HAEMATOLOGY Flashcards
1
Q
what are the investigations for CLL?
A
● Normal or low Hb
● Raised WCC with very high lymphocytes
● Blood film – smudge cells may be seen in vitro
2
Q
What is the treatment for CLL?
A
- Watch and wait
- Chemotherapy
- Monoclonal antibodies, e.g. rituximab
- Targeted therapy, e.g. bruton kinase inhibitors (ibrutinib)
- human IV immunoglobulins
3
Q
what is the epidemiology of ALL?
A
Mainly a childhood disease
highest prevalence between 2-4yrs
Associated with Down’s syndrome
Associated with ionising radiation
4
Q
what are the investigations for ALL?
A
● FBC and blood film
o WCC = high
o Blast cells on film and in bone marrow
● CXR and CT scan looking for mediastinal and abdominal lymphadenopathy
● Lumbar puncture to look for CNS involvement
5
Q
Give 3 environmental causes of leukaemia
A
- Radiation exposure
- Chemicals (benzene compounds)
- Drugs
6
Q
What is lymphoma?
A
Malignant proliferation of B and T lymphocytes in the lymph nodes
7
Q
Although predominantly in the lymph nodes, what other organs can lymphoma effect?
A
- Blood
- Bone marrow
- Liver
- Spleen
8
Q
Give 4 risk factors for lymphoma
A
- Primary immunodeficiency
- Secondary immunodeficiency - HIV, transplant recipients
- Infections - EBV, H. pylori, HTLV-1
- Autoimmune disorders - SLE, RA
9
Q
Describe the pathophysiology of lymphoma
A
Impaired immunosurveillance and infected B cells escape regulation and proliferate
10
Q
What are the 2 sub-types of lymphoma
A
- Hodgkins lymphoma
2. Non-hodgkins lymphoma
11
Q
What are signs and symptoms of Hodgkins lymphoma?
A
- Fever and sweating
- Enlarged rubbery non-tender nodes
- Systemic ‘B’ symptoms, e.g. fever
- Painful nodes on drinking alcohol
- some patients (commonly young women) have disease localised to the mediastinum
12
Q
What is needed for the diagnosis of Hodgkins lymphoma?
A
Presence of Reed-Sternberg cells (in lymph node biopsy)
13
Q
What blood results may you seen in someone with Hodgkins lymphoma?
A
High ESR FBC - anaemia (normochromic normocytic) Reed Sternberg cells Low Hb High serum lactase dehydrogenase
14
Q
Describe the staging go Hodgkins lymphoma
A
Stage 1 = confined to a single lymph node region
Stage 2 = Involvement of two or more nodal areas on the same side of the diaphragm
Stage 3 = Involvement of nodes on both sides of the diaphragm.
Stage 4 = Spread beyond the lymph nodes e.g. liver.
Each stage is either ‘A’ - absence of ‘B’ symptoms or ‘B’ - presence of ‘B’ symptoms
15
Q
What the treatment for Hodgkins lymphoma?
A
ABVD chemotherapy regime
marrow transplant
16
Q
What are the possible complications of treatment for Hodgkins lymphoma?
A
- Secondary malignancies
- IHD
- Infertility
- Nausea
- Alopecia
17
Q
What is non-hodgkins lymphoma?
A
Any lymphoma not involving Reed-Sternberg cells
18
Q
what are the signs and symptoms of non-hodgkins lymphoma?
A
Fever and sweating
Enlarged rubbery non-tender nodes
Systemic ‘B’ symptoms, e.g. fever
GI and skin involvement
19
Q
What is the treatment for non-hodgkins lymphoma?
A
Steroids
Monoclonal antibodies to CD20 -> Rituximab
CHOP regimen
20
Q
What is anaemia?
A
A reduced RBC mass +/- reduced Hb concentration
21
Q
What is the functions of Hb?
A
It carries and delivers oxygen to tissues
22
Q
What organs are responsible for the removal of RBCs?
A
- Spleen
- Liver
- Bone marrow
- Blood loss
23
Q
what are the causes of microcytic anaemia?
A
- Iron deficiency
- Chronic disease - cancer, HF, CKD
- Thalassaemia
24
Q
what are the causes of normocytic anaemia?
A
- Acute blood loss
- Chronic disease
- Combined haematinic deficiency (iron and B12 deficiency)
- renal failure
- pregnancy
- hypopituitarism, hypothyroidism, hypoadrenalism
25
Give 3 causes of macrocytic anaemia
1. B12/folate deficiency
2. Alcohol excess --> liver disease
3. Haemolytic anaemia
4. Hypothyroidism
5. bone marrow infiltration/failure
6. myeloma
26
Briefly describe the pathophysiology of anaemia
Reduced O2 transport --> tissue hypoxia --> compensatory mechanism = increased tissue perfusion, increased O2 transfer to tissue, increase RBC production
27
What pathological changes occur due to anaemia?
1. Heart/liver fat change
2. Ischaemia
3. Skin/nail atrophy
4. CNS death
5. Aggravate angina and claudication
28
What do reticulocytes show you?
Marker of balance between formation and removal of RBCs
29
Give 4 symptoms of anaemia
Non-specific
1. Fatigue
2. Dyspnoea
3. Headache
4. Faintness
5. Palpitations
6. Anorexia
30
Give 3 signs of anaemia
1. Conjunctival pallor
2. Hyper-dynamic circulation
3. Tachycardia
4. Systolic flow murmur
31
What investigations might you do in someone with anaemia?
1. FBC and Blood film
2. Reticulocyte count
3. B12, folate and ferritin levels
4. U+E's, LFT's, TSH levels
32
What is the treatment for anaemia?
Treat the underlying cause
33
Give 3 causes of iron deficiency anaemia
1. Blood loss
2. Poor absorption
3. Decreased intake in diet
4. Increased demand - growth/pregnancy
5. Hookworm
34
Describe the pathophysiology of iron deficiency anaemia
Lack of iron --> no haem production --> lack of effective RBCs
35
What would the results of investigations be for someone with iron deficiency anaemia?
MICROCYTIC HYPOCHROMIC ANAEMIA
| Low ferritin, low reticulocyte
36
How do you treat iron deficiency anaemia?
```
Improve diet and treat cause
Ferrous sulphate (iron supplement)IV iron if severe
```
37
Describe the pathophysiology of B12 deficiency/pernicious anaemia
a lack of B12/intrinsic factor --> B12 not absorbed in terminal ileum --> big facile RBCs
38
what are the causes of B12 deficiency/pernicious anaemia?
1. Autoimmune parietal cell destruction (pernicious)
2. Poor diet
3. Ileectomy
39
What are the specific signs of B12 deficiency/pernicious anaemia?
Inflamed tongue (glossitis), angular stomatitis, mild jaundice
Neurological - paraesthesia, psychological problems, ataxia
- dementia and visual disturbances
40
What would the results of the investigations be for someone with B12 deficiency/pernicious anaemia?
MACROCYTIC NORMOCHROMIC ANAEMIA with polysegmented neutrophils
Autoantibodies = intrinsic factor and coeliac antibodies(intrinsic factor antibodies are diagnostic)
41
How would you treat B12 deficiency/pernicious anaemia ?
Treat cause
B12 replacement - malabsorption = hydroxocobalamin IM
dietary = oral B12
42
Describe the pathophysiology of folate deficiency
In folate deficiency there is an impairment of DNA synthesis, resulting in delayed nuclear maturation resulting in large RBCs as well as decreased RBC production in the bone marrow
43
How do you treat folate deficiency?
Folic acid supplement - with B12
44
Describe the pathophysiology of haemolytic anaemia
RBC destroyed before 120 day lifespan --> compensatory reticulocytes from BM --> RBC destruction
- Extravascular
- Intravascular
45
Give 3 inherited causes of haemolytic anaemia
1. RBC membrane defect
2. Abnormal Hb - thalassaemia's, sickle cell
3. Enzyme defects - Glucose-6-phosphate dehydrogenase deficiency
46
Give 3 acquired causes of haemolytic anaemia
1. Autoimmune
2. Drug induced
3. Secondary to systemic disease
4. Malaria
47
What is the management for haemolytic anaemia
Dietary = folate and iron supplementation
AI cause = immunosuppression
Surgical = splenectomy
48
Name the 3 broad categories of red cell disorders
1. Haemoglobinopathies
2. Membranopathies
3. Enzymopathies
49
What is normal adult haemoglobin made of?
2 alpha and 2 beta chains
50
What is foetal haemoglobin made of?
2 alpha and 2 gamma chains
51
What is haemoglobin S?
Variant haemoglobin arising because of a point mutation in the beta globin gene
Mutation leads to a single AA change, Glutamate --> Valine
52
What two categories can haemoglobinopathies be divided in to?
1. Disorders of quality - abnormal molecule or variant haemoglobin (sickle cell)
2. Disorders of quantity - reduced production (thalassaemia's)
53
What is sickle cell disease?
A haemoglobin disorder of quality
| HbS polymerises --> sickle shaped RBC
54
What is the advantage of being a carrier of sickle cell disease?
Offers protection against falciparum malaria
| They are symptom free
55
Describe the inheritance pattern of sickle cell disease
sickle cell anaemia = Autosomal recessive Homozygous SS
| sickle cell trait = heterozygous
56
If both parents are carries of the sickle trait, what is the chance of their first child having sickle cell disease?
25% chance of having sickle cell
| 50% chance of being a carrier
57
How long do sickle cells last for?
5-10 days
58
Give 3 acute complications of sickle cell disease
1. Painful crisis
2. Sickle cell syndrome - blockage of blood vessels within bone leading to pain
3. Strokes in children
4. Infections
59
Give 3 chronic complications of sickle cell disease
1. Renal impairment
2. Pulmonary hypertension
3. Joint damage
4. growth and development problems
5. cardiomegaly, MI
6. hepatomegaly
7. retinopathy
8. impaired placental blood flow
60
What investigations are done to confirm a diagnosis of sickle cell disease?
- Blood film - Sickled erythrocytes seen
- Blood count - Hb range of 60-80 g/L
- Positive sickle solubility test
- Haemoglobin electrophoresis - Confirms diagnosis
- Aim for diagnosis at birth
61
Describe the treatment for sickle cell disease
- Precipitating factors should be avoided - e.g. infection, dehydration, cold
- Folic acid
- Acute attacks:
- IV fluids
- Analgesia
- Oxygen
- Possible blood transfusions
- Oral hydroxycarbamide to reduce frequency of crises
- Stem cell transplant
long term management
- hydroxyurea - increases HbF levels so is used as prophylaxis
- pneumococcal vaccine
62
What is the significance of parvovirus in someone with sickle cell disease?
Parvovirus is common infection in children
| Leads to decreased RBC production and an cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan
63
Describe the inheritance pattern for membranoapthies
Autosomal dominant
64
Name 2 common membranopathies
1. Spherocytosis
| 2. Elliptocytosis
65
Briefly describe the physiology of membranopathies
Deficiency in red cell membrane protein caused by genetic lesions
66
What are enzymopathies?
Enzyme deficiencies lead to shortened RBC lifespan
67
Name a common enzymopathy
G6PD deficiency
68
what are the clinical features of G6PD deficiency?
```
Most are asymptomatic
Pallor
Fatigue
Palpitations
Shortness of breath
Jaundice
Exacerbated by ingesting fava beans
```
69
Name 3 things that can precipitate G6PD deficiency
1. Broad beans / fava beans
2. Infection
3. Drugs - Primaquine, sulphonamide, quinolones
70
What is polycythaemia?
- increased RBC count
- increased haematocrit
- Due to a JAK2 mutation
71
What hormone is responsible for regulating RBC production?
Erythropoietin (EPO)
72
What stimulates EPO?
Tissue hypoxia
73
what are the primary causes of absolute polycythaemia?
Polycythaemia vera - overactive bone marrow causing increase in RBC mass
74
what are the secondary causes of absolute polycythaemia?
hypoxia
- Smoking
- Lung disease
- Cyanotic heart disease
- High altitude
- obstructive sleep apnoea
Excess EPO - renal disease
alcohol
75
what are the clinical features of polycythaemia?
```
Headaches and dizziness
Itching
Fatigue
Tinnitus
Erythromelalgia – burning sensation in fingers and toes
Hypertension
Angina
Hepatosplenomegaly (distinguishes 1o from 2o)
```
76
What is the treatment for polycythaemia?
```
No cure
Treatment aim is to maintain normal blood count
Venesection - relieves symptoms
Low does aspirin
Radioactive phosphorus in those over 70
```
77
Where are platelets produced?
In the bone marrow
| They are fragments of megakaryocytes
78
What hormone regulated platelet production?
Thrombopoietin - produced mainly in the liver
79
What is the lifespan of a platelet?
7-10 days
80
What organ is responsible for platelet removal?
Spleen
81
What can cause platelet dysfunction?
Reduced platelet number (thrombocytopenia)Reduced platelet function
82
What can cause decreased platelet production?
1. Congenital causes (e.g. malfunctioning megakaryocytes)
2. Infiltration of bone marrow (e.g. leukaemia)
3. Alcohol
4. Infection (e.g. HIV/TB)
5. Reduced TPO
6. Aplastic anaemia
83
What can cause increased platelet destruction?
1. Autoimmune (e.g. ITP)
2. Hypersplenism
3. Drug related (e.g. heparin induced)
4. DIC and TTP --> increased consumption
84
What can cause reduced platelet function?
1. Congenital abnormality
2. Medications - aspirin
3. VWF disease
4. Uraemia
85
Give 3 symptoms of platelet dysfunction
1. Mucosal bleeding - epistaxis, gum bleeding, menorrhagia
2. Easy bruising
3. Petechiae/purpura
4. Traumatic haematomas
86
Give 4 causes of bleeding
1. Trauma
2. Platelet deficiency - thrombocytopenia
3. Platelet dysfunction - aspirin induced
4. Vascular disorders
87
Give 3 things that can cause coagulation disorders
1. Vitamin K deficiency
2. Liver disease
3. Congenital - haemophilia
88
What is thrombotic thrombocytopenia (TTP)?
- Widespread adhesion and aggregation of platelets leads to microvascular thrombosis and consumption of platelets
- Occurs due to a reduction in ADAMTS-13 – a protease that is normally responsible for the degradation of vWF
89
what are the clinical features of thrombotic thrombocytopenia (TTP)
- Flu-like symptoms
- fever, fatigue, aches
- Purpura
- Epistaxis (nosebleeds)
- Easy bruising
- Menorrhagia (heavy periods)
- Haemoptysis (coughing up blood)
- Headache
- Abdominal pain
- GI bleeding
- Chest pain (rare)
90
What is the treatment for thrombotic thrombocytopenia (TTP)?
- Plasma exchange (removed ADAMTS13 autoantibodies)
- Splenectomy
- IV steroids
- IV methylprednisolone
- IV rituximab
- folic acid
- platelet transfusion = contraindicated
91
What is immune thrombocytopenia (ITP)?
Antibodies formed against platelet --> autoimmune platelet destruction via reticuloendothelial system
92
Give 3 causes of immune thrombocytopenia (ITP)
```
Primary = viral infection (children)
Secondary (chronic, adults)
- Autoimmune conditions
- Malignancies - CLL
- Infections - HIV/Hep C
```
93
what is the clinical presentation of immune thrombocytopenia (ITP)?
Can by asymptomatic
- Purpura
- bruising and purple/red rash
- Epistaxis (nosebleeds)
- Menorrhagia (heavy periods)
- Prolonged bleeding from the gums
- Severe headache
- Vomiting
- Fatigue
94
What is the management for immune thrombocytopenia (ITP)?
- first line = Corticosteroid (prednisolone) or IV immunoglobulin - IV IgG
- second line = Splenectomy or immunosuppression (rituximab)
95
Give 4 causes of folate deficiency
1. Dietary
2. Malabsorption
3. Increased requirement - pregnancy
4. Folate antagonists - methotrexate
96
Give 3 signs of haemolytic anaemia
1. Pallor
2. Jaundice
3. Splenomegaly
97
Give 2 specific symptoms of iron deficiency anaemia
1. Koilonychia - spoon nails
2. Brittle hair and nails
3. Atrophic glossitis
98
What is neutrophilia?
Too many neutrophils
99
Give 3 causes of neutrophilia
1. Infection
2. Inflammation
3. Cancer
4. CML = primary cause
100
What is lymphocytosis?
Too many lymphocytes
101
Give 3 causes of lymphocytosis
1. Viral infection
2. Inflammation
3. Cancer
4. CLL = primary cause
102
What is thrombocytopenia?
Not enough platelets
103
What is thrombocytosis?
Too many platelets
104
Give 3 causes of thrombocytosis
1. Infection
2. Inflammation
3. Cancer
4. Essential thrombocythaemia = primary cause
105
What is neutropenia?
Not enough neutrophils
106
What is the major risk associated with being neutropenic?
Susceptible to infection
107
Give 3 causes of neutropenia
1. Underproduction = marrow failure, marrow infiltration, marrow toxicity (e.g. drugs)
2. Increased removal = autoimmune, Felty's syndrome, cyclical
108
Give 2 causes of thrombocytopenia
1. Production failure - marrow suppression, marrow failure
| 2. Increased removal - immune response (ITP), consumption (DIC), splenomegaly
109
What is the definition of febrile neutropenia?
Temperature >38 degrees in a patient with neutrophil count <1x10^9/Lit is an emergency
110
Give 4 risk factors for febrile neutropenia
1. If the patient had chemotherapy <6 weeks ago
2. Any patient who has had a stem cell transplant <1 year ago
3. Any haematological condition causing neutropenia
4. Bone marrow infiltration
5. those on methotrexate, carbimazole and clozapine
111
Give a risk for spinal cord compression
Any malignancy that can cause compression - bone metastasis
| commonly seen in myeloma and lymphoma
112
What is hyper viscosity syndrome?
Increase in blood viscosity usually due to high levels of immunoglobulins
113
What does rituximab target?
Targets CD20 on the surface of B cells
114
What is the affect of sickle cell anaemia on reticulocyte count?
Raised
115
What clotting factors depend on vitamin K?
2, 7, 9, 10
116
Haemophilia A is due to deficiency of what clotting factor?
Factor 8 deficiency
117
Haemophilia B is due to deficiency of what clotting factor?
Factor 9 deficiency
118
How does warfarin work?
Antagonises vitamin K so reduction in clotting factors 2, 7, 9 and 10
119
How does heparin work?
Indirect thrombin inhibitor
It binds to and activates antithrombin which then inhibits thrombin and factor Xa
120
What 3 blood test values would be increased in someone with polycythaemia?
1. Hb
2. RCC
3. PCV
121
what are the clinical features of chronic lymphoblastic leukaemia (CLL)?
- often no symptoms
- may be anaemic
- weight loss, sweats, anorexia
- hepatosplenomegaly
- enlarged, rubbery, non-tender nodes
122
what is the progression of CLL like?
- may transform into aggressive lymphoma
- Richter's syndrome
- 1/3 never progress
- 1/3 progress slowly
- 1/3 progress actively
123
what are the complications of CLL?
- autoimmune haemolysis
- increased infection risk
- marrow failure
- richter's syndrome - transformation to aggressive lymphoma
124
what is the epidemiology of hodgkins lymphoma?
- male predominance
| - majority of cases occur in teenagers and the elderly
125
what are the 2 different groups of macrocytic anaemia?
- megaloblastic = erythroblasts with delayed nuclear nmaturation
- non-megaloblastic = normal erythroblasts
126
how is vitamin B12 absorbed in the body?
binds to intrinsic factor (made by parietal cells) and absorbed in terminal ileum
127
what is the role of vitamin B12?
essential for thymidine and DNA synthesis
128
what is the epidemiology of pernicious anaemia and B12 deficiency?
- common in elderly- women > men
| - more common in people with fair hair and blue eyes
129
what are the risk factors for pernicious anaemia?
- female
- elderly
- fair hair and blue eyes
- blood group A
- thyroid and addison's disease
130
what are the risk factors for folate deficiency?
- elderly
- poverty
- alcoholic
- pregnant
- crohn's/coeliac
131
what is the clinical presentation of folate deficiency?
- may be asymptomatic
- may present with anaemia symptoms
- glossitis
- no neuropathy
132
what investigations should be undertaken in folate deficiency?
- blood count and film = megaloblastic, RBCs macrocytic
- low serum and red cell folate low
- serum bilirubin may be raised
133
why do sickle cell anaemia symptoms typically take 3-6 months to develop?
synthesis of HbF is normal so disease doesn't manifest until HbF decreases to adult levels at about 6 months old
134
why can patients with sickle cell anaemia appear well despite being anaemic?
HbS release oxygen to tissues more readily than normal RBCs - will still feel well
135
what is the management for acute attacks in sickle cell anaemia?
IV fluids
analgesia
oxygen
antibiotics
136
what investigations should be undertaken for G6PD?
blood film - irregularly contracted cells, bite cells, reticulocytosis
G6PD enzyme levels low
137
what is the treatment for G6PD?
- blood transfusion
| - stop exacerbating drugs
138
what is the epidemiology of non-hodgkins lymphoma?
rare before 40
| strong link between EBV and Burkitt's lymphoma
139
which chemotherapy regimen is used for treating non-hodgkin's lymphoma?
R-CHOP
140
what investigations should be undertaken for polycythaemia?
- blood count = raised WBC and platelets
- raised Hb
- JAK2 mutation on genetic screen
- bone marrow biopsy - proliferation of granulocytes and megakaryocytes
- low serum EPO
141
what are the complications of polycythaemia?
thrombosis
| haemorrhage
142
which investigations should be undertaken for immune thrombocytopenia purpura (ITP)?
- bone marrow examination = thrombocytopenia with normal/increased megakaryocytes
- platelet autoantibodies
143
what are the causes of thrombotic thrombocytopenic purpura (TTP)?
```
idiopathic
autoimmune e.g. SLE
cancer
pregnancy
drug related
```
144
what is the clinical presentation of haemophilia A?
- mild = bleed after trauma
- moderate = bleeding after venepuncture and trauma
- severe = neonatal bleeding, spontaneous bleed, GI bleeds, haematuria
145
what is the treatment for haemophilia A?
- factor VIII
- fresh frozen plasma containing factor VIII for acute bleeds
- desmopressin
146
what type of inheritance is haemophilia?
x linked - male predominance
147
what is the clinical presentation of haemophilia B?
- bruising
- nosebleeds
- pallor
- heavy bleeding from minor injury
- bleeding from tooth loss in childhood
- joint pain and stiffness
- headache, vomiting
- GI bleed
148
what is the treatment for haemophilia B?
treatment must be started before diagnosis is confirmed
- recombinant factor IX
- vaccination against hep A and B
149
what is von Willebrand's disease?
- vWF deficiency
| - blood cannot clot- also called pseudohaemophilia- more common in females
150
what is the clinical presentation of von Willebrnad's disease?
- Bleeding from mucosa
- Epistaxis (nose bleeds)
- Menorrhagia (heavy periods)
- Spontaneous bleeding
- Blood clots during childbirth (rare)
- Spontaneous death (rare)
151
what is the management for von Willebrand's disease?
- Education on bleeding risks
- Stop any antiplatelet drugs and NSAIDs
- Tranexamic acid - used for minor bleeds
- Combined oral contraceptive to control menorrhagia in women
- Desmopressin -> increases vWF levels
- Platelet transfusions can be helpful in some
- Family screening should be offered
152
what are the causes of aplastic anaemia?
- inherited
- idiopathic
- benzene
- chemotherapeutic drugs
- antibiotics
- infections - EBV, HIV and TB
153
what is the pathophysiology of aplastic anaemia?
due to a reduction in the number of pluripotent stem cells, together with a fault in those remaining or an immune reaction against them so they are unable to repopulate the bone marrow
154
what is the clinical presentation of aplastic anaemia?
- anaemia
- increased susceptibility to infection
- bleeding- bleeding gums, bruising and blood blisters in mouth
155
what investigations are undertaken for aplastic anaemia?
- blood cell count
- pancytopenia and low reticulocyte count
bone marrow examination
- hypocellular with increased fat spaces
156
what is the treatment for aplastic anaemia?
- treat cause
- antibiotics for neutropenia
- RBC transfusion and platelets
- bone marrow transplant
- immunosuppressive therapy
- ATG and ciclosporin if under 40
157
what is haemolytic anaemia?
- premature breakdown of RBCs before normal lifespan
158
what are the causes of haemolytic anaemia?
- RBC membrane defects
- spherocytosis
- enzyme defects
- G6PD
- alpha and beta thalassaemia
- sickle cell anaemia
- autoimmune haemolytic anaemia
159
what is the epidemiology of myeloma?
- older adults 75+
| - more common in afro-caribbean's
160
what are the investigations for non-hodgkins lymphoma?
FBC - anaemia, high ESR
Raised lactose dehydrogenase
Lymph node biopsy
Bone marrow biopsy for classification
161
what is the epidemiology of hodkins lymphoma?
- Bimodal – peaks twice in life
- Young adults and elderly
- Male > female
- Associated with EBV, SLE, siblings
162
what is the epidemiology of non-hodgkins lymphoma?
Adults 40+
Associated with EBV and Burkitt’s lymphoma
Family history increases risk
163
what are the different types of non-hodgkins lymphoma?
low grade = follicular lymphoma
high grade = diffused large B cell lymphoma
very high grade = burkitt's lymphoma
164
what is the epidemiology of AML?
● Progresses rapidly with death in 2 months if untreated
● Commonest acute leukaemia in adults
● Associations with radiation and Down’s
165
what are the possible complications of AML?
infections such as sepsis
166
what is the epidemiology of CML?
- almost exclusively a disease of adults
- occurs between 40-60
- slight male predominance
167
what is the epidemiology of CLL?
- most common leukaemia- occurs later in life
- mutations, trisomy's and deletions influence risk
- Pneumonia may be a triggering event
- Progression – may stay stable for years or regress
- Death often due to complication of infection
- May transform into aggressive lymphoma – Richter’s syndrome
- 1/3 will never progress, 1/3 progress slowly, 1/3 progress actively
168
what is the pathophysiology of polycythaemia?
● A clonal stem cell disorder resulting in malignant proliferation of a clone derived from 1 pluripotent marrow stem cell
● Erythropoietin progenitor offspring do not need erythropoietin to avoid apoptosis
● Results in excess proliferation of RBCs, WBCs and platelets – cause raised haematocrit = hyper viscosity and thrombosis
169
what is the epidemiology of von Willebrand's disease?
Most common hereditary coagulopathy
Can be congenital or acquired
More common in females Poorer prognosis in blood type O
170
what are the different types of von Willebrand's disease?
- 3 types: Type 1, 2, 3, platelet type
- Type 1 is the most common (60-80%)
- Platelet type is the most rare (70 cases)
171
what are the investigations for von Willebrand's disease?
- FBC
- Fibrinogen level
- Platelet count - normal
- Clotting screen- Plasma vWF decreased
- Factor VIII levels - can be decreased as vWF is not present to protect it
172
what is the epidemiology of haemophilia A?
- majority are inherited
- x-linked
- male predominance
- 5 x more common than haemophilia B
173
what are the investigations for haemophilia A?
- FBC - low haematocrit, low Hb
- Normal prothrombin and bleeding time
- Prolonged activated partial thromboplastin time
- Heavily reduced factor VIII
- CT head - look for haemorrhages
174
what is the epidemiology of haemophilia B?
- Caused by Factor IX deficiency
- Male predominance (X-linked)
- Mild disease has factor IX levels of 6-30%
- Moderate disease has levels of 1-5%
- Severe disease has levels of <1% - this accounts for 50% of cases
175
what are the investigations for haemophilia B?
- Normal prothrombin time
- Prolonged activated partial thromboplastin time
- Low factor IX levels
- Endoscopy if GI bleed suspected
176
what are the clinical features of heterozygous sickle cell anaemia (trait)?
Symptom free
| Protection against falciparum malaria
177
what are the clinical features of homozygous sickle cell anaemia?
Acute pain in hands and feet
Long bone pain, e.g. femur, spine, ribs
Cognitive defects in children
Pulmonary hypertension and chronic lung disease (most common cause of death)
Splenic sequestration (cells get trapped)
178
what are the risk factors for sickle cell anaemia?
african
| family history
179
what is the pathophysiology of sickle cell anaemia?
- Results from a single base emulation of adenine to thymine
– valine substituted for glutamic acid at the 6th codon of the beta globin chain
- HbS is insoluble and polymerises when oxygenated
- Flexibility of cells is decreased – become rigid and sickled
- Initially reversible but then go on to lose membrane flexibility and become irreversibly sickled – these cells are dehydrated and dense
- Sickling results in a shorted RBC survival resulting in haemolysis and impaired passage of cells through the microcirculation leading to obstruction of small vessels and tissue infarction
180
what is G6PD deficiency?
G6PD is protective against oxidative damage
G6PD deficiency results in reduced red blood cells lifespan
181
what is the epidemiology of G6PD deficiency?
More common in Africa, the Middle East and SE Asia
| More common in males
182
what is the clinical presentation of microcytic anaemia?
in addition to anaemia symptoms:
● Brittle hair and nails
● Spoon shaped nails – koilonychia
● Atrophy of papillae of tongue – atrophic glossitis
● Angular stomatitis – ulceration of corners of the mouth
183
what is the epidemiology of malaria?
```
P. falciparum is the most common
P. malariae is the least common
Most common in Africa
Risks include: infants, pregnancy, old age
notifiable condition
```
184
what are the different species of malaria?
4 species: P. falciparum, P. vivax, P. ovale P. malariae
P. falciparum is the most common
P. malariae is the least common
185
what is malaria?
Parasitic infection, Plasmodium, spread by female anopheles mosquito
186
what are the clinical features of malaria?
Non-specific symptoms
- Fever, chills
- Headache
- Cough
- Splenomegaly
Severe disease in P. falciparum
- Shortness of breath
- Fits and hypovolaemia
- AKI and nephrotic syndrome
187
when do clinical features of malaria present?
Symptoms occur from 6 days post infection
P. vivax and P. ovale commonly present 6 months post infection - can relapse as it can lay dormant in the liver for years.
188
what are the investigations for malaria?
- Travel history
- Thick and thin blood smears
- Negative film can be seen
- If negative, 2 more films should be sent over the next 48 hours
- Rapid diagnostic tests
- Detect parasitic antigens
- PCR- FBC, LFTs, U&Es, blood gases, blood culture
- CXR, lumbar puncture
189
what is the treatment for malaria?
- Chloroquine for non-falciparum malaria
- Oral quinine sulphate for falciparum
- Add IV quinine dihydrochloride for severe disease
Do not treat those with G6PD deficiency
Need specialist help
190
what are the risk factors for iron deficiency anaemia?
● Undeveloped countries
● High vegetable diet
● Premature infants
● Introduction of mixed feeding delayed
191
what is anaemia of chronic disease?
Secondary to chronic disease
| Occurs in chronic infections such as TB, Crohn’s, RA, SLE, malignancy
192
what is the pathophysiology of anaemia of chronic disease?
● Decreased release of iron from bone marrow to developing erythroblasts
● Inadequate erythropoietin response to anaemia – decreased RBC survival
193
what do the investigations for anaemia of chronic disease show?
● Low serum iron and iron-binding capacity
● Increased or normal ferritin due to inflammatory response
● RBCs normo/micro-cytic and hypochromic (pale)
● Serum soluble transferrin normal
194
what is the management for anaemia of chronic disease?
● Treat underlying chronic condition
| ● Erythropoietin is effective in raising the Hb level and is used in cases of renal disease and inflammatory disease
195
what are the side effects of oral iron treatment?
nausea, abdominal discomfort, diarrhoea/constipation, black stool
196
what are the side effects of erythropoietin treatment?
flu-like symptoms,
hypertension,
raised platelets,
thromboembolism
197
how long do folate stores last for?
4 months
198
what is aplastic anaemia?
- Rare stem cell disorder
- Defined as pancocytopenia (this is a reduction in all the major cell lines; red cells, white cells and platelets) with hypocellularity (aplasia) of the bone marrow (marrow stops making cells)
- It is usually an acquired condition but may be inherited
199
what are the main causes of aplastic anaemia?
- inherited - Fanconi's anaemia
- idiopathic- benzene, toulene, glue sniffing
- chemotherapeutic drugs
- antibiotics
- infections - EBV, HIV, TB
200
what is the pathophysiology of aplastic anaemia?
Due to a reduction in the number of pluripotent stem cells, together with afault in those remaining or an immune reaction against them so that they areunable to repopulate the bone marrow
201
what are the clinical features of aplastic anaemia?
- anaemia
- increased susceptibility to infection
- bleeding
- bleeding gums
202
what are the results for investigations for aplastic anaemia?
- Blood count:
• Pancocytopenia with low reticulocyte count
- Bone marrow examination:
• Hypocellular marrow with increased fat spaces
203
what is the treatment of aplastic anaemia?
- treat cause
- RBC transfusion
- bone marrow transplant
- immunosuppressive therapy
- ATG and ciclosporin
204
what is the long term management for sickle cell anaemia?
- hydroxyurea - increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
- pneumococcal vaccine
205
how is heparin treatment reversed?
- proteamine
206
what is the mechanism of action for aspirin?
- irreversibly inhibits COX
| - inhibits thromboxane formation and therefore platelet aggregation is inhibited
207
what is the mechanism of action for clopidogrel?
inhibits ADP induced platelet aggregation
208
what is the most common cell origin for lymphoma (both hodgkins and non-hodgkins)?
B cell
209
what is ondansetron?
anti-emetic drug
210
what is the mechanism of action for ondansetron?
5HT3 antagonist
211
what is the mechanism of action for DOAC?
direct action on factor II or X
212
What is myeloma?
Cancer of differentiated B lymphocytes (plasma cells)
Multiple myeloma is a palliative disease, so everyone will relapse.
213
Describe the pathophysiology of myeloma
Accumulation of malignant plasma cells in bone --> progressive bone marrow failure
Production of one excess immunoglobulin (monoclonal paraprotein)
214
What monoclonal paraprotein is usually produced in myeloma?
```
IgG = 55%
IgA = 20%
```
215
Give 3 symptoms of myeloma
1. Tiredness
2. Bone/back pain
3. Infections
216
Give 4 signs of myeloma
```
old CRAB
old = over 75
1. Calcium is elevated
2. Renal failure
3. Anaemia
4. Bone lesions
```
217
Why is calcium elevated in myeloma?
Increased bone resorption and decreased bone formation so more calcium in the blood
218
Why might someone with myeloma have anaemia?
BM infiltrated with plasma cells = anaemia, neutropenia (infections) and thrombocytopenia (bleeding)
219
Why might someone with myeloma have renal failure?
Due to light chain deposition
220
What investigations might you do in someone who you suspect has myeloma?
```
FBC - anaemia, raised ESR
Blood film - rouleaux
Serum and urine electrophoresis - Bence Jones protein in urine
X-rays - pepper pot skull, fractures
CT - bone lesions, cord compression
```
221
What would you expect to see on the blood film taken from someone with myeloma?
Rouleaux formation (aggregation of RBCs)
222
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
Increase plasma cells
223
What are you looking for on electrophoresis in a patient with myeloma?
Monoclonal protein band
224
What would you expect to see on the x-ray taken from someone with myeloma?
Lytic 'punched out' lesions --> pepper pot skull, vertebral collapse
Fractures
Osteoporosis
225
What might the urine of someone with myeloma contain?
Bence-jones protein - immunoglobulin light chains with kappa or lamda lineage
226
What does a diagnosis of myeloma require?
1. Monoclonal protein band in serum or urine
2. Increased plasma cells on bone marrow biopsy
3. Hypercalcaemia/renal failure/anaemia
4. Bone lesion on skeletal survey
227
Describe the treatment for symptomatic myeloma
```
Bone pain = analgesia
Bisphosphonates (zolendronate)
Blood transfusion - for anaemia
Fluids and dialysis - renal failure
Chemotherapy
Stem cell transplant
```
228
How is myeloma bone disease usually assessed?
X-ray
229
Suggest 3 ways in which multiple myeloma can lead to AKI
1. Deposition of light chain
2. Hypercalcaemia
3. Hyperuricaemia
230
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic
231
What chemotherapy regime is used in patients with myeloma?
- CTD - Cyclophosphamide, thalidomide and dexamethasone
| - VAD - Vincristine, Adriamycin, dexamethasone (for fitter people)
232
What is leukaemia?
A malignant proliferation of haemopoietic stem cells (immature blood cells)
233
Name 4 sub types of leukaemia
1. AML - Acute Myeloid Leukaemia
2. CML - Chronic Myeloid Leukaemia
3. ALL - Acute Lymphoblastic Leukaemia
4. CLL - Chronic Lymphoblastic Leukaemia
234
What is acute myeloid leukaemia (AML)?
Neoplastic proliferation of blast cells (immature blood cells)
affects myeloid progenitor cells and myeloblasts
235
What are the risk factors for AML?
1. Preceding haematological disorders
2. Prior chemotherapy
3. Exposure to ionising radiation
4. Down's syndrome
236
what are the clinical features of AML?
- Anaemia -> breathlessness, fatigue, pallor
- low WCC = Infection
- low platelets = bleeding/bruising
- Hepatosplenomegaly
- Peripheral lymphadenopathy
- Gum hypertrophy
- Bone marrow failure and bone pain
237
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure
238
Why are hepatomegaly and splenomegaly symptoms of leukaemia?
Because of tissue infiltration
239
What investigations do you do on someone who you suspect has AML?
- FBC - anaemia, thrombocytopaenia
- WCC often raised (can be normal/low)
- Blood film - leukaemic blast cells
- Bone marrow biopsy - Auer rods
240
What would you expect to see on an FBC and bone marrow biopsy in someone you suspect to have AML?
FBC = anaemia and thrombocytopenia and neutropenia
| BM biopsy = leukaemic blast cells (with Auer rods)
241
What is chronic myeloid leukaemia (CML)?
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils)
242
What chromosome is present in >80% of people with CML?
Philadelphia chromosome
forms a fusion gene BCR/ABL on chromosome 22 – has tyrosine kinase activity – simulate cell division
243
what are the clinical features of CML?
1. Symptomatic anaemia
2. Abdominal pain = splenomegaly
3. Weight loss, tiredness, palor
4. Gout - due to purine breakdown
5. Bleeding - due to platelet dysfunction
6. fever and sweats in absence of infection
244
what are the investigations for CML?
- FBC - anaemia, raised myeloid cells, high WCC (eosinophilia, basophilia, neutrophilia)
- Increased B12
- Blood film - left shirt, basophilia
- Bone marrow biopsy - increased cellularity (hypercellular)
- Philadelphia chromosome seen in 80+% of cases t(9;2) - Stimulates cell division
245
What is the treatment for CML?
- Chemotherapy
- Tyrosine kinase inhibitors, e.g. Imatinib - Given orally
- Stem cell transplant
246
Why does the Philadelphia chromosome cause CML?
Froms fusion gene BCR/ABL on chromosome 22 --> tyrosine kinase activity --> stimulates cell division
247
What is acute lymphoblastic leukaemia (ALL)?
Uncontrolled proliferation of immature lymphoblast cells (lymphoid progenitor cells)
affects lymphoid progenitor cells and lymphoblasts
248
what are the clinical features of ALL?
- Anaemia = breathlessness, fatigue, pallor
- Low WCC = Infection
- low platelets = bleeding and bruising
- Hepatosplenomegaly
- Peripheral lymphadenopathy
- CNS involvement - headache, cranial nerve palsies
- SVC obstruction, dilated superficial chest veins
- Bone marrow failure and bone pain
249
What is the treatment for ALL?
- Blood and platelet transfusion
- Chemotherapy
- Steroids
- Allopurinol to prevent tumour lysis syndrome
- Intrathecal drugs, e.g. methotrexate
- Acute control of infections with IV antibiotics
- Neutropenia makes this high risk
- Stem cell transplant
250
What is Chronic lymphoblastic leukaemia (CLL)?
Proliferation of mature B lymphocytes leads to accumulation of mature B cells that have escaped apoptosis
Chronic malignant transformation of mature lymphoid cells
251
Describe the treatment for AML
- Blood and platelet transfusions
- IV fluids
- Allopurinol to prevent tumour lysis
- Infection control with IV antibiotics
- Chemotherapy
- Steroids
- Sibling matched allogenic bone marrow transplant
