Haem Flashcards
1
Q
Where are blood cells produced?
A
Within the bone marrow
The majority of bone marrow activity occurs in the axial skeleton and long bones of the appendicular skeleton.
2
Q
What are haematopoietic stem cells capable of?
A
Giving rise to all blood cell lineages and generally express the surface marker CD34.
3
Q
What does the term ‘pluripotent stem cells’ refer to?
A
Stem cells that can produce different varieties of mature cells depending on external stimulations.
4
Q
What are the two major divisions of a haematopoietic pluripotent stem cell?
A
Myeloid stem cell and lymphoid stem cell.
5
Q
What is a multipotent haematopoietic stem cell also known as?
A
Hemocytoblast.
6
Q
What determines the pathway a remaining cell will take after division?
A
The chemical signals received.
7
Q
List the components derived from myeloid stem cells.
A
- Megakaryoblast
- Proerythroblast
- Myeloblast
- Monoblast
8
Q
What cells do lymphoid stem cells produce?
A
Lymphocytes.
9
Q
What are the types of lymphocytes produced by lymphoid stem cells?
A
- B lymphocytes
- T lymphocytes
- Natural Killer (NK) cells.
10
Q
Where do B lymphocytes mature?
A
In the bone marrow.
11
Q
What do activated B cells produce?
A
CD20, which is the target of rituximab.
12
Q
What is the primary function of plasma cells?
A
To secrete high-affinity immunoglobulins against specific antigens.
13
Q
What happens to T lymphocytes after they are produced in the bone marrow?
A
They travel to the thymus for further differentiation.
14
Q
What surface proteins do T lymphocytes lack at their early stage?
A
CD4 or CD8.
15
Q
What process leads to the apoptosis of 99% of thymocytes during differentiation?
A
Positive and negative selection pressures.
16
Q
Differentiate between helper T cells and cytotoxic T cells.
A
- Helper T cells - CD4+ that release cytokines and bind peptides on antigen-presenting cells.
- Cytotoxic T cells - CD8+ that destroy pathogens.
17
Q
What do myeloid stem cells produce?
A
All myeloid cell lines.
18
Q
List the differentiated forms of myeloblasts.
A
- Neutrophils
- Basophils
- Eosinophils
- Monocytes.
19
Q
What do megakaryocytes produce?
A
Thrombocytes (platelets).
20
Q
What can be assessed through the examination of a blood film?
A
Characteristic findings beyond basic full blood examination values.
21
Q
What are some characteristic findings on a blood film?
A
- Target cells
- Spherocytes
- Burr cells
- Howell-Jolly bodies.
22
Q
Define haemostasis.
A
A complex and tightly regulated process to prevent bleeding.
23
Q
What initiates the intrinsic pathway of coagulation?
A
Contact activation from a damaged surface.
24
Q
What is the role of thrombin in coagulation?
A
Converts fibrinogen to insoluble fibrin.
25
What does a prolonged prothrombin time (PT) indicate?
Factor VII deficiency, vitamin K deficiency, or warfarin use.
26
What is the gold standard for diagnosing a pulmonary embolism (PE)?
CT Pulmonary Angiography.
27
What is the strongest risk factor for venous thromboembolism (VTE)?
Previous VTE.
28
What is Virchow's Triad?
Factors that predispose to venous thromboembolism: hypercoagulable state, venous stasis, endothelial damage.
29
What is the clinical significance of D-Dimer testing?
A screening test for VTE, but not specific.
30
What is the recommended treatment duration for an unprovoked pulmonary embolism?
At least 6 months.
31
Does below knee DVT require treatment?
No, below knee DVT does not require treatment.
## Footnote
Repeated ultrasonography should be performed to ensure resolution and exclude extension above the knee.
32
How long should treatment for pulmonary embolism (PE) be continued?
At least 3 months for all cases of PE.
## Footnote
Unprovoked PE should have at least 6 months of treatment.
33
When can anticoagulation be stopped for provoked PE?
Anticoagulation may be stopped at 3 months if the provoking factor has been removed.
34
What is the traditional approach for treating PE in the presence of malignancy?
Indefinite treatment with low molecular weight heparin.
## Footnote
The use of DOACs in malignancy is now established as a suitable alternative.
35
What medication reduces the risk of recurrent VTE after stopping anticoagulation?
Aspirin.
36
What are the risk factors for recurrence of VTE?
* Active cancer
* Thrombophilia
* Unprovoked VTE
* Number of VTE episodes
* Pulmonary embolism and DVT
* Elevated D-Dimer
* Proximal limb DVT
37
What is the average rate of recurrence for VTE within 12 months?
10%.
38
What is the risk of recurrence for unprovoked VTE at 5 years?
30%.
39
What is the annual risk of VTE in the setting of malignancy?
Very high, at 15%.
40
What types of heparin are used for parenteral anticoagulation?
* Unfractionated Heparin (UFH)
* Low Molecular Weight Heparin (LMWH)
* Fondaparinux
41
What is the half-life of subcutaneous low molecular weight heparin?
20 hours.
42
What is the mechanism of action for low molecular weight heparin?
Accelerates Factor Xa inhibition.
43
What is the laboratory monitoring required for unfractionated heparin?
aPTT and Factor Xa.
44
What is the reversal agent for warfarin?
Vitamin K, Prothrombinex, Fresh Frozen Plasma.
45
What is the mechanism of action for warfarin?
Inhibits Vitamin K oxide reductase, preventing the synthesis of Factors II, VII, IX, and X, as well as Protein C and S.
46
What are NOACs also known as?
Non-Vitamin K Oral Anticoagulants.
47
What landmark trial demonstrated the efficacy of Dabigatran?
RE-LY trial.
48
What does the acronym INR stand for?
International Normalized Ratio.
49
What is a common cause of macrocytic anaemia?
Vitamin B12 deficiency.
50
What are the three major causes of anaemia?
* RBC loss
* Decreased RBC production
* Increased RBC breakdown
51
What can cause chronic blood loss leading to anaemia?
* Gastrointestinal bleeding
* Lesions such as gastritis, peptic ulcer disease, angiodysplasia, large bowel malignancy.
52
What is the primary cause of iron deficiency anaemia?
Iron deficiency.
53
What type of anaemia is characterized by hypochromic, microcytic erythrocytes?
Iron deficiency anaemia.
54
What is the management for severe iron deficiency anaemia?
Intravenous iron supplementation.
55
What is a common dietary source of folate?
Leafy green vegetables.
56
What condition is often associated with anaemia in end-stage renal failure?
Decreased erythropoietin (EPO) synthesis.
57
What is the role of Hepcidin in anaemia of chronic disease?
Reduces iron uptake and inhibits release of iron to erythrocytes.
58
What is the inheritance pattern of thalassaemia?
Autosomal recessive.
59
What is the major cause of microcytic anaemia in non-iron deficient patients?
Thalassaemia.
60
What is the common treatment for severe beta thalassaemia?
Regular blood transfusions.
61
What is aplastic anaemia characterized by?
Severe pancytopenia.
62
What is a common infectious cause of aplastic anaemia?
Parvovirus B19.
63
What does the peripheral blood film show in aplastic anaemia?
Reducing counts of all cell lineages.
64
What is severe pancytopenia?
A condition characterized by all cell lineages being low - RBCs, leukocytes, and platelets.
65
What are common causes of severe pancytopenia?
* Inherited conditions (e.g., Fanconi Syndrome)
* Drug exposure (e.g., benzenes, phenytoin)
* Radiation (ionizing radiation)
* Infections (e.g., parvovirus B19)
66
What findings are typically observed in peripheral blood films of patients with severe pancytopenia?
Reducing counts of all cell lineages.
67
What is required to confirm the diagnosis of severe pancytopenia?
Bone marrow aspiration.
68
What does bone marrow aspiration reveal in severe pancytopenia?
A hypocellular marrow with increased numbers of adipocytes.
69
What is the optimal management for severe pancytopenia in young and fit patients?
Allogeneic stem cell transplantation.
70
What is a key challenge in managing severe pancytopenia?
Finding a HLA-matched donor.
71
What is the cure rate for allogeneic stem cell transplantation in severe pancytopenia?
Approaching 90%.
72
What immunosuppressive treatments may be effective in severe pancytopenia?
* Antithymocyte globulin
* Cyclosporine
73
What is the role of steroids in treating severe pancytopenia?
Steroids have no benefit.
74
In severe pancytopenia, what supportive therapies may be required?
* Irradiated packed red blood cell transfusions
* Platelet transfusions
75
What is granulocyte colony stimulating factor (G-CSF) noted for in severe pancytopenia?
It has not shown effectiveness in increasing cell counts.
76
What types of infections should be considered for prophylactic therapy in severe pancytopenia?
* Antibiotic
* Antiviral
* Antifungal
77
What is the difference between intravascular and extravascular haemolysis?
Intravascular haemolysis occurs within blood vessels, while extravascular occurs outside of them.
78
What are schistocytes and spherocytes indicative of?
They are major differentiating features in diagnosing types of haemolysis.
79
What lab findings are associated with haemolysis?
* Elevated bilirubin
* Elevated potassium
* Elevated LDH
80
What is reticulocytosis?
A high reticulocyte count due to the bone marrow's response to haemolysis.
81
What happens to haptoglobin levels in haemolysis?
Haptoglobin is decreased.
82
What is the most specific marker of haemolysis?
Urinary haemosiderin.
83
What is hereditary spherocytosis?
A condition with a prevalence of 1 in 2,000 people, characterized by spherocytes on blood films.
84
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant.
85
What mutation is commonly involved in hereditary spherocytosis?
Mutations in red cell membrane proteins like ankyrin, spectrin, or band 3.
86
What is the traditional test for diagnosing hereditary spherocytosis?
Osmotic fragility test.
87
What test is now commonly used to confirm hereditary spherocytosis?
Eosin-5-malemide (E5M) test.
88
What is the treatment for severe hereditary spherocytosis?
Splenectomy.
89
What is the typical presentation of sickle cell anaemia?
* Pain crises
* Acute chest syndrome
* Stroke risk
90
What is the genetic inheritance pattern of sickle cell anaemia?
Autosomal recessive.
91
What mutation causes sickle cell anaemia?
Single nucleotide mutation of the beta globin gene.
92
What is the lifespan of sickled RBCs compared to normal RBCs?
Sickled RBCs last approximately 20 days; normal RBCs last 120 days.
93
What is the most common complication of sickle cell disease?
Pain crises.
94
What is the risk of stroke in sickle cell disease patients by age 45?
Approximately 25%.
95
What is acute chest syndrome?
A condition presenting with dyspnoea, fever, and infiltrates, often due to infection.
96
What is the management for acute chest syndrome in sickle cell disease?
* Analgesia
* Rehydration
* Emergency red cell exchange
97
What is hydroxyurea used for in sickle cell disease?
To improve mortality and reduce sickle cell crises.
98
What condition is G6PD deficiency associated with?
The most common RBC enzyme defect.
99
What is the inheritance pattern of G6PD deficiency?
X-linked inheritance.
100
What is a common laboratory finding in G6PD deficiency?
Peripheral blood films show bite cells and Heinz bodies.
101
What triggers oxidative stress in G6PD deficiency?
* Infections
* Certain drugs (e.g., quinines, sulfonamides)
* Fava beans
102
What is the treatment for acute episodes of G6PD deficiency?
Blood transfusions and supportive care.
103
What is paroxysmal nocturnal haemoglobinuria (PNH)?
A rare condition with acquired genetic mutations affecting RBCs.
104
What gene is mutated in PNH?
The PIGA gene.
105
What are clinical features of PNH?
* Pancytopenia
* Red discolored urine
* High risk of thrombosis
106
What is the management for PNH?
* Eculizumab
* Anticoagulation
* Allogeneic Stem Cell Transplant in severe cases
107
What is warm autoimmune haemolytic anaemia characterized by?
IgG autoantibodies attaching to RBC proteins at 37°C.
108
What is the most common cause of warm autoimmune haemolytic anaemia?
Idiopathic (50% of cases).
109
What is the first-line treatment for warm autoimmune haemolytic anaemia?
Immunosuppression with steroids.
110
What is cold agglutinin disease characterized by?
IgM antibodies attaching to RBC proteins at cooler temperatures.
111
What are common causes of cold agglutinin disease?
* B cell lymphoproliferative disorders
* Infectious causes (e.g., Mycoplasma pneumonia)
112
What is the management for cold agglutinin disease?
* Avoidance of cold
* Treatment of underlying disorders
113
What is thrombotic thrombocytopenic purpura (TTP)?
A rare, acquired disease caused by autoantibodies to ADAMTS13.
114
What are key clinical manifestations of TTP?
* Microangiopathic haemolytic anaemia
* Renal failure
* Thrombocytopenia
115
What is the urgent management for TTP?
Plasmapheresis.
116
What is the triad of symptoms in haemolytic uraemic syndrome (HUS)?
* Haemolytic anaemia
* Thrombocytopenia
* Renal failure
117
What are common pathogens associated with HUS?
* E. Coli O157:H7
* Shigella
* Campylobacter
118
What is the management for HUS?
Supportive care; dialysis may be required.
119
What is atypical haemolytic uraemic syndrome (aHUS)?
A condition caused by complement system dysregulation.
120
What is the most common cause of aHUS?
Factor H deficiency.
121
What is the treatment for aHUS?
Eculizumab.
122
What is disseminated intravascular coagulopathy (DIC)?
A condition of widespread activation of the coagulation cascade.
123
What initiates the coagulation cascade in DIC?
Tissue factor activation.
124
What is the role of tissue factor in Disseminated Intravascular Coagulopathy (DIC)?
Tissue factor activation initiates the coagulation cascade, leading to widespread thrombosis.
125
What are the common causes of Disseminated Intravascular Coagulopathy (DIC)?
* Obstetric complications (abruption, pre-eclampsia, postpartum hemorrhage)
* Malignancy
* Sepsis (particularly Gram negative)
* Trauma or burns
* Transfusion associated acute hemolytic reaction
* Toxic reaction (snake envenomation)
126
What laboratory findings are associated with DIC?
* Abnormal coagulation studies
* Elevated prothrombin time (PT)
* Elevated activated partial thromboplastin time (aPTT)
* Low fibrinogen
* Increased D-Dimer
* Decreasing platelet count
* Intravascular hemolysis (schistocytes on blood film)
127
What is the primary management approach for DIC?
Manage the causative condition first.
128
What is the normal platelet count range?
150 - 400 x10^9/L
129
What stimulates the production of platelets?
Thrombopoietin stimulates megakaryocyte production of platelets.
130
What is Immune Thrombocytopenia (ITP)?
ITP involves IgG antibodies targeting platelet surface proteins, leading to opsonization and splenic sequestration of platelets.
131
What are the management options for Immune Thrombocytopenia (ITP)?
* Immunosuppression
* Steroids (first line)
* Steroid sparing agents (mycophenolate, azathioprine)
* Rituximab
* Splenectomy
* IVIG
* Thrombopoietin receptor agonists (Romiplostin, Eltrombopag)
132
What is Heparin Induced Thrombocytopenia (HIT)?
HIT is caused by IgG antibodies against heparin-platelet factor 4 complexes, leading to platelet activation and thrombosis.
133
What are the risk factors for Heparin Induced Thrombocytopenia (HIT)?
* Formulation of heparin (unfractionated higher risk)
* Delivery method (intravenous higher risk)
* Time of onset (5-10 days after treatment)
134
What is the 4T Score used for?
The 4T Score is used to assess the probability of Heparin Induced Thrombocytopenia (HIT).
135
What are the diagnostic criteria for HIT according to the 4T Score?
* Thrombocytopenia: >50% fall in platelet count
* Timing: onset between 5-10 days
* Thrombosis: proven arterial or venous thrombosis
* Other causes: none
136
What are the common causes of splenomegaly?
* Myeloproliferative neoplasms
* Hemolytic anemias
* Infections (CMV, EBV, Hepatitis)
* Portal hypertension
* Leukaemias
* Sickle cell anemia
137
What is the management for Drug Induced Thrombocytopenia?
Identify and discontinue the offending medication.
138
What is Thrombocytosis?
Thrombocytosis is an increase in platelet count often due to inflammation or myeloproliferative neoplasms.
139
What are the mutations associated with Essential Thrombocythemia (ET)?
* JAK2 (50%)
* CALR (40%)
140
What is Polycythemia Vera (PCV)?
PCV is a neoplastic disorder caused by a JAK2 V617F mutation, leading to increased production of myeloid cell lineages.
141
What are the three clinical stages of Polycythemia Vera?
* Latent
* Proliferative
* Spent
142
What are the laboratory findings in Polycythemia Vera?
* Elevated hemoglobin and hematocrit
* Low serum EPO
143
What is the first-line management for Polycythemia Vera?
Hydroxyurea or regular phlebotomy to lower hemoglobin levels.
144
What is the prognosis for Acute Myeloid Leukemia (AML)?
Prognosis is poor overall and depends on disease factors, patient factors, and prior hematological disorders.
145
What are some risk factors for Acute Myeloid Leukemia (AML)?
* Chemical exposures (previous chemotherapy, benzene)
* Radiation exposure
* Genetic predispositions (e.g., Down's Syndrome)
146
What is the significance of genetic mutations in AML?
They correspond to treatment response and prognosis, influencing management strategies.
147
What are some favourable genetic mutations in AML?
* t(8;21)
* inv16
* Biallelic CEBPA mutation
* NPM1 mutation
148
What are some unfavourable genetic mutations in AML?
* Complex karyotype
* t(6;9)
* inv3
* KMT2A rearrangement
* FLT3 ITD mutation
* RUNX1 mutation
149
What is the translocation of chromosomes 6 and 9 referred to?
t[6;9]
## Footnote
This translocation is associated with certain types of leukemia and might indicate an unfavorable prognosis.
150
What does inv3 refer to?
Inversion of chromosome 3
## Footnote
This genetic alteration is also linked to poor prognosis in certain hematological malignancies.
151
What mutation is associated with FLT3 ITD?
FLT3 ITD mutation
## Footnote
This mutation often indicates a poor prognosis in acute myeloid leukemia (AML).
152
Which mutations or markers are associated with a better prognosis?
t(8;21), inv16
## Footnote
These genetic alterations are generally linked to improved survival outcomes in AML patients.
153
Which mutations or markers are associated with an unfavorable prognosis?
t(6;9), inv3, FLT3, DNMT3A
## Footnote
These genetic factors are linked to a worse outcome in patients with AML.
154
What is the primary behavior of abnormal myeloid progenitor cells in the bone marrow?
They behave in a malignant fashion
## Footnote
This leads to uncontrolled replication and formation of blast cells instead of normal differentiation.
155
What does severe pancytopenia consist of?
Anaemia, leukopenia, thrombocytopenia
## Footnote
This condition results from the suppression of normal progenitor cells by malignant blast cells.
156
What symptoms do patients present with due to pancytopenia?
Symptomatic anaemia, infections, or bleeding
## Footnote
These symptoms arise from the lack of normal blood cells.
157
What is a possible rare presentation of AML?
Sweet's Syndrome or myeloid sarcomas
## Footnote
These conditions reflect atypical manifestations of the disease.
158
What does a full blood examination typically reveal in patients with AML?
Pancytopenia
## Footnote
Leukocyte counts may vary from low to high.
159
What are Auer rods?
Pencil shaped granules adjacent to the nucleus in blast cells
## Footnote
Their presence is indicative of certain types of leukemia.
160
What electrolyte derangements may occur secondary to tumor lysis syndrome?
Hyperkalaemia, hyperphosphataemia, hypocalcaemia, elevated uric acid, elevated lactate dehydrogenase
## Footnote
These imbalances result from the rapid breakdown of cells.
161
What is essential for diagnosing AML?
Bone marrow examination
## Footnote
This allows for genetic and molecular marker analysis, critical for diagnosis.
162
What is the standard chemotherapy regimen for AML?
'7 and 3' regimen
## Footnote
This includes cytarabine for 7 days and an anthracycline for days 1-3.
163
What is the prognosis for patients with favorable cytogenetics and molecular markers?
5-year survival - 70%
## Footnote
This indicates a significantly better outlook compared to those with unfavorable markers.
164
What is Acute Promyelocytic Leukaemia (APML) caused by?
t(15;17) causing cellular arrest at the promyelocytic stage
## Footnote
This genetic alteration prevents normal development of promyelocytes.
165
What treatment can bypass the cellular arrest in APML?
All-trans-retinoic acid (ATRA)
## Footnote
This treatment effectively promotes differentiation of abnormal promyelocytes.
166
What is the most common childhood cancer?
Acute Lymphoblastic Leukaemia (ALL)
## Footnote
It is a leading cause of cancer-related death in children.
167
What is a common mutation in ALL?
t(12;21), t(1;19), t(9;22)
## Footnote
The Philadelphia chromosome is particularly notable in adult ALL and chronic myeloid leukemia (CML).
168
What is the typical treatment regimen for ALL?
Anthracyclines, vincristine, asparaginase, and steroids
## Footnote
These regimens often last several months and can be highly toxic.
169
What are positive prognostic factors for ALL?
Age 2-6 years, normal or low white cell count, no CNS involvement, cytogenetics such as t(12;21) and hyperdiploidy
## Footnote
These factors correlate with better outcomes.
170
What is a potential complication during treatment for APML?
Differentiation syndrome
## Footnote
This can occur after treatment with ATRA, leading to severe symptoms.
171
What percentage of people may have low vWF levels without having von Willebrand disease?
Up to 1%
## Footnote
The majority of these individuals do not have bleeding problems.
172
What are the criteria for referring someone as having 'low vWF levels'?
Antigen level of 30-50% with no bleeding problems
173
What antigen level is likely to be considered indicative of von Willebrand disease?
vWF Antigen level of <30% or bleeding problems with 30-50% level
174
What inheritance pattern is associated with Type 1 von Willebrand disease?
Autosomal dominant
175
What inheritance pattern is associated with Type 2 von Willebrand disease?
Autosomal dominant
176
What inheritance pattern is associated with Type 3 von Willebrand disease?
Autosomal recessive
177
What percentage of von Willebrand disease cases are Type 1?
70% of cases
178
What percentage of von Willebrand disease cases are Type 2?
20% of cases
179
What percentage of von Willebrand disease cases are Type 3?
<5% of cases
180
What is desmopressin used for?
Management of von Willebrand disease
181
What is the primary function of the liver regarding coagulation factors?
Synthesis of most pro- and anticoagulant factors
182
What laboratory values may show abnormalities in liver disease?
Prolonged PT, INR, and aPTT; low fibrinogen levels
183
Despite prolonged PT and aPTT, what risk do patients with liver disease not have?
Autoanticoagulation
184
What is the management for liver disease coagulopathy with INR <2?
Observation
185
What vitamin is required for the formation of Factors II, VII, IX, and X?
Vitamin K
186
What is the recommended treatment for mild coagulopathy with no bleeding?
Oral vitamin K supplementation
187
Fill in the blank: Warfarin inhibits the formation of Factors II, VII, IX, and X by acting on the _______.
Vitamin K pathway
188
What is the incidence of acute haemolytic reactions due to ABO incompatibility?
High mortality rate
189
What is the universal donor blood group?
Blood group O
190
What are the indications for packed red blood cell transfusions?
* Active severe bleeding
* Symptomatic anaemia
* Haemoglobin concentration <70g/L
* Prior to surgery with expected blood loss
191
What complication can arise from platelet transfusions?
Platelet refractoriness
192
What is the storage temperature for platelets?
Room temperature (20-25°C)
193
What is cryoprecipitate used for?
* Hypofibrinogenaemia
* Disseminated intravascular coagulopathy
194
What is the therapeutic dose of cryoprecipitate?
1 unit per 10kg body weight
195
What is the primary cause of Chronic Myeloid Leukaemia (CML)?
The Philadelphia Chromosome (translocation t(9;22))
196
What is the fusion protein responsible for CML?
BCR:ABL
197
What are the three phases of CML?
* Chronic phase
* Accelerated phase
* Blast phase
198
What is the median age of diagnosis for Chronic Myeloid Leukaemia?
58 years
199
True or False: Acute haemolytic reactions can occur from ABO incompatibility.
True
200
What is the expected increment in hemoglobin from a single unit of packed red blood cells?
10g/L
201
What are the signs of febrile non-haemolytic reactions?
* Fever
* Tachypnoea
* Tachycardia
202
What is the primary management for febrile non-haemolytic reactions?
Ceasing the transfusion and treating with paracetamol
203
What is BCR-ABL?
A functional tyrosine kinase that activates cellular messaging to induce proliferation and inhibits DNA repair mechanisms
## Footnote
BCR-ABL is responsible for chronic myeloid leukaemia (CML)
204
What characterizes the chronic phase of CML?
High leukocyte count, predominantly neutrophils, metamyelocytes, and myelocytes, with increased basophils (basophilia)
## Footnote
Basophilia is very characteristic of CML.
205
What occurs during the accelerated phase of CML?
A short-lived period of rapid cell proliferation and increasing blast numbers
206
What is the blast phase of CML?
Transformation of the disease to acute leukaemia, characterized by large numbers of blasts resembling either AML or ALL
207
How is CML often detected?
Incidental finding on routine clinical examination or blood tests
208
What examination findings are typical in CML?
Massive splenomegaly
209
What does FBC analysis show in CML?
Very high numbers of mature neutrophils, often over 100 x10^9/L, and less mature stages including metamyelocytes and myelocytes
210
What is required for the diagnosis of CML?
Detection of t(9;22) on cytogenetics or finding the BCR-ABL gene on FISH or PCR test
211
What is the treatment breakthrough for CML?
Targeted tyrosine kinase inhibitors (TKIs)
212
What is the treatment approach for patients with CML?
All patients should be treated regardless of phase and symptoms due to expected disease progression
213
What is the first TKI produced?
Imatinib
214
What are common adverse effects of Imatinib?
* Gastrointestinal issues
* Muscle cramps
215
What mutations can lead to resistance to Imatinib?
T315I mutation
216
What is the prognosis for patients on oral TKI therapy?
Most patients achieve full remission
217
What is a significant finding in peripheral blood for prognosis?
Reduction of PCR detectable cells by Log1 or Log4 within specified timeframes
218
What is the most common leukaemia in the developed world?
Chronic Lymphocytic Leukaemia (CLL)
219
What is the median age of diagnosis for CLL?
Around 70 years of age
220
What are common presentation findings in CLL?
* Asymptomatic at diagnosis
* Moderately elevated lymphocyte counts
* Lymphadenopathy
221
What does the diagnosis of CLL involve?
Peripheral blood counts showing isolated lymphocytosis and flow cytometry detecting CD5 and CD23 positive lymphocytes
222
What is the preferred management for most CLL cases?
Observation
223
What are treatment options for CLL?
* Chemotherapy (Fludarabine plus cyclophosphamide)
* Targeted therapy (Rituximab, Ibrutinib, Venetoclax, Alemtuzumab)
* Stem cell transplantation (rarely)
224
What is the most common complication of CLL?
Hypogammaglobulinaemia
225
What does 'Richter's Transformation' involve?
Development of diffuse large B-cell lymphoma (DLBCL) in a previously affected nodal station by CLL
226
What defines Hodgkin Lymphoma's epidemiology?
Distinct bimodal distribution in young adults (20-35 years) and over 60 years of age
227
What are common symptoms in Hodgkin Lymphoma?
* Lymphadenopathy
* B-symptoms (weight loss, night sweats, fever)
228
What is required for the diagnosis of Hodgkin Lymphoma?
Histological examination showing Reed-Sternberg cells
229
What is the overall prognosis for Hodgkin Lymphoma?
Very good, with an average cure rate in excess of 85%
230
What chemotherapy regimen is used for limited stage Hodgkin Lymphoma?
ABVD Chemotherapy plus Radiotherapy
231
What is the most common form of Non-Hodgkin Lymphoma?
Diffuse Large B-Cell Lymphoma (DLBCL)
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What is the incidence of DLBCL?
10 per 100,000 people
233
What is the prognosis for DLBCL?
Relatively good and potentially curable
234
What is the management for Burkitt's Lymphoma?
Intensive chemotherapy
235
What is Post-Transplant Lymphoproliferative Disorder (PTLD)?
Life-threatening complication of immunosuppression following solid organ transplant
236
What is the spectrum of Plasma Cell Dyscrasias?
* MGUS
* Smoldering Myeloma
* Plasmacytomas
* Multiple Myeloma
* Waldenstrom's macroglobulinaemia
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What are common paraneoplastic conditions associated with Plasma Cell Dyscrasias?
* Amyloidosis
* Cryoglobulinaemia
* POEMS Syndrome
238
What is Waldenstrom's macroglobulinaemia?
A clonal expansion of both B-lymphocytes and plasma cells, classified as a plasma cell dyscrasia.
239
What does MGUS stand for?
Monoclonal Gammopathy of Undetermined Significance.
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What is the pathophysiology of MGUS?
Involves clonal replication of a single plasma cell producing a single type of immunoglobulin.
241
What is a paraprotein?
A single specific immunoglobulin that appears as a spike on serum protein electrophoresis.
242
What types of immunoglobulin are typically produced in myeloma?
IgG or IgA.
243
What are the types of light chains in immunoglobulin?
Kappa and lambda.
244
What is light chain myeloma?
A type of myeloma that produces only light chains.
245
True or False: Patients with MGUS are generally symptomatic.
False.
246
What does the diagnosis of MGUS require?
Paraprotein M-band <30g/L and plasma cells <10% on bone marrow biopsy.
247
What is the risk of transformation from MGUS to multiple myeloma?
1% per year.
248
What is smoldering myeloma?
A disease along the clinical spectrum of myeloma with a higher risk of progression to active myeloma.
249
What are the diagnostic criteria for smoldering myeloma?
Monoclonal paraprotein >30g/L, plasma cells 10-60% on bone marrow aspiration.
250
What is plasmacytoma?
A localized form of myeloma that usually forms in marrow-containing bones.
251
What is the management for plasmacytoma?
Localized radiotherapy.
252
What is the annual incidence of multiple myeloma?
7 per 100,000 people.
253
What is the median age at diagnosis for multiple myeloma?
70 years.
254
What is the most common cause for presentation in multiple myeloma?
Bony pain.
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What are the common symptoms of multiple myeloma?
* Anaemia
* Hypercalcaemia
* Bony deposits
* Renal failure.
256
What are the components of the CVD regimen for multiple myeloma?
* Cyclophosphamide
* Bortezomib
* Dexamethasone.
257
What is the major side effect of Bortezomib?
Peripheral neuropathy.
258
What is the prognosis for multiple myeloma?
Median survival is increasing beyond 4 years.
259
What characterizes Waldenstrom's Macroglobulinaemia?
High circulating levels of IgM paraprotein.
260
What is the classic presentation of Waldenstrom's Macroglobulinaemia?
Peripheral neuropathy.
261
What is the typical prognosis for Waldenstrom's Macroglobulinaemia?
Median survival is 7 years.
262
What is amyloidosis?
A group of conditions with abnormal protein deposition in tissues.
263
What is the most common form of amyloidosis?
AL Amyloidosis.
264
What is required for the diagnosis of amyloidosis?
Tissue histological assessment.
265
What does positive staining with Congo Red dye indicate?
Diagnosis of amyloidosis.
266
Which organ is commonly affected by amyloidosis leading to cardiomyopathy?
Heart.
267
What is TTR Amyloidosis?
Amyloidosis caused by misfolded transthyretin protein deposition.
268
What are the characteristic echocardiogram findings in amyloidosis?
* Increased LV wall thickness
* Reduced tissue doppler velocities
* Small pericardial effusion.
269
What treatment is available for TTR amyloidosis?
Tafamadis.
270
What are the two major forms of TTR amyloidosis?
Mutant and wild type
## Footnote
Mutant is an inherited genetic mutation of the TTR gene, while wild type is a slowly progressive deposition of excess TTR (senile form)
271
How can TTR amyloidosis with cardiac involvement be detected?
By performing a DPD bone scan demonstrating high uptake in cardiac tissue
272
What is Tafamadis?
One of the first studied drugs for TTR amyloidosis in the ATTR-ACT Study
273
What is the prognosis for patients with TTR amyloidosis?
Remains poor, with treatments extending survival by a matter of months
274
What are the most common forms of amyloidosis?
AL and AA amyloidosis
275
What is Factor V Leiden?
A genetic mutation that increases the risk of venous thromboembolism (VTE)
276
What is the prevalence of heterozygous Factor V Leiden mutation in the population?
Up to 596 of the population
277
What is the risk of VTE for heterozygous individuals with Factor V Leiden?
5x population risk
278
What is the risk of VTE for homozygous individuals with Factor V Leiden?
10-100x population risk
279
What is the normal function of Factor V?
Acts as a cofactor to Factor Xa, converting prothrombin to thrombin
280
What does Activated Protein C do?
Down regulates the activity of Factor V
281
How is the diagnosis of Factor V Leiden made?
Positive genetic test for the mutation
282
What is the Russell's Viper Venom Test?
A test that assesses the ability of Protein C to form an early clot in the presence of venom
283
What is the management for patients with homozygous Factor V Leiden?
Lifelong anticoagulation
284
Is there a curative treatment for Factor V Leiden?
No
285
What is Protein C deficiency?
A rare condition that results in an increased risk of VTE
286
What are the types of Protein C deficiency?
Type 1 involves a genetic mutation in Protein C synthesis; Type 2 involves a mutation affecting Protein C function
287
What is the risk of thrombosis in Protein C deficiency?
Extremely high, with an annual risk of VTE of 2-59%
288
What happens to Protein C levels in Protein C deficiency?
They are decreased
289
What is the management for Protein C deficiency?
Lifelong anticoagulation
290
What is Protein S deficiency?
A rare condition that reduces the effectiveness of Protein C
291
What is the risk of thrombosis in Protein S deficiency?
Mild to moderate, annual risk largely unknown
292
What is the management for Protein S deficiency?
Lifelong anticoagulation
293
What is the prothrombin gene mutation?
A genetic mutation that increases the risk of thrombosis
294
What is the incidence of prothrombin gene mutation in the population?
Approximately 2%
295
What is the risk of VTE for heterozygous individuals with a prothrombin gene mutation?
3x population risk
296
What characterizes Antithrombin III deficiency?
Low incidence (approximately 0.2% of the population) with a high risk of thrombosis
297
What is the annual risk of VTE in Antithrombin III deficiency?
29%
298
What is Antiphospholipid Syndrome (APLS)?
An autoimmune condition associated with increased thrombosis risk
299
What antibodies are involved in APLS?
* Anti-cardiolipin antibodies
* Lupus anticoagulant antibodies
* Anti-B2-glycoprotein antibodies
300
What is the management for patients with APLS?
Lifelong anticoagulation with warfarin
301
What is the inheritance pattern of Haemophilia?
X-linked recessive disorder
302
What are the two types of Haemophilia?
* Haemophilia A - deficiency of Factor VIII
* Haemophilia B - deficiency of Factor IX
303
What is the typical presentation of Haemophilia?
Haemarthrosis or intracranial haemorrhage
304
What is the management for Haemophilia A?
Replacement of Factor VIII
305
What is von Willebrand Disease (vWD)?
The most common bleeding disorder worldwide
306
What is the inheritance pattern of von Willebrand Disease?
Autosomal dominant inheritance (Types 1 and 2)
307
What is the diagnosis for Type 1 vWD?
vWF antigen level <30% of a normal control
308
What is the management for vWD?
Desmopressin in mild cases and factor replacement in severe cases
