Haematology Flashcards
1
Q
What is a myeloma?
A
A malignant proliferation of the Plasma cells (Type of B lymphocytes)
2
Q
Define multiple myeloma (MM)?
A
Malignant proliferation of plasma cells (B lymphocytes) accumulating in the bone marrow that affects multiple areas of the body
3
Q
What is the second most common haematological cancer?
A
Multiple Myeloma
4
Q
What is the pathogenesis of Multiple Myeloma?
A
Malignant proliferation of plasma cells (B lymphocytes) accumulating in the bone marrow
This leads to overproduction of Ig or Ig fragment (paraprotein)
Causes dysfunction of many organs (especially the kidney), bone marrow failure, destructive bone disease and hypercalcaemia
Characterised by excess secretion of a monoclonal antibody
5
Q
What is a paraprotein?
A
Paraprotein → abnormal immunoglobulins produced by clonal plasma cells
They can be intact immunoglobulins (usually IgG, IgA or IgM) or parts of immunoglobulins (usually light chains, very rarely heavy chains)
6
Q
What are the main paraproteins produced in multiple myeloma?
A
Typically excess production of 1 specific type of Ig.
55% are IgG
20% are IgA.
7
Q
What are the preceding steps before established multiple myeloma?
A
Development of monoclonal gammopathy of undetermined significance (MGUS)
Smouldering myeloma
8
Q
What is Monoclonal Gammopathy of Undetermined significance (MGUS)?
A
where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.
This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear.
May progress to MM and patients are often routinely monitored.
9
Q
What is Smouldering Myeloma?
A
where there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS
10
Q
What is Waldenstrom’s macroglobulinemia
A
Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
11
Q
What is the rate of progression of MGUS to MM?
A
1% per year
12
Q
What is the clinical presentation of multiple myeloma related to?
A
Infiltration of plasma cells
Secretion of monoclonal antibodies
13
Q
What are the Risk Factors of Multiple Myeloma?
A
Older age
Male
Black African ethnicity
Family history
Obesity
14
Q
Give some symptoms of Myeloma?
A
Tiredness
Bone/back pain
Infections
15
Q
What are the signs and symptoms of multiple myeloma?
A
OLD CRAB:
Old - 70+
C - Hypercalcaemia (& associated symptoms)
R - Renal Failure (hypercalcaemia causes calcium oxalate renal stones and immunoglobulin light chain kappa deposition is nephrotoxic)
A - Anaemia (Bone Marrow Infiltration causing; Neutropenia (infections), Thrombocytopenia (bleeding)
B - Bone Lesions - Pepperpot Skull
16
Q
How does bone disease arise in multiple myeloma?
A
Proliferation in bone marrow
Lytic lesions
Fractures
17
Q
How does impaired renal function arise in multiple myeloma?
A
Kappa Immunoglobulin light chains (Bence Jones Protein) are nephrotoxic.
& Hypercalcaemia
18
Q
Why may Renal disease worsen the effects of Anaemia in MM?
A
Renal disease can lead to EPO deficiency contributing to the anaemia
19
Q
How does hypercalcaemia arise in multiple myeolma?
A
Multiple myeloma-induced bone demineralisation and bone resorption
20
Q
How does recurrent/persistent bacterial infection arise in multiple myeloma?
A
Immune dysfunction and hypogammaglobulinemia
Suppression of normal plasma cell function
21
Q
Why does anaemia occur in multiple myeloma?
A
The cancerous plasma cells invade the bone marrow.
This is described as bone marrow infiltration.
This causes suppression of the development of other blood cell lines leading to:
Anaemia (low red cells),
Neutropenia (low neutrophils)
Thrombocytopenia (low platelets).
22
Q
What initial diagnostic investigations are ordered in someone with suspected multiple myeloma?
A
BLIP:
B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis
23
Q
What Investigations are needed to confirm a diagnosis of Multiple Myeloma?
A
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease.
>10% plasma cells
Imaging is required to assess for bone lesions. The order of preference to establish this is:
Whole body MRI
Whole body CT
XR - Skull for pepperpot lesions
24
Q
What is indicative of MM on bone marrow biopsy?
A
> 10% plasma cells
25
What bloods results would be indicative of multiple myeloma?
FBC - marrow failure
ESR - raise
Blood film - Rouleaux formation (RBC Aggregations)
U&Es - raised urea and creatinine
Hypercalcaemia
26
What are some important differential diagnoses of Multiple Myeloma?
MGUS
27
What is the treatment for MGUS and asymptomatic myeloma?
Watch and wait.
28
What is the principle behind treatment of MM?
Multiple myeloma is an incurable condition → treatment aims to increase periods of disease remission
29
What is the first line treatment for multiple myeloma?
A combination of chemotherapy with:
Bortezomid - proteasome inhibitor
Thalidomide
Dexamethasone - steroid
30
What else may you consider to treat multiple myeloma?
Stem cell transplant
Bisphosphonates - bone protection
31
Name the 3 broad categories of red cell disorders.
1. Haemoglobinopathies.
2. Membranopathies.
3. Enzymopathies.
32
What is a haemoglobinopathy?
Deficiency related to quality or quantity of haemoglobin production
33
What is a membranopathy?
Deficiency related to red blood cell membrane protein
34
What is an enzymopathy?
Deficiency related to RBC enzyme synthesis, leads to shortened lifespan due to oxidative stress
35
What is the normal range for haemoglobin?
120-180g/L
36
What is normal adult haemoglobin made of?
HbA1:
2 alpha and 2 beta chains.
37
What is foetal haemoglobin made of?
HbF:
2 alpha and 2 gamma chains.
38
What is haemoglobin S?
Haemoglobin S is a variant of Hb arising from a point mutation in the beta globin gene.
The mutation leads to a single amino acid change, valine -> glutamine.
39
What is sickle cell disease?
Auto recessive disorder
A Hb disorder of quality; polymerisation of HbS results in characteristic sickle shaped RBCs
40
What are the types of Sickle Cell disease based on Inheritance?
- Sickle cell anaemia (HbSS) = inheritance of 2 abnormal sickle genes
- Sickle cell disease (HbSC) = Inheritance of one abnormal sickle gene and second haemoglobin variant of the beta chain that causes sickling. E.g. haemoglobin C
- Sickle cell trait (HbS) = Inheritance of one abnormal sickle gene. Sickle carrier.
- Sickle-thalassaemia (H
41
What is the lifespan of a Sickle Cell?
5-10 days - described as haemolytic
42
What is the Pathophysiology of Sickle Cell Anaemia?
- HbS will polymerise at periods of hypoxia and acidosis
- Sickling is precipitated by low oxygen, dehydration, infection, cold exposure and acidosis
- This leads to vaso-occlusion and significantly shortens the life span of an RBC to 10-20 days
- This is due to chronic haemolysis
43
What can precipitate sickling in Sickle Cell Anaemia?
Trauma
Cold
Stress
Exercise
44
Why does Sickle Cell Anaemia not present until after 6 months of age?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
Prior to 6 months of age the body still produces HbF
45
What are reticulocytes?
Immature RBCs that still have RNA material.
Their percentage increases in haemolytic anaemia
46
What effect does Sickle Cell Anaemia on reticulocyte count?
Raised - 2-3% (normally 0.45-1.8%)
47
Why is reticulocyte count raised in Sickle Cell Anaemia?
Sickle cell disease is haemolytic - increased degradation of RBC's
48
What is the pathogenesis of sickle cell disease?
Point mutation in the Beta globin gene (GAG to GTG) swapping valine for glutamic acid.
This causes irreversible RBC sickling which makes the RBC fragile.
A decreased surface area also means the RBCs are less efficient.
49
What are the symptoms of Sickle Cell disease?
Jaundice - haemolytic anaemia releasing bilirubin
+ complications of anaemia
50
Give 4 acute complications of sickle cell disease.
1. Vaso-occlusive painful Crisis
2. Stroke in children.
3. Splenic Sequestration crisis - blocked blood flow to spleen
4. Infections - due to hyposlenysm
51
Give 3 chronic complications of sickle cell disease.
1. Renal impairment.
2. Pulmonary hypertension.
3. Joint damage.
52
What are some complications of Sickle cell disease?
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
53
What is Vaso-occlusive Crisis (AKA painful crisis) in sickle cell disease?
Sickle shaped blood cells clogging capillaries causing distal ischaemia.
It is associated with dehydration and raised haematocrit.
Symptoms are typically pain, fever and those of the triggering infection.
54
What is Splenic Sequestration Crisis?
Red blood cells blocking blood flow within the spleen.
This causes an acutely enlarged and painful spleen.
The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).
55
What is the significance of parvovirus for someone with sickle cell disease?
Common infection in children (URTI), leading to decreased RBC production
56
What is the diagnostic test for Sickle cell disease?
Newborn screening - heel prick test
FBC + blood film - increased reticulocytes, sickled RBCs, Howell Jolly bodies
Hb Electrophoresis - diagnostic.
57
What are the treatments of acute complicated attacks in sickle cell disease?
IV fluids
Analgesia (NSAIDs)
O2
58
What are the long term treatments for sickle cell disease?
Avoid Dehydration
Hydroxycarbamide - stimulates HbF production
Blood transfusion
Bone marrow transplant
59
What is the relationship between Sickle cell disease and Malaria?
Having one copy of the sickle cell gene reduces the severity of malaria and is protective.
There is a high proportion of the population in Africa & other malaria associated areas with at least one sickle cell gene.
60
What is thalassaemia?
An autosomal recessive disorder of haemoglobin quantity.
There is reduced synthesis of one or more globin chains with leading to a reduction in Hb -> anaemia.
Degree of anaemia depends on the type of mutation
Px with defects in Alpha chains have alpha Thalassaemia
Px with defects in Beta chains have beta Thalassaemia
61
If someone has beta thalassaemia do they have more alpha or beta globin chains?
They have very few beta chains, alpha chains are in excess.
62
Which is more common, alpha or beta thalassaemia?
Beta thalassaemia is more common
63
What are some potential signs and symptoms of Thalassaemia?
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
64
Why do you get splenomegaly in thalassaemia?
RBCs in thalassaemia are more fragile and break down easily.
In thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in splenomegaly.
65
What are mutations that result in alpha Thalassaemia?
4 genes on chromosome 16
Deletion mutations
66
What is produced in alpha thalassaemia as a result of the decreased alpha chains?
Excess beta chains form an unstable beta tetramer (HbH)
This is a poor carrier of O2
67
Where is alpha thalassaemia most prevalent?
- Sub-Saharan Africa
- Middle East
- Mediterranian
- Areas of Asia
68
What are mutations that result in Beta Thalassaemia?
2 genes on chromosome 11
Can have abnormal functional genes or deletion genes that are non functional resulting in different types of Beta Thalassaemia
69
What are the 3 types of Beta Thalassaemia?
Thalassaemia Minor
Thalassaemia Intermedia
Thalassaemia Major
70
What is Thalassaemia Minor?
One abnormal and One functional beta globin gene
Causes mild microcytic anaemia
71
What is Thalassaemia Intermedia?
Either:
2 defective beta globin genes - retain some function
OR
1 defective and 1 deletion gene
Causes a more significant microcytic anaemia
72
What is Thalassaemia Major?
Px with Homozygous Beta globin deletion genes.
No functioning beta globin genes
Causes severe anaemia and failure to thrive.
73
What is the diagnosis of Thalassaemia?
FBC - MCV = shows microcytic anaemia
Haemoglobin Electrophoresis - diagnoses Globin abnormalities
DNA Testing - determine genetic abnormality
74
Why is Iron overload an issue in Thalassaemia?
Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
75
How is Iron overload in Thalassaemia managed?
Monitored Serum Ferritin levels
Limiting transfusions
Iron Chelation
76
What is the key clinical symptom of Beta Thalassaemia?
Chipmunk Face - due to enlarged forehead and cheekbones due to decreased RBCs and extramedullary haematopoiesis
77
What is the treatment for Thalassaemia?
Regular Blood transfusions
Iron Chelation - prevent Iron overload
Splenectomy
Folate supplements
Bone marrow stem cell transplant
78
What is a potential Curative option for thalassaemia?
Bone marrow stem cell transplant
79
Describe the inheritance pattern for Membranopathies
Autosomal dominant
80
Name two most common Membranopathies
Spherocytosis (horizontal) - more severe, present neonatal jaundice and haemolysis
Elliptocytosis (vertical)
81
Describe the pathophysiology of Membranopathies
Deficiency of red cell membrane proteins caused by genetic lesions; haemolytic anaemia.
82
What are the common clinical features of Membranopathies?
Jaundice
Anaemia
Splenomegaly
83
What is Hereditary Spherocytosis?
Deficiency in structural membrane protein Spectrin
Makes RBCs more spherical and rigid
Causes Splenomegaly
84
What are the symptoms of Hereditary Spherocytosis?
General Anaemia
Neonatal Jaundice
Splenomegaly
50% have Gallstones
85
What is the diagnosis of Hereditary Spherocytosis?
Direct Coombs Negative (positive = Autoimmune Haemolytic Anaemia)
FBC and blood film:
Normocytic Normochromic
Increased Reticulocytes
Spherocytes
86
What is the treatment for Hereditary Spherocytosis?
Splenectomy
Neonatal Jaundice - Phototheraphy
87
Name a common Enzymopathy.
G6PD deficiency
88
What is G6PD Deficiency?
X linked recessive enzymopathy causing 1/2 RBC lifespan and RBC degradation
89
Why does a deficiency in glucose-6-phosphate dehydrogenase lead to shortened red cell lifespan?
G6PD is required for glutathione synthesis
Glutathione protects Red blood cells against oxidative damage
90
How does G6PD deficiency present?
Mostly asymptomatic unless precipitated.
May have haemolysis leading to anaemia and jaundice
91
What is the diagnostic investigations for G6PD Deficiency?
Reduced G6PD levels
Blood film:
Normal in between attacks
Attack - increased reticulocytes and HEINZ bodies and BITE cells
92
What is the treatment for GP6D Deficiency?
Avoid Precipitants - Oxidative drugs
Blood transfusions when attacks come on.
93
What precipitants can lead to attacks of GP6D Deficiency?
Naphthalene
Anti-malarials
Aspirin
FAVA beans
Nitrofurantoin
94
What are lymphomas?
Disorders (cancers) caused by malignant proliferation of lymphocytes inside the lymphatic system.
These cancerous cells accumulate in the lymph nodes causing lymphadenopathy
95
What are the two main categories of lymphoma?
Hodgkin's Lymphoma - a specific disease
Non-Hodgkin's Lymphoma - encompasses all other lymphomas
96
What are the main Lymph node sites?
Cervical Lymph Nodes
Axillary Lymph Nodes
Inguinal Lymph Nodes
97
What are some Potential causes of Lymphoma?
Primary Immunodeficiency - Ataxia Telangiectasia
Secondary Immunodeficiency - HIV, Transplant recipients
Infection - EBV, HIV, HTL virus, H-pylori
Autoimmune disorders - SLE
98
What is the pathophysiology of Lymphoma?
Not well understood
Thought to be multifactorial - Genetic factors + Environment
Impaired Immunosurveillance
Infected B cells escape regulation and proliferate
99
What is Hodgkin's Lymphoma?
Cancerous Proliferation of Lymphocytes
Bimodal age distribution - affects teens (13-19) and elderly (75+)
Associated with EBV infection
100
What are the 2 types of Hodgkin's Lymphoma?
Classical - Reed Sternberg cells with mirror-Image nuclei
Nodular Lymphocyte Predominates Hodgkin's Lymphoma (NLPL) - Reed Sternberg cell variant - Popcorn cell
101
What are the risk factors for Hodgkin's Lymphoma?
HIV
Epstein-Barr Virus
Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
Family history - affected sibling
102
How does Hodgkin's Lymphoma normally Present?
Lymphadenopathy - non-tender, feel rubbery
Pain in lymph nodes when drinking alcohol.
B symptoms - Fever, Weight loss, Night sweats
103
What are the B Symptoms associated with Lymphoma/other haematological disorders?
Fever
Weight Loss >10% in 6 months
Night Sweats
104
What other symptoms may be associated with Hodgkin's Lymphoma?
Fatigue
Pruritus' (itching)
cough
SOB
Abdominal Pain
Recurrent infections
105
What are the diagnostic investigations for Hodgkin's Lymphoma?
Lymph Node Biopsy - Reed Sternberg cell positive with mirror image nuclei
Lactate Dehydrogenase - Often raised by not specific to Hodgkin's
Decreased Hb, Increased ESR - indicates worse prognosis
CT/MRI - Fir staging and diagnostics
106
What type of Biopsy is done to Diagnose Lymphoma?
Core Needle Biopsy
Lymph Node Excision
107
What are Reed Sternberg cells?
Abnormally large B cells with multiple nuclei that are the key finding on lymph node biopsy in Hodgkin's Lymphoma.
108
What is the Ann Arbor Staging system?
Used for Staging Hodgkin's and Non-Hodgkin's Lymphoma
Stage 1 - Single Lymph node region
Stage 2 - In more than 1 lymph node region but same side of the diaphragm
Stage 3 - Lymph nodes both above and below Diaphragm affected
Stage 4 - Widespread involvement including other non-lymphatic organs (lungs/liver)
A = NO B symptoms
B = HAS B symptoms
109
What other organs may be affected in Stage 4 Hodgkin's Lymphoma?
Blood
Bone Marrow
Liver
Spleen
110
What is used to stage lymphomas using the Ann Arbor staging system?
CT/MRI/PET scans
111
What is the Treatment for Hodgkin's Lymphoma?
ABVD Chemotherapy:
Adriamycin
Bleomycin
Viricistine
Dacarbazine
(Potentially Radiotherapy)
112
What are the different courses of treatment for Hodgkin's Lymphoma?
Stage IA - IIA (< 3 areas involved):
Short course ABVD
Stage IIA - IVB (> 3 areas involved):
Longer courses of ABVD
113
What is the Aim of Treatment for Hodgkin's Lymphoma?
To cure the condition
Usually successful however there is a risk of relapse and SE of treatment.
114
What are some side effects of Hodgkin's Lymphoma Treatment?
Chemotherapy:
Alopecia
N+V
Myelosuppression & BM failure = Infection
Radiotherapy - Increased risk of second malignancies
115
What is Febrile Neutropenia?
A condition marked by Fever and very low neutrophil numbers in the blood.
Massive risk in Px who have had recent/High dose Chemo (or on Carbimazole)
116
What is the treatment for Febrile Neutropenia?
Immediate Broad Spec Antibiotics
(Amoxicillin + Fluoroquinolone)
117
What is Non-Hodgkin's Lymphoma?
All lymphomas without Reed Sternberg cells.
80% are B cell origin and 20% T cell origin.
118
Give some Key Non-Hodgkin's Lymphomas
Low Grade - Follicular
High Grade - Diffuse Large B cell Lymphoma
Very high Grade - Burkitt Lymphoma
119
What are the risk factors of Non-Hodgkin's Lymphoma?
HIV
Epstein-Barr Virus
H. pylori (MALT lymphoma)
Hepatitis B or C infection
Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes
Family history
120
What are some Specific Symptoms of Burkitt Lymphoma?
Linked to EBV infection.
Causes Massive Jaw Lymphadenopathy in children
121
What are the symptoms of Non-Hodgkin's Lymphoma?
Variable symptoms due to the range of subtypes however Px generally present in a similar way to Hodgkin's Lymphoma:
Painless Rubbery Lymphadenopathy
B Symptoms
Lymph nodes NOT Painful with Alcohol.
122
What are the Diagnostic tests for Non-Hodgkins Lymphoma?
Lymph Node Biopsy - No RS/Popcorn Cells confirms NHL lymphoma
CT/MRI for Ann Arbor Staging
123
What is the Treatment for Non-Hodgkin's Lymphoma?
R-CHOP:
Rituximab - Targets CD20 on B cells
Cyclophosphamide
Hydroxy-Daunorubicin
Vincristine (Oricovin)
Prednisolone
+ radiotherapy
124
Describe the prognosis of low-grade Non-Hodgkin's Lymphoma
Slow growing, advanced at presentation, incurable
Median survival; 10 years
125
Describe the prognosis of high-grade Non-Hodgkins Lymphoma
Nodal presentation; presents early than low grade, therefore often curable
Aggressive - can make patient very unwell.
126
How does the treatment for low and high-grade Non-Hodgkins Lymphoma, differ?
In general, if the patient is symptomless - watch and wait.
Low grade; no chemotherapy may be required - radiotherapy may be curative in localised disease.
If symptomatic, radiotherapy, combination chemotherapy and mAb
127
How does the treatment differ between High grade Non-Hodgkin's lymphoma that is detected early and late?
Early - 3 months of RCHOP with radiotherapy
Late - 6 months of RCHOP with Radiotherapy
128
What is Myelodysplastic Syndrome?
Myelodysplastic syndrome is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
There are a number of specific types of myelodysplastic syndrome.
129
What happens to the blood cell maturation in Myelodysplastic Syndrome?
Causes low levels of blood components that originate from the myeloid cell line:
Anaemia - Low RBC
Neutropenia - Low neutrophils
Thrombocytopenia - Low platelets
130
What do patients have an increased risk of developing if they have Myelodysplastic Syndrome?
Acute Myeloid Leukaemia (AML)
131
How does Myelodysplastic Syndrome Present?
May be Asymptomatic and the diagnosis is made incidentally
May present with symptoms of:
Anaemia - fatigue, pallor, SOB
Neutropenia - Recurrent/severe infections
Thrombocytopenia - Bleeding/bruising
132
What are the diagnostic investigations for Myelodysplastic syndrome?
FBC - Low RBC, Neutrophils, Platelets
Blood Film - Blasts present (immature myeloid derived progenitors)
Bone marrow aspiration biopsy
133
What is the management of Myelodysplastic Syndrome?
Watchful Waiting
Supportive Treatment with blood transfusions if severely anaemic
Chemotherapy
Stem Cell Transplant
134
Define Leukaemia?
The malignant Proliferation (Cancer) of a particular line of haematopoietic stem cells in the bone marrow. This causes unregulated production of certain types of blood cells.
135
What is the pathophysiology of Leukaemia?
A genetic mutation in one of the precursor cells (myeloblast or lymphoblast) in the bone marrow leads to excessive production of a single type of abnormal white blood cell.
This can lead to suppression of other cell lines causing underproduction of those types.
This causes Pancytopenia - Combination of anaemia, leukopenia and thrombocytopenia
136
Why is there suppression of other cell lines in leukaemia?
Rapid proliferation of one leukocyte takes up lots of space in the bone marrow.
This leaves less space for functioning cells to be produced.
137
What are the 4 main types of leukaemia?
Acute Myeloid Leukaemia (AML)
Acute Lymphoblastic Leukaemia (ALL)
Chronic Myeloid Leukaemia (CML)
Chronic Lymphoblastic Leukaemia (CLL)
138
What age ranges are at increased risk of the different types of leukaemia?
Mnemonic: ALL CeLL mates have CoMmon AMbitions
under 5 and over 45 - ALL
Over 55 - CLL
Over 65 - CML
Over 75 - AML
139
What age group does ALL commonly affect?
children under 5
140
What clinical symptoms are associated with Leukaemia?
Fatigue - anaemia
Fever + infections
Failure to thrive (children)
Pallor due to anaemia
Petechiae and abnormal bruising due to thrombocytopenia
Abnormal bleeding - thrombocytopenia
Lymphadenopathy
Hepatosplenomegaly
141
What is the presentation of leukaemia?
Quite non specific.
Symptoms are associated with affects of pancyotpenia
142
AML arises from abnormalities in which type of cell?
Common myeloid progenitor cells → abnormal myeloblasts
143
ALL arises from abnormalities in which type of cell?
Common lymphoid progenitor cells → abnormal lymphoblasts
144
CLL arises from abnormalities in which type of cell?
Mature B-lymphocyte
145
CML arises from abnormalities in which type of cell?
Basophils, neutrophils and eosinophils
146
CMML arises from abnormalities in which type of cell?
Mature moncytes
147
What may be the white cell counts for some of the different types of leukaemia?
Symptomatically high WCC
- >100x10^9/L for AML
- >200x10^9/L for ALL
- >400x10^9/L for CML
148
What diagnostic investigations are used in leukaemia?
FBC - Pancytopenia
Blood film - abnormal cells/inclusions
Lactate Dehydrogenase - often raised by non-specific
Bone Marrow Biopsy - Diagnostic
CXR - lymphadenopathy
CT/MRI for staging of lymphomas/other tumours
149
What are the different types of Bone marrow biopsy that may be used to diagnose leukaemias?
Bone Marrow Aspiration - liquid sample of cells
Bone Marrow Trephine - solid core of bone marrow
Bone marrow Biopsy - uses a specialist needle
150
What is Acute Myeloid Leukaemia (AML)?
Neoplastic myeloblast proliferation
Most common acute leukaemia in adults and most commonly affects over 75 yrs.
151
What are the genetics of AML?
t(15:17)
Association with Downs and Radiation
152
What is the progression of AML like?
Rapid progression
If not Tx ASAP then 3 year survival =20%
153
What are the symptoms of AML?
General Sx of Leukaemia
Gum Infiltration
154
What is the Diagnosis of AML?
FBC - Pancytopenia
Blood Film - High proportion of blast cells, Myeloperoxidase
AUER RODS (myeloperoxidase cytoplasmic aggregates in neutrophils)
BM Biopsy - > 20% myeloid Blast cells
155
What are Auer Rods?
Associated with AML
myeloperoxidase cytoplasmic aggregates in neutrophils
156
What is the treatment of AML?
Chemotherapy + ATRA
Consider Abx Prophylaxis for neutropenia
Give ALLOPURINOL if on Chemo - Prevent Tumour Lysis Syndrome
Last resort - BM Transplant
157
What is Tumour Lysis Syndrome?
Caused by the release of Uric Acid from cells that are destroyed by chemotherapy.
Uric acid can form crystals in interstitial tissue and the kidneys causing AKI.
Tx with Allopurinol
158
What is Chronic Myeloid Leukaemia?
Neoplastic Myelocyte proliferation (precursor for eosinophils, basophils, Neutrophils)
159
What are the Genetics of CML?
Philadelphia chromosome (chromosome 9)
Cytogenetic translocation t(9:22)
160
What is the Pathogenesis of CML?
Philadelphia chromosome translocation
BCR ABL gene fusion causing Tyrosine Kinase irreversibly switched on.
Tyrosine kinase increases cell proliferation
161
What are the symptoms of CML?
General Sx of Leukaemia
MASSIVE Hepatosplenomegaly
162
What is the diagnosis of CML?
FBC - Pancytopenia (but granulocytosis)
BM biopsy - increased granulocytes
Philadelphia chromosome genetic test using FISH - look for BCR-ABLE
163
What is the treatment for CML?
Chemotherapy
Imatinib - T.K inhibitor
164
What is the risk of CML?
Risk of progression to AML
165
What is Acute Lymphoblastic Leukaemia (ALL)?
Neoplastic Lymphoblast proliferation
Most common Childhood malignancy - 75% of cases < 6 yrs
166
What are the genetics of ALL?
Mostly B cell lineage (not T cell)
t(12:22) w/ good prognosis
Associated with DOWNs (30x increased risk)
167
What are the symptoms of ALL?
General Sx of Leukaemia
except 6yr olds with DOWNs
hepatosplenomegaly
168
What is the diagnosis of ALL?
FBC - Pancytopenia
Blood film - increased lymphoblast cells
BM Biopsy - >20% Lymphoblasts (diagnostic)
Immunofluorescence - TdT +tve lymphoblasts
169
What is the treatment for ALL?
Chemotherapy
Consider ALLOPURINOL
Generally good prognosis
170
What is Chronic Lymphocytic Leukaemia (CLL)?
Neoplastic proliferation of Lymphocytes (most B cells)
Most common leukaemia overall often affecting adults >55yrs
multifactorial
171
What are the symptoms of CLL?
Often Asymptomatic
If Sx:
General Sx of Leukaemia
Lymphadenopathy (non tender)
Hepatosplenomegaly
172
What is the diagnosis of CLL?
FBC - Pancytopenia (except has lymphocytosis)
Blood Film - SMUDGE CELLS
Immunoglobulins - Hypogammaglobulinaemia
173
Why is there Hypogammaglobulinaemia in CLL?
B cells proliferate but do not differentiate into plasma cells and therefore few Igs are produced.
174
What is the Treatment of CLL?
Progressive = Chemotherapy
Old = Palliative Care
Bone Marrow Transplant can be Curable
Consider IV Igs for hypogammaglobulinaemia
175
What is a complication of CLL?
Richter Transformation:
B cells massively accumulate in Lymph nodes causing massive lymphadenopathy.
CLL transforms to aggressive lymphoma
176
What are some complications of Chemotherapy used to treat leukaemia?
Failure
Stunted growth/development in children
Infections - immunodeficiency
Neurotoxicity
Infertility
Tumour Lysis Syndrome
177
What is a normal haematocrit?
45%
178
What is haematopoiesis?
Synthesis of blood cells
179
Where does haematopoiesis happen?
Bone marrow
180
How is haematopoiesis regulated?
Through the action of cytokines
181
Define myeloproliferative neoplasms
Haematological malignancies
Chronic conditions - present and evolve over many years
182
How do myeloproliferative neoplasms manifest?
Accumulation of mature blood cells in circulation
183
Where do myeloproliferative neoplasms arise from?
Haematopoietic stem cells
184
What causes myeloproliferative neoplasms?
Genetic mutations in haematopoietic stem cells
Cells inappropriately and permanently switched on by signalling cytokines that control haematopoiesis
185
What genes are associated with Myeloproliferative diseases?
Mutations in:
JAK2
MPL
CALR
186
What are the 3 main myeloproliferative disorders?
Primary Myelofibrosis
Polycythaemia Vera
Essential Thrombocytopenia
187
What condition do myeloproliferative disorders have the risk of progressing to?
Acute Myeloid Leukaemia (AML)
188
What Proliferating cell line causes:
Primary Myelofibrosis
Polycythaemia Vera
Essential Thrombocytopenia
Primary Myelofibrosis - Haematopoietic Stem Cell
Polycythaemia Vera - Erythroid Cells
Essential Thrombocytopenia - Megakaryocyte
189
What is polycythaemia?
Erythrocytosis of any cause
190
How common is polycythaemia vera?
Rare
2 cases/100,000 per year
191
What is the prognosis of polycythaemia vera?
13 years
192
What are some causes of Polycythaemia?
Primary - Polycythaemia Vera
Secondary - Hypoxia, increased EPO, Dehydration, Alcohol
193
What causes Polycythaemia Vera?
JAK2 mutation V617 - EPO constantly switched on
Accounts for 95% of cases
194
What are the symptoms of Polycythaemia Vera?
Itchy after a bath
Burning in fingers and toes - Eryhtromyalgia
Reddish, Plethoric Complexion
Hepatosplenomegaly
Hyperviscosity of blood - increased RBCs = increased haematocrit
195
What are the diagnostic investigations of Polycythaemia Vera?
FBC - Increased RBCs (+ WCC and Platelets),
Increased Hb
Genetic Test - JAK2V617 positive
196
What is the treatment of Polycythaemia Vera?
Non curative
Aim to maintain normal blood count and haematocrit (<45%):
Venesection + Aspirin
Hydroxycarbamide - in high risk patients
197
What are some main complications of Polycythaemia Vera?
Arterial Thrombosis - Stroke/MI
Venous Thrombosis - DVT, Splanchnic vein thrombosis, Portal vein Thrombosis
198
What are the differential diagnosis for polycythaemia vera?
Eliminate secondary causes:
Lung disease
Alcohol
Apparent erythrocytosis
EPO (erythropoietin) secreting tumours
199
What is the prognosis of essential thrombocythaemia?
Life expectancy is normal
200
What is Essential Thrombocythaemia?
Elevated Platelet Count
201
What is the cause of Essential Thrombocythaemia?
JAK mutation
TPO switched on
202
How is Thrombocytosis Diagnosed
FBC - increased platelets
Blood film - Platelet Islands/aggregations
Check For iron status
Increased ESR - signs of infection
Increased CRP - signs of infection
203
What is the management of Essential Thrombocythaemia?
Assess and manage CVD risk
<60yrs - Aspirin alone
>60yrs or high risk - Aspirin + Hydroxycarbamide
204
What are the differential diagnosis of essential thrombocythaemia?
Eliminate secondary causes:
Infection
Inflammation (including post-surgical)
Solid tumours
Steroids
Iron Deficiency
205
What are the complications of essential thrombocythaemia?
Arterial thrombosis
Venous thrombosis
206
What is the prognosis of myelofibrosis?
5 years
207
What is Myelofibrosis?
Proliferation of the cell lines in the bone marrow lead to fibrosis
208
What is the cause of myelofibrosis?
Predominantly JAK2 mutation
209
What are the symptoms of myelofibrosis?
Weight loss
Fatigue
Features of cytopenia
210
What is the management of myelofibrosis?
Supportive management:
Blood transfusions, EPO, treat infection
Hydroxycarbamide
Allogeneic stem cell transplant
Ruxolitinab (JAK1/2 inhibitor)
211
What are the stimulants of Erythropoiesis?
- Hypoxia
- EPO secreted by kidneys
- Thyroid hormone and testosterone can stimulate as well
212
What substances are required for healthy erythropoiesis?
1. Iron - For haemoglobin formation
2. Vitamin B12 and folic acid - Required for DNA maturation and condensation. Without it, you will have massive red blood cells
213
Discuss the process of erythropoiesis.
- Occurs in red bone marrow of the epiphyses of bone
- EPO will stimulate myeloid stem cell to commit to RBC lineage - proerythroblast
- Proerythroblast will become basophillic erythroblast due to increase in mRNA of haemoglobin products
- Nucleus condenses and organelles are ejected
214
What is the structure of haemoglobin?
- Haemoglobin has a quaternary structure
- 4 haem groups
- 4 four polypeptide chains (α1, α2, β1, and β2)
215
What is the signal for RBC breakdown?
Loss of RBC structure through breakdown of the cytoskeletal components spectrin and ankrin
216
What is the process of RBC breakdown?
- Macrophages or Kupffer cells in the spleen, liver or bone marrow phagocytose RBC
- Globin alpha and beta chains > recycled as AA
- Haem > iron and protoporphyrin
- Iron > ferritin > haemosiderin
- Protoporphyrin > Biliverdin > Bilirubin
217
Describe bilirubin metabolism.
- Haem > Biliverdin > Bilirubin
- Bilirubin binds with albumin = unconjugated bilirubin - travels to liver
- Unconjugated bilirubin combines with glucuronic acid (via UGT) = conjugated bilirubin
- Conjugated bilirubin forms bile, which gets pushed into the duodenum
- Bacteria in the gut breaks down conjugated bilirubin into urobilinogen (AKA faecal stercobilinogen)
- Urobilinogen can be reabsorbed and excreted via the urine as urobilin (makes urine yellow)
- Urobilinogen can become stercobilin and excreted in the faeces (makes poo brown)
218
What is anaemia?
- Low level of haemoglobin in the blood
- It is the result of an underlying disease, and not a disease itself
219
What are the normal haemoglobin and mean cell volume ranges for men and women?
Men:
Haemoglobin - 120-165 g/L
MCV - 80-100 femtolitres
Women;
Haemoglobin - 130-180 g/L
MCV - 80-100 Femtolitres
220
What is Mean Cell (corpuscular) Volume?
Size of the red blood cells
221
What level is considered anaemic in men and women?
- <135 g/L for men
- <115 g/L for women
222
What are the 3 main categories of anaemia?
- Microcytic anaemia (low MCV indicating small RBCs)
- Normocytic anaemia (Normal MCV indicating normal sized RBCs)
- Macrocytic anaemia (Large MCV indicating large RBCs)
223
What are the different MCVs in the different types of anaemia?
Microcytic - CMV <80
Normocytic - CMV 80-95
Macrocytic - CMV >95
224
What can be reasons for Low blood count/anaemia?
Increased Loss:
BLEEDING
Haemolysis
Decreased Production:
Iron deficiency
B12 deficiency
Folate deficiency
BM failure
225
What are the main causes of microcytic anaemia?
TAILS:
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency anaemia
- Lead poisoning
- Sideroblastic anaemia
226
What are the main causes of normocytic anaemia?
AHAHA:
Acute blood loss
Haemolytic anaemia
Anaemia of chronic disease
Aplastic anaemia
Hypothyroidism + Renal disease
227
What are the main causes of Macrocytic Anaemia?
Megaloblastic:
B12 deficiency
Folate Deficiency
228
What are the main causes of macrocytosis (large RBCs)?
Split into Megaloblastic and Normoblastic:
Megaloblastic:
- B12 Deficiency
- Folate Deficiency
Normoblastic:
- Alcohol
- Reticulocytosis
- Hypothyroidism
- Liver disease
- Drugs (Azathioprine)
229
What is a hypochromic cell?
Pale cells due to less haemoglobin
230
What is a Megaloblastic Anaemia?
An anaemia characterised by very large RBCs:
B12 deficiency
Folate Deficiency
231
What are the general Symptoms of Anaemia?
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions such as angina, heart failure or peripheral vascular disease
232
What are the general signs of anaemia?
Pale skin
Conjunctival Pallor
Tachycardia
Raised Respiratory Rate
233
What are some symptoms specific to iron deficiency anaemia?
Pica - dietary cravings for abnormal things such as dirt
Hair loss - Can indicate Iron Deficiency Anaemia
234
What are some Signs of specific causes of Anaemia?
Iron Deficiency Anaemia:
Koilonychia - Spoon shaped nails
Angular Chelitis
Brittle hair and nails
Haemolytic Anaemia:
Jaundice
Thalassaemia:
Bone Deformities
235
What is Anaemia of Chronic Disease?
Secondary anaemia due to underlying pathology.
Commonest anaemia in hospitals
236
What is Iron Deficiency Anaemia?
Iron is required for the synthesis of Haemoglobin.
Therefore in Iron deficiency there is impaired synthesis of haemoglobin leading to Microcytic anaemia.
237
What is the most common form of anaemia world wide?
Iron Deficiency anaemia
238
What are some reasons a person may become iron deficient/causes of iron deficiency anaemia?
Iron is being lost (BLEEDING)
Insufficient dietary iron
Iron requirements increase (for example in pregnancy)
Inadequate iron absorption
239
Where is Iron mainly absorbed?
Duodenum and Jejunum
240
How is Iron Transported and stored?
Transported - Transferrin
Stored - Ferritin and Haemosiderin
241
Why do medications that reduce stomach acid production lead to impaired absorption of iron?
Iron is kept in the soluble ferrous (Fe2+) form by the stomach acid.
When it enters the intestines and the acid drops, it changes to Insoluble ferric iron (Fe3+)
The ferric iron is required for absorption.
PPIs will increase insoluble ferric iron in the stomach that cannot be absorbed.
242
What conditions may reduce iron absorption?
GI tract Cancer
Oesophagitis and Gastritis - GI bleeding
IBD, Colitis and Coeliacs - Impaired absorption
243
What are the Signs and Symptoms of Iron deficiency anaemia?
General Anaemia Sx
Koilonychia
Angular Stomatitis, Cheilitis
Atrophic Glossitis
244
What are the diagnostic investigations for Iron Deficiency Anaemia?
FBC - MCV = Low (microcytic anaemia)
Blood Film - Hypochromic RBC, Target cells, Howell Jolly Bodies
Iron Studies - Low Ferritin (<15), Low transferrin Saturation (<15%), Increased Total Iron Binding Capacity (TIBC)
Endoscopy if >60 yrs
245
What is the treatment of Iron Deficiency Anaemia?
Oral Fe - Ferrous Sulphate (Ferrous Gluconate if poorly tolerated)
Blood Transfusion
246
What are some Side effects of Treating Iron deficiency anaemia with Ferrous sulphate?
Cause GI Upset
Diarrhoea
Constipation
Black stools
247
What is Sideroblastic Anaemia?
A microcytic anaemia characterised by infective haematopoiesis
248
What is the Pathogenesis of Sideroblastic anaemia?
Defective Hb synthesis within Mitochondria
Often X linked inheritance
A Functional Iron deficiency where there is increased Fe but it is not used in Hb Synthesis
249
What is the diagnosis of Sideroblastic anaemia?
FBC - Microcytic
Blood film - Ringed Siderobasts
250
What is the Treatment for Sideroblastic Anaemia?
- Mainly supportive
- Iron chelation (Desferrioxamine)
- Consider B6 (Pyridoxine) is hereditary
251
What is Pernicious Anaemia?
- Autoimmune condition in which atrophic gastritis leads to a lack of intrinsic factor secretion from the parietal cells in the stomach
- Dietary B12 remains unbound and cannot be absorbed at the terminal ileum
- Therefore B12 deficiency leads to impaired maturation of RBCs and anaemia
252
What is vitamin B12 deficiency?
- Macrocytic anaemia with peripheral neuropathy and neuropsych complaints
- It is a megaloblastic anaemia, as well as folate deficiency anaemia
253
What are the causes of B12 deficiency?
- Poor diet (Vegan, vegetarian, old age)
- Decreased gastric breakdown (Atrophic gastritis)
- Malabsorption (Pernicious anaemia)
- Drugs (Metformin, PPI, H2 antagonists)
254
What is the cause of pernicious anaemia?
Autoimmune atrophic gastritis
255
What is B12 used for and how is it absorbed?
- DNA synthesis cofactor and the production of red blood cells
- required for cell division - Without it, cells remain large (megaloblast)
- It is normally present in meat, fish and dairy, and it absorbed in the terminal ileum combined with intrinsic factor
256
What is the normal physiology of Vitamin B12 absorption
B12 typically binds to Transcobalamin in the saliva (provides protection against stomach acid)
Parietal cells release Intrinsic factor (IF)
IF forms complexes with Vit B12 which is then absorbed in the ileum
B12 is then used for RBC production
257
What is the Pathophysiology of B12 deficiency and Pernicious anaemia?
Autoimmune destruction of Parietal cells
Therefore reduced intrinsic factor produced
Therefore poor absorption of B12
B12 cannot be used to produced RBCs
Anaemia
258
What are the symptoms of Pernicious anaemia?
General Anaemia Sx
Lemon Yellow Skin
Angular Stomatitis and glossitis
Neurological SX - B12 def causes demyelination
259
What neurological symptoms may be seen in Pernicious anaemia?
Symmetrical paraesthesia
Muscle Weakness
260
What are the diagnostic investigations of B12 Deficiency and Pernicious Anaemia?
MCV Increased - macrocytic anaemia
Blood film - Megaloblasts + Oval Macrocytes
Low serum B12 levels
Anti-IF antibodies and Anti-parietal Abs
261
How long does B12 deficiency and pernicious anaemia take to develop?
Years
262
What is the treatment of Pernicious anaemia?
Dietary advice (Salmon and eggs)
B12 Supplements
PO Hydroxocobalamin
263
What is Folate Deficiency Anaemia?
- A type of MACROcytic anaemia with absence of neurological signs
- Folate is required for cell division and DNA synthesis.
Without it maturing RBCs wont divide - Megalobastic
264
How long does Folate deficiency anaemia take to develop?
Months
265
What are the causes of folate deficiency anaemia?
- Poor diet (poverty, alcohol, elderly)
- Increased demand (Pregnancy, renal disease)
- Malabsorption (Coeliac)
- Drugs, alcohol and methotrexate
266
What is the hallmark symptom of megalobastic anaemia?
Headache
Loss of appetite and weight
267
What are the signs and symptoms of folate-deficiency anaemia?
General Anaemia Sx
Angular Stomatitis and Glossitis
No Neurological Sx - distinguish between B12 Def.
268
What is the diagnostic test for Folate deficiency Anaemia?
FBC and Blood film - Macrocytic and Megaloblasts
Decreased serum folate
269
What is the treatment for Folate deficiency anaemia?
Dietary advice - leafy greens and brown rice
Folate supplements
If pancytopenic then give packed RBC Transfusion
270
What is Haemolytic Anaemia?
Anaemia caused by haemolysis - early breakdown of RBCs
271
What are the hereditary causes of haemolytic anaemia?
- Enzyme defects (G6P dehydrogenase deficiency)
- Membrane defects (Spherocytosis, elliptocytosis)
- Abnormal Hb production (Sickle cell, thalassaemia)
272
What is Autoimmune Haemolytic Anaemia?
Autoimmune Abs against RBCs causing intra and extravascular haemolysis
273
What are the types of Autoimmune haemolytic anaemia?
- Divided into two subtypes depending on temperature:
- WARM type - IgG mediated - occurs at normal or warm temperatures (Idiopathic)
- COLD type - IgM mediated - also called cold agglutinin disease
274
What is the specific test to Diagnose Autoimmune Haemolytic Anaemia?
Direct Coombs Test - Agglutination of RBCs with Coombs reagent
275
What are the signs and symptoms of haemolytic Anaemia?
- Anaemia symptoms (Pallor, fatigue, dyspnoea)
- Jaundice (Increase in bilirubin)
- Splenomegaly (increased haemolysis)
- Dark urine (PNH)
276
What are the investigations for haemolytic anaemia?
Low Hb
FBC - Normocytic Anaemia
Blood film - Shistocytes
Direct coombs Test - positive
277
What is the treatment of Coombs +ve haemolytic anaemia?
- Treat underlying condition
- RBC transfusion and folic acid
- Prednisolone
- Rituximab
- Splenectomy
278
How does CKD cause anaemia?
Decreased EPO causes reduced erythropoiesis
Normocytic and Normochromic anaemia
279
What is Aplastic Anaemia?
A Pancytopenia where BM fails and stops making haematopoietic stem cells.
Causes - Idiopathic
FBC - Normocytic anaemia with decreased reticulocytes
280
What are the main causes of splenomegaly?
Infection
Liver disease
Autoimmune disease - SLE/RA
Cancers
281
What is Haemophilia A?
A bleeding disorder caused by a deficiency in Factor VIII
282
What is Haemophilia B?
A bleeding disorder caused by a deficiency in Factor IX
283
What are the genetics of Haemophilia?
These are X linked Recessive disorders and therefore will only tend to affect males.
284
What are signs and symptoms of Haemophilia?
Excessive Bleeding to minor trauma
Intra-cranial haemorrhage, haematomas, chord bleeding in neonates
Spontaneous bleeding into joints and muscles
285
What diagnostic investigations are used to diagnosed Haemophilia?
Bleeding scores
Coagulation factor assays
Genetic testing
286
What is the management of Haemophilia?
Affected clotting factors (VIII or IX) can be replaced by IV.
Desmopressin can stimulate the release of VwF
Antifibrinolytics - Tranexamic Acid
287
What is Von Willebrand Disease (VWD)?
An autosomal dominant condition where there is a deficiency, absence or malfunction of VWF leading to abnormal bleeding.
288
What is the most common inherited cause of abnormal bleeding?
Von Willebrand Disease
289
What is the presentation of VWD?
Hx of easy, prolonged or heavy bleeding:
Bleeding gums w/ bruising
Nose bleeds (Epistaxis)
Menorrhagia (heavy menstrual bleeding)
FHx of VWD.
290
What is the diagnosis of VWD?
Hx or FHx of abnormal bleeding
Bleeding assessment tools
291
What is the management of VWD?
Does not require day to day Tx
Tx is in response to major bleeding or trauma.
Tx:
Desmopressin can be used to stimulates the release of VWF
VWF can be infused
Factor VIII is often infused along with plasma-derived VWF
292
What can be given to Women with VWD that suffer from heavy periods?
Tranexamic acid
293
What is Rheumatic Fever?
Autoimmune disease that mostly occurs after a group A strep infection.
It causes joint pain and can affect other areas such as the heart (carditis) brain and skin.
294
How would a patient with Rheumatic fever present?
Fever
Joint pain
Recent infection (sore throat/scarlet fever)
Chest pain
SOB
295
What are some risk factors for rheumatic fever?
Infection
FHx of rheumatic fever
Overcrowded living.
296
What are the first line investigations to diagnose rheumatic fever?
Blood tests:
ESR/CRP
WCC
Blood cultures
ECG - Shows heart block
ECHO - if mitral regurgitation murmur
297
What is the Treatment for Rheumatic fever?
Benzylpenicillin
Diuretic +/- ACEi if heart failure present
298
What is infectious mononucleosis?
Glandular Fever caused by EBV infection.
299
What conditions are associated with EBV?
Burkitts Lymphoma
Hodgekin's Lymphoma
nasopharyngeal carcinoma
300
Who is typically presenting with infectious mononucleosis?
15-24yr olds
EBV spread via saliva or body fluids
301
What is the Diagnostic investigations for glandular fever?
FBC
Blood film - Atypical Lymphocytes
EBV serology
EBV PCR
302
What is the management of glandular fever?
Generally self limiting
Supportive therapy
Good hydration and analgesics
303
What is autoimmune thrombocytic Purpura?
Autoimmune destruction of platelets (IgG)
304
What are the symptoms of Autoimmune Thrombocytic Purpura?
Purpuric rash
305
What is the treatment of Autoimmune thrombocytic purpura?
Prednisolone
+
IV IgG
306
What is Thrombotic Thrombocytic purpura?
ADAMTS-13 deficiency (VWF cleaving enzyme) therefore VWF remains as aggregates at endothelial injury sites.
307
What are the symptoms of Thrombotic thrombocytic purpura?
Purpuric rash
AKI
Haemolytic anaemia
Neurological Sx
308
What are the investigations for Thrombotic thrombocytic purpura?
Thrombocytopenia
Schistocytes
ADAMTS-13 deficiency
309
How is Thrombotic thrombocytic purpura treated?
Plasmapharesis
2nd line - Prednisolone + Rituximab
310
What is Prothrombin time and INR?
What is the normal range?
PT - how long it takes for the blood to clot.
INR - international normalised ratio
PT range = 11-13.5 seconds
INR = 0.8-1.1
311
What is the aPTT test?
Partial thromboplastin time (activated Partial Thromboplastin Time)
Normal range is 21-35 seconds.
When higher than normal this suggests there may be bleeding or liver disease etc.
