Haematology conditions Flashcards
1
Q
What is aplastic anaemia?
A
Rare stem cell disorder characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (Pancytopenia)
Leads to pancytopenia and hypoplastic marrow (Marrow stops making cells)
2
Q
What causes aplastic anaemia?
A
Most are AI triggered by drugs, viral infection or irradiation
>40% idiopathic
Acquired (Drugs, chemicals, radiation, viral infection, paroxysmal nocturnal haemoglobinuria)
Inherited (Fanconi’s anaemia, dyskeratosis congenita)
3
Q
What are the symptoms of aplastic anaemia?
A
Slow-onset (months) or Rapid-onset (Days)
Anaemia symptoms
Thrombocytopenia (Easy bruising, bleeding gums, epistaxis)
Leukopenia (increased frequency and severity of infections)
4
Q
What are the signs for aplastic anaemia?
A
Pallor Petechiae Bruises Multiple infections No Organomegaly
5
Q
What investigations are done for aplastic anaemia?
A
FBC (Low Hb, Low platelets, Low WCC, Normal MCV, Low/absent reticulocytes)
Blood film (exclude leukaemia)
Bone marrow trephine biopsy
Fanconi’s anaemia (Check for presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents)
6
Q
What is Haemolytic anaemia?
A
Premature erythrocyte breakdown caused by shortened erythrocyte life span (<120 days) with anaemia.
Occurs in circulation to damaged RBCs or in the reticuloendothelial system
7
Q
What causes Haemolytic anaemia?
A
Hereditary sepherocytosis Hereditary elliptocytes G6PD deficiency Pyruvate kinase deficiency Sickle cell disease Thalassemia AIHA Isoimmune Drugs (Penicillin, Quinine) Trauma (MAHA) Malaria Sepsis Marchiafava-Micheli disease
8
Q
What are the symptoms of Haemolytic anaemia?
A
Jaundice Heamaturia Dark Urine Anaemia Can often be asymptomatic Family history Race Recent travel
9
Q
What are the signs of haemolytic anaemia?
A
Pallor
Jaundice
Hepatosplenomegaly
Leg ulcers
10
Q
Which investigations are needed for Haemolytic anaemia??
A
- FBC (Low Hb, High reticulocytes, High MCV, High unconjugated bilirubin, low haptoglobin)
- U&Es
- Folate
Blood film
[May identify specific abnormal cells pointing to the diagnosis]
Urine (Haemoglobin, Blood, high urobilinogen)
Direct coomb’s test
Osmotic fragility test / spectrin mutation analysis
Ham’s test
Hb electrophoresis or enzyme assays
Bone marrow biopsy (Rare)
11
Q
Which cells on the blood film points to diagnosis?
A
Hypochromic microcytic anaemia - thalassemia
Spherocytes - Hereditary spherocytosis or AIHA
Elliptocytes - Hereditary Elliptocytes
Sickle cells - Sickle cell anaemia
Schistocytes - MAHA
Malarial parasites
Heinz bodies (bite cells) - G6PD deficiency
12
Q
What is Coomb’s test?
A
A test for AIHA, identifies erythrocytes coated with antibodies
13
Q
What is Ham’s test?
A
Lysis or erythrocytes in acidified serum in paroxysmal nocturnal haemoglobinuria
14
Q
What is Macrocytic anaemia?
A
Anaemia with Red blood cells that are larger than normal.
Usually results from abnormal haematopoiesis so that red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally
15
Q
What causes macrocytic anaemia?
A
Oval macrocytes
Pernicious Anaemia
B12 deficiency
Folate deficiency
Drugs (Methotrexate, hydroxyurea, azathiopine, zidovudine)
Non megaloblastic causes (Alcohol excess, Myelodysplasia, multiple myeloma, hypothyroidism, aplastic anaemia, haemolysis, drugs, pregnancy)
16
Q
What are the symptoms of macrocytic anaemia?
A
Mild is asymptomatic Shortness of breath Fatigue Palpitations Exacerbation of angina Looking pale Family history of AI disease Previous GI surgery Symptoms of cause (weight loss, diarrhoea)
17
Q
What are the signs of macrocytic anaemia?
A
Pallor Tachycardia Breathlessness Pernicious anaemia (mild jaundice, glossitis, angular somatitis, weight loss) For B12 deficiency: - Peripheral neuropathy - Ataxia - Subacute combined degeneration of the spinal cord - Optic atrophy - Dementia - Positive babinski's sign
18
Q
What are the investigations for macrocytic anaemia?
A
FBC LFT ESR TFT Serum B12 Red cell folate Anti-parietal cell Blood film Schilling test BM biopsy
19
Q
What is the management of Pernicious anaemia?
A
No neurological deficits:
- IM hydroxycobalamin 3x/week for 2 weeks then 1mg/3 months
Neurological deficits:
- 1mg every other day until no further improvement then 1mg/2 months
20
Q
What is the management of B12/Folate deficiency?
A
B12: Dietary supplements (PO cyanocobalamin)
Folate: Oral folic acid
If both B12 and folate, need to do B12 first
21
Q
What are the complications of macrocytic anaemia?
A
Pernicious anaemia - Gastric cancer, subacute combined degeneration of spinal cord
Folate in pregnancy leads to increased risk of neural tube defects
22
Q
What is Microcytic anaemia?
A
Anaemia assocaited with low MCV (<80fl)
23
Q
What causes microcytic anaemia?
A
Iron deficiency (Blood loss, reduced absorption, increased demands, reduced intakes)
Anaemia of chronic disease
Sideroblastic anaemia
Thalassemia
24
Q
What are the symptoms of microcytic anaemia?
A
Tiredness Lethargy Malaise Dyspnoea Pallor Palpitations Exacerbation of ischaemic conditions Lead poisoning
25
What are the signs of microcytic anaemia?
```
Anaemia:
- Pallor
- Brittle nails and hair
- Kolionychia
- Glossitis
- Angular stomatitis
Lead poisoning signs:
- Blue gumline
- Peripheral nerve lesions
- Encephalopathy
- Convulsions
- Reduced consciousness
```
26
What investigations are done for microcytic anaemia?
```
FBC (Low Hb, MCV; reticulocytes)
Iron studies
Serum Lead
CRP/ESR
Blood film
Haemoglobin electrophoresis
```
27
What is seen on blood film for causes of microcytic anaemia?
```
IDA
- Microcytic
- Hypochromic
- Anisocytosis
- Poikilocytosis
Sideroblastic anaemia
- Dimorphic blood film
- Hypochromic microcytic cells
Lead poisoning
- Basophilic stippling
Sideroblastc anaemia
- Ring sideroblasts in bone marrow
```
28
Which special investigations are needed for Iron deficiency anaemia if >40 and post-menopausal women or males?
Upper GI endoscopy
Colonoscopy
Urine dip
29
What is the management for Iron deficiency anaemia?
Oral iron supplements (Ferrous fumarate)
| IV iron if oral ineffective
30
What is the management for sideroblastic anaemia?
Treat cause
Pyroxidine in inherited forms
Blood transfusion and iron chelation
31
What is the management for lead poisoning?
Remove source
| Dimercaprol or D-Penicillinamine
32
What are the complications of microcytic anaemia?
High-output cardiac failure
| complications related to cause
33
What is normocytic anaemia?
Anaemia with a normal MCV (80-100)
34
What causes normocytic anaemia?
```
Acute blood loss (peptic ulcer, oesophageal varices, trauma)
Failure of RBC production
Heamolysis
Uncompensated increase in plasma volume
Pooling in the spleen
Anaemia of chronic disease
```
35
What causes a failure of RBC production?
```
Bone marrow failure or suppression
Bone marrow infiltration
Renal failure
Vitamin B2/B6 deficiency
Hypothyroidism
```
36
What are the symptoms of RBC production?
Breathlessness
Fatigue
Conjunctival pallor
37
What are the signs of RBC production?
Conjunctival pallor
| Angular stomatitis
38
What investigations are done for Normocytic anaemia?
FBC (check Hb and MCV)
Check ferritin for IDA
Check history for haemorrhage
If WCC low or platelets low, suspect marrow failure
39
What is Polycythaemia?
An increase in haemoglobin concentration above the upper limit of normal for a person's age and sex
40
What are the 2 classes of Polycythaemia?
Relative polycythaemia
| Absolute polycythaemia
41
What is the difference between relative polycythaemia and absolute polycythaemia?
Relative polycythaemia = Normal red cell mass but low plasma volume
Absolute polycythaemia = Increased red cell mass
42
What causes polycythaemia?
```
Primary
- Polycythaemia rubra vera
Secondary
- Appropriate increase in EPO
- Inappropriate increase in EPO
- Relative polycythaemia
```
43
What causes polycythaemia rubra vera?
- Characterised by clonal proliferation of myeloid cells
- Have varied morphological maturity and haematopoietic efficiency
- Mutations in JAK2 tyrosine kinase are involved
44
What are the causes of increased EPO?
```
Appropriate:
- Chronic hypoxia
Inappropriate:
- Renal
- Hepatocellular carcinoma
- Fibroids
- Cerebellar haemangioblastoma
- secondary polycythaemia due to EPO abuse
```
45
What are the causes of Relative polycythaemia?
- May be acute - dehydration
- Chronic from associated with obesity, hypertension, high alcohol and tobacco intake
- Gaisbock's syndrome
46
What are the risk factors for polycythaemia?
```
Age
Hypertension
Diabetes
Smoking
Alcohol
COPD
Altitude
Congenital heart disease
Cancer
Family history
```
47
What are the symptoms of polycythaemia?
```
Headache
Dyspnoea
Tinnitus
Blurred vision
Pruritus after hot bath
Burning sensation in fingers and toes (erythromyalgia)
Night sweats
Thrombosis
Pain from peptic ulcer disease
Angina
Gout
Choreiform movements
```
48
What are the signs of polycythaemia?
```
Plethoric complexion (red, ruddy)
Scratch marks from itching
Conjunctival suffusion (redness of the conjunctiva)
```
49
What are the investigations for polycythaemia?
```
FBC (High Hb, High Hct, Low MCV)
Isotope dilution techniques
JAK2 mutation
EPO
Bone marrow trephine and biopsy
Secondary: High serum EPO, Exclude lung disease, Check for EPO-secreting tumours
```
50
What is sickle cell disease?
Autosomal recessive single gene defect in the beta chain of the haemoglobin, which results in production of sickle cell haemoglobin.
May occur if one HbS obtained from one parent or another bad haemoglobin e.g. Beta thalassaemia inherited from another patient
51
What causes sickle cell disease?
Sickling with RBCs containing sickle haemoglobin become rigid and distorted into a crescent shape
Valin replaes glutamic acid at 6th AA of beta globin chain
52
Which factors precipitate sickling?
Infeciton
Hypoxia
Acidosis
Dehydration
53
What are the risk factors for sickle cell disease?
Genetic
54
What are the symptoms of sickle cell disease?
```
Autosplenectomy
Abdominal pain due to mesenteric ischaemia
Bone pain
Avascular necrosis
Myalgia and arthralgia
Leg ulcers
Low flow priapism
CNS
Retina
Painful erection
Impotence
Breathlessness
Cough
Pain
Fever
Symptoms of aplastic anaemia
Anaemia and infection
```
55
What are the signs of sickle cell disease?
Secondary to vaso-occlusion, ischaemia or infarction
- Bone - joint or muscle tenderness or swelling
- Short digits - infarction in small bones of hands
Retina - cotton wool spots due to retinal ischaemia
Organomegaly (spleen)
Priapism
Lethargy
Pallor
56
What are the investigations for sickle cell disease?
FBC
U&Es
Blood film (Sickle cells, anisocytosis, hyposplenism (target cells, howell jolly bodies))
Sickle solubility test (Dithionate - increase turbidity)
Hip X-ray (femoral head common site of avascular necrosis)
MRI/CT head (neuro complications)
57
What are the managements for acute sickle cell disease?
```
Oxygen
IV fluids
Strong analgesia
Antibiotics
Antihistamine
Cross match blood
Transfusion if Hb/reticulocytes fall
```
58
What is the chronic management of sickle cell disease?
```
Infection prophylaxis (penicillin V, vaccines - Pneumococcus, Haemophilus influenzae B)
Folic acid (severe or pregnant)
Hydroxyurea/hydroxycarbamide
Red cell transfusion
Stroke prevention
Advice
Surgical
```
59
What are the complications of sickle cell disease?
```
Anaemia
Opioid dependence
Iron overload from chronic transfusion
Liver complications and cholelithiasis
Avascualr necrosis of hip or shoulder
Dactylitis
Leg ulcer
Cardiovascular malformations
Priapism
Splenic sequesteration
Pulmonary HTN
Renal abnormalities
Growth and developmental delay
Stroke and CNS disease
Proliferative retinopathy and retinal haemorrhages
Transient red cell aplasia
Malaria
Learning difficulties
```
60
What is Thalassaemia?
A group of genetic disorders characterised by reduced globin chain synthesis. Under or no production of globin chain.
61
What causes thalassaemia?
Autosomal recessive
| Result in imbalance of globin chain production an deposition in erythroblasts and erythrocytes
62
What are the types of thalassaemia?
Alpha thalassaemia
| Beta thalassaemia
63
What are the risk factors for thalassaemia?
Family history
| Mediterranean origin
64
What are the symptoms of thalassaemia?
```
Beta:
- Severe anaemia
- Present 3-6 months
Alpha/Beta:
- May be asymptomatic
- Detected during routine blood tests or due to family history
```
65
What are the signs of Thalassaemia?
Beta thallasemia major
- Pallor
- Malaise
- Dyspnoea
- Mild Jaundice
- Extramedullary haematopoiesis (frontal bossing & hepatosplenomaegaly)
- Thalassaemia facies (chipmunk-like cheeks, prominent forehead)
- Hepatosplenomegaly
- Osteopenia
- Patients with Beta-thalassemia intermedia
66
What are the investigations for thalassaemia?
```
FBC (Anaemia, microcytic, low MCH)
Blood film
- Hypochromic microcytic anaemia
- Target cells (alpha)
- Howell jolly bodies
- Nucleated red cells
- High reticulocyte count
Hb Electrophoresis (Absent or reduced HbA, high HbF)
Bone marrow (Hypercellular, erythroid hyperplasia)
Genetic testing
Skull X-ray
```
67
What is antiphospholipid syndrome?
Condition characterised by presence of antiphospholipid antibodies in the plasma, venous and arterial thromboses, recurrent foetal loss and thrombocytopenia
68
What causes antiphospholipid syndrome?
Occurs as a primary disease but 20-30% associated with SLE
APL directed against plasma proteins bound to anionic phospholipids
APL develop in susceptible individuals
Once APL present, a 'second-hit' needed to develop the syndrome
69
What are the risk factors for antiphospholipid syndrome?
```
History of SLE
AI disorders (thyroid/coeliac/addison's)
```
70
What are the symptoms of antiphospholipid syndrome?
```
Recurrent miscarriages
History of arterial thromboses (stroke)
History of venous thromboses (DVT, PE)
Headaches, Migraines
Chorea
Epilepsy
```
71
What are the signs of antiphospholipid syndrome?
Livedo reicularis
Signs of SLE - malar flush, discoid lesions, photosensitivity
Signs of valvular heart disease
72
What are the investigations for antiphospholipid syndrome?
FBC (Low platelets)
ESR (normal)
U&Es (APL nephropathy)
Clotting screen (High aPTT)
ALT ELISA (Positive) or lupus anticoagulant assays
Antibodies present (Lupus anticoagulant, anti-cardiolipin, antiphospholipid anti b2-microglobulin)
73
What is disseminated intravascular coagulation?
Disorder of clotting cascade that complicates a serious illness
74
What are the forms of DIC?
Acute overt
| Chronic non-overt
75
What causes DIC?
Endothelial damage and the release of granulocyte/macrophage procoagulant substances lead to activation of coagulation
Leads to explosive thrombin generaltion, depleting clotting factors and plateletes, whilst also activating fibrinolytic system
This leads to bleeding in SC tissues, skins and mucous membranes
Occlusion of blood vessels by fibrin in microcirculation leads to MAHA and ischaemic organ damage
76
What preceedes DIC?
Infection (Gram negative sepsis)
Obstetric complications (missed miscarriages, severe pre-eclampsia, placental abruption, amniotic emboli)
Malignancy (acute promyelocytic leukaemia [acute]; Lung, breast and GI malignancy [chronic])
Severe trauma or surgery
77
What are the symptoms of DIC?
Severeuly unwell with symptoms of underlying disease
Confusion
Dyspnoea
Evidence of bleeding
78
What are the signs of DIC?
```
Underlying disease
Fever
Evidence of shock (Hypotension, tachycardia)
Acute DIC
- Petechiae, purpura, ecchymoses
- Epistaxis
- Mucosal bleeding
- Overt haemorrhage
- Signs of end organ damage
- Oliguria due to renal failure
Chronic DIC
- Signs of deep vein and arterial thrombosis or embolism
- Superficial venous thrombosis
```
79
What investigations are done for DIC?
```
FBC (Low platelets, Low Hb)
Clotting factors (High aPTT/PT)
D-dimer (High)
High fibrin degradation products, low fibrinogen
Peripheral blood film (schistocytes)
```
80
What causes haemolytic uraemic syndrome?
Triad of symptoms occurring primary or secondary
Can be 2 main forms, or caused by TTP
- D+ - Diarrhoea associated
- D- - No prodromal illnesses
81
What are the 3 symptoms of Haemolytic Uraemic Syndrome?
- Microangiopathic haemolytic anaemia (MAHA) [IV haemolysis and RBC fragmentation]
- Acute Renal failure
- Thrombocytopenia
82
What causes Haemolytic uraemic syndrome?
Infection (E.Coli, shigella, HIV)
Drugs (COCP, ciclosporin, mitomicin)
Familial genetics
Secondary causes: HTN, malignancy, pregnancy, SLE
83
What causes D+ haemolytic uraemic syndrome?
Shiga like toxin from E. Coli taken up by immune cells and transported to nephron endothelium GP3 receptor where it is taken up.
84
How does Haemolytic Uraemic syndrome cause renal fialure?
Take up of shiga like toxin at the nephron, causing apoptosis of endothelial cells, triggering haemostasis and so blood clots, forming renal failure
85
What are the risk factors for Haemolytic uraemic syndrome?
Contaminated food/water
Community outbreak of toxogenic E.coli
Exposure to infected individuals
Genetic predisposition (dominant/recessive)
86
What are the symptoms of Haemolytic uraemic syndrome?
```
Severe abdominal colic and diarrhoea, often bloody
Malaise
Fatigue
Nausea
Oliguria
Haematuria
```
87
What are the signs of Haemolytic uraemic syndrome?
```
Pallor
Slight Jaundice
Bruising
Generalised oedema
Hypertension
Retinopathy
Abdominal tenderness
```
88
What are the investigations for haemolytic uraemic syndrome?
FBC (Normocytic anaemia, low plateltes, high neutrophils)
U&Es (High urea, cretinine, potassium and low sodium)
Clotting (Normal aPTT and fibrinogen levels)
LFT (High bilirubin and LDH)
Haptoglobin (decreased)
Blood film (schistcytes, high reticulocytes and spherocytes)
Urine (proteinuria and haematuria)
ABG (Low pH, low bicarbonate, low PaCO2, normal anion gap)
Renal biopsy (distinguish D- or D+)
Stool culture/PCR (detect shiga toxin)
89
What is Haemophilia?
Bleeding diathesis resulting from inherited deficiency of a clotting factor
90
What are the subtypes of Haemophilia?
```
Haemophilia A (Factor VIII)
Haemophilia B (Factor IX)
Haemophilia C (Factor XI)
```
91
What causes haemophilia?
Haemophilia A and B are X-linked recessive
Haemophilia A due to flip tip inversion in factor VIII gene in X chromosome
Haemophilia B behaves clinically like Haemophilia A
92
What are the risk factors for haemophilia?
Age > 60 years
Family history
Male
AI disorders (IBD/DMT1)
93
What are the symptoms of Haemophillia?
```
Begin in childhood, or after surgery/trauma
Haemarthroses
Haematomas
Haematuria
Excessive bruising/bleeding
Deep bleeding
```
94
What are the signs of haemophilia?
```
Multiple bruises
Muscle haematomas
Joint deformity
Nerve palsies
Signs of IDA
```
95
What investigations are done for Haemophillia?
Clotting screen (High aPTT)
Coagulation factor assays
Other investigations may be performed if there are complications
96
What is Immune thrombocytopenic purpura?
Immune destruction of platelets resulting in bruising or a bleeding tendency
97
What causes immune thrombocytopenic purpura?
Autoantibodies are generated which bind to platelet proteins (GIpIIb/IIIA) causing thrmobocytopenia
Often idiopathic but seen acutely in children post-viral infection and chronically in adults
98
What are potential causes of ITP?
Infection (malaria, EBV, HIV)
AI disorders (SLE, thyroid disease)
Malignancies
Drugs (Quinine)
99
What are the risk factors for ITP?
Women
| <10 or >65
100
What are the symptoms for ITP?
```
MEME
M - Mucosal bleeding
E - Easy bruising
M - Menorrhagia
E - Epistaxis
```
101
What are the signs of ITP?
Visible petechiae and bruises
| Signs of other illness (e.g infectons, wasting, splenomegaly) would suggest other causes
102
What investigations are done for ITP?
Diagnosis of exclusion, exclude:
- Myelodysplasia
- Acute Leukemia
- Marrow infiltration
103
What is Thrombotic thrombocytopenia purpura?
Pentad of symptoms inclduing triad of HUS.
- MAHA
- Acute renal failure
- Thrombocytopenia
- Fever
- Fluctuating CNS signs
104
What causes TTP?
Deficiency of vWF cleaing enzymes leaves increased vWF multimers
Causes pathophysiological process as with HUS
Increased vWF multimers > clotting > fibrin deposition > microthrombi/damaged RBCs > Clogged up vessels > Fibroid necrosis > Renal failure
105
What are the risk factors for TTP?
```
Black ethnicitiy
Female
Obesity
Pregnancy
Cancer therapies
```
106
What are the symptoms of TTP?
```
GI: Severe abdominal colic and diarrhoea, often bloody
Malaise
Fatigue
Nausea
Oliguria
Haematuria
```
107
What are the signs of TTP?
```
Pallor
Slight jaundice (due to haemolysis)
Brusing
Generalised oedema
Hypertension
Retinopathy
Abdominal tenderness
Weakness
Reduced vision
Fits
Reduced consciousness
```
108
What are the investigations for TTP?
FBC (Normocytic anaemia, low platelets, high neutrophils)
U&Es (High urea, creatinine, potassium and low sodium)
Clotting (Normal aPTT and fibrinogen levels)
109
What is Von Willebrand's disease?
Bleeding disorder which may present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after trauma and easy bruising
110
What are the 3 common types of von Willebrand disease?
Type 1: Working vWF but not enough
Type 2: Normal levels but dont work
Type 2: No vWF
111
What causes vWD?
Caused by abnormality in the expression/function of vWF
| Usually autosomal dominant
112
What are the risk factors for vWD?
Family history
Consanguineous relationships
Lymphoproliferative/myeloproliferative disorders
113
What are the symptoms of vWD?
```
Easy brusing
Epistaxis
Prolonged bleeding
Menorrhagia
Haematochezia
Haematuria
Heavy bleeding
```
114
What are the investigations for vWD?
Bleeding time - High
aPTT - High
Factor VIII/IX/XI - Low
vWF ag - Low in type 1 and 3, normal in type 2
Ristocetin cofactor - normal in type 2, abnormal in type 1 and 3
115
What is ALL?
Malignancy of the bone marrow and blood characterised by proliferation of lymphoblasts (Primitive lymphoid cells)
116
What causes ALL?
Lymphoblasts undergo malignancy transformation and proliferation
This leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues
117
What are the risk factors for ALL?
Age < 6, mid 30s, mid 80s
Environmental (Radiation, viruses)
Genetic (Down's, Neurofibromatosis type 1, Fanconi's anaemia, Xeroderma pigmentosa)
118
What are the symptoms of ALL?
```
Symptoms of bone marrow failure
- Anaemia (Fatigue, dyspnoea)
- Bleeding (Spontaneous bruising, bleeding gums, menorrhagia)
- Opportunistic infections
Symptoms of organ infiltration:
- Tender bones
- Enlarged lymph nodes
- Mediastinal compression
- Meningeal involvement (headache, visual disturbances, nausea)
```
119
What are the investigations for ALL?
```
FBC (Normocytic normochromic anaemia, low platelets, variable WCC)
Blood film (Abundant lymphoblasts)
Bone marrow aspirate or trephine biopsy (hypercellular with 20% lymphoblasts)
Immunophenotyping
Cytogenetic
Cytochemistry
LP
CXR
Bone radiographs
```
120
What is AML?
Malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood.
121
How is AML classified?
FAB (French-American- Britich) system into 8 morphological variants
122
What causes AML?
Myeloblasts undergo malignant transformation and proliferation
Leads to replacement of normal marrow and bone marrow failure
Utility due to mutation of transcription factors
123
What are the symptoms of AML?
```
Bone marrow failure
- Anaemia (lethargy, dyspnoea)
- Bleeding (Thrombocytopenia or DIC)
- Opportunistic or recurrent infections
Tissue infiltration:
- Gum swelling or bleeding
- CNS involvements (headaches, nausea, diplopia)
```
124
What are the signs of AML?
```
Bone marrow failure:
- Pallor
- Cardiac flow murmur
- Ecchymosis
- Bleeding
- Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections)
Tissue infiltration:
- Hepatosplenomegaly
- Skin rashes
- Gum hypertrophy
- Deposit of Leukaemic blasts in the eye, tongue and bone (rare)
```
125
What are the investigations of AML?
FBC (Low Hb, plateletes, variable WCC)
Blood film (myeloblasts, auer rods, bilobed nucleus)
BM aspirate / biopsy (Hypercellular with >20% blasts - diagnostic)
Immunotyping (Surface Antibodies - differentiate from ALL)
Cytogenetics
126
What is CLL?
Progressive accumulation of functionally incompetent mature B cells, which are monoclonal in origin, which have escaped programmed cell death.
127
What causes CLL?
Malignant cells may accumulate as a result of their inability to undergo apoptosis
The most common chromosomal changes include:
- Trisomy 12
- 11q and 13q deletions
128
What are the risk factors for CLL?
Agent orange
129
What are the symptoms of CLL?
```
Asymptomatic
May be anaemic or infection-prone
Systemic symptoms (Lethargy, Malaise, night sweats)
Symptoms of BM failure:
- Recurrent infections
- Herpes zsoter infection
- Easy bruising or bleeding
If severe: Weight loss, sweats, anorexia
```
130
What are the signs of CLL?
```
Non-tender lymphadenopathy - enlarged, rubbery, non-tender
Hepatomegaly
Splenomegaly
Late stage signs of BM failure:
- Pallor
- Cardiac flow murmur
- Purpura/Ecchymosis
```
131
What investigations are done for CLL?
CLL associated with AI phenomena e.g. Haemolytic anaemia (warm agglutinins) or thrombocytopenia
FBC (Lymphocytosis, low Hb, Low platelets, Serum Ig)
Blood film
- small lymphocytes with rims of cytoplasm
- smudge cells
Bone marrow aspirate or biopsy
- Lymphocytic replacement of normal marrow
Cytogenetics
132
What is CML?
Malignant clonal disease characterised by uncontrolled proliferation of myeloid cells in the bone marrow and blood, distinguished from AML by its slower progression
- Myeloproliferative disorder
133
What causes CML?
```
Malignant proliferation of stem cells
95% have a philadelphia chromosome (BCRABL)
Variations of CML include:
- Ph-negative CML
- Chronic neutrophilic leukaemia
- Eosinophilic leukaemia
```
134
What are the phases of CML?
1. Relatively stable chronic phase (4-6yr duration)
2. Accelerated phase (3-9 months)
3. Acute Leukaemia phase - blast transformation
135
What are the risk factors for CML?
65-74
Ionising radiation
Benzene
136
What are the symptoms of CML?
```
Asymptomatic
Hypermetabolic symptoms:
- Weight loss
- Malaise
- Sweating
Bone marrow failure:
- Lethargy
- Dyspnoea
- Easy bruising
- Epistaxis
- Abdominal discomfort and early satiety (splenic enlargement)
- Rare symptoms (Gout & Hyperviscosity symptoms [visual disturbances, headaches, priapism])
```
May present during a blast crisis with symptoms of AML and ALL
137
What are the signs of CML?
```
Splenomegaly
Hepatomegaly
Signs of bone marrow failure:
- Pallor
- Bleeding
- Ecchymosis
```
138
What are the investigations for CML?
```
FBC:
- High uric acid
- Low haemoglobin
- High B12 and transcobalamin I
- Low neutrophil ALP score
- High WCC with whole spectrum of myeloid cells
Blood film (immature granulocytes)
Bone marrow aspirate/biopsy (Hypercellular with raised myeloid-erythroid ratio)
Cytogenetics (Phliadelphia chromosome)
```
139
What is Hodgkin's lymphoma?
A condition caused by malignant proliferation of lymphocytes, originating in the lymph nodes or other lymphoid tissues.
140
What causes Hodgkin's lymphoma?
Unknown
Likely to be environmental trigger in a genetically susceptible individual
EBV genome detected in 50% of hodgkin's lymphoma
141
What are the risk factors for hodgkin's lymphoma?
```
Affeted sibling
EBV
SLE
Post-transplantation
Westernisation
Obese
```
142
What are the symptoms of hodgkin's lymphoma?
Painless enlarging mass (enlarged, painless, non-tender, rubbery, superficial)
- Most commonly found in neck
- Can be axilla or groin
Mass may become painful after alcohol
Mediastinal lymph node involvement can cause mass effect
B symptoms
Other symptoms: Pruritis, Cough, Dyspnoea
143
What are the B symptoms of Lymphoma?
Fever >38 degrees
Night sweats
Weight loss (>10% body weight in past 6 months)
144
What are the signs of Hodgkin's lymphoma?
Non-tender firm rubbery lymphadenopathy (Cervical, axillary or inguinal)
Splenomegaly (rarely hepatosplenomegaly)
Cachexia
Anaemia
Skin excoriations
Signs of intrathoracic disease (e.g. pleural effusion, SVC obstruction)
Signs of intrathoracic disease (pleural effusions, SVC obstruction)
145
What investigations are done for Hodgkin's lymphoma?
```
FBC (anaemia, thrombocytopenia, neutropenia)
CRP/ESR (Raised)
LDH (Raised)
U&Es (Hypercalcaemia)
HIV, HBV and HCV serology
Blood film (lymphoma cells)
Bone marrow aspiration and biopsy
Imaging (CXR, CT, PET)
Lymph node biopsy
Staging (Ann-Arbor)
```
146
What is Non-hodgkin's lymphoma?
Malignancies of lymphoid cells originating in lymph nodes or other lymphoid tissue.
147
What are the 2 types of Non-hodgkin's lymphoma?
B-cell (90%)
| T-cell
148
What is seen on Blood film of b-cell non-hodgkin's lymphoma?
Diffuse large B-cell lymphoma
Follicular lymphoma
Mucosa associated lymphoid tissue
149
What is seen on blood film of T-cell non-hodgkin's lymphoma?
Peripheral T-cell lymphoma
Skin lymphoma
Anaplastic large cell lymphoma
150
What makes a lymphoma a non-hodgkin's lymphoma?
Any lymphoma without Reed-sternberg cells!
151
What causes Non-Hodgkin's lymphoma?
Complex process involving the accumulation of multiple genetic lesions
Changes in genome associated with oncogenic viruses (EBV & Burkitt's lymphoma)
152
What organisms cause genetic aberrations?
Viruses: EBV/HTLV-1/Herpes virus 8/HIV
Bacteria: H. Pylori
Autoimmune disorders: Sjorgen's/SLE
Pesticides
153
What are the extranodal disease in non-hodgkin's lymphoma?
Skin
Oropharynx
Gut: Gastric MALT or non-MALT gastric lymphomas
Small bowel lymphomas
154
What are the risk factors for Non-Hodgkin's lymphoma?
```
Age >50 years
Male
Immunosuppression/Chemo
EBV
HTLV-1
HIV
H. Pylori
SLE
Sjorgen's
```
155
What are the symptoms for Non-Hodgkin's lymphoma?
Painless enlarging mass (In neck, axilla or groin) - superficial lymphadenopathy
Systemic symptoms (less frequently than hodgkin's)
Organ involvement
156
What are the systemic symptoms of NHL?
Fever
Night sweats
Weight loss >10% body weight
Symptoms of hypercalcaemia
157
What are the organ related symptoms for NHL?
```
Extranodal disease
Skin rashes
Headache
Sore throat
Abdominal discomfort
Testicular swelling
```
158
What are the signs of NHL?
```
Painless, firm, rubbery lymphadenotpathy
Skin Rashes (mycosis fungoides)
Abdominal mass
Hepatosplenomegaly
Signs of bone marrow involvement
- Anaemia
- Infections
- Purpura
```
159
What are the investigations for NHL?
```
FBC (Anaemia, neutropenia, thrombocytopenia)
ESR/CRP (Rasied)
LDH (Raised)
U&Es (Hypercalcaemia)
HIV, HBV, HCV
Blood film (lymphoma cells)
Bone marrow aspiration and biopsy
Imagign (CXR/CT?PET)
Lymph node biopsy
Staging (Ann-Arbor)
```
160
What is multiple myeloma?
Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of monoclonal immmunoglobulin (paraprotein, usually IgG or IgA)
161
What is multiple myeloma classification based on?
Immunoglobulin production
162
What causes multiple myeloma?
```
Unknown
Possible Viral triggers
Chromosomal aberrations are frequent
Associated with ionising radiation
Agricultural world or occupational chemical exposures
```
163
What are the risk factors for multiple myeloma?
Abnormal free light chain ratio
Monoclonal gammopathy of undetermined significance
Radiation/petroleum exposure
Family history of multiple myeloma
164
What are the CRAB symptoms of multiple myeloma?
```
CRAB!
C - Calcium (High)
R - Renal Impairment (Thirst and polyuria)
A - Anaemia (Tiredness)
B - Bone pain/lesions
```
165
What are the other symptoms of multiple myeloma?
Recurrent bacterial infection
Nausea
Constipation
Hyperviscosity (Bleeding/headaches/visual disturbances)
166
What are the signs of multiple myeloma?
```
Pallor
Tachycardia
Flow murmur
Signs of heart failure
Dehydration
Purpura
Hepatosplenomegaly
Carpal tunnel syndrome
Peripheral neuropathies
```
167
What are the investigations for multiple mueloma?
FBC (Normochromic, normocytic anaemia)
Creatinine (Raised)
Albumin (raised)
ESR (Raised)
U&Es (Raised)
Blood film (Rouleaux with bluish-black background)
Serum or Urine electrophoresis (paraprotein and light chain excretion)
X-rays (Osteopenia/osteolytic lesions/pepper pot skull/pathological fractures)
Bone marrow aspirate (Raised plasma cells)`
168
What is Myelodysplasia?
A series of haematological conditions that manifest as marrow failure.
169
What characterises myelodysplasia?
Chronic pancytopenia (anaemia, neutropenia, thrombocytopenia) with low reticulocyte count and abnormal cellular maturation)
170
What are the 5 subgroups of Myelodysplasia?
```
Refractory anaemia (RA)
RA with Ringed sideroblasts
RA with excess blasts (RAEB)
Chronic myelomonocytic leukaemia (CMML)
RAEB in transformation (RAEB-t)
```
171
What causes myelodysplasia?
May be primary (intrinsice bone marrow problem)
May arise in patients who have received chemotherapy or radiotherapy for previous malignancies
Patients may have chromosomal abnormalities
172
What are the risk factors for myelodysplasia?
Chemotherapy
Radiotherapy
Down's syndrome
Congenital Neutropenia
173
What are the symptoms of Myelodysplasia?
Symptoms of bone marrow failure
- Anaemia (Fatigue, dizziness)
- Neutropenia (Recurrent infections)
- Thrombocytopenia (easy bruising, epistaxis)
Check risk factors:
- Occupational exposure to toxic chemicals
- Prior chemo or radiotherapy
174
What are the signs of myelodysplasia?
Signs of bone marrow failure:
- Anaemia (pallor, cardiac flow murmur)
- Neutropenia (infections)
- Thrombocytopenia (Purpura or ecchymoses)
- Gum hypertrophy
- Lymphadenopathy
- Spleen NOT enlarged (except in CML)
175
What are the investigations for Myelodysplasia?
FBC (pancytopenia)
Blood film
- Normocytic/Macrocytic red cells
- Ring sideroblasts seen in marrow
176
What is Myelofibrosis?
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis associated with extramedullary haematopoiesis and splenomegaly.
177
What causes Myelofibrosis?
Primary stem cell defect
Results in increased numbers of abnormal megakaryocytes with stromal proliferation secondary to growth factors released by megakaryocytes
30% of patents have a previous history of polycythaemia rubra vera or essential thrombocythaemia (overproduction of platelets by the bone marrow)
178
What are the risk factors for myelofibrosis?
Rare
| Peak onset 50-70
179
What are the symptoms for myelofibrosis?
```
Systemic symptoms:
- Weight loss
- Anorexia
- Fever
- Night sweats
- Pruritis
- Abdominal discomfort
Uncommon:
- LUQ pain
- Indigestion
- Bleeding
- Bone pain
- Gout
- Infections
```
180
What are the signs of myelofibrosis?
```
Splenomegaly
Hepatomegaly
Pallor
Petechiae
Haemarthrosis
Blood on PR
```
181
What are the investigations for myelofibrosis?
FBC (Variable Hb, WCC and platelets)
- Later stages: Anaemia, leukopenia, thrombocytopenia
LFTs (Abnormal)
Blood film (Leucoerythroblastic changes, Tear drop poikilocyte red cell)
Bone marrow aspirate or biopsy (aspiration usually unsuccessful - 'dry tap' due to fibrosis)
Trephine bone marrow biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining - Diagnostic
