Haem Flashcards
1
Q
List some examples of extra-vascular haemolysis.
A
Autoimmune haemolytic anaemia
Hereditary spherocytosis
2
Q
List some examples of intra-vascular haemolysis.
A
Malaria
G6PD deficiency
Pyruvate kinase deficiency
Mismatched blood transfusion
MAHA
Paroxysmal nocturnal haemoglobinuria
3
Q
What is the most common cause of intravascular haemolysis worldwide?
A
Malaria
4
Q
List some consequences of haemolytic anaemia.
A
Anaemia
Erythroid hyperplasia
Increased folate demand
Susceptibility to parvovirus B19 infection
Propensity to gallstones
Increased risk of iron overload
Increased risk of osteoporosis
5
Q
Why is parvovirus B19 infection dangerous in patients with haemolytic anaemia?
A
It infects erythroid cells in the bone marrow and arrests their maturation
If this happens in someone with shortened red cell survival, it can cause a dramatic drop in Hb (aplastic crisis)
NOTE: this can be identified by observing a low reticulocyte count
6
Q
Why do people with haemolytic anaemia have an increased risk of developing gallstones?
A
Increased generation of bilirubin
7
Q
List some laboratory features of haemolytic anaemia.
A
Anaemia
Increased reticulocytes
Polychromasia
Increased LDH
Increased bilirubin
Reduced/absent haptoglobins
Haemoglobinuria
Haemosiderinuria
8
Q
What is polychromasia?
A
Red cells take up both eosinophilic and basophilic dye giving them a bluish appearance – this is due to the presence of reticulocytes
9
Q
What is increased LDH a marker of?
A
LDH is an enzyme found in high concentrations within red cells
Increased LDH suggests intravascular haemolysis
10
Q
What are haptoglobins? What is the significance of reduced haptoglobins?
A
Haptoglobins are proteins in the bloodstream that bind to and remove free haemoglobin from the bloodstream
Low haptoglobins suggests that there is a lot of free haemoglobin in the bloodstream
11
Q
Which stains are used for haemosiderinaemia?
A
Perl’s stain
Prussian blue stain
12
Q
What does the presence of haemoglobinuria and haemosiderinaemia imply?
A
Intravascular haemolysis
13
Q
Describe the inheritance of hereditary spherocytosis.
A
75% family history (autosomal dominant)
25% de novo mutations
14
Q
What is the hall mark of red cells in hereditary spherocytosis?
A
Osmotic fragility – red cells show increases sensitivity to lysis in hypotonic saline
15
Q
What is another test for hereditary spherocytosis?
A
Reduced binding to eosin 5-maleimide (dye)
This is shown by flow cytometry
16
Q
Describe the appearance of the blood film in hereditary spherocytosis.
A
The cells lack a central area of pallor because they have lost the biconcave shape
The cells are small and more densely stained
There may be polychromatic cells (due to the presence of a young red cell population)
17
Q
Outline the blood film and FBC features of eliptocytosis.
A
The red cells are elliptical but there is no polychromasia and the blood count is likely to be normal because there is little haemolysis
18
Q
Describe the inheritance pattern of G6PD deficiency.
A
X-linked recessive
19
Q
List some triggers for haemolysis in G6PD deficiency.
A
Drugs (antimalarials, antibiotics, dapsone, vitamin K)
Infections
Fava beans
Naphthalene mothballs
20
Q
Describe the appearance of the blood film in G6PD deficiency during acute haemolysis.
A
Contracted cells
Nucleated red cells
Bite cells
Hemighosts (Hb retracted to one side of the cell)
21
Q
What is a Heinz body? What is it suggestive of?
A
Denatured haemoglobin
Suggestive of oxidative haemolysis
22
Q
Which stain is used to look for Heinz bodies?
A
Methylviolet
23
Q
What is a characteristic blood film feature of pyruvate kinase deficiency?
A
Echinocytes – red cells with a lot of short projections
24
Q
What is a characteristic blood film feature of pyrimidine 5-nucleotidase deficiency?
A
Basophilic stippling
NOTE: this is also seen in lead poisoning because lead inhibits pyrimidine 5-nucleotidase
25
What are Ham’s test and flow cytometry for GPI-linked proteins used for?
Paroxysmal nocturnal haemoglobinuria
NOTE: Ham’s test looks at the sensitivity of red cells to lysis by acidified serum
26
Outline the principles of management of haemolytic anaemia.
Folic acid supplementation
Avoidance of triggers in G6PD deficiency
Blood transfusions/exchange
Immunisations against blood-borne viruses
Monitor for chronic complications (e.g. gallstones)
Splenectomy if needed
27
List some indications for splenectomy related to haemolytic anaemia.
Pyruvate kinase deficiency
Hereditary spherocytosis
Severe eliptocytosis/pyropoikilocytosis
Thalassemia syndromes
Autoimmune haemolytic anaemia
28
What is the main risk of splenectomy?
Overwhelming sepsis due to susceptibility to capsulated bacteria (e.g. pneumococcus)
NOTE: risk can be reduced by using penicillin prophylaxis and immunisations
29
List some specific criteria for splenectomy.
Transfusion dependence
Growth delay
Physical limitation
Hypersplenism (where it causes pooling and physical symptoms)
Age > 3 years and < 10 years
30
Which cell level does CML tend to occur in?
Pluripotent haematopoietic stem cell
31
Which cell level does AML tend to occur in?
Pluripotent haematopoietic stem cell or multipotent myeloid stem cell
32
Which chromosomal duplications are most commonly associated with AML?
8 and 21 (there is a predisposition seen in Down syndrome)
33
Which chromosomal aberration causes APML?
Translocation 15;17
34
What is a characteristic feature of APML? Why does this occur?
Haemorrhage – this is because APML is associated with DIC and hyperactive fibrinolysis
35
In what way are the promyelocytes in APML considered ‘abnormal’?
They contain multiple Auer rods
36
Describe how the variant version of APML is different from the original version.
The variant form has granules that are below the resolution of a light microscope
They also tend to have bilobed nuclei
37
Which microscopic feature is pathognomonic of myeloid leukaemias?
Auer rods
38
Which stain can be used to distinguish myeloid leukaemias from other leukaemias?
Myeloperoxidase, sudan black, non-specific esterase
39
List the clinical features of AML.
Bone marrow failure (anaemia, neutropaenia, thrombocytopaenia)
Local infiltration (splenomegaly, hepatomegaly, gum infiltration, lymphadenopathy, CNS, skin)
Hyperviscosity if WBC is very high (can cause retinal haemorrhages and exudates)
40
Outline the tests that may be used to diagnose AML.
Blood film
Bone marrow aspirate
Cytogenetic studies (done in EVERY patient)
Molecular studies and FISH
41
Outline the supportive care given for AML.
Red cells
Platelets
FFC/cryoprecipitate in DIC
Antibiotics
Allopurinol (prevent gout)
Fluid and electrolyte balance
Chemotherapy
42
List some determinants of prognosis in AML.
List some determinants of prognosis in AML.
43
What are the four phases of chemotherapy for ALL?
Remission induction
Consolidation and CNS therapy
Intensification
Maintenance
44
List some investigations used in the diagnosis of ALL.
FBC and blood film
Bone marrow aspirate
Immunophenotyping
Cytogenetic/molecular analysis
45
How long does chemotherapy for ALL usually take? Why is it longer in boys?
2-3 years
Longer in boys because the testes are a site of accumulation of lymphoblasts
46
Outline the supportive care for ALL.
Blood products
Antibiotics
General medical care (central line, gout management, hyperkalaemia management, sometimes dialysis)
47
List some pro-coagulant factors in the body.
Platelets
Endothelium
vWF
Coagulation cascade
48
List some anti-coagulant factors in the body.
Fibrinolysis
Anti-thrombins
Protein C/S
Tissue factor pathway inhibitor
49
What is the life span of platelets?
10 days
NOTE: this is important because it means that the effect of antiplatelet drugs lasts for 10 days after stopping the drug
50
What are the two ways in which platelets can adhere to sub-endothelial structures?
DIRECTLY – via GlpIa
INDIRECTLY – via binding of GlpIb to vWF (this is MORE IMPORTANT)
51
Which factors, released by platelets after adhesion, promote platelet aggregation?
Thromboxane A2
ADP
52
Describe the effects of aspirin and other NSAIDs on the arachidonic acid pathway.
Aspirin is an irreversible COX inhibitor
Other NSAIDs reversibly inhibit COX
53
What is the rate-limiting step for fibrin formation?
Factor 10a
54
What are the effects of thrombin?
Activates fibrinogen
Activates platelets
Activates profactors (factor 5 and 8)
Activates zymogens (factor 7, 11 and 13)
55
Name the complex that is responsible for activating prothrombin to thrombin.
Prothrombinase complex
56
What is required for adequate production/absorption of vitamin K?
Bacteria in the gut produce vitamin K
It is fat-soluble so bile is needed for vitamin K to be absorbed
57
What is the most common cause of vitamin K deficiency?
Warfarin
58
Name two factors that convert plasminogen to plasmin.
Tissue plasminogen activator
Urokinase
59
Name two factors that directly inhibit plasmin.
Alpha-2 antiplasmin
Alpha-2 macroglobulin
60
What is the role of thrombin-activatable fibrinolysis inhibitor (TAFI)?
Inhibitor of fibrin breakdown
61
Describe the action of antithrombins.
Bind to thrombin in a 1:1 ratio and this complex is excreted in the urine
62
How many types of antithrombin are there?
Five (antithrombin-III is the most active)
63
What is the most thrombogenic hereditary condition?
Antithrombin deficiency
64
Why does Factor V Leiden cause a prothrombotic state?
The factor 5a will be resistant to breakdown by protein C
65
What is the role of tissue factor pathway inhibitor?
TFPI neutralises the tissue factor-factor 7a complex once it has initiated the clotting cascade
66
List some genetic defects that cause excessive bleeding.
Platelet abnormalities
Vessel wall abnormalities
Clotting factor deficiencies
Excess clot breakdown
67
List some acquired defects that cause excessive bleeding.
Liver disease
Vitamin K deficiency
Autoimmune diseases (platelet destruction)
Trauma
Anti-coagulants/anti-platelets
68
What is the difference between immediate and delayed bleeding with regards to the underlying pathological process?
Immediate – issue with the primary haemostatic plug (platelets, endothelium, vWF)
Delayed – issue with the coagulation cascade
69
Describe the key clinical differences between platelet disorders and coagulation factor disorders.
Platelet disord
· Bleeding from skin and mucous membranes
· Petechiae
· Small, superficial ecchymoses
· Bleeding after cuts and scratches
· Bleeding immediately after surgery/trauma
· Usually mild
Coagulation factor disorders
· Bleeding into soft tissues, joints and muscles
· No Petechiae
· Large, deep ecchymoses
· Haemarthroses
· No bleeding from cuts and scratches
· Delayed bleeding from surgery or trauma
· Often SEVERE
70
What can cause immune-mediated thrombocytopaenia?
Idiopathic
Drug-induced (e.g. quinine, rifampicin)
Connective tissue disorder (e.g. SLE)
Lymphoproliferative disease
Sarcoidosis
71
List two non-immune mediated conditions that cause thrombocytopaenia.
DIC
MAHA
72
What are the main differences between acute and chronic ITP?
Acute
· Mainly children
· Usually there is a preceding infection
· Abrupt onset of symptoms
· Lasts 2-6 weeks
· Spontaneously resolves
Chronic
· Mainly occurs in adults
· More common in females
· Can be abrupt or indolent
· Does not resolve spontaneously
73
How is ITP treated?
Mainly with steroids and IVIG based on the platelet count
74
Give some examples of causes of thrombocytopaenia that can be diagnosed by blood film.
Vitamin B12 deficiency
Acute leukaemia
75
What clotting study abnormality would be seen in Haemophilia?
Prolonged APTT
76
Outline the clinical features of haemophilia.
Haemarthroses (MOST COMMON)
Soft tissue haematomas (e.g. shortened tendons, muscle atrophy)
Prolonged bleeding after surgery/dental extractions
NOTE: haemophilia A and B are clinically indistinguishable
77
What is a typical lesion seen in coagulation factor disorders?
Ecchymoses
78
What is the most common coagulation disorder? What is its inheritance pattern?
Von Willebrand disease
Autosomal dominant – type 1 and 2
Autosomal recessive – type 3
79
What is the main clinical feature in von Willebrand disease?
Mucocutaneous bleeding
80
Outline the classification of von Willebrand disease.
Type 1 – partial quantitative deficiency
Type 2 – qualitative deficiency
Type 3 – complete quantitative deficiency
81
Describe the expected laboratory test results for the three types of von Willebrand disease.
Type 1 – low antigen, low activity, normal multimer
Type 2 – normal antigen, low activity, normal multimer
Type 3 – very low antigen, very low activity, absent multimer
82
Name a source of vitamin K.
Green vegetables
Vitamin K is synthesised by intestinal flora
83
List some causes of DIC.
Sepsis (MOST COMMON)
Trauma (e.g. fat embolism)
Obstetric complications (e.g. amniotic fluid embolism)
Malignancy
Vascular disorders
Reaction to toxin
Immunological (e.g. transplant rejection)
84
Describe the typical clotting study results in DIC.
Prolonged APTT and PT
Prolonged TT
Decreased fibrinogen
Increased FDP
Decreased platelets
Schistocytes (due to shearing of red blood cells as it passes through a fibrin mesh)
85
Outline the treatment of DIC.
Treat underlying disorder
Anticoagulation with heparin
Platelet transfusion
FFP
Coagulation inhibitor concentrate
86
What are Janus Kinases?
A family of four tyrosine kinase receptors associated with haemopoietic cell growth factor receptors
87
What is a chronic myeloproliferative disorder?
A group of clonal disorders of haemopoietic stem cells characterised by the overproduction of one or more mature myeloid cellular elements in the blood
There is a trend towards increased fibrosis in the bone marrow
Some cases will develop into acute leukaemia
88
Outline the usual presentation of myeloproliferative disorders.
Preponderance to thrombosis
Splenomegaly
Haemorrhage
89
List some chronic myeloproliferative disorders.
Polycythaemia vera
Essential thrombocythaemia
Idiopathic myelofibrosis
Idiopathic erythrocytosis
Chronic granulocytic leukaemia
90
Describe the clinical presentation of polycythaemia vera.
Incidental finding
Symptoms of hyperviscosity (headaches, visual disturbances, fatigue, dyspnoea)
Increased histamine release (Aquagenic pruritus, peptic ulceration)
Splenomegaly
Plethora
Erythromelalgia (red painful extremities)
Thrombosis
Retinal vein engorgement
Gout
91
Describe the appearance of a bone marrow biopsy in polycythaemia vera.
Increased cellularity (mainly erythroid cells)
Slight reticulin fibrosis and megakaryocyte abnormalities
92
What investigation finding is considered diagnostic of polycythaemia vera?
Presence of JAK 2 V617F mutation
93
Which other JAK mutation is a significant finding and which condition is it associated with?
Exon 12 mutation
It is associated with idiopathic erythrocytosis
94
What are some causes of JAK 2 V617F negative polycythaemia?
Pseudopolycythaemia
True polycythaemia that is secondary to increased EPO (e.g. hypoxia, renal disease, tumours)
95
What is idiopathic erythrocytosis?
Isolated erythrocytosis with low EPO
Treated with venesection only
NO JAK 2 V617F mutation, but some cases will have an exon 12 mutation
96
Outline the prognosis of idiopathic erythrocytosis and polycythaemia vera.
Idiopathic erythrocytosis – no adverse prognosis if Hct is maintained
Polycythaemia vera – most survive 10 years, causes of death include thrombosis, leukaemia and myelofibrosis
97
What is essential thrombocythaemia?
Myeloproliferative disorder mainly involving the megakaryocyte lineage (platelet count > 600 x 109/L)
98
What proportion of essential thrombocythaemia patients have JAK 2 mutations?
50%
99
Outline the treatment options for essential thrombocythaemia.
Aspirin
Anagrelide (specific inhibitor of platelet formation – may accelerate myelofibrosis)
Hydroxycarbamide (MAIN TREATMENT – may be leukaemogenic)
Alpha-interferon (may be used in patients < 40 years)
100
Describe the prognosis of essential thrombocythaemia.
Normal life span
Leukaemic transformation in about 5% of patients after 10 years
Myelofibrosis is uncommon
101
Define chronic idiopathic myelofibrosis.
A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haemopoiesis
102
Describe the typical clinical presentation of myelofibrosis.
Incidental finding
Cytopaenias
Thrombocytosis
Splenomegaly (can be MASSIVE)
Hepatomegaly
FLAWS
Gout
103
Describe the two stages of myelofibrosis.
Pre-fibrotic = blood changes are mild with hypercellular marrow
Fibrotic = splenomegaly, blood changes, dry tap, prominent fibrosis and later osteosclerosis
104
Describe the appearance of myelofibrosis on a blood film.
Leukoerythroblastic picture
Tear drop poikilocytes
105
What are some features of the bone marrow in myelofibrosis?
Dry tap
Trephine biopsy will show increased reticulin or collagen fibrosis, prominent megakaryocyte hyperplasia and new bone formation
106
Outline the treatment options for myelofibrosis.
Symptomatic treatment (e.g. transfusions for anaemia)
Splenectomy
Cytoreductive therapy (hydroxycarbamide and thalidomide)
Bone marrow transplant (in younger patients)
107
Describe the prognosis of myelofibrosis.
Median 3-5 year survival
108
Which types of cancer are associated with causing secondary polycythaemia?
Renal cell carcinoma
Liver cancer
Due to the production of EPO
109
What are the typical laboratory findings of iron deficiency anaemia?
Low ferritin
Low transferrin saturation
High TIBC
110
What is leucoerythroblastic anaemia?
Anaemia characterised by the presence of red and white cell precursors
111
What are the morphological features of leucoerythroblastic anaemia seen on blood film?
Tear drop red blood cells (aniso- and poikilocytosis)
Nucleated RBCs
Immature myeloid cells
112
What does leucoerythroblastic anaemia tend to be caused by?
Bone marrow infiltration (leukaemia, lymphoma, myeloma, solid tumours, myelofibrosis, military TB, severe fungal infection)
113
Which test distinguishes immune-mediated and non-immune mediated haemolytic anaemia?
DAT or Coombs’ test
DAT +ve means that the haemolytic anaemia is mediated through immune destruction of red cells
114
What morphological change is seen on the blood film of patients with autoimmune haemolytic anaemia?
Spherocytes
115
List some causes of non-immune haemolytic anaemia.
Infection (e.g. malaria)
Microangiopathic haemolytic anaemia (MAHA)
116
List some key features of MAHA.
Usually caused by underlying adenocarcinoma
Red cell fragments
Low platelets
DIC/bleeding
117
Outline the mechanism of MAHA.
An underlying adenocarcinoma produces procoagulant cytokines that activate the coagulation cascade
This leads to DIC and the formation of fibrin strands in various parts of the microvasculature
Red cells will be pushed through these fibrin strands and fragment
NOTE: always consider underlying adenocarcinoma in any patient presenting with MAHA
118
What is the main difference seen in the blood film of patients with acute and chronic leukaemia?
Chronic – mature white cells are raised
Acute – immature blast cells are raised
119
List some causes of neutrophilia.
Corticosteroids (due to demargination)
Underlying neoplasia
Tissue inflammation (e.g. colitis, pancreatitis)
Myeloproliferative/leukaemia disorder
Infection
120
List some infections that characteristically do not cause neutrophilia.
Brucella
Typhoid
Many viral diseases
121
List some key features of a reactive neutrophilia on a blood film.
Band cells (presence of immature neutrophils (band cells) show that the bone marrow has been signalled to release more WBCs)
Toxic granulation
Clinical signs of infection/inflammation
122
What are some key blood film and clinical features suggestive of a myeloproliferative disorder?
Neutrophilia
Basophilia
Immature myelocytes
Splenomegaly
NOTE: you may see raised Hb and raised platelets in CML if it affects those lineages
123
What are some key blood film features suggestive of AML?
Neutrophilia
Myeloblasts
124
List some causes of monocytosis.
Bacteria: TB, Brucella, typhoid
Viral: CMV, VZV
Sarcoidosis
Chronic myelomonocytic leukaemia
125
List some causes of reactive eosinophilia.
Parasitic infection
Allergy (e.g. asthma, rheumatoid arthritis)
Underlying neoplasms (e.g. Hodgkin’s lymphoma, T cell lymphoma, NHL)
Drug reaction (e.g. erythema multiforme)
126
Which gene mutation causes chronic eosinophilic leukaemia?
FIP1L1-PDGFRa fusion gene
127
Which type of virus typically causes basophilia?
Pox viruses
128
List some causes of reactive lymphocytosis.
Infection (EBV, CMV, toxoplasmosis, rubella, HSV)
Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia)
Sarcoidosis
129
How would the lymphocytes seen on a blood film due to a viral infection be different from leukaemia/lymphoma?
Viral infection: reactive or atypical lymphocytes (EBV)
CLL or NHL: small lymphocytes and smear cells
130
What is light chain restriction?
An individual B cell will either express kappa or lambda light chains (not both)
In response to an infection, you will get a polyclonal B cell response so there will be a roughly even mixture of kappa and lambda light chains
In lymphoproliferative disorders, monoclonal proliferation of a B cell expressing only one type of light chain (e.g. kappa) will mean that the proportion of kappa relative to lambda will increase (e.g. showing an overwhelming majority of kappa)
131
What percentage of hospital deaths are caused by PE?
5-10%
132
List some anticoagulant molecules produced by the endothelium.
Thrombomodulin
Endothelial protein C receptor
Tissue factor pathway inhibitor
Heparans
NOTE: it does not normally produce tissue factor
133
Which antiplatelet factors are produced by the endothelium?
NO
Prostacyclin
134
What is the mechanism of action of heparin?
Increases anticoagulant activity by potentiating anti-thrombin III
135
How is unfractionated heparin monitored?
It has variable pharmacokinetics and a variable dose-response
Must be monitored with APTT or anti-Xa levels
136
How can the action of warfarin be reversed?
Administering vitamin K – takes 12 hours
Giving factors 2, 7, 9 and 10 – immediate
137
What is the antidote for heparin?
Protamine
138
Describe the gender difference regarding the risk of recurrent of VTE.
Men have a greater risk of recurrence
NOTE: proximal thrombosis has a higher rate of recurrence than distal thrombosis
139
What should all patients > 60 years old with idiopathic thromboembolic disease be offered?
CT scan to check for an underlying cause
140
Define myelodysplastic syndrome.
Biologically heterogenous group of acquired haematological stem cell disorders. elderly pts
141
What are the key characteristics of myelodysplastic syndromes?
Development of a clone of marrow stem cell with abnormal maturation resulting in functionally defective blood cells and a reduction in cell counts
This leads to cytopaenia, functional abnormalities of cell maturation and an increased risk of transformation to leukaemia
142
How do myelodysplastic syndromes typically present?
Symptoms/signs of bone marrow failure developing over weeks/months
143
List and describe some blood and bone marrow features of myelodysplastic syndromes.
Pelger-Huet anomaly (bilobed neutrophils)
Dysgranulopoiesis of neutr7ophils (failure of granulation)
Dyserythropoiesis of red blood cells (lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of precursor red cells)
Dysplastic megakaryocytes (micro-megakaryocytes)
Increased proportion of blast cells in the bone marrow (normally < 5%)
144
What might you see if you stained for iron in the bone marrow of a patient with a myelodysplastic syndrome?
Ringed sideroblasts (accumulation of iron around the nuclei of red blood cell precursors)
145
What is the presence of myeloblasts with Auer rods suggestive of?
Acute myeloid leukaemia
146
List some factors that are taken into account when classifying types of myelodysplastic syndrome.
Cell lineage affected
Blast cell proportions
Cytogenetics
Presence of ringed sideroblasts
Cytopaenias
147
What are the five prognostic variables that are used to calculate prognostic risk using the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes?
Bone marrow blast percentage
Karyotype
Haemoglobin
Platelets
Neutrophils
NOTE: high risk is considered a score > 6, low risk < 1.5
148
What are the usual causes of death in patients with myelodysplasia?
1/3 infection
1/3 bleeding
1/3 leukaemia
149
What are the two treatments that can prolong life in myelodysplastic syndromes?
Allogeneic stem cell transplantation
Intensive chemotherapy
NOTE: as most MDS patients are elderly, they often cannot tolerate treatment
150
List some other treatments that may be used in myelodysplastic syndromes.
Supportive Care (blood products, antimicrobials, growth factors (e.g. EPO, GM-CSF))
Biological modifiers
· Immunosuppression
· Azacytidine (hypomethylating agent)
· Decitabine
· Lenalidomide (used in 5q minus syndrome)
Oral chemotherapy (e.g. hydroxyurea)
Low-dose chemotherapy (SC low-dose cytarabine)
151
List some causes of primary bone marrow failure.
Fanconi anaemia (multipotent stem cell)
Diamond-Blackfan syndrome (red cell progenitor)
Kostmann syndrome (neutrophil progenitor)
Acquired: idiopathic aplastic anaemia (multipotent stem cell)
152
List some secondary causes of bone marrow failure.
Marrow infiltration
Haematological malignancies
Solid tumours spreading to bone marrow
Radiation
Drugs
Chemicals (e.g. benzene)
Autoimmune
Infection (e.g. parvovirus B19)
153
List some drugs that can cause bone marrow failure.
Cytotoxic drugs (predictable, dose-dependent)
Phenylbutazone, Gold salts (idiosyncratic, rare)
Antibiotics – chloramphenicol, sulphonamides
Diuretics – thiazide
Antithyroid drugs – carbimazole
154
What is the most common cause of aplastic anaemia?
Idiopathic (70-80%)
155
List some inherited causes of aplastic anaemia.
Fanconi anaemia
Schwachman-Diamond syndrome
Dyskeratosis Congenita
156
What are some investigative features of aplastic anaemia?
Peripheral blood – cytopaenia
Bone marrow – hypocellular
157
List some differential diagnosis for pancytopaenia and hypocellular marrow.
Hypoplastic MDS/AML
Hypocellular ALL
Hairy cell leukaemia
Atypical mycobacterial infection
Anorexia nervosa
ITP (although Hb and RBC will be normal)
158
What is the Camitta criteria for severe aplastic anaemia?
2 out of 3 peripheral blood features:
· Reticulocytes < 1% (< 20 x 109/L)
· Neutrophils < 0.5 x 109/L
· Platelets < 20 x 109/L
Bone marrow cellularity < 25%
159
How might the age of the patient influence decisions regarding their management?
Immunosuppressive therapies tend to be used in older patients
SCT tends to be used in younger patients (80% cure rate)
160
What is the most common cause of inherited aplastic anaemia?
Fanconi anaemia
161
What is the inheritance pattern of Fanconi anaemia?
Autosomal Recessive or X-linked Recessive
162
List some somatic abnormalities that are seen in Fanconi anaemia.
Short stature
Hypopigmented spots/café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Hypogonadism
Developmental delay
NOTE: these are only present in 70% of patients
163
List some complications of Fanconi anaemia.
Aplastic anaemia (90%)
Myelodysplasia
Leukaemia
Cancer (epithelial)
Liver disease
164
What are the characteristic features of dyskeratosis congenita?
Bone marrow failure
Cancer predisposition
Somatic abnormalities
165
What are the three main somatic features of dyskeratosis congenita?
Abnormal skin pigmentation
Nail dystrophy
Leukoplakia
166
Which genes are involved in dyskeratosis congenita and what are the inheritance patterns?
X-linked recessive (MOST COMMON) – DKC1 gene (defective telomere functioning)
Autosomal dominant – TERC (RNA components of telomerase)
Autosomal recessive – no mutation identified
NOTE: abnormal telomeric structure and function is heavily implicated in dyskeratosis congenita
167
Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.
NHL = 80%
Hodgkin = 20
168
List some oncogenes that are implicated in lymphoma/leukaemia.
Bcl2
Bcl6
Cyclin D1
c-Myc
169
List some examples of how constant antigenic stimulation can lead to lymphoma.
H. pylori à gastric MALT marginal zone NHL of the stomach
Sjogren syndrome à marginal zone NHL of the parotid
Coeliac disease à small bowel T cell lymphoma, enteropathy-associated T cell NHL
170
List two examples of viral infections that can lead to lymphoma.
Direct viral integration: HTLV1
· HTLV1 infects T cells by vertical transmission
· May cause adult T cell leukaemia/lymphoma (very aggressive)
· Caused by viral genome integrating into T cell genome and driving proliferation
EBV infection and immunosuppression
· EBV established latent infection in B cells which is kept in check by cytotoxic T cell (kill EBV antigen-expressing B cells)
· Loss of T cell function (e.g. HIV, post-transplant immunosuppression) can lead to EBV-driven lymphoma
171
What are the main markers used for B and T cells?
T cell = CD3, CD5
B cell = CD20
172
Outline the WHO classification of lymphoma.
Hodgkin lymphoma
· Classical
· Lymphocyte predominant
Non-Hodgkin lymphoma
· B cell (MOST COMMON)
o Precursor B cell neoplasm
o Peripheral B cell neoplasm (low and high grade)
· T cell
o Precursor T cell neoplasm
o Peripheral T cell neoplasm
173
Give an example of a chromosomal translocation that is diagnostic of lymphoma.
11;14 = Mantle Cell Lymphoma
174
Give an example of a chromosomal translocation that is prognostic in lymphoma.
2;5 = anaplastic large cell lymphoma
175
List some types of low grade lymphoma.
Follicular lymphoma
Small lymphocytic lymphoma (CLL)
Marginal zone lymphoma
Mantle cell lymphoma
176
Name a type of intermediate grade lymphoma.
Burkitt’s lymphoma
177
Name a type of high grade lymphoma.
Diffuse large B cell lymphoma
178
Describe the histological features of follicular lymphoma.
Follicular pattern – the follicles are neoplastic and spread from the node into adjacent tissues
Cells have a germinal centre cell origin (positive staining for CD10 and Bcl6)
179
Describe the typical presentation of small lymphocytic lymphoma.
Lymphadenopathy or high blood lymphocyte count in middle-aged or elderly patients
180
Outline the histological features of small lymphocytic lymphoma.
Small lymphocytes
Arise form naïve B cells or post-germinal centre memory B cells
Cells are CD5 and CD23 positive
They replace the entire lymph node so that you can no longer identify follicles or T cell areas
181
What is marginal zone lymphoma?
Arise mainly in extra-nodal sites (e.g. gut, spleen)
Thought to arise due to chronic antigenic stimulation
Arise from post-germinal centre memory B cells
Low-grade disease can be treated by non-chemotherapeutic methods (e.g. H. pylori eradication)
182
Outline the typical presentation of mantle cell lymphoma.
Typically affects middle-aged males
Affects lymph nodes and the GI tract
Often present with disseminated disease
NOTE: median survival = 3-5 years
183
Outline the key histological features of mantle cell lymphoma.
Located in the mantle zone of the lymph node
Arise from pre-germinal centre cells
Show aberrant expression of cyclin D1 and CD5
184
Outline the typical presentation of Burkitt’s lymphoma.
Jaw or abdominal mass in children and young adults
Associated with EBV
NOTE: this is very aggressive
185
Outline the histological features of Burkitt’s lymphoma.
Arises from germinal centre cells
Starry sky appearance
186
Outline the typical presentation of diffuse large B cell lymphoma.
Middle-aged and elderly patients with lymphadenopathy
187
Outline the histological features of diffuse large B cell lymphoma.
Arise from germinal centre or pre-germinal centre B cells
Large lymphoid cells
Lymph node is effaced so follicles and germinal centres cannot be identified
188
List some prognostic association of diffuse large B cell lymphoma.
Good prognosis – germinal centre phenotype
Poor prognosis – p53-positive and high proliferation fraction
189
Outline the typical presentation of T cell lymphomas.
Middle-aged and elderly patients with lymphadenopathy
NOTE: these are aggressive
190
Outline some key histological features of T cell lymphomas.
Large T lymphocytes
Associated reactive cell population (especially eosinophils)
191
List some types of T cell lymphoma and their associations.
Adult T cell leukaemia/lymphoma – HTLV1
Enteropathy-associated T cell lymphoma – Coeliac disease
Cutaneous T cell lymphoma (mycosis fungoides)
Anaplastic large cell lymphoma
192
Outline the typical presentation of anaplastic large cell lymphoma.
Children and young adults with lymphadenopathy
NOTE: this is aggressive
193
Outline the key histological features of anaplastic large cell lymphoma.
Large epithelioid lymphocytes
T cell or null phenotype (anaplastic)
194
List some key differences between Hodgkin and Non-Hodgkin Lymphoma.
Hodgkin is more localised (usually one nodal site)
Hodgkin spreads contiguously to adjacent lymph nodes
NOTE: NHL tends to involve multiple lymph node sites and spread discontinuously
195
Outline some histological features of classical Hodgkin lymphoma.
Nodular sclerosis
Mixed cell population of Reed-Sternberg cells
Lymphoma cells are few in number and are scattered around
Eosinophils
Arise from germinal centre or post-germinal centre cells
196
What are the diagnostic markers for Hodgkin lymphoma?
CD15
CD30
197
Describe the typical presentation of nodular lymphocyte predominant Hodgkin lymphoma.
Isolated lymphadenopathy
NO association with EBV
198
Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.
B cell rich nodules
Scattered around L&H cells
Reactive population in the background consisting of small lymphocytes
NO eosinophils and macrophages
199
Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?
Positive = CD20
Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)
200
Which chemotherapy regimen is usually used for Hodgkin lymphoma?
ABVD: Adriamycin, Bleomycin, Vincristine, Dacarbazine
NOTE: this is usually given at 4-weekly intervals for 2-6 cycles
201
What are some possible long-term consequences of chemotherapy for Hodgkin lymphoma?
Pulmonary fibrosis
Cardiomyopathy
202
How might a relapse of Hodgkin lymphoma be treated?
High-dose chemotherapy
Autologous stem cell transplant
NOTE: intensifying chemotherapy will lead to an increased cure rate but it will also lead to an increase in secondary cancers
203
What proportion of lymphomas are Non-Hodgkin Lymphoma?
85%
204
What is the fastest growing human cancer?
Burkitt’s lymphoma
205
Describe the typical presentation of Non-Hodgkin lymphoma.
Painless lymphadenopathy
Compression symptoms
B symptoms
206
What are some important tests to perform in non-Hodgkin lymphoma and why are they important?
LDH – marker of cell turnover
HIV serology – HIV can predispose to NHL (HTLV1 serology may also be important)
Hepatitis B serology – NHL treatment may deplete B cells resulting in fulminant liver failure due to reactivation of hepatitis B in chronic carriers
207
What are the two most common types of non-Hodgkin lymphoma?
Diffuse large B cell lymphoma (DLBCL) (40%)
Follicular lymphoma (35%)
208
Which factors are taken into account by the international prognostic index (IPI) for lymphoma?
Age > 60
High LDH
Performance status 2-4
Stage III or IV
More than one extranodal site
209
What treatment option may be considered for patients with diffuse large B cell lymphoma who relapse?
Autologous stem cell transplantation
210
What is the usual first-line treatment approach to follicular lymphoma?
Watch and wait
Only treat it clinically indicated (e.g. compression symptoms, massive nodes, recurrent infection)
211
Which genetic abnormality is associated with follicular lymphoma?
T(14;18) – resulting in over-expression of Bcl2 (which is an anti-apoptosis gene)
NOTE: follicular lymphoma is incurable but is indolent
212
List some diseases that can lead to marginal zone lymphoma.
H. pylori infection – gastric MALToma
Sjogren’s syndrome – parotid lymphoma
Hashimoto’s thyroiditis – thyroid lymphoma
Psittaci infection – lacrimal gland
213
Where is marginal zone lymphoma most commonly seen and how does it tend to present?
Usually in the stomach
Presenting with dyspepsia or epigastric pain
Usually Stage 1[E] (E = extranodal)
B symptoms are uncommon
214
What are the main features of enteropathy-associated T cell lymphoma?
Mature T cells
Involves small intestines
Aggressive
Caused by chronic antigenic stimulation by gliadin/gluten
215
Describe the typical presenting features of enteropathy-associated T cell lymphoma.
Abdominal pain/obstruction/bleeding/perforation
Malabsorption
Systemic symptoms
216
Why is it important to prevent EATL by following a strict gluten-free diet?
EATL responds poorly to chemotherapy and is usually fatal
217
What is the most common leukaemia in the Western world?
Chronic lymphocytic leukaemia
218
What are the typical laboratory findings in a patient with CLL?
Lymphocytosis
Smear cells
Normocytic normochromic anaemia
Thrombocytopaenia
Bone marrow lymphocytic replacement of normal marrow elements
NOTE: it is indolent so is often only picked up on routine blood tests
219
What distinctive antigen phenotype (presence and absence) is suggestive of Mature B cells
CD19 positive
CD5 negative
220
What distinctive antigen phenotype (presence and absence) is suggestive of Mature T cells
CD19 negative
CD5 positive
CD3 positive
CD4 or CD8 positive
221
Which antigen phenotype is suggestive of CLL?
CD5+ B cells (i.e. CD19+ and CD5+)
NOTE: this could potentially also be mantle cell lymphoma
222
Which staging system is used for CLL?
Rai and Binet
Binet: stages A-C depending on number of lymphoid areas (< or > 3, Hb and platelets)
223
Which laboratory tests are used in CLL to help gauge prognosis?
CD38 expression (associated with poor prognosis)
Cytogenetics (FISH)
Immunoglobulin gene mutation status (IgH mutated or unmutated)
224
How does VH gene mutations affect prognosis?
Unmutated = poor prognosis
Mutated = better prognosis
225
What is an important chromosomal abnormality in CLL that is tested for using FISH?
Deletion of 17p (Tp53)
This is part of the p53 tumour suppressor gene
This deletion is associated with a poor prognosis
226
Describe the immunoglobulin levels you would expect to see in CLL?
Hypogammaglobulinaemia
Because the malignant B cells are suppressing antibody production by other B cells
227
What is the term used to describe CLL changing into a high grade lymphoma?
Richter transformation – 1% risk per year
228
What are some supportive measures used in the treatment of CLL?
Vaccination (flu, pneumococcus)
Infection prophylaxis and treatment (may include aciclovir, PCP prophylaxis, IVIG)
229
How would autoimmune cytopaenias caused by CLL be treated?
Steroids
NOTE: 2nd line is rituximab
230
What is the first line treatment for TP53 intact CLL?
FCR – Fludarabine, Cyclophosphamide, Rituximab
NOTE: less intensive options may include, rituximab and bendamustine or obinutuzumab (anti-CD20) and chlorambucil (alkylating agent)
231
Under what conditions might CLL be considered high risk?
Patients with TP53/17p deletion
Refractory disease or early relapse (< 24 months)
232
What are some newer treatment options for high risk CLL?
Bruton Tyrosine Kinase Inhibitors – ibrutinib, idelalisib
Bcl2 Inhibitors – venetoclax
CAR-T therapy
233
How can myeloproliferative neoplasms be broadly categorised?
Philadelphia positive: CML
Philadelphia negative: polycythaemia vera, essential thrombocythaemia, primary myelofibrosis
234
Outline the typical presentation of primary myelofibrosis.
Cytopaenias (anaemia, thrombocytopaenia)
Thrombosis
MASSIVE splenomegaly
Hepatomegaly
Hypermetabolic state (FLAWS)
235
What might you expect to see in the blood film of a patient with primary myelofibrosis?
Leucoerythroblastic picture
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytes
236
What are some bad prognostic features in primary myelofibrosis?
Severe anaemia
Thrombocytopaenia
Massive splenomegaly
NOTE: median survival is 3-5 years
237
What might you expect to see in the FBC of a patient with CML?
Leucocytosis (MASSIVE)
Normal or raised Hb and platelets
238
What would you expect to see in abundance in the blood film of a patient with CML?
Neutrophils
Basophils
Myelocytes (NOT blasts)
NOTE: myelocytes are immature myeloid cells that are NOT blasts (analogous to reticulocytes for red blood cells)
239
Briefly describe the natural history of CML before targeted treatment because available?
5-6 years stable phase
6-12 months accelerated phase
3-6 months blast crisis
240
What is the Philadelphia chromosome?
CML is caused by a translocation between 9;22 producing a derivative chromosome, 22q, which is called the Philadelphia chromosome
241
List some normal FBC changes that you would expect to see in pregnancy.
Mild anaemia (net dilution due to increased plasma volume)
High MCV (NOTE: could be caused by B12 and folate deficiency)
High neutrophils
Low platelets
242
What is the recommended daily intake of iron in pregnancy?
30 mg/day
243
How much does the platelet count tend to drop by in pregnancy?
Roughly 10%
NOTE: there is an increase in platelet size
244
Why is epidural anaesthesia a risk in patients with thrombocytopaenia and at what platelet count would this be considered dangerous?
Can cause spinal haematoma
A platelet count > 70 x 109/L is required
245
How is ITP in pregnancy treated?
IVIG
Steroids
Anti-D (if RhD-negative)
246
How might the baby be affected by ITP?
Unpredictable degree of penetration
Check cord blood
Platelet count may fall for 5 days after delivery
Bleeding may occur in 25% of those severely affected
Usually a normal delivery (but avoid forceps, ventouse)
247
How is the relative risk of thromboembolic disease in pregnancy different from the general population?
10 fold
248
List some other conditions in pregnancy that can increase the risk of thromboembolic disease.
Hyperemesis/dehydration
Pre-eclampsia
Obesity
Thrombophilia
Age (> 35 years)
Parity
Multiple pregnancy
Ovarian hyperstimulation (IVF)
249
How long should be left after the last heparin dose before an epidural can be performed?
24 hrs = treatment dose heparin
12 hrs = prophylactic dose heparin
NOTE: there is a hypothesis that thrombosis tendency in pregnancy is associated with impaired placental circulation
250
What are the key features of antiphospholipid syndrome?
Recurrent miscarriage
DVT/PE
Thrombocytopaenia
251
Which antibodies are present in antiphospholipid syndrome?
Lupus anticoagulant
Anticardiolipin antibodies
252
How might miscarriage in women with antiphospholipid syndrome be treated?
Aspirin and heparin
253
What can trigger DIC in pregnancy?
Amniotic fluid embolism
Placental abruption
Missed miscarriage
Pre-eclampsia
Sepsis
254
What are the possible complications that a mother with sickle cell disease may encounter during pregnancy?
More frequent vaso-occlusive crises
Foetal growth restriction
Miscarriage
Preterm labour
Pre-eclampsia
Venous thrombosis
255
How can sickle cell disease in pregnancy be managed?
Red cell transfusion
Prophylactic transfusion
Alloimmunisation
256
How does RDW change in iron deficiency anaemia and thalassemia trait?
IDA – increased
Thalassemia trait – normal
257
List some key features of multiple myeloma.
Cancer of monoclonal plasma cells
Abundance of monoclonal immunoglobulin
Osteolytic bone lesions
Anaemia
Infections (due to deficient polyclonal response)
Kidney failure (due to hypercalcaemia)
258
What is the pre-malignant condition for multiple myeloma?
Monoclonal gammopathy of uncertain significance (MGUS)
259
How common is multiple myeloma compared to other haematological malignancies?
2nd most common after B cell lymphoma
260
What is another term of activated B cells?
Centroblasts
261
What are the main clinical features of multiple myeloma?
Calcium (high)
Renal failure
Anaemia
Bone lesions (pain, pathological fractures)
Monoclonal paraprotein
NOTE: patients with MGUS have no clinical features – there are some arbitrary cut-offs for MGUS/multiple myeloma based on monoclonal serum protein, bone marrow plasma cells and annual risk of progression to multiple myeloma
262
What is the median survival for patients with multiple myeloma?
3-4 years
263
Describe the histological appearance of mature plasmacytic cells.
Nucleus is pushed to one side of the cell
Clumped chromatin
Large cytoplasm (low nuclear-to-cytoplasmic ratio)
264
Describe the histological appearance of immature plasmablastic cells.
Prominent nucleoli
Reticular chromatin
Less abundant cytoplasm
NOTE: the presence of these cells is associated with a poor prognosis
265
Which antigens do myeloma cells test positive for on immunohistochemistry?
CD138
CD38
CD56/CD58
Monotypic cytoplasmic immunoglobulin
Light chain restriction
266
Which antigens do myeloma cells test negative for on immunohistochemistry?
CD19
CD20 (unlike B cell lymphomas and CLL)
Surface immunoglobulin
267
How does multiple myeloma lead to lytic bone disease?
The myeloma cells release osteoclast activating factors and osteoblast inhibiting factors
268
Outline the mechanisms by which multiple myeloma causes kidney injury.
Immunoglobulin light chains activate inflammatory mediators in the proximal tubule epithelium
Proximal tubule necrosis
Fanconi syndrome (renal tubule acidosis with failure of reabsorption in the proximal tubule) with light chain crystal deposition
Cast nephropathy
269
What are the four main domains of treatment of multiple myeloma?
Classical cytostatic drugs (e.g. melphalan)
Steroids (very cytotoxic to lymphocytes)
Immunomodulators (IMIDs e.g. thalidomide)
Proteasome inhibitors
270
Describe how the consequences of rhesus incompatibility are different from ABO incompatibility in a patient receiving a blood transfusion.
ABO – immediate haemolytic transfusion reaction (can be fatal)
Rhesus – delayed haemolytic transfusion reaction
271
List some other red cell antigens that can lead to transfusion reactions.
C, c, E, c
Duffy and Kidd (particularly important for delayed transfusion reactions)
272
Which patient group should receive K negative blood?
Women of childbearing potential
273
How long do red cells survive in storage?
35 days in 4 degrees
274
How soon after leaving storage do red cells need to be transfused?
4 hours
NOTE: red cells can be returned to the fridge within 30 mins of leaving storage
275
If a patient develops a reaction to a plasma transfusion, what is the most likely cause?
Allergic reaction
NOTE: plasma is frozen so it is unlikely to get contaminated by bacteria
276
List some indications for transfusion.
Major blood loss
Peri-operative care
Post-chemotherapy
Symptomatic anaemia
277
By how much would 1 unit of RBC increase the haemoglobin level in a 70 kg patient?
10 g/L
278
Which patient groups would cell salvage be used for?
Patients with rare blood groups
Jehovah’s witnesses
279
Which patient groups require CMV-negative blood?
For intra-uterine and neonatal transfusions
Elective transfusion in pregnancy
280
Which patients require irradiated blood and why?
Highly immunosuppressed patients
These patients cannot destroy donor lymphocytes and the presence of lymphocytes in donated blood can cause graft-versus-host disease
281
Which patients require washed blood?
Patients who have severe allergic reactions to donors’ plasma proteins
This takes 4 hours so must be requested in advance
NOTE: IgA deficient patients are more likely to need washed blood
282
List some indications for platelet transfusions.
Massive transfusion
Prevent bleeding (post-chemotherapy)
Prevent bleeding (surgery)
Platelet dysfunction
283
List some contraindications for platelet transfusion.
Heparin-induced thrombocytopaenia
TTP
284
By what level will 1 unit of platelets increase the platelet count in a 70 kg adult?
By what level will 1 unit of platelets increase the platelet count in a 70 kg adult?
30-40 x 109/L
285
List some indications for FFP transfusion.
Massive transfusion
DIC
Liver disease
286
What does FFP contain?
All the coagulation factors
287
What is the adult dose of FFP?
15 mL/kg
288
How many mLs is 1 unit of FFP?
250 mL
289
List some causes of acute transfusion reactions.
Acute haemolytic (ABO incompatibility)
Allergic/anaphylaxis
Infection (bacterial)
Febrile non-haemolytic
Respiratory (TACO and TRALI)
290
List some causes of delayed transfusion reactions.
Delayed haemolytic transfusion reaction
Infection (viral, malaria, vCJD)
TA-GvHD
Post-transfusion purpura
Iron overload
291
What is the most common transfusion reaction?
Transplant-associated circulatory overload (TACO)
292
What are some early features that might be suggestive of acute transfusion reaction?
Rise in temperature or pulse
Fall in BP
NOTE: these can occur before the patient experiences any symptoms
293
List some symptoms of an acute transfusion reaction.
Fever
Rigors
Flushing
Vomiting
Dyspnoea
Pain at transfusion site
Collapse
294
What are the clinical features of a febrile non-haemolytic transfusion reaction?
Occurs during/soon after transfusion (of blood or platelets)
Rise in temperature, chills and rigors
NOTE: this used to be common before blood was leucodepleted
295
What causes febrile non-haemolytic transfusion reactions?
Release of cytokines from white cell during storage
296
How is febrile non-haemolytic transfusion reaction treated?
Slow/stop the transfusion and treat with paracetamol
297
Describe the clinical features of an allergic transfusion reaction
Mild urticarial or itchy rash
Sometimes causes a wheeze
298
How is an allergic transfusion reaction managed?
Stop or slow the transfusion
IV antihistamines
299
List some symptoms of an acute haemolytic transfusion reaction.
Chest/loin pain
Fever
Vomiting
Flushing
Collapse
Haemoglobinuria
Low BP
High HR
High Temp
300
In an acute haemolytic transfusion reaction, why is it important to take a blood sample?
Send for FBC, biochemistry, coagulation, repeat X-match and DAT
301
Describe the storage and shelf-life of platelets.
Stored at 22 degrees for 7 days
NOTE: they are screened for bacterial before release
302
Which patient group is more likely to have severe allergic reactions to blood products?
IgA deficient patients (anti-IgA antibodies may develop in response to exposure to IgA in donor’s blood)
303
What causes TACO and what are the main clinical features?
Usually caused by a lack of attention to fluid balance (especially in cardiac failure, hypoalbuminaemia, extremes of age)
Leads to pulmonary oedema
SOB
Low oxygen saturations
High HR
High BP
NOTE: this is very common
304
What are the main clinical features of TRALI?
Looks like ARDS
SOB
Drop in oxygen saturation
Rise in HR
Rise in BP
305
Outline the mechanism of TRALI.
Anti-WBC antibodies in donor blood interact with WBC in the patient
Aggregates of WBCs get stuck to pulmonary capillaries resulting in the release of neutrophil proteolytic enzymes and toxic oxygen metabolites
This leads to lung damage
306
What are the main differences between TACO and TRALI?
JVP is not raised and the patient will not respond to frusemide in TRALI
307
How can TRALI be avoided?
Using male donors (haven’t been pregnant) who haven’t had a transplant so they will not have produced antibodies against HLA
308
What are the consequences of alloimmunisation with regards to blood transfusions?
Repeat transfusion with blood containing the antigen will lead to extravascular haemolysis
This is IgG mediated so will take 5-10 days
309
What is the dangerous effect of parvovirus infection?
Causes temporary red cell aplasia
310
Which patients are most affected by parvovirus infection?
Foetuses
Patients with haemolytic anaemias (e.g. sickle cell disease)
311
What are the clinical manifestations of transfusion-associated Graft-versus-Host Disease?
Diarrhoea
Liver failure
Skin desquamation
Bone marrow failure
Death (weeks to months)
312
How can transfusion-associated Graft-versus-Host Disease be prevented?
Irradiate blood components for very immunocompromised patients
313
At what point after transfusion does post-transfusion purpura happen?
7-10 days after transfusion of platelets or red blood cells
NOTE: it usually resolves in 1-4 weeks but can cause life-threatening bleeding
314
How is post-transfusion purpura treated?
IVIG
315
How can iron overload be prevented?
Iron chelators (e.g. exjade)
316
When should all women have a group and screen during pregnancy?
12 weeks
28 weeks
317
If anti-D antibodies are detected in a pregnant women, what further steps should be taken?
Check if the father has the antigen
Monitor the level of antibody
Check cffDNA
Monitor foetus for signs of anaemia (MCA Doppler ultrasound)
Deliver the baby early because it gets a lot worse around term
318
What intervention may be performed if the foetus is found to be very anaemic?
Intrauterine transfusion into the umbilical vein
NOTE: anti-D is the most important antibody for causing haemolytic disease of the newborn
319
Outline the mechanism of action of anti-D immunoglobulin.
RhD-positive cells of the foetus get coated by exogenous anti-D
These will then be removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother’s immune system
320
List some occasions in which anti-D immunoglobulin should be given.
At delivery if the baby is found to be RhD-positive
Spontaneous miscarriages if surgical evacuation was needed
Surgical termination of pregnancy
Amniocentesis and chorionic villous sampling
Abdominal trauma
External cephalic version
Stillbirth or intrauterine death
321
Which test is done if a sensitising event occurs > 20 weeks to determine if more anti-D is needed?
Kleihauer test
322
What is the main cellular marker of stem cells?
CD34
323
What is the risk of dying from bone marrow transplant?
More than 50%
It is the most expensive and risky elective procedure
324
What are the most common reasons for autologous stem cell transplantation?
Myeloma
Lymphoma
CLL
325
When is allogeneic bone marrow transplantation used?
When it is very unlikely that the patient’s disease will be eradicated from the bone marrow by standard chemotherapy
NOTE: suitable for acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune deficiencies
326
List some parameters used to gauge outcome of transplantation techniques.
Overall survival
Disease-free survival
Transplant-related mortality
Relapse incidence
327
Outline the process of peripheral blood sampling for stem cells.
Hormones (e.g. G-CSF) is given to stimulate granulocyte production
This leads to the bone marrow producing some stem cells along with the granulocytes
G-CSF is given for 5 days and stem cells are harvested on the 5th day
The donor is connected to a centrifuge which spins the blood, removes the white cell component, reassembles the red cells and plasma and reinfuses it into the patient
328
What factor (related to stem cell harvesting) does the success of a bone marrow transplant depend on?
Number of CD34 cells per kg of weight of the recipient
329
List some complications of stem cell transplantation.
Graft failure
Infections
GvHD
Relapse
330
List some other factors affecting the outcome of a bone marrow transplant.
Age
Disease phase (early or late)
Gender of recipient and donor
Time to BMT
Donor (sibling or not)
NOTE: this is used to calculate the EBMT risk score
331
List some risk factors for infection that are related to bone marrow transplantation.
Neutropaenia
Breakdown of protective barriers
Decreased antibody levels
Depressed T cell responses
332
Which parts of the body are affected in acute graft-versus-host disease?
Skin
GI tract
Live
333
Which parts of the body are affected in chronic graft-versus-host disease?
Skin
Mucosal membranes
Lungs
Liver
Eyes
Joints
334
Why must patients receiving chemotherapy or radiotherapy have a treatment-free interval before stem cell transplantation?
Chemotherapy and radiotherapy can damage tissues leading to the release of loads of cytokines which activate antigen-presenting cells which present antigens to donor lymphocytes
335
List some risk factors for acute graft-versus-host disease
Degree of HLA disparity
Recipient age
Conditioning regimen
Recipient and donor gender combination (male donors with female patients have worse GvHD)
Stem cell source
Disease phase
Viral infections
336
List some treatment options for GvHD.
Corticosteroids
Ciclosporin A
FK506
Mycophenolate mofetil
Monoclonal antibodies
Photophoresis
Total lymphoid irradiation
337
List some drugs used to prevent GvHD.
Methotrexate
Corticosteroids
Ciclosporin A
FK506
T cell depletion
Post-transplant cyclophosphamide
338
Which component of the transplanted cells is responsible for GvHD?
It is the mature lymphocytes within the cell population (i.e. not the stem cells) that are responsible for GvHD
You cannot, however, remove these mature lymphocytes from the sample because they are important in preventing relapse
339
What are the main differences between the blood count of neonate and an adult?
Higher WCC (neutrophils, lymphocytes)
Higher Hb
Higher MCV
340
How are the enzyme levels in the red blood cells of neonates different to adults?
They have 50% of the concentration of G6PD of adults
341
List some causes of polycythaemia in a foetus.
Twin-to-Twin transfusion syndrome
Intrauterine hypoxia
Placental insufficiency
342
List some causes of anaemia in a foetus.
Twin-to-twin transfusion syndrome
Foetal-to-maternal transfusion
Parvovirus B19 infection
Haemorrhage from cord or placenta
343
What is another term to describe congenital leukaemia?
Transient abnormal myelopoiesis (TAM)
344
Describe the usual course of congenital leukaemia.
Remits spontaneously within the first 2 months of life
However, 25% of infants will relapse after 1-2 years
NOTE: the leukaemia is myeloid with major involvement of the megakaryocyte lineage
345
Define thalassemia.
A group of conditions resulting from a reduced rate of synthesis of one or more globin chains as a result of a genetic defect
346
What is the normal HbA2 level in a healthy adult?
< 3.5%
347
What feature of hyposplenism might you see on a blood film of a patient with sickle cell anaemia?
Howell Jolly bodies
348
Why does sickle cell anaemia in a child differ from sickle cell anaemia in an adult?
Mainly because the distribution of red bone marrow (contains haematopoietic precursors) differs
Red bone marrow is vascular, metabolically active and susceptible to infarction
Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia
349
How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?
Adults – only happens in central skeleton
Infants/Children – can happen anywhere (including hands and feet causing hand-foot syndrome)
350
How is splenic function different in children with sickle cell anaemia compared to adults and what risks does this pose?
Children still have functioning spleens meaning that a child is much more likely to undergo splenic sequestration
This can lead to severe anaemia, shock and death
Teenagers and adults don’t tend to experience splenic sequestration because recurrent infarction has left their spleen small and fibrotic
However, as the risk of splenic sequestration declines with time, the risks of hyposplenism increase
351
Define splenic sequestration
Acute pooling of a large percentage of circulating red cells in the spleen
352
How is splenic sequestration managed?
Parents should be taught how to palpate the spleen and to seek help when the child is acutely unwell with a large spleen
Blood transfusion
353
Which complications of sickle cell anaemia occur in younger children (2-10 years old)?
Acute chest syndrome (caused by infarction of the ribs and lungs)
Painful crises
Stroke (SCD is the most common cause of stroke in children)
354
Which infectious agents are children with sickle cell anaemia particularly vulnerable to?
Pneumococcus
Parvovirus B19 (causes aplastic anaemia)
355
Why do children with sickle cell anaemia have increased folate demands?
Hyperplastic erythropoiesis
Growth spurts
Reduced red cell lifespan
356
List some clinical features of poorly controlled beta thalassemia major.
Anaemia à heart failure, growth retardation
Erythropoietic drive à bone expansion, hepatomegaly, splenomegaly
Iron overload à heart failure, gonadal failure
357
What are the principles of treatment of beta thalassemia major?
Accurate diagnosis and family counselling
Blood transfusion
Iron chelation
358
List some types of inherited haemolytic anaemia.
Red cell membrane – hereditary spherocytosis, hereditary eliptocytosis
Haemoglobin molecule – sickle cell anaemia
Glycolytic pathway – pyruvate kinase deficiency
Pentose shunt – G6PD deficiency
359
List some differential diagnoses for haemophilia.
Inherited thrombocytopaenia/platelet defect
Acquired defects of coagulation (e.g. ITP, acute leukaemia)
Non-accidental injury
Henoch-Schonlein purpura
360
Describe the typical presentation of ITP.
Petechiae
Bruises
Blood blisters in the mouth
361
List some differential diagnoses for ITP.
HSP
Non-accidental injury
Coagulation factor defect
Inherited thrombocytopaenia
Acute leukaemia
362
List some treatment approaches for ITP.
Observation (most common)
Corticosteroids
High dose IVIG
IV anti-RhD (if RhD positive)
363
How is hyposplenism managed?
Vaccination
Prophylactic penicillin
Advice about other risks (e.g. malaria, dog bites)
364
What is a mediastinal mass in a child with a high WBC likely to be?
Thymoma
365
Which type of leukaemia can cause a thymoma?
Acute lymphoblastic leukaemia of T cell lineage
366
What is a bad prognostic feature in leukaemia?
Very high WCC
367
Which techniques are used to determine whether cells are lymphoid or myeloid?
Cytochemistry
Immunophenotyping
368
How is a diagnosis of acute promyelocytic leukaemia confirmed?
Cytogenetic/FISH/molecular genetic analysis
15;17 translocation forming the PML: RARA fusion gene
369
How is acute promyelocytic leukaemia treated?
Platelets
Chemotherapy
All-trans-retinoic acid (ATRA)
370
Aside from chronic leukaemia, which other condition must you consider in an elderly patient with anaemia?
Myelodysplastic syndrome
371
How is polycythaemia vera treated?
Venesection + hydroxycarbamide
NOTE: venesection alone is NOT sufficient if the patient also has a high platelet count
372
Outline the mechanisms by which anaemia of chronic disease causes anaemia.
Reduced red cell lifespan
Cytokine release (IFN-gamma, IL1, TNF)
Reduced proliferation of erythroid precursors
Suppression of endogenous EPO production
Impaired iron utilisation
373
Describe the typical ferritin and transferrin levels you’d expect to see in anaemia of chronic disease.
Ferritin – high or normal (acute phase protein)
Transferrin – reduced
374
Which HLA genotype is associated with Hodgkin lymphoma?
HLA-DPB1
NOTE: EBV is found in >79% of people over 50 years
375
List some blood film features of iron deficiency anaemia.
Pencil cells
Anisocytosis
Poikilocytosis
Hypochromic
376
Which type of major infection is classically seen in AML?
Gram-negative septicaemia
