lymphoma (usually diffuse large B cell lymphoma).
What type of leukaemia does Richter transformation happen in?
CLL
What key feature indicates Richter transformation?
Rapidly enlarging lymph nodes
Inheritance of G6PD deficiency?
X-linked recessive
What Abx used in UTIs can predispose to haemolysis in G6PD deficiency?
Nitrofurantoin
How can mechanical heart valves lead to haemolytic anaemia?
Valves can cause intravascular haemolysis as the turbulent blood flow around the mechanical valve causes mechanical damage to the erythrocyte.
What is the management of an acute flare of RA?
Analgesia + corticosteroids
Define heparin induced thrombocytopenia
A drop of platelet by >30%.
This tends to be seen after 5-10 days of heparin treatment.
What are smudge cells seen on blood film pathognomonic of?
CLL
What are smudge cells in CLL?
In CLL, lymphocytes are fragile so may be damaged during slide preparation, resulting in smudge/smear cells.
Who does CLL typically present in?
Male patients >60
How is CLL often picked up?
Incidentally as a raised WCC
What is the treatment of choice in acute and severe faciparum malaria?
IV artesunate
What organism typically causes osteomyelitis in sickle cell?
Salmonella species
What is the gold standard investigation in osteomyelitis?
MRI
How does CML typically present?
In middle aged patients with massive splenomegaly
What is a haemolytic crisis?
When a large number of RBCs are destroyed over a short time.
Rapid fall in Hb, raised reticulocytes and prehepatic hyperbilirubinaemia.
What is hereditary spherocytosis?
An autosomal dominant condition which causes defects in the erythrocyte cell membrane.
Results in premature haemolysis of erythrocytes.
What is anaemia of chronic disease?
A reduction of RBC production in response to chronic disease.
Can cause a normocytic or microcytic anaemia.
What are some causes of anaemia of chronic disease?
- Chronic infections e.g. TB
- Malignancies e.g. lymphoma
- Autoimmune e.g. RA, SLE
Why may ferritin be raised in anaemia of chronic disease?
In response to systemic inflammation
What are some features in a person aged 0-24 years that should prompt a very urgent FBC (within 48 hours) to investigate for leukaemia?
- Pallor
- Persistent fatigue
- Unexplained fever
- Unexplained persistent infections
- Generalised lymphadenopathy
- Persistent or unexplained bone pain
- Unexplained bruising
- Unexplained bleeding
What is the median age of presentation of myeloma?
70 y/o
Features of myeloma? Mneumonic: CRABBI
C - hyperCalcaemia
R - renal impairment
A - anaemia
B - bleeding
B - bone lesions (pain and pathological fractures)
I - infection
How is calcium affected in myeloma?
Hypercalcaemia –> constipation, nausea, anorexia and confusion
What is multiple myeloma?
A haematological malignancy characterised by plasma cell proliferation.
It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
What causes anaemia in myeloma?
Bone marrow crowding suppresses erythropoiesis leading to anaemia
What causes bleeding in myeloma?
Bone marrow crowding also results in thrombocytopenia.
What causes increased infection in myeloma?
A reduction in the production of normal immunoglobulins.
How can amyloidosis affect the tongue?
Macroglossia
How can myeloma lead to stroke?
Hyperviscosity of blood (due to raised plasma cells).
What will a blood film show in myeloma?
Rouleaux formation
Features of CML?
1) Anaemia -> lethargy
2) Weight loss & sweating
3) Splenomegaly -> abdo discomfort
4) an increase in granulocytes at different stages of maturation
5) +/- thrombocytosis
What are granulocytes?
Neutrophils, eosinophils, basophils & mast cells.
1st line treatment of CML?
Tyrosine kinase inhibitor e.g. imatinib
In which condition does he urine classically turns deep red on standing?
Acute intermittent porphyria
What is acute intermittent porphyria?
A rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem.
Results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen.
How does AIP characteristically present?
With abdominal (pain & vomiting) and neuropsychiatric symptoms (depression, motor neuropathy) in 20-40-year-olds.
AIP is more common in females (5:1)
What medication can be used to stimulate the release of vWf in endothelial cells?
Desmopressin (analogue of ADH)
What is the most common inherited bleeding disorder?
Von Willebrand’s disease
Management of acute haemolytic transfusion reaction?
Stop transfusion & supportive care e.g. IV fluids
What is indicated by a ‘starry sky’ appearance on micropscopy?
Burkitt’s lymphoma
Management of polycythaemia vera?
1) Aspirin –> reduces the risk of thrombotic events
2) Venesection –> 1st line to keep Hb in normal range
3) Chemotherapy
What is a significant cause of morbidity and mortality in polycythaemia vera?
Thrombotic events
What are 3 key complications of polycythaemia vera?
1) Thrombotic events
2) 5-15% of patients progress to myelofibrosis
3) 5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)
What are the thalassaemias?
A group of genetic disorders characterised by a reduced production rate of either alpha or beta chains
What is beta-thalassaemia trait?
An autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia.
It is usually asymptomatic
Features of beta thalassaemia trait?
1) Mild hypochromic, microcytic anaemia (microcytosis is characteristically disproportionate to the anaemia)
2) Raised HbA2 (>3.5%)
How is a diagnosis of G6PD deficiency made?
G6PD enzyme assay.
Note –> levels should be checked at time of presentation and around 3 months after an acute episode of haemolysis to avoid false negatives.
How can an acute episode of haemolysis give false negative results in G6PD deficiency in an enzyme assay?
RBCs with the most severely reduced G6PD activity will have hemolysed –> reduced G6PD activity –> not measured in the assay –> false negative results.
What Abx can cause haemolysis?
Ciprofloxacin
Features of lead poisoning?
1) Abdo pain
2) Peripheral neuropathy (mainly motor)
3) Neuropsychiatric features
4) Fatigue
5) Constipation
6) Blue lines on gum margin
What is usually used for diagnosis of lead poisoning?
Blood lead level –> levels >10 mcg/dl are considered significant
What is seen on a FBC in lead poisoning?
Microcytic anaemia
What is a key differential for lead poisoning?
Acute intermittent porphyria (both present with abdo pain and motor peripheral neuropathy).
What will serum protein electrophoresis show in myeloma?
Raised concentrations of monoclonal IgA/IgG proteins will be present.
What investigation confirms the diagnosis of myeloma?
Bone marrow aspiration –> plasma cells are significantly raised.
Does Hodgkin’s lymphoa cause an increase in lymphocytes on a FBC?
No, but it can cause normocytic anaemia and eosinophilia.
What are 3 viral causes of neutropenia?
1) HIV
2) EBV
3) Hepatitis
What are 3 drugs that can cause neutropenia?
1) Cytotoxics
2) Carbimazole
3) Clozapine
What are some conditions that can cause neutropenia?
1) Haematological malignancy e.g. myelodysplastic malignancies, aplastic anemia
2) Rheumatological conditions
3) SLE
4) RA
5) Severe sepsis
6) Haemodialysis
Which stage of the Ann-Arbor clinical staging of lymphomas involves lymph nodes on both sides of the diaphragm?
Stage III
Which stage of the Ann-Arbor clinical staging of lymphomas involves a single lymph node?
Stage I
Which stage of the Ann-Arbor clinical staging of lymphomas involves 2 or more lymph nodes/regions on the same side of the diaphragm?
Stage II
How can hypercalcaemia affect urine?
Polyuria
How may myeloma present on FBC?
1) Anaemia
2) Thrombocytopenia
What is the most common inherited thrombophilia?
Activated protein C resistance (Factor V Leiden)
How long should patients with active cancer who are diagnosed with VTE be prescribed a DOAC for?
Minimum of 6 months
While a 3-month course may be adequate for patients with a provoked VTE, cancer patients with VTE require an extended duration of anticoagulation therapy (6 months).
A blood smear showing Howell-Jolly bodies indicates what condition?
Sickle cell disease
What is the reversal agent of rivaroxaban and apixaban?
andexanet alfa
What is the reversal agent for dabigatran?
Idarucizumab
Mechanism of rivaroxaban & apixaban?
Factor Xa inhibitor
Mechanism of dabigatran?
Direct thrombin inhibitor
What are 4 complications of CLL?
1) anaemia
2) hypogammaglobulinaemia –> leading to recurrent infections
3) warm autoimmune haemolytic anaemia
4) transformation to high grade lymphoma (Richter’s transformation)
What is Ritcher’s transformation?
This ccurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma.
Patients often become unwell very suddenly.
What symptoms indicate Ritcher’s transformation?
- lymph node swelling
- fever without infection
- weight loss
- night sweats
- nausea
- abdominal pain
What is the most common organism causing neurtropenic sepsis?
Coagulase-negative, Gram-positive bacteria - particularly Staphylococcus epidermidis.
This is probably due to the use of indwelling lines in patients with cancer.
What can be used as prophylaxis for neutropenic sepsis (if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment)?
Fluoroquinolone
Mx of neutropenic sepsis?
Piperacillin with tazobactam (Tazocin)
Reticulocyte count in aplastic crisis?
Reduced
What is the test for hereditary spherocytosis?
EMA binding assay
What 2 conditions are spherocytes on a blood smear found in?
1) Hereditary spherocytosis
2) Autoimmune haemolytic anaemia
How can mixed anaemia present?
Co-presentation of iron deficiency anaemia and B12 deficiency anaemia may lead to a normocytic anaemia.
This can be differentiated from anaemia of chronic disease due to low/normal ferritin and wide distribution of red blood cell volume (i.e. raised RDW due to different size RBCs).
Under homeostatic conditions, coagulation and fibrinolysis are coupled.
Describe both
Coagulation: activation of the coagulation cascade –> thrombin –> converts fibrinogen to fibrin –> stable fibrin clot.
Fibrinolysis: activation of the fibrinolytic system generates plasmin –> responsible for lysis of fibrin clots.
he breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products).
Blood picture in DIC?
1) Low platelets
2) Low fibrinogen
3) Raised PT and APTT
4) Raised fibrin degradation products
5) Schistocytes due to microangiopathic haemolytic anaemia
What is the 1st line imaging in multiple myeloma?
Whole body MRI (look for bone lesions)
Mx of DVT in case of positive D-dimer but -ve US?
Stop anticoag, repeat US in 7 days
What is the pathophysiology of factor V Leiden?
Resistance of factor V to action of protein C (i.e. can’t be inactivated –> prothrombotic state).
Referral for children and young people (0-24y) with unexplained petechiae or hepatosplenomegaly?
Refer for immediate specialist assessment (i.e. same day)
What is the 1ary cause of polycythaemia?
polycythaemia rubra vera
What are 4 2ary causes of polycythaemia?
1) COPD
2) altitude
3) obstructive sleep apnoea
4) excessive EPO: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
Mx of antiphospholipid syndrome in pregnancy?
Aspirin + LMWH
When is aspirin vs LMWH commenced in antiphospholipid syndrome in pregnancy?
Aspirin: once the pregnancy is confirmed on urine testing
LWMH: once a fetal heart is seen on US
What are 2 typical blood film findings in hyposplenism?
1) Howell-Jolly bodies
2) Sidetocytes
What are some causes of hyposplenism? (7)
1) splenectomy
2) sickle-cell
3) coeliac disease, dermatitis herpetiformis
4) Graves’ disease
5) SLE
6) amyloid
What condition do bite cells and blister cells on a blood film indicate?
G6PD deficiency
Which medication is known to precipitate renal failure in patients with multiple myeloma?
NSAIDs
What is the most common inherited bleeding disorder?
Haemophilia A –> caused by a deficiency in factor VIII
What is myelodysplastic syndrome?
This arises from genetic mutations in hematopoietic stem cells.
The key pathophysiological feature of MDS is ineffective hematopoiesis leading to peripheral cytopenias despite a typically hypercellular bone marrow.
What cancer is there a risk of progression to in myelodysplastic syndrome?
AML
BP in TACO vs TRALI?
TACO - HTN
TRALI - hypotension
Haemophilia A vs B?
A –> deficiency of factor VIII
B –> deficiency of factor IX
How often do patients with sickle cell disease require the pneumococcal vaccine?
Every 5 years
What condition is associated with ‘tear-drop’ poikilocytes on blood film?
Myelofibrosis
What happens during a sequestration crisis in sickle cell?
The sickle cells cause the spleen to become grossly enlarged.
This is more common in early childhood as repeated sequestration and infarction of the spleen during childhood gradually results in an auto-splenectomy.
A sequestration crisis may result in severe anaemia, marked pallor and cardiovascular collapse due to loss of effective circulating volume.
What type of leukaemia can patients with polycythaemia vera progress to?
AML (or myelofibrosis)
What indicates a poor prognosis in Hodgkin’s lymphoma?
Prescence of B symptoms (weight loss, fever, night sweats)
Is anaemia of chronic disease more likely to be normocytic or microcytic?
Normocytic
Where is iron mainly absorbed?
Duodenum & jejunum
What is sideroblastic anaemia?
The body produces enough iron but is unable to put it into the haemoglobin (iron levels will be normal/high).
Iron levels in sideroblastic anaemia?
High
What 2 drugs can cause haemolytic anaemia?
1) Methyldopa
2) Penicillin
How can PPIs result in iron deficiency?
PPIs reduce stomach acid
Stomach acid is essential for turning Fe3+ (insoluble) into Fe2+ (soluble).
Role of G6PD?
Protects cells from oxidative damage
Where is vitamin B12 absorbed?
Distal ileum
