Haematology Flashcards
1
Q
What are the 4 types of leukaemia?
A
- Acute lymphoblastic
- Acute myeloid
- Chronic lymphocytic
- Chronic myeloid
2
Q
Define myelodysplastic syndrome
A
A precursor syndrome to leukaemia occurring due to a defect in myeloid stem cells.
3
Q
Give the presentation of myelodysplastic syndromes
A
- Elderly
- Pancytopenia (anaemia, infection, bleeding)
Blood film: thrombocytopenia, neutropenia, anaemia, monocytosis
Bone marrow aspirate: raised blast cells
4
Q
Give the management of myelodysplastic syndromes
A
Conservative:
-Supportive care (incl. red cell/platelet infusion)
Gentle chemotherapy and bone marrow transplantation
5
Q
Describe the epidemiology of ALL
A
The most common cancer in children.
Commonly seen age 2-4
Associated with trisomy 21 and radiation exposure.
6
Q
Give the pathophysiology of ALL
A
Arrest of cell maturation and uncontrolled proliferation of blast cells resulting in build-up of immature lymphoid cells (normally give rise to T and B cells).
These are dysfunctional cells which occupy bone marrow volume and deny normal cells vital resources - resulting in pancytopenia.
Eventually ‘spill out’ into blood
7
Q
Describe the presentation of ALL
A
Marrow failure:
-Anaemia: breathlessness, fatigue, angina, claudication, pallor
-Infection: fever, mouth ulcers, infection
-Bleeding: including bruising
Bone pain (due to marrow infiltration)
Hepatosplenomegaly (if liver/spleen infiltration)
Lymphadenopathy (if node infiltration)
Mediastinal infiltration (mediastinal mass, SVC obstruction)
CNS symptoms (rare - due to CNS infiltration)
8
Q
Give the investigations for ALL
A
- FBC (raised WCC)
- Blood film (blast cells present)
- Bone marrow aspirate (blast cells present)
- CT TAP (for mediastinal mass/lymphadenopathy)
- Lumbar puncture (if CNS involvement)
9
Q
Give the management of ALL
A
- Blood and platelet transfusion
- Prophylactic antibiotics/antivirals/antifungals
- Chemotherapy
- Bone marrow transplantation
- Allopurinol (xanthine oxidase inhibitor, thus reducing uric acid and preventing tumour lysis syndrome)
10
Q
Describe the pathophysiology of AML
A
Neoplastic proliferaton of blast cells derived from marrow myeloid (give rise to basophils, neutrophils, eosinophils).
These are dysfunctional cells which occupy bone marrow volume and deny normal cells vital resources - resulting in pancytopenia.
11
Q
Describe the epidemiology of AML
A
The most common leukaemia in those aged >60
Progresses rapidly to death in 2 months if untreated
12
Q
Describe the presentation of AML
A
Gum hypertrophy
Marrow failure (anaemia, infection, bleeding)
Hepatosplenomegaly
Diffuse intravascular coagulation
(Less likely to see bone pain/organ infiltration than in ALL)
13
Q
Describe the investigations for AML
A
- FBC: raised WCC
- Blood film: myeloid precursor cells
- Bone marrow aspirate: myeloid precursor cells
Auer rods seen in myeloid precursor cells!!!
14
Q
Describe the management of AML
A
- Blood and platelet transfusion
- Prophylactic antibiotics/antivirals/antifungals
- Chemotherapy
- Bone marrow transplantation
- Allopurinol
15
Q
Describe the epidemiology of CML
A
Almost exclusively a disease of adults (40-60)
> 80% have the Philadelphia chromosome
16
Q
Give the pathophysiology of CML
A
Uncontrolled proliferation of mature myeloid cells which occupy bone marrow space and prevent normal blood cell production.
17
Q
Give the presentation of CML
A
- Anaemia
- Abdo discomfort (splenomegaly)
- Weight loss
- Tiredness
- Pallor
- Fever and sweats without infection
- Bleeding
18
Q
Give the investigations for CML
A
- FBC: raised WCC (especially myeloid cells (granulocytes) e.g. neutrophils, eosinophils, basophils), low Hb (normochromic and normocytic)
- Bone marrow aspirate: hypercellular
19
Q
Give the management of CML
A
- Oral imatinib (tyrosine kinase inhibitor - inhibits proliferation of malignant cells)
- Stem cell transplant
20
Q
What are the 3 stages of CML?
A
Chronic phase: may be asymptomatic
Accelerated phase: sign that disease is progressing, as blast cells build up in bone marrow and pancytopenia occurs (leading to anaemia, infection, bleeding)
Blast crisis: the acute terminal phase of CML where it rapidly progresses and behaves like an acute leukaemia. There is >20% blast cells in the blood/bone marrow with large clusters forming in the marrow, a worsening of pancytopenia and potentially a chloroma (a solid focus of leukaemia outside the bone marrow)
21
Q
Describe the epidemiology of CLL
A
The most common leukaemia, occurring predominantly in later life (very rare in children)
22
Q
Describe the pathophysiology of CLL
A
Accumulation of mature B cells which have escaped apoptosis and undergone cell cycle arrest.
23
Q
Describe the presentation of CLL
A
Asymptomatic
Anaemia, recurrent infection
Weight loss, sweats, anorexia
Hepatosplenomegaly
Enlarged, rubbery lymph nodes
24
Q
Give the investigations for CLL
A
- FBC: normal or low Hb, raised WCC with very high lymphocytes
- Blood film: smudge cells
25
Give the management of CLL
1. Chlorambucil (chemotherapy) with prednisolone
2. Human IV Ig
3. Stem cell transplantation
4. Blood transfusions
26
Describe the prognosis for CLL
Rule of 3's:
-1/3 never progress
-1/3 progress slowly
-1/3 progress actively
May be stable for many years with death often occurring due to infection.
27
Describe Richter's syndrome
The transformation of CLL into an aggressive high-grade lymphoma
28
Define lymphoma
Malignant proliferation of lymphocytes which accumulate in the lymph nodes and cause lymphadenopathy
29
Describe the histological features of the classifications of lymphoma
Hodgkin's lymphoma: Reed-Sternberg (classical)/popcorn cells present (nodular lymphocyte predominant Hodgkin's lymphoma)
Non-Hodkin's lymphoma: any other lymphoma
30
Describe the epidemiology of Hodgkin's lymphoma
Teenagers (13-19) and elderly (>65)
31
Describe the risk factors for lymphoma
HIV
Transplant recipients
Autoimmune disorders
EBV
Affected sibling
32
Describe the presentation of Hodgkin's lymphoma
Painless cervical lymphadenopathy - "rubbery"
Hepatosplenomegaly
Weight loss, fever, night sweats
Cough (due to mediastinal lymphadenopathy)
SVC obstruction (emergency - fullness in head, facial oedema)
33
Describe the diagnostic investigations for Hodgkin's lymphoma
Lymph node excision
Bone marrow biopsy
CT/MRI TAP (for staging)
34
Describe the staging system for lymphoma
Ann-Arbor Classification:
I - confined to single lymph node or region
II - two or more nodal areas on the same side of the diaphragm
III - involvement of nodes on both sides of the diaphragm
IV - spread beyond lymph nodes (i.e. to bone marrow)
Each stage further divided to A/B:
A - no systemic symptoms other than pruritus
B - presence of fever/night sweats/weight loss
35
Describe the management of Hodgkin's lymphoma
ABVD chemotherapy
Radiotherapy
36
Describe ABVD chemotherapy
A - adriamycin
B - bleomycin
V - vinblastine
D - dacarbazine
37
Describe the complications of radiotherapy
Second malignancies
IHD
Lung fibrosis
Hypothyroidism
38
Describe the complications of chemotherapy agents
Doxorubicin - cardiotoxicity
Bleomycin - pulmonary fibrosis
Cisplatin - oto/nephrotoxicity
Methotrexate - hepatotoxicity
Cyclophosphamide - haematuria
Vincristine/vinblastine - peripheral neuropathy
39
Describe the epidemiology of Non-Hodgkin's lymphoma
All lymphomas without Reed-Sternberg/popcorn cells
80% of B-cell origin
40
Describe the presentation of Non-Hodgkin's lymphoma
Superficial lymphadenopathy
Fever, night sweats, weight loss
Pancytopenia (infection, anaemia, bleeding/bruising)
41
Describe the sub-classification of Non-Hodgkin's lymphoma
Low grade (e.g. Follicular lymphoma) - slow growing, advanced at presentation, incurable
High grade (e.g. diffuse large B-cell lymphoma) - nodal presentation
42
Describe the diagnostic investigations for Non-Hodgkin's lymphoma
Lactose dehydrogenase - sign of increased cell turnover and thus cell proliferation, indicating worse prognosis if raised
Lymph node excision
Bone marrow biopsy
CT/MRI TAP
43
Describe the management of Non-Hodgkin's lymphoma
R-CHOP chemotherapy
Radiotherapy
44
Describe R-CHOP chemotherapy
R - rituximab
C - cyclophosphamide
H - hydroxy-daunorubicin
O - oncovin (vincristine)
P - prednisolone
45
Describe Burkitt's lymphoma
B-cell lymphoma with jaw lymphadenopathy
Strong link with EBV
46
Describe the pathophysiology of myeloma
Cancer of differentiated B-lymphocytes (plasma cells) which produce antibodies.
Accumulation of malignant plasma cells in the bone marrow leading to progressive marrow failure.
Malignant plasma cells produce only one type of antibody (usually IgG), and so levels of this Ig are high while all others are low. This results in immunoparesis and increased susceptibility to infection.
47
Describe the presentation of myeloma
OLD CRAB
Old
C - calcium elevated
R - renal failure (nephrotic syndrome) - due to raised Ig being deposited in the kidneys and resulting in thirst
A - anaemia
B - bone pain - due to lytic lesions as a result of increased osteoclast activation and inhibition of osteoblasts
Recurrent infection (due to neutropenia)
48
Describe the diagnostic investigations for myeloma
FBC - anaemia
ESR
Blood film - normochromic normocytic anaemia, Rouleaux formation
U&E's - high calcium and alk phos
Urinalysis - Bence-Jones protein present (light-chain Ig)
Plain XR - lytic 'punched-out' lesions, 'pepper-pot' skull, vertebral collapse, fracture, osteoporosis
Bone marrow biopsy - increased plasma cells
49
Describe the management of myeloma
Chemotherapy (CTD or VAD)
Stem cell transplant
Analgesia (avoid NSAIDs due to renal impairment)
Bisphosphonate (e.g. zoledronate)
Blood transfusions and erythropoietin (for anaemia)
Rehydrate (to prevent renal damage)
Dialysis
Antibiotics for infection
50
Describe CTD chemotherapy
Cyclophosphamide
Thalidomide
Dexamethasone
Used in those who are less fit.
51
Describe VAD chemotherapy
Vincristine
Adriamycin
Dexamethasone
Used in fitter individuals
52
Define febrile neutropenia
AKA neutropenic sepsis
Temperature >38C in a patient with neutrophils <1.0x10^9 L^-1
Haematological emergency! Infection with insufficient neutrophils to fight!
53
Describe the risk factors for febrile neutropenia
Recent chemotherapy
Recent stem-cell transplant
Those on methotrexate, carbimazole, clozapine
Haematological condition resulting in neutropenia (e.g. aplastic anaemia, autoimmune disease, leukaemia)
54
Give the presentation of febrile neutropenia
Pyrexia (>38C)
Generally unwell, sweats, rigors, cough, sore throat, abdo pain, diarrhoea
Tachycardia, hypotension, tachypnoea
55
Describe the management of febrile neutropenia
Broad spectrum antibiotics
56
Describe the risk factors of malignant spinal cord compression
Any malignancy (due to bone metastases, local tumour extension) - e.g. myeloma, lymphoma
57
Describe the presentation of malignant spinal cord compression
Back pain
Weakness/numbness in legs
Loss of bladder/bowel control
Saddle paraesthesia
Decreased perineal sensation
Decreased anal tone
58
Describe the management of malignant spinal cord compression
Strict bed rest
MRI whole spine
Analgesia
High dose steroid (e.g. dexamethasone)
59
Describe the pathophysiology of tumour lysis syndrome
A life-threatening metabolic derangement that occurs when malignant cells break down, resulting in neurological, cardiac and renal complications.
60
Describe the blood characteristics of tumour lysis syndrome
High uric acid
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
61
Describe the risk factors for tumour lysis syndrome
High tumour burden (amount of cancer)
High grade disease (rapid cell turnover)
Pre-existing renal impairment
Increasing age
Drugs which increase uric acid
62
Describe the management of tumour lysis syndrome
Aggressive hydration
Dialysis
Allopurinol - reduces uric acid production
63
Describe hyperviscosity syndrome
Increase in blood viscosity, usually due to high levels of immunoglobulins.
Leads to vascular stasis and hypoperfusion
64
Describe the causes of hyperviscosity syndrome
Multiple myeloma (raised Ig)
Leukaemia (raised cell numbers)
Polycythaemia
65
Describe the presentation of hyperviscosity syndrome
Mucosal bleeding
Visual disturbance (hypoperfusion of retina)
Vertigo, hearing loss, paraesthesia, ataxia, headaches, seizure (hypoperfusion of brain)
SOB
Bruising
Gum bleeding
Nystagmus
66
Give the diagnostic investigations for hyperviscosity syndrome
Plasma viscosity levels
Immunoglobulin levels
FBC
CT head
67
Describe the management of hyperviscosity syndrome
Hydration and avoid transfusion
Plasmapheresis - removes circulating Ig
68
Describe the presentation of hypercalcaemia
'Bones, stones, moans and psychiatric groans':
-Bone pain
-Renal stones
-Abdo pain
-Confusion
Constipation
Nausea
Polyuria
Anorexia
Mostly seen in multiple myeloma.
Shortened QR interval, cardiac arrest.
69
Give the management of hypercalcaemia
IV hydration (3-4L per day)
Bisphosphonates (reduce Ca2+ production)
70
Describe the presentation of anaemias
Fatigue
Headaches
Dyspnoea
Angina
Anorexia
Intermittent claudication
Palpitations
Pallor
Tachycardia
Cardiac failure
71
Describe the causes of microcytic anaemia
Iron deficiency
Anaemia of chronic disease
Thalassaemia
Congenital sideroblastic anaemia
Lead poisoning
72
Define ferritin and transferrin
Ferritin - intracellular iron storage protein
Transferrin - plasma protein which transports iron to the bone marrow for erythropoiesis
73
Describe the epidemiology of iron deficiency anaemia
Most common cause of anaemia
Commonly seen in menstruating women
74
Describe the caused of iron deficiency anaemia
GI bleeding
Menstruation
Poor diet
Hookworm
Increased demand (e.g. pregnancy, growth)
Malabsorption (e.g. coeliac)
75
Describe the pathophysiology of iron deficiency anaemia
Less iron available for haem synthesis, therefore decrease in heamoglobin.
This causes microcytic hypochromic RBCs to form.
76
Describe the presentation of iron deficiency anaemia
General symptoms of anaemia
Brittle nails and hair
Koilonychia - spooning of the nails
Atrophic glossitis
Angular stomatitis
77
Give the diagnostic investigations for iron deficiency anaemia
FBC - low Hb and MCV, low reticulocytes (reduced production)
Blood film - microcytic, hypochromic RBCs
Iron studies - low ferritin and serum iron
Investigate cause (e.g. endoscopy)
78
Give the management of iron deficiency anaemia
Find and treat cause
Oral iron (e.g. ferrous sulphate) - may cause GI disturbance
79
Describe anaemia of chronic disease
Anaemia secondary to a chronic disease (if the body is sick, so is the bone marrow - as such there is reduced erythrocyte production)
Microcytic
80
Describe the epidemiology of anaemia of chronic disease
The second most common anaemia
Seen in Crohn's, RA, TB, SLE, malignancy
81
Describe the pathophysiology of anaemia of chronic disease
Decreased release of iron from the bone marrow to developing erythrocytes, leading to inadequate erythropoietin response to anaemia and decreased erythrocyte survival.
82
Describe the presentation of anaemia of chronic disease
Generalised anaemia features in the presence of a chronic disease
83
Describe the diagnostic investigations for anaemia of chronic disease
Serum iron and total iron binding capacity are low
Serum ferritin normal/raised
Blood film - hypochromic microcytic anaemia
84
Give the management of anaemia of chronic disease
Erythropoietin
Treat underlying cause
85
What non-haematological cause can result in a raised ferritin
Inflammation! Ferritin is an acute phase reactant!
86
Describe the classifications of macrocytic anaemia
Megaloblastic - erythroblasts with delayed nuclear maturation due to delayed DNA synthesis (e.g. pernicious anaemia, folate deficiency)
Non-megaloblastic - normal erythroblasts (e.g. haemolysis, alcohol)
87
Describe the aetiology of B12 deficiency anaemia
Pernicious anaemia
Veganism
Removal of terminal ileum (where B12 absorbed)
88
Describe the pathophysiology of pernicious anaemia
Autoimmune destruction of parietal cells, resulting in atrophic gastritis and a loss of intrinsic factor production (produced by parietal cells) resulting in subsequent B12 malabsorption.
89
Describe the presentation of pernicious anaemia
Generic anaemia symptoms
Jaundice (due to haemolysis - body attempts to remove megaloblasts)
Glossitis, angular stomatitis
Neurological features (symmetrical paraesthesia, dementia, psychiatric pathology)
90
Describe the investigations for pernicious anaemia
FBC: high MCV, low reticulocytes, low Hb
LFT: high bilirubin
Haematinics: low B12
Blood film: megaloblastic macrocytic anaemia (hypersegmented neutrophil polymorphs)
Intrinsic factor antibodies
91
Give the management of pernicious anaemia
Oral vit B12
IM hydroxocobalamin
92
Where is folate absorbed?
Duodenum and proximal jejenum
93
What is the function of folate?
DNA synthesis
94
Describe the pathophysiology of folate deficiency
Folate is required for DNA synthesis.
In deficiency there is delayed nuclear maturation and decreased erythropoiesis.
Deficiency may also cause neural tube defects in fetus.
95
Describe the aetiology of folate deficiency anaemia
Poor intake (e.g. poverty, alcoholism)
Increased demand (e.g. pregnancy, increased cell turnover)
Malabsorption (coeliac, Crohn's)
Antifolate drugs (e.g. methotrexate, trimethoprim)
96
Describe the presentation of folate deficiency anaemia
Asymptomatic
Glossitis
NO NEUROPATHY - unlike B12 deficiency
General symptoms of anaemia
97
Describe the investigations for folate deficiency anaemia
FBC: raised MCV
Haematinics: low folate
Blood film: megaloblastic anaemia (hypersegmented neutrophil polymorphs)
GI investigation
Serum bilirubin
98
Describe the management of folate deficiency anaemia
Folic acid supplementation
Also give B12 to prevent subacute degeneration of the spinal cord (correct B12 before folate to also prevent this)
99
Describe the pathophysiology of haemolytic anaemia
Normocytic or macrocytic
Premature breakdown of erythrocytes
Reticulocytes released prematurely - these are macrocytic
100
Describe the aetiology of haemolytic anaemia
Hereditary spherocytosis
G6PD deficiency
Thalassaemias
Sickle cell disease
Autoimmune haemolytic anaemia
101
Describe the investigations for haemolytic anaemia
Raised conjugated bilirubin
Raised urinary urobilinogen
Raised faecal stercobilinogen
Reticulocytosis
102
Describe the epidemiology of hereditary spherocytosis
Most common hereditary haemolytic anaemia
Autosomal dominant
103
Describe the pathophysiology of hereditary spherocytosis
Defect in red cell membrane resulting in spherocytosis and a subsequent decrease in the surface area to volume ratio of erythrocytes.
Spherocytes are more rigid and so are unable to pass through the splenic microcirculation - become trapped in the spleen
Cells have a shortened lifespan and are destroyed (haemolysis)
104
Describe the investigations for hereditary spherocytosis
Blood film: spherocytes and reticulocytes
FBC: low Hb, raised reticulocytes
LFTs: raised bilirubin
Coomb's test: negative (rules out autoimmune haemolytic anaemia)
105
Describe the presentation of hereditary spherocytosis
Jaundice at birth
Anaemia
Splenomegaly
Leg ulcers
Gallstones (due to raised uric acid secondary to haemolysis)
106
Describe the management of hereditary spherocytosis
Splenectomy (relieves symptoms)
Subsequently give vaccinations and prophylactic antibiotics due to reduced immune function following splenectomy.
107
Describe the aetiology of G6PD deficiency
Heterogenous x-linked mutation (therefore more common in males)
108
Describe the pathophysiology of G6PD deficiency
G6PD is normally vital to protect erythrocytes from oxidative damage, and so in deficiency there is a reduced erythrocyte lifespan
109
What does G6PD stand for?
Glucose-6-phosphate dehydrogenase
110
Describe the presentation of G6PD deficiency
Asymptomatic
Oxidative crisis
In attacks due to rapid intravascular haemolysis:
-Rapid anaemia
-Jaundice
-Chronic haemolytic anaemia
-Haemoglobinuria
111
Describe the cause of oxidative crisis in G6PD deficiency
Reduction in glutathione production, precipitated by:
-Aspirin
-Antibiotics
-Fava beans
112
Describe the investigations for G6PD deficiency
Blood count normal between attacks
Irregularly contracted cells
Bite cells (indentation in cell membrane)
Reticulocytosis
Low G6PD levels
113
Describe the management of G6PD deficiency
Stop offending drugs
Blood transfusion
114
Describe the aetiology of alpha thalassaemia
Defects in alpha globin chains due to genetic defect on chromosome 16
Autosomal recessive
115
Describe the pathophysiology of thalassaemia
Defects in globin chains resulting in abnormal haemoglobin - underproduction of one globin chain
Red blood cells are more likely to be destroyed due to imbalanced globin chains (more a or b chains)
This results in splenomegaly
Bone marrow swells to increase erythropoiesis
Iron overload may occur
116
Describe the aetiology of beta thalassaemia
Defect in beta globin chains due to mutation on chromosome 16
Autosomal recessive
Either abnormal copies of gene that retain some function or deletion genes where there is no function in beta globin chains.
117
Describe beta thalassaemia minor
Carriers of abnormally functioning beta globin gene, with one normal and one abnormal gene
Causes a mild microcytic anaemia with no treatment usually required
118
Describe beta thalassaemia intermedia
Two abnormal copies of the beta globin gene causing a more severe microcytic anaemia
May require blood transfusions - but not often
119
Describe beta thalassaemia major
Homozygous deletion genes so no functioning beta globin chains at all
Usually presents in childhood with severe anaemia, failure to thrive
Manage with regular transfusions, splenectomy, bone marrow transplant
120
Describe the presentation of thalassaemia
Microcytic anaemia
Fatigue
Pallor
Jaundice
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences (due to bone marrow overgrowth)
121
Describe the investigations for thalassaemia
FBC - microcytic anaemia, reticulocytosis
Blood film: nucleated RBCs in peripheral circulation
Haemoglobin electrophoresis - diagnose globin abnormality
DNA testing
122
Describe the management of thalassaemia
Regular life-long transfusions (if B thalassaemia major)
Iron chelation therapy (to prevent overload)
Splenectomy
Bone marrow transplant
123
Describe the presentation of iron overload
Fatigue
Cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
124
Describe the management of iron overload
Iron chelation therapy:
-Oral deferiprone
-SC desderrioxamine
-Ascorbic acid (increases urinary excretion of iron)
125
Describe the aetiology of sickle cell anaemia
Autosomal recessive disorder (25% chance of developing disease from 2 carrier parents, 50% chance of also being a carrier)
126
Describe the pathophysiology of sickle cell anaemia
Abnormal B-globin chains
Single base mutation resulting in the production of sickle cell haemoglobin (HbS)
Manifests around 6 months (when all fetal haemoglobin is depleted)
HbS is insoluble and polymerises when deoxygenated, leading to RBC membrane rigidity and irreversible deformity into a sickled shape
This leads to shortened RBC survival and haemolysis, as well as impaired passage of cells through the microcitculation - causing obstruction, tissue infarction and intense pain
127
Describe sickle cell trait
Heterozygous sickle cell disease (carrier)
Asymptomatic except in hypoxia when vaso-occlusive crises may occur
128
Describe the presentation of sickle cell anaemia
Vaso-occlusive crises:
-Pain in long bones, hands and feet (due to AVN of bone marrow)
-CNS infarction
Acute chest syndrome:
-Vaso-occlusive crisis of pulmonary vasculature
-SOB, chest pain, hypoxia
Pulmonary hypertension
Anaemia - due to chronic haemolysis
Splenic sequestration - sickle cells trapped in the spleen resulting in acute painful enlargement
Aplastic crisis
129
Describe the investigations for sickle cell anaemia
FBC: low Hb, raised reticulocytes
Blood film: sickled erythrocytes
Sickle solubility test positive
Haemoglobin electrophoresis - shows HbS
130
Describe the management of sickle cell anaemia
Prophylactic vaccinations and folic acid supplementation
PO hydroxycarbamide (chemotherapy drug)
Acute painful attacks: IV fluid, analgesia, oxygen, antibiotics (if required)
Blood transfusion (in acute chest sybndrome, aplastic crisis, splenic sequestration)
131
Describe the pathophysiology of aplastic anaemia
Rare stem cell disorder resulting in pancytopenia with hypocellularity of the bone marrow (marrow stops making cells)
Reduction in the number of pluripotent stem cells alongside a fault in those remaining, so they are unable to repopulate the bone marrow
132
Describe the presentation of aplastic anaemia
Pancytopenia:
-Anaemia
-Infection
-Bleeding/bruising
133
Describe the aetiology of aplastic anaemia
Inherited (e.g. Fanconi's anaemia)
Idiopathic
Chemotherapy
134
Which drugs can precipitate haemolysis in G6PD deficiency?
sulph- drugs:
-sulphonamides (e.g. acetazolamide)
-sulphasalazine
-sulfonylureas (e.g. gliclazide, glipizide)
135
Which symptoms imply poor prognosis in lymphoma?
B' symptoms imply a poor prognosis
-weight loss > 10% in last 6 months
-fever > 38ºC
-night sweats
136
Which signs may be seen on a blood film in coeliac's disease?
Target cells and Howell-Jolly bodies may be seen in coeliac disease
Secondary to hyposplenism
137
What is the preferred anticoagulant for AF in those with renal impairment
Apixaban is the preferred NOAC for patients with renal impairment due to minimal renal drug clearance
138
At what rate should RBCs be transfused in a non-urgent scenario?
In a non-urgent scenario, a unit of RBC is usually transfused over 90-120 minutes
139
Describe the management of aplastic anaemia
Exclude other causes of pancytopenia (e.g. leukaemia)
Treat cause
Red cell and platelet transfusion
Bone marrow transplantation
Immunosuppressive therapy (e.g. ciclosporin)
140
Describe the epidemiology of polycythaemia vera
Janus-kinase-2 (JAK-2) gene
Most common age >60
141
Describe the presentation of polycythaemia vera
Clonal stem cell disorder resulting in malignant proliferation of a RBC clone derived from one pluripotent marrow stem cell.
The progenitor offspring do not require erythropoietin to avoid apoptosis, so there is excessive RBC proliferation resulting in raised haematocrit, hyperviscosity and thrombosis.
142
Describe the presentation of polycythaemia vera
Asymptomatic
Headache
Pruritus (worse when warm, i.e. when in bath)
Burning sensation in fingertips/toes
Gout
Hepatosplenomegaly
143
Describe the management of polycythaemia vera
Venesection
Chemotherapy - hydroxycarbamide
Low dose aspirin and allopurinol
FBC - for diagnosis
Bone marrow biopsy and genetic screen for JAK2
144
Describe the aetiology of DVT
Immobility, surgery, leg fracture, COCP, long haul flight, malignancy.
Factor V Leiden
Anti-phospholipid syndrome
145
Describe the diagnosis of DVT
D-dimer: elevated (normal result excludes DVT but a raised result does not confirm)
Compression ultrasound (in DVT you will not be able to compress the popliteal vein)
Doppler ultrasound
146
Describe the presentation of DVT
Painful, tender, red, swollen, hot calf
Engorged superficial veins
Ankle oedema
Sx of pulmonary embolism
147
Describe the management of DVT
LMWH - e.g. enoxaparin
Oral DOAC (or warfarin) for 6 months
Compression stockings
IVC filter if recurrent
148
Describe the pathophysiology of ITP
Thrombocytopenia occurring secondary to immune destruction of platelets
149
Describe the presentation of primary ITP
Children - acute onset
Mucocutaneous bleeding, sudden self-limiting purpura
May follow infection or recent vaccination
150
Describe the presentation of secondary ITP
Adults - chronic
Often associated with other autoimmune disorders (plus CLL and HIV)
150
Describe the presentation of secondary ITP
Adults - chronic
Often associated with other autoimmune disorders (plus CLL and HIV)
151
Describe the general presentation of ITP
Easy bruising
Epistaxis
Menorrhagia
Gum bleeding
Purpura - red or purple skin spots due to bleeding underneath
152
Describe the diagnosis of ITP
Bone marrow aspiration - thrombocytopenia
Platelet autoantibodies
153
Describe the management of ITP
1st line: corticosteroids (prednisolone), IV Ig
2nd line: splenectomy, immunosuppressant (e.g. azathioprine)
154
Summarise disseminated intravascular coagulation
Bleeding disorder in response to illness or disease which result in dysregulated blood clotting.
There is a tendency to both paradoxical bleeding and clotting simultaneously despite the usual balance.
155
Describe the pathophysiology of DIC
Develops alongside pre-existing condition (e.g. malignancy)
Intravascular activation of the coagulation cascade.
Microvascular thrombosis occurs which can cause multi-organ failure secondary to ischaemia.
Subsequent 'consumptive coagulopathy' - lack of clotting factors as they are all being used up elsewhere - leads to thrombocytopenia and increased risk of bleeding.
156
Describe the presentation of DIC
Bleeding from unusual sites (e.g. ears, nose, GI/GU tracts, sites of venepuncture/cannulation)
Widespread bruising
New confusion/disorientation cerebral hypoperfusion)
Petechiae, purpura, localised infection of digits, hypotension.
157
Describe the management of DIC
Supportive care (e.g. platelet transfusion)
Treat underlying cause
158
Describe the inheritance pattern seen in haemophilia A
X-linked recessive - so more common in males
Mother usually a carrier.
159
Describe the presentation of haemophilia A
Neonates and young children - may be fatal from acute intra-cranial bleed
Haematoma/haemarthrosis/GI haemorrhage
Excessive bleeding after procedures and trauma
160
Describe the pathophysiology of haemophilia A
Factor VIII deficiency
Von Willebrand's disease also affects factor VIII, but indirectly. vWF helps prolong the life of factor VIII.
161
Describe the diagnosis of haemophilia A
Prolonged APTT (PT normal), low factor VIII
162
Describe the management of haemophilia A
Prevent acute bleeding:
-Prophylactic factor VIII infusion
-Avoid NSAIDs, IM injection, contact sports etc.
Acute bleeding episodes:
-Factor VIII infusion, FFP or recombinant factor VIII
-Tranexamic acid (antifibrinolytic)
-Desmopressin (mbolises stored factor VIII)
163
Describe the inheritance pattern seen in haemophilia B
X-linked recessive
Rarer than haemophilia A and von Willebrand disease
164
Describe the difference in presentation between clotting and platelet disorders
Clotting: haematoma, haemarthrosis etc
Platelet: petechiae, purpura, bruising
165
Describe the pathophysiology of haemophilia B
Deficiency in factor IX
166
Describe the presentation of haemophilia B
Haemorrhage with minor trauma and surgical procedures (incl. dental procedures)
Spontaneous haemorrhage (e.g. haemarthrosis, ICH, epistaxis)
167
Describe the diagnosis of haemophilia B
Prolonged APTT (PT normal)
Factor IX deficiency with normal factor VIII and vWF
Imaging in acute bleeds
168
Describe the management of haemophilia B
Acute bleeds:
-Recombinant factor IX
Long-term management:
-Prophylactic factor IX infusion
-Avoid IM injection, contact sports
-Hep A/B injection due to risk of contracting from FFP
169
Describe the life expectancy in haemophilias
Normal - if treated
170
Describe the inheritance pattern seen in haemochromatosis
Autosomal recessive disorders of iron metabolism
Mutations in C282Y gene
171
Describe the pathophysiology of haemochromatosis
Genetic defect results in excessive iron absorption from the diet with subsequent accumulation in the tissues.
172
Describe the presentation of haemochromatosis
Dark skin discolouration
Malaise, lethargy, weakness
Erectile dysfunction
Liver disease (due to hepatic involvement) - cirrhosis, HCC
Diabetes (due to pancreatic involvement)
Arthritis, heart failure, neurological signs
173
Describe the diagnosis of haemochromatosis
Raised ferritin, raised serum iron
Deranged LFTs - consider liver biopsy
Genetic testing
174
Describe the management of haemochromatosis
Exclude iron overload anaemia (sideroblastic, thalassaemia)
Venesection
Avoid alcohol, iron supplements and Vit C.
Liver transplantation
