Haematology Flashcards
1
Q
What percentage of blood is plasma and what does this consist of?
A
55%
Plasma proteins–> e.g. albumin and carrier proteins, coagulation factors (e.g. fibrinogen) and immunoglobulins
Water
2
Q
What percentage of blood is cells?
A
45%
RBC + Leukocytes + Platelets
3
Q
What is serum and what does it contain?
A
Blood plasma without the clotting factors.
Contains:
Glucose
Electrolytes (sodium and potassium)
Proteins (e.g. immunoglobulins and hormones)
4
Q
Where do blood cells develop?
A
Bone marrow
5
Q
Where is the majority of bone marrow found?
A
Pelvis, vertebrae, ribs, sternum
6
Q
What can a pluripotent haematopoietic stem cell differentiate into?
A
Myeloid stem cell
Lymphoid stem cell
Dendritic cell
7
Q
What can myeloid stem cells differentiate into?
A
Megakaryocytes
Erythrocytes
Myeloblasts
8
Q
What do Megakaryocites produce?
A
Platelets
9
Q
What do RBC’s develop from?
A
Reticulocytes that come from myeloid stem cells.
10
Q
What is the life span of a:
- platelet?
- RBC?
A
- 10 days
2. 120 days
11
Q
What is the role of platelets?
A
To aggregate (clump together) and plug gaps where blood clots need to form.
12
Q
What can myeloblasts differentiate into?
A
Basophil Neutrophil Eosinophil Monocyte Mast cells
13
Q
What do monocytes differentiate into?
A
Macrophages
14
Q
What can lymphoid stem cells differentiate into?
A
B lymphocytes
T lymphocytes
Natural killer cells
15
Q
What do B lymphocytes differentiate into?
A
Plasma cells
Memory B cells
16
Q
What do T lymphocytes differentiate into?
A
CD4 cells (T helper cells) CD8 cells (cytotoxic T cells) Natural killer cells
17
Q
Where do B lymphocytes mature?
A
Bone marrow
18
Q
Where to T lymphocytes mature?
A
Thymus gland
19
Q
What are reticulocytes?
A
Immature red blood cells that are slightly larger than standard erythrocytes and still have RNA material in them which has a reticular (mesh-like) appearance.
20
Q
What is the normal percentage of reticulocytes in the blood and why may it increase?
A
1% of RBC
Percentage goes up when there is a rapid turnover of RBC’s such as in haemolytic anaemia.
21
Q
What is anaemia?
A
Low level of haemoglobin in the blood.
A result of disease-not a disease itself
22
Q
What is haemoglobin?
A
A protein found in RBC’s, responsible for picking up oxygen in the lungs and transporting it to the cells of the body.
23
Q
What should you measure to see if a patient has anaemia?
A
Haemoglobin levels
Mean cell volume (MCV)
24
Q
What is the mean cell volume?
A
The size of their red blood cells
25
What is the normal haemoglobin and MCV levels in women?
```
Haemoglobin= 120-165 g/L
MCV= 80-100 femtolitres
```
26
What is the normal haemoglobin and MCV levels in men?
```
Haemoglobin= 130-180 g/L
MCV= 80-100 femtolitres
```
27
What are the 3 types of anaemia (based on size)?
Microcytic
Normocytic
Macrocytic
28
What is microcytic anaemia?
Low MCV anaemia indicating small RBC's
29
What is normocytic anaemia?
Normal MCV indicating normal sized RBCs
30
What is macrocytic anaemia?
Large MCV indicating large RBC's
31
What are the causes of microcytic anaemia?
```
TAILS:
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Siderobastic anaemia
```
32
What are the main causes of normocytic anaemia?
```
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism
```
33
What are the two main causes of macrocytic anaemia?
Megaloblastic anaemia
| Normoblastic anaemia
34
What is megaloblastic anaemia?
The result of impaired DNA synthesis preventing the cell from dividing normally. Instead it keeps growing into a larger abnormal cells.
35
What is the cause of megaloblastic (macrocytic) anaemia?
Vitamin deficiency:
B12 deficiency
Folate deficiency
36
What are the causes of normoblastic macrocytic anaemia?
```
Alcohol
Reticulocytosis
Hypothyroidism
Liver disease
Drugs (e.g. Azathioprine)
```
37
What are the main generic symptoms of anaemia?
```
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions (e.g. angina, heart failure, PVD)
```
38
What are the symptoms specific to iron deficiency anaemia?
Pica
| Hair loss
39
What is pica?
Dietary cravings for abnormal things such as dirt
40
What are the generic signs of anaemia?
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
41
What signs are specific to iron deficiency anaemia?
Koilonychia (spoon shaped nails)
Angular chelitis (red, swollen patches in corners of mouth)
Atrophic glossitis (smooth tongue)
Brittle hair and nails
42
What are the initial investigations into anaemia?
```
Haemoglobin
MCV
B12
Folate
Ferritin
Blood film
```
43
What further investigations could be done to diagnose anaemia?
Oesophago-gastroduodenoscopy (OGD) / colonoscopy to investigate cause of unexplained iron deficiency anaemia.
Bone marrow biopsy if cause unclear/
44
Under what circumstances may a patient become iron deficient?
Insufficient dietary iron
Iron requirements increase (e.g. pregnancy)
Iron being lost (e.g. slow bleeding in colon cancer)
Inadequate iron absorption
45
Where is the majority of iron absorbed?
Duodenum and jejenum
46
How is absorbed iron kept in the soluble ferrous (Fe2+) form?
Due to acid in the stomach
47
What happens when the acid levels drop?
Ferrous iron changes to the insoluble ferric (Fe3+) form
48
How do medications such as proton pump inhibitors interfere with iron absorption?
Reduce the stomach acid, meaning it stays in the soluble ferrous form for less time
49
What can cause inadequate iron absorption?
Medications such as proton pump inhibitors
| Conditions that cause inflammation of the duodenum/ jejunum (e.g. Coeliac or Crohn's disease)
50
What are the most common causes of iron deficiency anaemia?
- Blood loss --> most common cause in adults
- Dietary insufficiency--> most common cause in growing children
- Poor iron absorption
- Increased requirements during pregnancy
51
What are the most common causes of iron deficiency anaemia due to blood loss?
```
Monorrhagia (heavy period)
Loss from the GI tract:
- Gi tract cancer
- Oesophagitis
-Gastritis
-IBD
```
52
How does iron travel around the blood?
As ferric ions (Fe3+) bound to transferrin (carrier protein)
53
What is total iron binding capacity (TIBC)?
The total space on the transferrin molecule for iron to bind.
54
What is the transferrin saturation?
The proportion of transferring molecules that are bound to iron/
55
How is the transferrin saturation calculated?
Serum iron/ Total iron binding capacity
56
What form does iron take when it is deposited and stored in cells?
Ferritin (Fe2+)
57
What causes raised blood ferritin?
Extra ferritin is released from cells in inflammation (E.g. infection or cancer)
58
What does low blood ferritin suggest?
Iron deficiency
59
Why is serum iron not a very useful measure?
It varies significantly throughout the day. (e.g. in the morning and after meals)
60
What happens to TIBC/ transferrin levels in iron deficiency?
The levels increase
61
What measurement gives the best indication of the total iron in the body?
Transferrin
62
What is the normal transferrin level in adults?
30%
| Normal range= 15-50%
63
What blood tests are used to diagnose iron deficienct anaemia/ iron overload?
Serum ferritin
Serum iron
Total iron binding capacity
Transferrin saturation
64
What is the normal range of serum ferritin?
41-400 ug/L
65
What is the normal range of serum iron?
12-30 μmol/L
66
What is the normal range of TIBC?
45-80 μmol/L
67
What factors can give the impression of iron overload?
Iron supplementation
| Acute liver damage (lots of iron is stored in the liver)
68
What are the 3 main methods of management for iron deficient anaemia?
1. Blood transfusion
2. Iron infusion
3. Oral iron
69
What are the benefits/ risks of using a blood transfusion to treat iron deficiency anaemia?
Immediately corrects the anaemia and is very quick.
| Does not treat underlying iron deficiency and carries risks.
70
What are the benefits/ risks of using an iron infusion to treat iron deficiency anaemia?
Very quickly corrects the iron deficiency
| Small risk of anaphylaxis and should be avoided during sepsis
71
What is given as oral iron to treat iron deficiency anaemia and how much?
Ferrous sulfate 200mg three times a day
72
What are the benefits/ risks of oral iron to treat iron deficiency anaemia?
Least invasive.
Slowly corrects the deficiency.
Causes constipation and black coloured stools.
73
By how much could you expect haemoglobin to rise when correcting iron deficiency anaemia?
10 grams/ litre per week
74
What is pernicious anaemia?
An autoimmune condition where antibodies form against the parietal cells or intrinsic factor, preventing the absorption of B12 and causing B12 deficiency anaemia
75
What are the causes of B12 deficiency anaemia?
caused by insufficient dietary intake or by pernicious anaemia
76
Where in the body is B12 absorbed and what does it need in order to be absorbed?
Ileum
| Needs intrinsic factor produced by the parietal cells of the stomach.
77
What are the main symptoms caused by B12 deficiency?
Neurological symptoms:
- Peripheral neuropathy--> numbness or paraesthesia (pins and needles)
- Loss of proprioception/ vibration sense
- Visual changes
- Mood/ cognitive changes
78
How is pernicious anaemia diagnosed?
Testing for autoantibodies:
Intrinsic factor antibody
Gastric parietal cell antibody
79
How can B12 dietary deficiency be treated?
Oral replacement (Cyanocobalamin)
80
Why can oral B12 replacement not be used to treat pernicious anaemia?
Because the problem is with absorption not intake.
81
How can pernicious anaemia be treated?
1mg of intramuscular hydroxycobalamin (B12) 3 times weekly for 2 weeks, then every 3 months.
82
What is haemolytic anaemia?
Anaemia caused by destruction of red blood cells (haemolysis)
83
What inherited conditions cause haemolytic anaemia and how?
Cause RBC's to be more fragile and break down faster than normal:
- Hereditary Spherocytosis
- Hereditary Elliptocytosis
- Thalassaemia
- Sickle Cell Anaemia
- G6PD Deficiency
84
What acquired conditions cause haemolytic anaemia and how?
Lead to increased breakdown of RBC's:
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia
- Prosthetic valve related haemolysis
85
What does an abnormal rate of RBC destruction cause?
Anaemia
Splenomegaly--> Spleen becomes filled with destroyed RBCs
Jaundice--> Bilirubin is released during the destruction
86
What investigations can be done to diagnose haemolytic anaemia?
Full blood count
Blood film--> Shows schistocytes (fragments of RBC's)
Direct Coombs test (shows autoimmune causes)
87
What is hereditary spherocytosis?
The most common inherited haemolytic anaemia.
Autosomal dominant condition that causes sphere shaped RBCs that are fragile and break down easily when passing through the spleen.
88
How is hereditary spherocytosis haemolytic anaemia treated?
With folate supplementation and splenectomy
89
What is hereditary elliptocytosis?
Same as hereditary spherocytosis except RBCs are ellipse shaped instead of spheres.
90
What is G6PD Deficiency?
Type of haemolytic anaemia caused by a defect in the RBC enzyme G6PD.
91
What are the two types of Autoimmune Haemolytic Anaemia (AIHA)?
-Warm type
-Cold type
Based on the temperatures at which the auto-antibodies function to cause destruction of RBCs
92
What is Alloimmune Haemolytic Anaemia?
When there are foreign RBCs or antibodies circulating in the patients blood causing an immune reaction that destroys them.
93
What causes Alloimmune Haemolytic Anaemia?
Blood transfusion reactions
| Haemolytic disease of the newborn
94
What is Paroxysmal Nocturnal Haemoglobinuria?
Rare condition that occurs when a specific genetic mutation in the haematopoeitic stem cells in the bone marrow results in a loss of proteins on the surface of RBCs that inhibit the complement cascade.. This results in its activation and therefore the destruction of RBCs
95
What is Microangiopathic Haemolytic Anaemia (MAHA)?
Where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Usually secondary to an underlying condition
96
What is Prosthetic Valve Haemolysis?
Haemolytic anaemia caused by turbulence around the valve and collision of red blood cells with the implanted valve. ( Valve churns up the cells and they break down.)
97
Where in the body is folate absorbed and what does it do?
Absorbed in the jejunum.
| Essential for DNA synthesis and RBC formation.
98
What happens if the body does not have enough folic acid?
The body makes abnormally large RBCs that don't work properly and there is decreased RBC production in the bone marrow.
99
What are the main causes of folate deficiency?
Poor folate diet
Malabsorption
Pregnancy
Anti-folate drugs (e.g. mehtotrexate)
100
What foods are high in folat?
Green vegetables
101
How can you differentiate B12 and folate deficiency anaemia based on symtpoms?
Unlike B12, there is no neuropathy
102
What investigations can be done to diagnose folate deficiency anaemia?
FBC
Blood film - show macrocytic anaemia
Serum and erythrocyte folate levels
103
How is folate deficiency anaemia treated?
Treat underlying cause
| Folic acid supplementation (particularly consider during pregnancy)
104
What is the structure of haemoglobin?
2 alpha and 2 beta-globin chains
105
What is thalassaemia?
Anaemia caused by an autosomal recessive genetic defect in the protein chains that make up haemoglobin.
106
What causes alpha thalassaemia?
Genetic defects in alpha-globin chains
107
What causes beta thalassamia?
Genetic defects in beta-globin chains
108
What happens to RBCs in thalassaemia?
They are more fragile and break down more easily
109
What happens to the spleen in thalassaemia?
The spleen collects all the destroyed RBCs and swells, causing splenomegaly
110
What happens to the bone marrow in thalassaemia?
It expands to produce extra red blood cells for the chronic anaemia.
111
What does bone marrow expansion in thalassaemia cause?
Susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences
112
What are the potential signs and symptoms of thalassaemia?
```
Microcytic anaemia
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead/ cheekbones
```
113
How is thalassaemia diagnosed?
Full blood count--> Shows microcytic anaemia
Haemoglobin electrophoresis--> diagnoses globin abnormalities
DNA testing--> Looks for genetic abnormalities
(Pregnant women offered screening)
114
Why is important to monitor serum ferritin levels in thalassaemia?
Iron overload can occur
115
Why does iron overload occur in thalassaemia?
As a result of faulty creation of blood cells, recurrent transfusions and increased absorption of iron in response to anaemia.
116
What are the effects of iron overload?
```
Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis/ joint pain
```
117
How is iron overload managed?
Limit transfusions
| Iron chelation
118
What chromosome contains the gene that codes for alpha-globin chains?
Chromosome 16
119
What chromosome contains the gene that codes for beta-globin chains?
Chromosome 11
120
How is alpha-thalassaemia managed?
```
Monitor full blood count
Monitor complications
Blood transfusions
Splenectomy
Bone marrow transplant
```
121
What are the 3 types of beta-thalassaemia and what are they based on?
The defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in beta-globin at all. This leds to 3 types:
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
122
What is thalassaemia minor?
Carriers of abnormally functioning beta globin gene- have one abnormal and one normal gene.
Causes mild microcytic anaemia and does not usually require active treatment.
123
What is thalassaemia intermedia?
When patients have two abnormal copies of the beta-globin gene. Can either be two defective genes of one defective gene and one deletion gene.
Causes more significant microcytic anaemia and patients require monitoring and occasional blood transfusions.
124
What is thalassaemia major?
Patient sare homozygous for deletion genes. This means they have no functioning beta-globin genes at all. This usually presents with sever anaemia and failure to thrive in early shildhood.
125
What does thalassaemia major cause?
Severe microcytic anaemia
Splenomegaly
Bone deformities
126
What is sickle cell anaemia?
A genetic condition that causes sickle (crescent) shaped red blood cells which are more fragile and easy to destroy, leading to haemolytic anaemia
127
What happens to fetal haemogloin (HbF) at 6 weeks of age?
It is replaced by HbA
128
What kind of haemoglobin do sickle cell patients have and what does it cause?
Abnormal variant: HbS
| Causes RBCs to have an abnormal sickle shape
129
What causes sickle cell anaemia?
Autosomal recessive condition caused by an abnormal gene for beta-globin on chromosome 11.
130
What does having only one copy of the abnormal haemoglobin gene lead to?
Sickle-cell trait- usually asymptomatic.
131
What are the benefits of having sickle-cell trait
Reduces the severity of malaria.
132
How is sickle cell anaemia diagnosed?
- Pregnant women at risk of being carriers are offered testing during pregnancy.
- Newborn screening heel prick test at 5 days old.
133
What are the complications of sickle cell disease?
```
Anaemia
Increased risk of infection
Stroke
Avascular necrosis
Pulmonary hypertension
Painful and persistent penile erection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
```
134
How is sickle cell anaemia managed?
```
Avoid triggers of crises (e.g. dehydration)
Ensure vaccines are up to date
Antibiotic prophylaxis
Hydroxycarbamide
Blood transfusion for severe anaemia
Bone marrow transplant
```
135
What is the benefit of hydroxycarbamide in sickle cell anaemia treatment?
It can be used to stimulate the production of fetal haemoglobin (HbF)- HbF does not lead to sickling of RBCs so has a protective effect against sickle cell crises
136
What are sickle cell crises?
A range of acute crises linked to sickle cell disease
| that can range from mild to life threatening.
137
What are the main triggers of sickle cell crises?
```
Spontaneous
Infection
Dehydration
Cold
Significant life events
```
138
How are sickle cell crises managed?
No specific treatment, just support:
- Treat any infection
- Keep warm
- Keep well hydrated
- Simple analgesia
139
What are some examples of sickle cell crises?
Vaso-occlusive crisis
Splenic sequestration crisis
Aplastic crisis
Acute chest syndrome
140
What is a vaso-occlusive crisis?
Pain and fever caused by sickle cells clogging capillaries and causing distal ischaemia.
It can cause dehydration, raised haematocrit and priapism.
141
What is priapism and how is it treated?
Painful prolonged erection caused by blood being trapped in the penis.
Treated with aspiration of blood from the penis.
142
What is a splenic sequestration crisis?
When red blood cells block blood flow in the spleen, causing an acutely enlarged and painful spleen, severe anaemia and hypovolaemic shock.
143
How is splenic sequestration crisis treated?
Supportive management with blood transfusions and fluid resuscitation.
Splenectomy used in cases of recurrent crises.
144
What is an aplastic crisis?
When there is a temporary loss of the creation of new blood cells- usually resolves within a week
145
What triggers an aplastic crisis?
Infection with parvovirus B19.
146
What is acute chest syndrome?
Fever or respiratory symptoms with new infiltrates in chest X-ray, caused by sickling in the small blood vessels in the lungs.
147
What can cause acute chest syndrome?
Infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli)
148
How is acute chest syndrome managed
Antibiotics or antivirals to treat infection.
Blood transfusions
Incentive spirometry
Artifical ventilation.
149
What is laukaemia?
Cancer of a line of bone marrow stem cells.
150
How are leukaemias classified?
By how rapidly the progress (chronic or acute)
| By the cell line that is affected (myeloid or lymphoid)
151
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
152
What causes leukaemia?
A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell. This leads to suppression of production other cell lines, resulting in pancytopenia
153
What is pancytopenia?
Combination of low red blood cells (anaemia), low white blood cells (leukopenia) and low platelets (thrombocytopenia).
154
What are the progressive ages of the different leukaemias?
'ALL CeLLmates have CoMmon AMbitions'
- Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
- Over 55 – chronic lymphocytic leukaemia (CeLLmates)
- Over 65 – chronic myeloid leukaemia (CoMmon)
- Over 75 – acute myeloid leukaemia (AMbitions)
155
What are the typical features of leukeamia?
Non-specific:
- Fatigue
- Fever
- Failure to thrive
- Pallor
- Petechiae/ abnormal bruising
- Abnormal bleeding
- Lymphadenopathy
- Hepatosplenomegaly
156
What is petechiae?
Tiny purple, red or brown spots that appear on the skin as a result of bleeding. (non-blanching rash)
157
What causes bruising and petechiae?
Thrombocytopenia (low platelets)
158
What are the differential diagnosis of petechiae?
```
Leukaemia
Meningococcal septicaemia
Vasculitis
HSP
Idiopathic
Non-accidental injury (abuse)
```
159
How is leukaemia diagnosed?
```
Full blood count
Blood film
Lactase dehydrogenase blood test
Bone marrow biopsy
Chest X ray
Lymph node biopsy
Lumbar puncture
CT/ MRI/ PET scan
```
160
What are the different types of bone marrow biopsy?
Bone marrow aspiration--> Liquid sample full of cells taken from within bone marrow
Bone marrow trephine-->Solid core sample of bone marrow taken to assess cells and structure
Bone marrow biopsy--> Taken from iliac crest under local anaesthetic with a specialist needle.
161
What happens in acute lymphoblastic leukaemia?
When a malignant change in a lymphocyte precursor cell causes acute proliferation of a single line of lymphocyte (usually B), causing them to replace the other cell types being created leading to pancytopenia.
162
What is the epidemiology of acute lymphoblastic leukaemia?
Most common cancer in children and peaks around 2-4 years. Can also affect adults over 45.
Associated with Down's syndrome and Philadelphia chromosome translocation.
163
What would a blood film show in Acute Lymphoblastic Leukaemia?
Blast cells
164
What is the pathophysiology of Chronic Lymphocytic Leukaemia?
When there is a chronic proliferation of a single type of well differentiated lymphocyte (usually B).
165
What are the presentations of Chronic Lymphocytic Leukaemia?
```
Over 55
Often asymptomatic
Can present with:
-Infections
-Anaemia
-Bleeding
-Weight los.s.
-Warm autoimmune haemolytic anaemia.
```
166
What is Richter's transformation?
When Chronic Lymphocytic Leukaemia transforms into a high-grade lymphoma
167
What does a blood film show in Chronic Lymphocytic Leukaemia?
Smear or smudge cells- caused during the preperation of the film where aged or fragile white blood cells rupture and leave a smudge.
168
What are the three phases of Chronic Myeloid Leukaemia?
1. Chronic phase
2. Accelerated phase
3. Blast phase
169
What happens during the chronic phase of Chronic Myeloid Leukaemia?
Lasts around 5 years and is often asymptomatic/ diagnosed incidentally with raised white cell count.
170
What happens during the accelerated phase of Chronic Myeloid Leukaemia?
When the abnormal blast cells take up a high proprtion of cells in the bone marrow and blood (10-20%). Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
171
What happens in the blast phase of Chronic Myeloid Leukaemia?
Abnormal blast cells make up >30% of bone marrow and blood cells. Has sever symtpoms and pancytopenia. Is often fatal.
172
What genetic change is indicative of chronic myeloid leukaemia?
Philadelphia chromosome: Translocation of genes between chromosome 9 and 22 (t(9:22) translocation)
173
What is acute myeloid leukaemia?
Cancer of the myeloid cells- many different types with slightly different cytogenetic differences and presentations.
174
What can cause acute myeloid leukaemia?
Transformation from a myeloproliferative disorder (e.g. polycythaemia ruby era or myelofibrosis)
175
What will a blood film show in acute myeloid leukaemia?
High proportion of blast cells with Auer rods (rods inside the blast cell cytoplasms)
176
Which is the most common leukeamia in adults overall?
Chronic lymphocytic leukeamia
177
What is the most common acute adult leukaemia?
Acute myeloid leukaemia
178
How is leukaemia primarily treated?
With chemotherapy and steroids. Can also use radiotherapy, bone marrow transplant and surgery
179
What are the complications of chemotherapy?
- Failure
- Stunted growth/ development
- Infections due to immunodeficiency
- Neurotoxicity
- Infertility
- Secondary malignancy
- Cardiotoxicity
- Tumour lysis syndrome
180
What is tumour lysis syndrome?
Caused by the release of uric acid from cells that are destroyed in chemotherapy. Uric acid forms crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury.
181
What are lymphomas?
A group of cancers that affect the lymphocytes inside the lymphatic system., causing lymphadenopathy (abnormally large lymph nodes)
182
What are the two main categories of lymphoma?
Hodgkin's lymphoma
| Non-Hodgkin's lymphoma
183
What is Hodgkin's lymphoma?
Specific disease caused by proliferation of lymphocytes
184
What proportion of lymphomas are Hodgkin's and what is the age distribution?
1 in 5
| Bimodal age distribution (peaks around 20 and 75)
185
What are the risk factors for lymphoma?
HIV
Epstein-Barr Virus
Autoimmune conditions
Family history
186
What is the key presenting symptoms in Hodgkin's lymphomas?
Lymphadenopathy--> englarged lymph node that feel rubbery.
| May be painful when drinking alcohol
187
Where are the lymph nodes?
Neck, axilla and ingual region
188
What are the B symptoms of lymphoma?
Systemic symptoms: Fever, weight loss, night sweats
189
What are other symptoms of Hodgkin's lymphoma?
```
Fatigue
Itching
Cough
S.O.B
Abdominal pain
Recurrent infections
```
190
What investigations can be done to diagnose lymphoma?
Lactase dehydrogenase (LGH) bloofd test
Lymph node biopsy
CT/ MRI/ PET scan
191
What is the key lymph node biopsy finding in patients with Hodgkin's lymphoma?
Reed-Sternberg cell- abnormally large B cells that have multiple nuclei and nucleoli inside them. (owl-like appearance)
192
What is the Ann Arbor staging system?
Classifies lymphomas as to whether they are above or blow the diaphragm
193
What is a stage 1 lymphoma?
Confined to one region of lymph nodes
194
What is a stage 2 lymphoma?
In more than one region but on the same side of the diaphragm (either above or below)
195
What is a stage 3 lymphoma?
Affects lymph nodes both above and below the diaphragm
196
What is a stage 4 lymphoma?
Widespread involvement including non-lymphatic organs such as the lungs or liver
197
What are the key treatments of lymphoma?
Chemotherapy and radiotherapy
198
What is Non-Hodkins lymphoma?
Very large group of lymphomas including Burkitt, MALT and Diffuse large B cell lymphoma.
199
What are the risk factors for non-Hodgkin's lymphomas?
```
HIV
Epstein-Barr Virus
H. pylori
Hep. B or C
Exposure to pesticides or trichloroethylene
Family history
```
200
How are Hodgkin's and non-Hodgkin's lymphomas differentiated?
Lymph node bipsy
201
What is myeloma?
A cancer of the plasma cells.
202
What is the pathophysiology of myeloma?
Genetic mutation in a specific type of plasma cell, resulting in large quantities of a single type of antibody being produced.
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What is multiple myeloma?
Where the myeloma affects multiple areas of the body
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What is MGUS?
Monoclonal gammopathy of undetermined significance- An excess of a single type of antibody without other features of cancer/ myeloma
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What is a smouldering myeloma?
Where there is progression of MGUS with higher levels of antibodies or antibody components- premalignant and more likely to progress into myeloma.
206
What is Waldenstrom's macroglobulinemia?
A type of smouldering myeloma where there is excessive IgM specifically
207
What is the most likely antibody to be in excess in myeloma?
IgG 50% of the time. (monoclonal paraprotein)
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Why does myeloma lead to anaemia?
Cancerous plasma cells invade the bone marrow (infiltration), causing suppression of the development of other blood cell lines leading to anaemia, neutropenia and thrombocytopenia.
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What is myeloma bone disease?
When myeloma results in the abnormal breakdown of bone.
210
What causes myeloma bone disease
A result of increased osteoclast acitivty and suppressed osteoblast activity, resulting in the metabolism becoming imbalances and more bone being reabsorbed than constructed.
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What causes myeloma bone disease?
Cytokines released from plasma cells (and stromal cells when they are in contact with plasma cells)
212
Where are the most common places for myeloma bone disease to happen?
Skull, spine, long bones, ribs.
213
What are osteolytic lesions?
The areas of bone that become very thin due to myeloma bone disease and can lead to fractures
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What are plasmacytomas?
Individual tumours made up of cancerous plasma cells that can occur in the bones or soft tissue.
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What does myeloma cause?
Anaemia
Myeloma Bone disease
Myeloma renal disease
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Why do patients with myeloma get renal impairment?
- High levels of antibodies block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Medications used to treat it can be harmful
217
What is the normal plasma viscosity compared to water?
1.3-1.7 X that of water
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When does plasma viscosity increase?
When there are more proteins in the blood (e.g. immunoglobulins and fibrinogen)
219
What does raised plasma viscosity cause?
- Easy bruising
- Easy bleeding
- Reduced or loss of sight
- Purple discolouration of extremities
- Heart failure
220
4 features of myeloma- CRAB?
Calcium (elevated)
Renal failure
Anaemia
Bone lesions/ pain
221
What patients would you suspect myeloma in?
Over 60 with persistent bone pain, back pain or unexplained fractures
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What are the initial investigations into suspected myeloma?
FBC (low white cell count in myeloma)
Calcium (Raised in myeloma)
ESR (Raised in myeloma)
Plasma viscosity (Raised in myeloma)
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What tests would be done if and of the initial myeloma investigations were positive?
An urgent serum protein electrophoresis and urine Bence-Jones protein test.
```
(BLIP:
Bence-Jones protein test
L- serum-free Light chain assay
I- Serum Immunoglobulins
P- Serum Protein electrophoresis)
```
Bone Marrow biopsy
Imagine
224
What would be found on an X-ray of a myeloma patient?
Punched out lesions
Lytic lesions
Raindrop skill
225
What are the aims of the management of myeloma?
To control the disease and improve quality of life
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What is the first line treatment of myeloma?
Combination of chemotherapy with:
| Bortezomid, Thalidomise or Dexamethasone
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How is myeloma bone disease managed?
- Bisphosphates: suppress osteoclast activity
- Radiotherapy to bone lesions
- Orthopaedic surgery can stabilise bones
- Cement augmentation- injecting cement into fractures/ lesions to improve stability
228
What are myeloproliferative disorders?
Type of bone marrow cancer that consists of a group of conditions that occur due to uncrontrolled proliferation of a single type of stem cell.
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What are the three main myeloproliferative disorders?
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
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What is stem cell line mutation causes primary myelofibrosis?
Hematopoietic stem cells
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What is stem cell line mutation causes Polycythaemia vera?
Erythroid cells
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What is stem cell line mutation causes essential thrombocythaemia?
Megakaryocytes
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What can myeloproliferative disorders progress/ transform into?
Acute myeloid leukaemia
234
What mutations are myeloproliferative disorders associated with?
JAK2 *
MPL
CALR
235
What is myelofribrosis?
Where proliferation of the cell line leads to fibrosis of the bone marrow- it is replaced by scar tissue
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Why does myelofibrosis occur?
As a response to cytokines that are released from proliferating mutated stem cells. (e.g. Fibroblast growth factor)
237
What does myelofibrosis cause?
- Affects the production of blood cells, leading to anaemia and leukopenia
- Haematopoiesis starts to happen in other areas such as the liver and spleen, causing hepato and splenomegaly and portal hypertension
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What are the main systemic presentations of myeloproliferative disorders?
Fatigue
Weight loss
Night sweats
Fever
239
What signs and symptoms might there by in myeloproliferative disorders?
- Anaemia
- Splenomegaly/ Hepatomegaly
- Portal hypertension
- Low platelets
- Thrombosis
- Raised RBCs
- Low white blood cells
240
What are the three common signs of polycythaemia vera?
Conjunctival plethora (excessive redness to eyes)
Ruddy complexion
Splenomegaly
241
What is the test of choice to diagnose myeloproliferative disorders?
Bone marrow biopsy (dry bone marrow aspiration)
242
How is primary myelofibrosis managed?
- May just be monitored
- Allogenic stem cell transplantation
- Chemotherapy
- Supportive management of associated conditions (e.g. anaemia, splenomegaly)
243
How is polycystaemia vera managed?
Venesection (keeps haemoglobin in normal range)
Aspirin
Chemotherapy
244
How is essential thrombocythaemia managed?
Aspirin
| Chemotherapy
245
What is myelodysplastic syndrome?
Group of symptoms caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
246
What is thrombocytopenia?
A low platelet count ( <150 X 10^9/L)
247
What are the main causes of thrombocytopenia due to problems with production?
```
Sepsis
B12 or folic acid deficiency
Liver failure (causes reduced thrombopoietin production)
Leukaemia
Myelodysplastic syndrome
```
248
What are the main causes of thrombocytopenia due to problems with destruction?
```
Medications
Alcohol
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Heparin-induced thrombocytopenia
Haemolytic-uraemic syndrome
```
249
How does mild thrombocytopenia present?
Asymptomatic- found incidentally on FBC
250
How do platelet counts below 50 x 10^9/L present?
Easy/ spontaneous bruising and prolonged bleeding times (e.g. nosebleeds, bleeding gums, heavy periods, easy bruising, blood in urine or stools)
251
How do platelet counts below 10 x 10^9/L present?
High risk for spontaneous bleeding (e.g. intracranial haemorrhage or GI bleeds)
252
What are some differential diagnoses of abnormal/ prolonged bleeding?
Thrombocytopenia (low platelets)
Haemophilia A and haemophilia B
Von Willebrand Disease
Disseminated intravascular coagulation (usually secondary to sepsis)
253
What is purpura?
Purple blood spots/ skin hemorrhages.
254
What is immune thrombocytopenic purpura (/autoimmune/ idiopathic/ primary TP)?
Condition where antibodies are created against platelets, causing an immune response against them and resulting in their destruction
255
How can Immun thrombocytopenic purpura be managed?
Steroids (prednisolone)
IV immunoglobulins
Monoclonal antibodies (Rituximab)
Splenectomy
256
What is thrombotic thrombocytopenic purpura?
Condition where tiny blood clots develop throughout the small vessels of the body, using up platelets and causing thrombocytopaenia.
257
Why does microangiopathy occur in thrombotic thrombocytopenic purpura?
Blood clots develop due to a shortage of ADAMTS13 protein which normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation.
258
What is Heparin induced thrombocytopenia?
The development of antibodies against platelets in response to exposure to heparin.
259
What is Von Willebrand Disease?
The most common inherited cause of abnormal bleeding.
260
What causes Von Willebrand disease?
Genetic (autosomal dominant) causes cause a deficiency, absence or malfunctioning of von Willebrand factor.
261
What is von Willebrand factor?
A blood glycoprotein involved in hemostasis.
262
What are the key presentations of von Willebrand disease?
```
History of easy, prolonged or heavy bleeding:
Bleeding gums
Nose bleeds
Heavy menstrual bleeding
Family history of VWD
```
263
How is von Willebrand disease diagnosed?
Based on a history of anbormal bleeding, family history, bleeding assessment and lab investigations
264
Why is there no easy definitive von Willebrand disease investigation?
Wide range of genetic causes
265
How and when is von Willebrand disease managed?
Only needs managing in response to major bleeding or trauma or in preparation for operations:
Desmopressin
VWF
Factor VIII
266
What is haemophilia?
Inherited severe bleeding disorders
267
What is Haemophilia A caused by?
A deficiency in factor VIII
268
What is Haemophilia B caused by?
Deficiency in factor IX
269
What type of inheritance pattern is haemophilia and therefore who does it affect?
```
X linked recessive
Mostly men (as they only have one X chromosome)
```
270
What are patients with haemophilia at risk of?
Excessive bleeding in response to minor trauma
| Spontaneous haemorrhage without traume
271
How can haemophilia present in neonates?
Intracranial haemorrhage
Haematomas
Cord bleeding
272
What are the main presentations of haemophilia?
```
Spontaneous bleeding into joints (haeemoathrosis)
Spontaneous bleeding into muscles
Abnormal bleeding in:
-Gums
-GI tract
-Urinary tract
-Retroperitoneal space
-Intracranial
```
273
How is haemophilia diagnosed?
Based on bleeding scores, coagulation factor assays and genetic testing
274
How is haemophilia managed?
Affected clotting factors (VIII or IX) replaced by IV infusion.
Treatment of acute bleeding episodes.
275
What is venous thromboembolism?
Common condition where blood clots (thrombosis) develop in the circulation
276
Why does venous thromboembolis occur?
Secondary to stagnation of blood and hyper-coagulable states
277
What is it called when a thrombosis develops in the venous circulation?
Deep vein thrombosis
278
What is the key concern in venous thromboembolism?
That the thrombus will embolise and travel to the right side of heart/ lungs and become a pulmonary embolism.
279
What are the risk factors for DVT?
```
Immobility
Recent surgery
Long haul flights
Pregnancy
Hormone therapy with oestrogen
Malignancy
Polycythaemia
Systemic lupus
Thrombophilia
```
280
What are thrombophilias?
Conditions that predispose patients to develop blood clots. e.g.:
Antiphospholipid syndrome, Antithrombin deficiency e.t.c.
281
What should every patient admitted to hospital be assessed for and what should they recieve?
Should be assessed for their risk of VTE and receive prophylaxis if they are at increased risk/
282
How does DVT present?
```
Unilateral calf/ leg swelling
Dilated superficial veins
Tenderness over site
Oedema
Colour change to leg
```
283
What is the Wells score?
Test to predict the risk of a patient presenting with symptoms having a DVT or pulmonary embolism, accounting for risk factors such as recent surgery and clinical findings.
284
How is DVT diagnosed?
D-dimer blood test.
| Ultrasound doppler of leg
285
What is the initial management of DVT?
Low molecular weight heparin (anticoagulant)
| Should be started before confirming diagnosis.
286
What are options for longer term anticoagulant to treat DVT?
Warfarin
NOAC/ DOACs
LMWH
287
How long should anticoagulation be continued for?
3 months if obvious reversible cause
> 3 months if cause unclear, recurrent VTE or irreversible cause (thrombophilia0
6 months in active cancer
288
What are inferior vena cava filters?
Devices inserted into the inferior vena cava to filter our blood clots travelling from the venous system to the heart and lungs.
289
What is polycythaemia?
An increase in red blood cell mass, making blood thicker and less able to travel through blood vessels and organs.
290
What is absolute Polycythaemia and what are the two types?
Caused by an increase in RBC mass.
Primary: Abnormality in bone marrow cells that produce RBCs
Secondary: Underlying condition causes more erythropoietin to be produced, stimulating excess RBC production
291
What is the main cause of primary absolute polycythaemia?
polycythaemia vera
292
What are the main causes of secondary polycythaemia?
COPD, Sleep apnoea, kidney disease, high altitude (hypoxia or inapprotiately high erythropoietin secretion)
293
What is relative polycythaemia and what causes it?
When there is a normal RBC mass but decreased plasma volume. Caused by apparent polycythaemia and dehydration
294
What are the main causes of apparent polycythaemia?
Obesity, smoking, excess alcohol intake, certain medicines
295
What treatments can be used for polycythaemia?
```
Venesection
Chemotherapy to slow production of RBCs
Medicines to prevent blood clots
Treat underlying cause
Lifestyle changes to prevent clots
```
296
What are the main complications of polycythaemia vera?
Thrombosis (pulmonary embolisms, DVT) and haemorrhage
297
What is polycythaemia vera?
When an acquired mutation in the JAK2 gene causes bone marrow cells to produce too many RBCs.
298
What hormone is in control of platelet production and where is it released from?
Thrombopoietin
| Liver (and kidneys)
299
What are the main reasons for platelet dysfunction?
Reduced platelet number--> Decrease in production of increase in destruction
Normal numbers but reduced function--> Congenital abnormality, Medication, von Willebrand disease, uraemia.
300
What is thrombocytopenia?
Deficiency of platelets in blood.
