Haematology Flashcards
1
Q
What is the process of blood formation called?
A
Haemopoiesis
2
Q
The haemopoietic system includes what five components?
A
Bone marrow, liver, spleen, lymph nodes and thymus
3
Q
What is the average lifespan of red cells?
A
120 days
4
Q
What is the average lifespan of platelets?
A
7 days
5
Q
What is the average lifespan of granulocytes?
A
7 hours
6
Q
What are reticulocytes?
A
Young red cells
7
Q
Reticulocytes represents what percentage of total circulating red blood cells?
A
0.5-2.5%
8
Q
What makes up a haem group?
A
A single molecule of protoporphyrin IX bound to a single ferrous ion (Fe2+)
9
Q
What symptoms may arise from anaemia?
A
Fatigue, faintness and breathlessness
10
Q
In patients with concurrent atheromatous disease, what more serious symptoms can anaemia precipitate?
A
Angina pectoris and intermittent claudication
11
Q
What signs might be observable in the anaemic patient? (4)
A
Skin and mucous membranes may be pale
Tachycardia
Systolic flow murmur
Cardiac failure (in elderly people/ those with compromused cardaicfunction)
12
Q
What does microcytosis usually represent about the structure of a red blood cell?
A
Decreased haemoglobin content
13
Q
What is the most common cause of anaemia worldwide?
A
Iron deficiency anaemia
14
Q
What are the causes of iron deficiency anaemia? (4)
A
Blood loss
Increased demands (such as growth and pregnancy)
Decreased absorption
Poor dietary intake
15
Q
What signs does iron deficiency produce? (3)
A
Brittle hair and nails
Atrophic glossitis
Angular stomatitis
16
Q
Ansiocytosis and poikilocytosis are both features seen on a blood film of an iron-deficient patient; what do these two terms mean?
A
Ansiocytosis - variation in size
Poikilocytosis - variation in shape
17
Q
What investigations are indicated in a suspected case of iron deficiency anaemia?
A
Blood count and blood film
Serum ferritin (reflecting iron stores) are low
Serum iron is low
18
Q
How is iron deficiency managed?
A
Find and treat underlying cause
Oral iron supplementation e.g. ferrous sulphate/gluconate
19
Q
What is sideroblastic anaemia?
A
A rare disorder of haem synthesis characterised by refractory anaemia in the peripheral circulation and ring sideroblasts in the bone marrow
20
Q
What are ring sideroblasts?
A
Erythroblasts with iron deposits in the mitochondria and reflect impaired utilisation of iron within the red cell
21
Q
What causes sideroblastic anaemia?
A
It may be inherited or acquired (secondary to myelodysplasia, alcohol excess, lead toxicity)
22
Q
What is anaemia of chronic disease?
A
Anaemia occuring in patients with either:
- Chronic inflammatory diseases (such as Crohn’s disease or rheumatoid arthrtitis)
- Chronic infections (e.g. tuberculosis)
- Malignancy
- Chronic kidney disease
23
Q
As seen on a blood film; what type of anaemia is anaemia of chronic disease?
A
Normochromic, normocytic anaemia
24
Q
How is anaemia of chronic disease managed?
A
Treatment of the underlying chronic disease and sometimes erythropoietin
25
What is the most important investigation of a macrocytic anemia?
Measurement of serum B12 and red cell folate
26
What is megaloblastic anaemia?
A macrocytic anaemia charactersed by the presence of megaloblasts in the bone marrow (immature red cells with delayed nucelar maturation relative to that of the cytoplasm)
27
What is the most common cause of megaloblastic anaemia?
Vitamin B12/folate deficiency
28
What is pernicious anaemia?
An autoimmune condition in which there is atrophic gastritis with loss of function of the parietal cells and hence a failure to produce intrinsic factor (essential for uptake of vitamin B12)
29
What are the clinical features of pernicious anaemia?
```
Insidious onset
Glossitits (sore, red tongue)
Angular stomatitis
Mild jaundice
Neurological features (due to B12 deficiency)
```
30
What neurological features may be present in B12 deficiency?
Symmetrical damage of the spinal cord leading to progressive weakness, ataxia, and eventual paraplegia
Dementia and visual distrubances may also occur
31
What is the main difference in the symptom profile between B12 deficiency and folate deficiency?
In folate deficiency there are no neurological features
32
What might cause folate deficiency? (4) (Non exhsautive list)
Pregnancy, coeliac disease, acohol excess, trimethoprim
33
What is aplastic anaemia?
Defined as a pancytopenia (deficiency of all blood cells) due to bone marrow failure
34
What are the clinical features of aplastic anaemia? Why do they occur?
Deficiency of red cells, white cells and platelets
Causing anaemia, susceptibility to infection and bleeding
Physcial findings include bruising, bleeding gums, epistaxis and mouth infections
35
How is aplastic anaemia investigated and confirmed?
Trephine bone marrow biopsy for assessment of bone marrow cellularity
36
What causes aplastic anaemia?
Most commonly encountered due to chemotoxic drugs and radiation
37
What is the management strategy for aplastic anaemia?
Withdrawal of the offending agent (chemotoxic drug for example) followed by definitive therapy such as blood and platelet transfusions
38
What medical emergancy may occur in apalstic anaemia?
Neutropenic sepsis
39
How might neutropenic sepsis present?
Neutropenic patient (neutrophil count <1 x10^9/L) who is pyrexial, or has new-onset confusion, tachycardia, hypotension, dyspnoea or hypothermia
40
List some blood investigations which are necessary in the case of neutropenic sepsis
```
FBC
Differential white cell count
CRP
U/Es
Liver biochemistry
Clotting screen
Blood cultures
```
41
What radiological investigations might you consider in the neutropenic patient?
- Chest X-ray
| - Consider further imaging if there are localising signs e.g. CT abdomen/pelvis
42
What empirical antibiotics are indicated in the case of suspected neutropenic sepsis?
Piperacillin and aminoglycoside (to cover Gram-negatives and Pseudomonas)
Consider adding vancomycin if clincal deterioration, fever persists or suspected MRSA infection
43
What is haemolytic anaemia?
Anaemia resulting from increased destruction of red cells with a reduction in lifespan and therefore a compensatory rise in premature reticulocytes
44
Haemolysis may be either intravascular or extravascualar - which is more common?
Extravascular (within the reticuloendothelial system, mainly the spleen)
45
What investigations may indicate a intravascular haemolysis?
Raised level of plasma haemoglobin
Positive Schumm's test (methaemalbumin in plasma)
Low/absent haptoglobins (complex formed from free haemoglobin - removed rapidly by the liver)
Haemosiderinuria - haemosiderin in the urine
46
Inherited haemolytic anaemias are due to defects in one of three components - what are they?
Defects in either:
- Cell membrane
- Haemoglobin structure
- Metabolic procresses of the red cell
47
Hereditary spherocytosis is an example of an inherited haemolytic anaemia caused by a defect in which red cell component?
Cell membrane
48
What inheritance does hereditary spherocytosis show?
Autosomal dominant
49
What is the pathophysiology of hereditary spherocytosis?
Deficiency in spectrin (most commonly) leading to increase permeability to sodium ions, causing rigid and spherical red cells which are prematurely removed by the spleen (extravascular)
50
What symptoms may arise in hereditary spherocytosis?
Ranges from asymptomatic to severe haemolysis (anaemia, jaundice, splenomegaly)
51
What types of crises may occur in any haemolytic anaemia?
Megaloplastic
Aplastic
Haemolytic
52
What does aplastic crisis usually occur as a result of in the course of normal haemolytic disease?
After infection (particularly erythro(paro)virus)
53
What does megaloblastic crisis usually occur as a result of in the course of normal haemolytic disease?
Folate deficiency caused by hyperactivity of the bone marrow
54
What biliary pathology may occur as a result of chronic haemolytic disease?
Pigment gallstones
55
What investigations may confirm hereditary spherocytosis?
Blood count demonstrates reticulocytosis and anaemia
Blood film shows spherocytes
Evidence of haemolysis (raised serum bilirubin and urinary urobilinogen)
56
How is hereditary spherocytosis managed?
Splenectomy indicated in adulthood to relieve symtptoms
| not in childhood due to risk of fulminant infections
57
What are thalassaemias?
A group of genetic disorders causing reduced rate of production of one or more globin chains used in the synthesis of haemoglobin (ineffective erythropoiesis)
58
There are three main forms of beta-thalassaemia; what are they?
1. beta-thalassaemia minor (trait) - carrier state due to heterozygous genetic profile
2. beta-thalassaemia intermedia - moderate penetrance causing mild anaemia and other thalassaemic features
3. beta-thalassaemia major - presents in first year of life with significant thalassaemic features, severe anaemia and hepatosplenomegaly
59
What are the talassaemic features? Why do they occur?
Hypertrophy of inept bone marrow causes:
- Bony abnormalities (enlarged maxilla, prominent frontal and parietal bones)
- Recurrent leg ulcers
- Gallstones
60
How is thalassaemia diagnosed?
Haemoglobin electrophoresis
61
How is thalassaemia treated?
Regular blood transfusions (keeping Hb >100g/L) - suppressing ineffective erythropoiesis and bony abnormalities
Aduvant chelation therapy required to prevent iron overload and folate supplementation.
62
Describe the clincal spectrum of alpha-thalassaemia
Ranging from mild anaemia with microcytosis to severe condition incompatible with life resulting in stillbirht (hydrops fetalis)
63
What are sickle syndromes?
A family of haemoglobin disorders in which the sickle beta-globin gene is inherited.
64
Why does sickle cell anaemia not present and features until around 6 months of age?
Production of foetal haemoglobin (HbF) is unaffected and so sickle disease doesnt manifest until HbF decreases to adult levels (at 6 months of age)
65
Sickle cell anaemia has marked phenotypic variation. Outline some of the clinical features which may present.
Vaso-occlusion - acute dactylitis in children is more likely. In adults, long bone, rib, spinal and pelvic pain more likely.
Other vaso-occulsive complications: avascular necrosis of bones, retinal iscahemia, cerebral infarction, priapism
Anaemia - usually exists in a steady state Hb 60-80g/L with a high reticulocyte count (10-20%)
Other complications: Chronic kidney disease, leg ulcers, osteomyelitis, pulmonary hypertension, acute chest syndrome
66
What events may precipitate a rapid destabilisation of haemoglobin levels in a patient with sickle cell disease? (2)
Splenic sequestration - spleen becomes engorged with red cells leading to rapid enlargement of spleen (can also occur in the liver)
Aplatic anaemia - commonly due to eythrovirus B19 infection
67
What is acute chest syndrome?
Medical emergancy characterised by fever, cough, dyspnoea and pulmonary infiltrates on chest X-ray
68
How are painful crises managed?
Morphine 0.1mg/kg IV or SC every 20 mins with aduvants
Also prescribe: laxatives (lactulose 10ml BD), anti-pruritics, antiemetics, anxiolytics, antibiotics
Oxygen, rehydration
Check for acute chest or liver/splenic sequestration
69
In patients with recurrent painful crises, what drug is indicated to help prevent them?
Hydroxycarbamide (raises concentration of foetal haemoglobin)
70
What is the most common red cell enzyme deficiency causing haemolytic anaemia?
Glucose-6-phosphate dehydrogenase deficiency (G6PD)
71
What is the inheritance pattern of G6PD?
X-linked
72
What are the clinical features of G6PD?
Neonatal jaundice, chronic haemolytic anaemia, acute haemolysis (precipitated by fava beans, nitrofurantoin and other drugs)
73
How are autoimmune haemolyses categorised?
Depending on whether the antibody reacts best at body temperature (warm antibodies) or at lower temperatures (cold)
74
What is mechanical haemolytic anaemia?
Red cells are injured by physical trauma in the circulation. Can be due to a number of things:
- Leaking prosthetic valves
- March haemoglobinuria ( damage to red cells from prolonged marching)
- Microangiopathic haemolysis (e.g. in DIC)
75
What are myeloproliferative disorders?
Disorders of uncontrolled clonal proliferation of one or more cell lines in the bone marrow.
76
Name the myeloproliferative disorders?
Polycythaemia vera
Essential thrombocytopaenia
Myelofibrosis
Chronic myeloid leukaemia
77
What are the symptoms of polycythaemia vera?
All as a result of both hypervolaemia and hyperviscocity
Headache, vertigo, tinnitus, visual disturbance, angina pectoris, intermittent claudication, pruritis, venous thrombosis
78
What signs may be found in polycythaema vera?
Plethoric complexion, hepatosplenomegaly (distinguishes primary from secondary polycythaemia)
79
What other conditions are people with polycythaemia vera at risk of?
Gout - due to increased uric acid production
| Haemorrhage - due to friable haemostatic plugs
80
How is polycythaemia vera treated?
Venesection (maintain PCV <0.45L/L) - may be sufficient
Chemotherapy:
1. Hydroxycarbamide to reduce platelets
2. Low dose aspirin - reduce recurrence of thromboses
3. Anagrelide - useful for thrombolysis
4. Radioactive phosphorus - to combat risk of leukaemic conversion
5. Allopurinol - decrease uric acid levels
81
What is essential thombocythaemia?
Conditon characterised by normal haemoglobin levels and white cell counts but elevated platelets
82
How may essential thombocythaemia present?
Either with bleeding or thromboses
83
How is essential thrombocythaemia diagnosed?
An otherwise well with a platelet count of over 1000 x10^9/L is generally considered to be sufficient for diagnosis
84
How is essential thrombocythaemia treated?
Hydroxycarabamide and/or anagrelide if required
85
List some differnetial diagnoses for essential thrombocythaemia
```
Reactive thrombocytosis
Autoimmune rheumatic disorders
Malignancy
Polycythaemia vera
Myelodysplasia
```
86
What is myelofibrosis?
A condition characterised by haemopoietic stem cell proliferation associated with marrow fibrosis
87
How does myelofibrosis present?
Insidious onset of weakness, weight loss and lethargy
Bleeding may occur in thrombocytopaenic patient
Hepatomegaly and massive splenomegaly
88
What are the four most common causes of death in myelofibrosis?
Transformation into acute myeloid leukaeia
Progression of myelofibrosis
Cardiovascular disease
Infection
89
What investigations might support your diagnosis of myelofibrosis?
1. Blood count (showing anaemia)
2. Trephine bone marrow biospy (increased fibrosis)
3. Absent philidelphia chromosome (distiinguishes myelofibrosis from chronic myeloid leukaemia)
4. JAK2 mutation (present in 50% of cases)
90
How is myelofibrosis managed?
Transfusions (correct anaemia)
Allopurinol (prevent gout)
JAK2 inhibitors (e.g. rutixumab)
Allogenic stem cell transplant in young patients (offers only hope to cure)
91
What is myelodysplasia?
A group of acquired marrow disorders caused by defects in stem cells; resulting in progressive bone marrow failure and potential evolution into acute myeloid leukaemia
92
How is myelodysplasia diagnosed?
Paradoxical appearance of peripheral pancytopenia on blood film and hypercellular bone marrow (due to prematuer loss of cells by apoptosis)
93
What blood constituents are present in fresh frozen plasma?
All coagulation factors
94
What blood constituents are present in cryoprecipitate?
| 3
Factor VIII
Von Willebrand factor
Fibrinogen
95
What complications may occur after a transfusion (excluding massive transfusion)?
(5)
1. ABO mismatch (most severe)
2. Febrile reactions (due to activation of anti-leucocyte antibodies in the recipient)
3. Anaphylactic reactions (in IgA deficient patients)
4. Infection
5. Heart failure (particularly in elderly)
96
What complications may occur during/after massive transfusion?
Hypocalcaemia
Hyperkalaemia
Hypothermia
97
What are the five types of white cells found in the peripheral blood?
Neutrophils, eosinophils, basophils (all called granulocytes) and lymphocytes and monocytes
98
What are monocytes?
Precursors to tissue macrophages
99
What pathological processes do eosinophils play a part in?
```
Allergic reactions
Helminth infections and protozoa
Asthma
Malignancy
Hyper-eosinophilic syndrome
```
100
What is hyper-eosinophilic syndrome?
Restrictive cardiomyopathy, hepatosplenomegaly and very high eosinophils (>0.4 x10^9/L)
101
What is immune thrombocytopenic purpura (ITP)?
Immune destruction of platelets
102
Describe the different occurrences of immune thrombocytopenic purpura in adults and children
In children - usually follows viral infection rapidly and is self-limiting
In adults - less acutely and often seen concurrently with other immune conditions e.g. SLE
103
How is immune thrombocytopenic purpura diagnosed?
Diagnosis of exclusion
Platelet antibodies not essenstial for diagnosis but may be seen in 60-70% of patients
104
How is immune thrombocytopenic purpura managed?
First-line therapy - oral corticosteroids or IV IgG where rapid rise in platelets is optimal (pre-surgery)
Second-line therapy - splenectomy and thrombopoietin receptor agonists (e.g. romiplostim)
105
What is thrombotic thrombocytopenic purpura?
Widespead adhesion and agglutination of platelets leading to microvascular thrombosis and profound thombocytopenia (<150 x10^9/L)
106
Deficiency of what protease causes thrombotic thrombocytopenic purpura
ADAMTS-13
107
What can cause thrombotic thrombocytopenic purpura?
Congenital or sporadic or autoantibody-associated (pregnancy, infection etc.)
108
What are the symptoms of thrombotic thrombocytopenic purpura?
Florid purpura, renal failure, fluctuant cerebral dysfunction and haemolytic anaemia
109
How is thrombotic thrombocytopenic purpura treated? What is counter-intuitively contraindicated?
Plasmapheresis
High dose steroids
Platelet concentrates are contraindicated
110
What is Haemophilia A caused by? What is the inheritance pattern?
X-linked recessive disorder resulting in a deficiency of factor VIII
111
Haemophiliac is categorised into mild, moderate and severe entities. Describe each.
1. Mild (>5U/dL) - bleeding only with trauma
2. Moderate (1-5U/dL) - severe bleeding following injury and occaisional spontaneous bleeding
3. Severe (<1U/dL) - severe spontaneous bleeding into muscles/joints causing crippling arthropathy
112
What investigations would help confirm the diagnosis of Haemophilia A?
Prolonged APTT
| Normal PT and vWF
113
How is haemophilia A treated?
- IV infusion of recombinant factor VIII (with supplies at home too)
- Synthetic vasopressin (used to increase production in patients with mild haemophilia)
- Advice about lifestyle e.g. avoiding contact sports
114
What is the difference between haemophilia A and B? What treatment options differ in haemophilia B?
Haemophilia B is a deficiency of factor IX
Vasopressin is ineffective and therefore not used in treatment of haemophilia B
115
What is von Willebrand's disease?
hereditary deficiency of von Willebrand Factor (vWF)
116
What is the function of von Willebrand factor?
Contributes to platelet adhesion to damaged subendothelium and stabilisaton of factor VIII
117
Outline the three different types of von Willebrand's disease
```
Type 1 (quantitative) - decreased vWF
Type 2 (qualitative) - poor functioning vWF
Type 3 (absolute deficiency) - absence of vWF
```
118
Outline the inheritance pattern of the types of von Willebrand's disease
Type 1 and 2 are autosomal dominant
| Type 3 is autosomal recessive
119
What investigations might help support a diagnosis of von Willebrand's disease?
1. Prolonged bleeding time (indicating poor platelet adhesion)
2. Prolonged APTT
3. Normal PT
120
Vitamin K is reuqired for the formation of which coagulation factors?
Factors II, VII, IX and X
121
What may cause vitamin K deficiency?
Malnutrition, malabsorption or warfarin use
122
How is vitamin K deficiency treated?
IM Vitamin K supplementation
123
What is disseminated intravascaulr coagulation (DIC)?
Widespread generation of fibrin within blood vessels. There is massive consumption of platelets and coagulation factors
124
What are the most comon causes of disseminated intravascaulr coagulation (DIC)? (4)
- Sepsis
- Major trauma (surgery, burn etc.)
- Advanced cancer
- Obstetric complications (amniotic embolism, abruptio placentae)
125
What is the clinical presentation of disseminated intravascaulr coagulation (DIC)?
Varies from no bleeding at all to complete haemostatic failure
Thrombotic events may occur too
126
What investigations are indicated in the susepcted case of disseminated intravascaulr coagulation (DIC)?
Blood count - showing severe thrombocytopenia
Prolonged APTT, PT and bleeding time
Blood film - fragmented red cells
127
How is disseminated intravascaulr coagulation (DIC) treated?
```
Treat the underlyig cause
Platelet concentrates (maintain platelets above 50 x10^9/L
```
Cryoprecipitate and red cells are also indicated in bleeding patients
128
Aterial thrombi are formed of what blood constituent and arise due to what underlying chronic pathology?
Platelets adhere to atheroma (atherosclerosis)
129
Where do arterial thrombi occur?
Areas of turbulent blood flow e.g. bifurcating arteries
130
What are venous thrombi formed of?
Fibrin and red cells
131
Where do venous thrombi occur?
Originate around the valves of veins; partiularly in the deep veins of the leg
132
What sort of drugs target venous thombi?
Heparin and warfairn (anti-coagulants)
133
What sort of drugs target arterial thrombi?
Aspirin and clopidegrel (anti-platelets)
134
Fondapariunux is an anti-coagulant; what coagulation factor does it inhibit?
Factor X (similar in action to herapin)
135
What is dabigatran and what is it prescribed for?
Direct thrombi inhibitor; given as prophylaxis for venous thromboembolism following hip or knee replacement surgery
136
What is the target INR of a paitent to prevent thromboembolism?
2.5 (3.5 if recurrent venous thromboembolism despite monotherapy with warfarin)
137
What are the two most common side effects of iron supplementation?
Constipation and diarrhoea
138
What are common side effects of B12 supplementation? What is the potential severe side effect on resolution of severe B12 deficiency anaemia?
Itching, fever, nausea and diziness
Potential for severe hypokalaemia due to intracellular shift on anaemia resolution
139
What does NOAC stand for?
Novel Oral Anti-Coagulants
140
What is alpha-fetoprotein?
Serum tumour biomarker for hepatocellular carcinoma and non-seminomatous germ cell tumour of the testes
141
What is beta-human chorionic gonadotropin (beta-HCG) ?
A serum tumour biomarker for choriocarcinoma, germ cell tumours of the testes and lung cancer
142
What is the tumour biomarker for prostate cancer?
Prostate specific antigen (PSA)
143
Chorioembryonic antigen (CEA) may be raised in what cancers?
Colorectal cancer
| Some gastrointestinal malignancies
144
What is the tumour biomarker for ovarian cancer?
CA-125
145
What is CA19-9?
Serum tumour biomarker for upper gastrointestinal malignancies
146
What is CA15-3?
Serum tumour biomarker for breast cancer
147
What is osteopontin?
Serum tumour biomarker for mesothelioma
148
Outline the four sources of haemopoietic stem cell transplant
Allogenic - bone marrow from another individual
Autologous - bone marrow harvested from self
Syngenic - bone marrow from identical twin
Umbilical cord
149
What is superior vena cava syndrome?
Arising from any upper mediastinal mass (most commonly lung cancer or lymphoma) - characterised by compression of the superior vena cava
150
What is the presentation of superior vena cava syndrome?
Difficulty breathing or swallowing
Odematous face
Venous congestion in the neck (dilated veins)
151
How is superior vena cava syndrome treated?
Immediate steroids and vascular stenting
| Potentially radiotherapy/chemotherapy to shrink mass
152
What is acute tumour lysis syndrome?
A condition characterised by rapid breakdown of tumour following commencement of treatment.
153
What biochemical abnormalities arise in acute tumour lysis syndrome?
Hyperphosphataemia (and secondary hypercalcaemia)
Hyperkalaemia
Hyperuraemia
154
What is the main complication of acute tumour lysis syndrome?
Acute kidney injury due to urate and calcium phosphate deposition in renal tubules
155
Acute Lymphoblastic Leukaemia has a propensity to involve the CNS. For this reason, what extra treatment measure is taken?
Intrathecal chemotherapy (prophylaxis)
Sometimes cranial irratiation is used in high risk patients
156
What are the clinical features of acute leuakemia?
Bone marrow failure (anaemia, thormbocytopenia and prepensity to infection)
Sometimes there is lymphadenopathy and heaptosplenomegaly
157
What genetic funding is characteristic of chronic myeloid leukaemia?
Philidelphia chromosome mutation
158
What is the presentation of chornic myeloid leukaemia?
Insidious onset of fever, weight loss, sweating and symptoms of anaemia
Massive splenomegaly is characeristic
159
Outline the phases of chronic myeloid leukaemia
Chronic-phase - lasts 3-4 years
| Blastic transformtion - usually acute myeloid leukaemia (causing rapid death)
160
What is the first-line treatment for chronic-phase chronic myeloid leukaemia?
Imatinib (tyrosine kinase inhibitors)
Not effective after blastic transformation
161
What is chronic lymphocytic leukaemia?
Incurable disease of the elderly characterised by uncontrolled proliferation of mature B lymphocytes
162
Outline the course of chronic lymphocytic leukaemia
Indolent course and generally asymptomatic
Later on, symptoms of bone marrow failure and hepatosplenomegaly
163
What investigations would support a diagnosis of chronic lymphocytic leukaemia?
Blood count - lymphocytosis, anaemia, thrombocytopenia
Blood film - smudge cells (artefact of small mature lymphocytes)
Immunophenotyping - essential to exclude reactive lymphocytosis
Cytogenetics - identify specific mutation
164
What is the standard first-line therapy for chronic lymphocytic leukaemia?
Combination of fludarabine, cyclophosphamide, rutixumab
165
What is lymphoma?
B and T cell malignancies of the lymphoid system
166
How are lymphomas classified?
Classified as either Hodgkin (specific entity) or Non-Hodgkin (over 50 subtypes)
167
What virus is most strongly associated with Hodgkin lymphoma?
Epstein-Barr Virus
168
What demographic is Hodgkin lymphoma most likely to present in?
It is typically a disease of young adults
169
What are the clinical features of Hodgkin lymphoma?
Lymphadenopathy (often cervical) with rubbery consistency
Potentially hepatosplenomegaly
Systemic "B" symptoms
Constitutional symptoms
170
What are systemic "B" symptoms often seen in Hodgkin lymphoma?
Fever
Drenching night sweats
Weight loss (>10% of body weight in 6 months)
171
What constitutional symptoms may be featured in Hodgkin lymphoma?
Pruritus
Fatigue
Anorexia
Alcohol-induced pain at site of lymphadenopathy
172
What investigations would help you confirm the diagnosis of Hodgkin lymphoma?
Blood count - anaemia (normochromic and normocytic)
ESR - raised (used as indicator of disease activity)
Serum lactate dehydrogenase (poor prognostic marker)
Chest X-ray - mediatinal widening
Diagnosis by lymph node biospy (seeing Reed-Steinberg cells)
Staging by CT and PET scans
173
How is early-stage Hodgkin lymphoma treated?
Breif chemotherapy followed by field irradiation
174
How is late-stage Hodgkin lymphoma treated?
Cyclical combination of chemotherapy and field irradiation
175
Non-hodgkin lymphoma (NHL) is comprised of over 50 subtypes. The majority of NHLs are formed from which cell lineage?
80% are of B cell origin
176
Some Non-Hodgkin Lymphomas are associated with specific infections; what lymphoma is associated with helicobacter pylori?
Gastric mucosal assocaited lymphoid tissue (MALT) lymphoma
177
What is the classical presenation of Non-Hodgkin Lymphoma?
Presentation of a painless peripheral lymph node enlargement
Systemic featues and/or bone marrow infilatration may also occur
178
What investigations are indicated in the case of Non-Hodgkin Lymphoma?
Blood count - anaemia, leucocytosis, thrombocytopenia
Abnormal LFTs
Serum lactate dehydrogenase (prognostic factor)
Bone marrow biospy (confirms marrow involvement)
Lymph node biopspy for definitive diagnosis
179
What is multiple myeloma?
Malignant proliferation of plasma cells in the bone marrow producing paraproteins (immunoglobulins); most commonly IgA or IgG
180
What are the clinical features of multiple myeloma?
Bone destruction - increased osteoclastic activity causing lytic lesions and pathological fractures
Bone marrow infiltration - causing anaemia, infections and bleeding
Acute kidney injury - due to light chain deposits in tubules, hypercalcaemia and hyperuraemia.
Paraprotein aggregates in blood - hyperviscocity causing blurred vision and gangrene
181
What investigations allow the diagnosis of multiple myeloma?
Two of three of the following must be present:
1. Paraproteinaemia/ urinary Bence-Jones protein
2. Radiological evidence of bony features
3. Plasma cell proliferation on bone marrow aspirate
182
How is multiple myeloma managed?
Good supportive care - including transfusion/erythropoietin, prompt infection treatment, treatment of acute kidney injury, analgesia, plasmapheresis for hyperviscocity
Chemotherapy and autologous stem cell transplant
183
A patient preents with paraproteinaemia but has no other signs of myeloma. What is this called?
Monoclonal Gammopathy of Unknown Significance
