Haematology Flashcards
1
Q
Aetiology of Acute Myeloblastic Leukaemia
A
Malignant proliferation of precursor myeloblasts in bone marrow
2
Q
Risk factors for Acute Myeloblastic Leukaemia
A
Other haematological disorders, exposure to radiation, chemotherapy, Down’s syndrome, Neurofibromatosis, exposure to Benzene, increasing age
3
Q
What is the most common Acute Leukaemia in adults?
A
Acute Myeloblastic Leukaemia
4
Q
Presentation of Acute Myeloblastic Leukaemia
A
Anaemia, leukopenia (infections), thrombocytopenia (bleeding), infiltration of leukaemic cells (hepatosplenomegaly, gum hypertrophy)
5
Q
Diagnosis of Acute Myeloblastic Leukaemia
A
Bone marrow- blast cells > 20% in blood/bone marrow
6
Q
Management of Acute Myeloblastic Leukaemia
A
Supportive- fertility cryopreservation, blood products
Chemotherapy
Bone marrow transplant
7
Q
Prognosis of Acute Myeloblastic Leukaemia
A
50% 5-year survival
8
Q
What is Acute Lymphoblastic Leukaemia?
A
Malignant proliferation of lymphoblast precursor cells in bone marrow, mostly B cells
Lymphoblast precursor cells proliferate and replace normal cells of bone marrow- spill into peripheral circulation
9
Q
What is the most common cancer in children?
A
Acute Lymphoblastic Leukaemia
10
Q
What is the most common age of presentation of Acute Lymphoblastic Leukaemia?
A
Age 2-4 years
11
Q
Presentation of Acute Lymphoblastic Leukaemia
A
Fatigue, dizziness, palpitations, bone and joint pain, infections, fever, splenomegaly, dyspnoea, thrombocytopenia, pallor, petechiae, lymphadenopathy
12
Q
Diagnosis of Acute Lymphoblastic Leukaemia
A
Bone marrow- blast cells > 20% in blood/bone marrow
13
Q
How is Acute Lymphoblastic Leukaemia classified?
A
Into B and T cells
14
Q
Management of Acute Lymphoblastic Leukaemia
A
Chemotherapy/Radiotherapy, stem cell transplant
15
Q
Prognosis of Acute Lymphoblastic Leukaemia
A
80% cured
16
Q
What is Chronic Lymphoblastic Leukaemia?
A
Malignant proliferation of mature lymphocytes, usually B cells
17
Q
Presentation of Chronic Lymphoblastic Leukaemia
A
Lymphocytosis in blood
Lymphadenopathy
Splenomegaly
18
Q
Management of Chronic Lymphoblastic Leukaemia
A
Chemotherapy
19
Q
What is Chronic Myeloid Leukaemia?
A
Proliferation of mature myeloid cells
- neutrophils, basophils, eosinophils
20
Q
Which genetic mutation is linked to Chronic Myeloid Leukaemia?
A
Philadelphia chromosome t9;22 chromosomal translocation
–> tyrosine kinase activity
21
Q
Management of Chronic Myeloid Leukaemia
A
Imatinib is a tyrosine kinase inhibitor
Cured by bone marrow transplant
22
Q
Which age group is affected by Chronic Myeloid Leukaemia?
A
Middle aged to elderly
23
Q
Where is lymphoma found?
A
Mostly in lymph nodes, but also in blood, bone marrow, spleen, liver
24
Q
Aetiology of lymphoma
A
Cancer of lymphatic system- malignant growth of lymphocytes (WBCs)
25
Which age groups are affected by Hodgkin's Lymphoma?
Young adults + Elderly
26
Presentation of Hodgkin's Lymphoma
Painless lymphadenopathy, hepatosplenomegaly, B symptoms, anaemia
Lump in neck painful on alcohol consumption
27
Investigation of Hodgkin's Lymphoma
Lymph node biopsy- Reed Sternberg cells
28
What is found on lymph node biopsy in Hodgkin's Lymphoma?
Reed Sternberg cells
29
Management of Hodgkin's Lymphoma
Stage 1-2a: short combo chemotherapy then radiotherapy
Stage 2a-4a: longer combo chemo
Relapse: high dose chemo then autologous bone marrow transplant
Rituximab: anti-CD20
30
Which group of people are most likely to get Non-Hodgkin's Lymphoma?
Immunodeficient- drugs, HIV
31
How is Non-Hodgkin's Lymphoma classified?
Cell of origin: T or B
| Stage of lymphatic maturation- high grade or low grade
32
What are high grade Non-Hodgkin's Lymphomas?
Diffuse large B cell lymphoma
| Burkitt Lymphoma
33
What are low grade Non-Hodgkin's Lymphomas?
Follicular Lymphoma
| Splenic marginal zone lymphoma
34
Presentation of Non-Hodgkin's Lymphoma
Painless superficial lymphadenopathy, B symptoms, pancytopenia
Extra-nodal disease: Gastric MALT, small bowel lymphomas, skin, bone, oropharynx, CNS, lung
35
Aetiology of Multiple Myeloma
Malignant proliferation of plasma cells in bone marrow
- B cells that produce Ig
- Bone marrow destruction + failure from infiltration
36
What is the spectrum of pre-malignant conditions for Multiple Myeloma?
MGUS (Monoclonal Gammopathy of Undetermined Significance)
- -> Asymptomatic Myeloma
- -> Multiple Myeloma
37
What is the peak age for Multiple Myeloma?
Age 70
38
How is Multiple Myeloma classified?
By antibody
39
Which is the most common type of Multiple Myeloma?
IgG
40
Features of Multiple Myeloma
CRAB:
- hyperCalcaemia due to bone resorption
- Renal failure- deposition of light chains in renal tubules
- Anaemia (normocytic)
- Bony lesions- pain or pathological fractures
41
X-ray findings in Multiple Myeloma
Lytic bone lesions eg pepper-pot skull
Vertebral collapse
Fractures
Osteoporosis
42
Management of Multiple Myeloma
```
Chemo then autologous bone marrow transplant
Correct anaemia
Fluids for renal failure
Manage infection
Analgesia/radiotherapy for bone pain
```
43
How are MGUS, Asymptomatic myeloma and Multiple myeloma differentiated?
```
MGUS:
- <10% plasma cells
- +ve monoclones
- Asymptomatic
Asymptomatic myeloma:
- >10% plasma cells
- +ve monoclones
- Asymptomatic
Multiple myeloma:
- >10% plasma cells
- +ve monoclones
- Symptomatic
```
44
What is Systemic Sclerosis?
Autoimmune production of antibodies --> abnormalities in small blood vessels, fibrosis of skin and internal organs due to excessive collagen production and deposition, immune activation
45
Types of Systemic Sclerosis
Diffuse or Limited
46
Presentation of limited Systemic Sclerosis
CREST
- Calcinosis
- Raynaud's
- oEsophageal dysmotility
- Sclerodactyly
- Telangiectasia
47
Which antibodies may be present in Systemic Sclerosis?
Anti-topoisomerase I
Anti-centromere (ACA) - limited
Anti-RNA polymerase III - diffuse
48
Management of Systemic Sclerosis
Symptomatic treatment
| Immunotherapy- Methotrexate
49
Mechanism of action of Heparin
Binds to antithrombin + increases its activity, indirect thrombin inhibitor
50
How can Heparin be monitored?
APTT
51
How is LMW Heparin excreted?
Renally excreted
52
Mechanism of action of aspirin
COX inhibitor, inhibits thromboxane formation --> inhibits platelet aggregation
53
Mechanism of action of Clopidogrel
Inhibits ADP-induced platelet aggregation
54
Mechanism of action of Warfarin
Prevents synthesis of Factor 2, 7, 9, 10; antagonises vitamin K, prolongs PT
55
How can Warfarin be monitored?
INR- target 2-3
| Also prolongs PT
56
How can Warfarin be reversed?
Vitamin K or FFP
57
What is target INR for somebody on Warfarin therapy?
2-3 (normal < 1)
58
Mechanism of action of DOACs
Direct Oral Anticoagulants
Anti-IIa and Anti-Xa inhibitors
- Rivaroxaban + Apixaban- Xa
- Dabigatran- direct thrombin inhibitor
59
How can DOACs be reversed?
Beriplex
60
Name the 4 blood groups
A, B, AB, O
61
What type of immunoglobulin crosses the placenta in rhesus disease?
IgG anti-D
62
What coagulation disorder does bleeding into muscles and joints suggest?
Haemophilia
63
How do mucocutaneous bleeding disorders present?
Easy bruising, prolonged bleeding, epistaxis, gum bleeding, GI blood loss
64
What is the function of Neutrophils?
Phagocytose and kill bacteria
65
What is the function of Monocytes?
Produced in bone marrow and enter tissues as macrophages, some become dendritic cells which present antigens to the immune system
66
What is the function of Basophils?
Migrate to tissues and become mast cells, contain granules of histamine, surface IgE
67
What is the function of Eosinophils?
Protection against parasites, role in inflammation and allergy
68
What is the function of Lymphocytes?
Immunity, generate antibodies against foreign antigen, some have memory --> vaccination
69
Risk factors for Arterial thrombosis
Smoking, hypertension, diabetes, obesity, stress, hyperlipidaemia
70
How does Arterial thrombosis present?
MI
CVA
PVD
71
Management of Arterial thrombosis
Thrombolytics- alteplase, streptokinase
72
How does Venous thrombosis present?
PE
| DVT
73
Investigations for Venous thrombosis
D-dimer, Doppler, CTPA
74
Risk factors for Venous thrombosis
Surgery, immobilisation, oestrogens, malignancy, Factor V Leiden, Antithrombin deficiency, Protein C/S deficiency
75
Management of Venous thrombosis
LMW Heparin initially
| Then oral Warfarin for 3-6mths (depending on provoked vs unprovoked)
76
Prevention of Venous Thrombosis
Prevention: LMWH, TEDs hydration, early mobilisation
77
Hazards of blood transfusion
Early: ABO incompatibility reaction, fluid overload, febrile/urticarial reaction, bacterial/malarial reaction
Late: RhD/Antibody sensitisation, delayed transfusion reaction, Hep B/C, HIV, CJD, iron overload
78
Indications for FFP transfusion
Liver disease, DIC, dilutional coagulopathy
79
Indications for Platelet transfusion
To correct bleeding due to thrombocytopenia
80
Why does liver disease cause bleeding disorders?
Liver is the site of synthesis of coagulation factors and fibrinogen
--> Prolonged bleeding + PT time
81
Why does vitamin K deficiency cause bleeding disorders?
Vitamin K is needed for synthesis of coagulation factors 2, 7, 9 and 10
Deficiency --> prolonged bleeding and PT time
82
How is vitamin K deficiency prevented?
Subcut vitamin K injection in all newborn babies
83
How is Haemophilia inherited?
Sex-linked: males affected, female carriers
84
Which type of Haemophilia is more common?
A is more common than B
85
Which blood test is abnormal in Haemophilia?
Raised APTT- as measures factor 8+9
86
What is deficient in i) Haemophilia A and ii) Haemophilia B?
A: deficiency of factor 8
B: deficiency of factor 9
87
Presentation of Haemophilia
Severe bleeding disorder- bleed into muscles and joints
88
Management of Haemophilia
Recombinant factor 8 (A) or 9 (B)
89
What is the inheritance pattern of Thalassaemia?
Autosomal recessive
90
Aetiology of Thalassaemia
Decreased or absent of 1 or more polypeptide chains (a or B) that form Hb
--> reduced Hb in red cells --> anaemia
91
How does Thalassaemia trait present?
Asymptomatic
92
How does Alpha thalassaemia present?
Lethal in utero
93
How does Beta thalassaemia major present?
Anaemia- 'Cooley's anaemia'
94
When is Thalassaemia screened for?
Conceptual screening
95
How is Thalassaemia diagnosed?
Hb electrophoresis
96
Investigations in Thalssaemia
Hb electrophoresis for diagnosis
Conceptual screening
Skeletal survey
97
What are the findings in a skeletal survey in Thalassaemia?
Skull x-ray: hair-on-end appearance
Deformed ribs, long bones + flat bones
CXR: Cardiomegaly + cardiac failure
98
How is Thalassaemia staged?
Stage 1-3 based on symptoms, transfusions, echo + ECG
99
Management of Thalassaemia
Thalassaemia intermedia- occasional transfusions
| Thalassaemia major- regular hypertransfusion, iron chelation- Desferrioxamine to avoid overload
100
Which blood test result can be skewed in Thalassaemia?
HbA1c
101
Aetiology of Von-Willebrand's disease
Congenital (type 1, 2 or 3) or Acquired (lymphoproliferative/myeloproliferative disorders)
vWF assists platelet plug formation by attracting platelets to site of damage, binds to factor 8 to prevents its clearance from plasma
--> Platelet dysfunction
--> Deficience of Factor VIII
102
Management of Von-Willebrand's disease
Educate to bleeding risk, avoid NSAIDs, anti-platelets
Tranexamic acid for minor bleeding
Desmopressin increases factor 8 + vWF temporarily by releasing endothelial stores
COCP/IUCD for menorrhagia
103
What is the aetiology of Immune thrombocytopenia?
Autoimmune disorder with reduced platelets
Antibodies bind to platelet antigens
--> platelet destruction and inhibition of platelet production
104
Causes of Immune thrombocytopenia
Secondary to anti-phospholipid syndrome, SLE, viral infections (CMV, HIV, HCV), H pylori, lymphoproliferative disorders
Following immunisations in children
105
How is persistent and chronic Immune thrombocytopenia defined?
Persistent: 3-12mths
Chronic: > 12 months
106
Prognosis of immune thrombocytopenia
Usually recovers after 6-8 weeks
107
Presentation of immune thrombocytopenia
Asymptomatic or petechiae, bruising, epistaxis, haematuria, GI bleeds, menorrhagia, intracranial bleeds
108
Management of Immune thrombocytopenia
Trauma prevention, avoid NSAIDs + aspirin
| Prednisolone, anti-D, immunisations, IVIg
109
Aetiology of Disseminated Intravascular Coagulation
Systemic activation of blood coagulation, which generates fibrin --> thrombosis of medium and small vessels --> organ dysfunction
Simultaneous bleeding and microvascular thrombosis
110
Causes of Disseminated Intravascular Coagulation
Sepsis, eclampsia, leukaemia, major trauma, transplant rejection, surgery, recreational drugs, transfusion reaction
111
Presentation of Disseminated Intravascular Coagulation
Bleeding from unrelated sites, large bruises, confusion, fever, petechiae/purpura, haemorrhagic bullae, thrombosis
112
How is Disseminated Intravascular Coagulation staged/scored?
International society of thrombosis and haemostasis score based on blood tests
113
Management of Disseminated Intravascular Coagulation
Treat the cause
| Platelet transfusion, FFP, LMW Heparin- all based on symptoms
114
What level of Hb is classed as anaemia?
125 in men
| 115 in women
115
How is anaemia classified?
By MCV:
- < 80 = Microcytic
- 80-100 = Normocytic
- > 100 = Macrocytic
116
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Chronic disease
117
Causes of normocytic anaemia
Acute bleeding
Haemolysis
Aplastic anaemia
Chronic disease
118
Causes of Macrocytic anaemia
Vit B12/Folate deficiency
Hypothyroidism
Pernicious anaemia eg Addison's/Graves
119
Causes of Polycythaemia
True:
- Epo driven- COPD, cysts/tumours
- Epo independent- Polycythaemia rubra vera
Not true- volume depletion
120
Aetiology of Polycythaemia Rubra Vera
Too many RBCs produced in bone marrow
| JAK-2 mutation
121
Presentation of Polycythaemia Rubra Vera
Fatigue, pruritus (worse after hot shower), splenomegaly, thrombosis, peptic ulceration, bleeding, erythromelalgia (burning pain and redness in body), cyanosis with high Hb
122
Diagnostic criteria for Polycythaemia Rubra Vera
Hb, JAK-2, Bone marrow biopsy, erythropoeitin
123
Management of Polycythaemia Rubra Vera
```
Long-term phlebotomy
Low dose aspirin
JAK2 inhibtiros- Ruxolitinib
Anti-histamines for pruritus
Cytoreductive treatments- Hydroxycarbamide
```
124
Causes of secondary immunodeficiency
Malignancy, drugs (cytotoxic), HIV, malnutrition, protein loss (nephrotic syndrome)
125
Features of immunodeficiency
Infections- opportunistic eg PCP
FTT, diarrhoea
Vasculitis, arthritis
Gastric carcinoma, Liver disease
126
Management of Immunodeficiency
Healthy lifestyle, dental checks
Live vaccines contraindicated in T cell deficiency
Prophylactic antibiotics/antivirals for some
IV/Subcut Ig replacement
T cell deficiency --> bone marrow transplant
127
What is Aplastic Anaemia?
Pancytopenia with hypocellular bone marrow in the absence of abnormal infiltrate or marrow fibrosis
128
At what age groups does aplastic anaemia peak?
10-25 and over 60s
129
Causes of Aplastic Anaemia
```
Majority idiopathic
Congenital eg Fanconi's anaemia
Acquired infection eg EBV
Drugs eg Naproxen
Toxic exposure
Pregnancy
Sickle cell aplastic crisis
```
130
Features of Aplastic Anaemia
Anaemia, thrombocytopenia, infection
131
Diagnosis of Aplastic Anaemia
Hb < 100
Platelets < 50
Neutrophils < 1.5
132
Management of Aplastic Anaemia
```
Haematopoeitic stem cell transplant
Immunosuppressants
Blood/platelet transfusion
Iron chelation
Prophylactic antibiotics + antifungals
```
133
What is the inheritance pattern of G6PD deficiency?
X-linked
134
Aetiology of G6PD deficiency
Low G6PD --> low glutathione --> increased red cell susceptibility to oxidative stress --> Neonatal jaundice, intravascular haemolysis, gallstones, splenomegaly
135
Presentation of G6PD deficiency
Neonatal jaundice
Intravascular haemolysis
Gallstones
Splenomegaly
136
What is seen on blood film in G6PD deficiency?
Heinz bodies
| Bite + blister cells
137
How is G6PD deficiency diagnosed?
G6PD enzyme assays
138
What is G6PD?
Glucose-6-phosphate dehydrogenase, deficiency can lead to haemolytic anaemia
139
Which drugs can trigger haemolysis in G6PD deficiency?
Primaquine, Ciprofloxacin, Sulphonamides, Sulfasalazine, Sulphonylureas
140
Causes of iron deficiency anaemia
Reduced intake
Increased requirement: pregnancy, childbirth, coeliac disease
Chronic blood loss- GI/menorrhagia
141
Management of iron deficiency anaemia
Treat the cause
Ferrous sulphate 200mg oral TDS until Hb normal then 3 months to rebuild stores
Consider IV if caused by malabsorption
142
Causes of B12 deficiency
Lack of intrinsic factor- pernicious anaemia (gastrectomy)
| Failure of absorption in terminal ileum- resection, Coeliac
143
Management of B12 deficiency anaemia
Parenteral Hydroxocobalamin (B12)
144
What other problem can B12 deficiency cause other than anaemia?
Peripheral neuropathy
145
What is folate necessary for in the body?
DNA synthesis
146
Causes of folate deficiency
Dietary, malabsorption (Coeliac)
| Increased requirement- pregnancy, drugs, psoriasis
147
Management of Folate deficiency
Oral folate 5mg daily
148
Causes of Haemolytic anaemia
Congenital: hereditary spherocytosis, G6PD deficiency, sickle cell, thalassaemia
Acquired: haemolytic disease of the newborn, blood transfusion reaction, SLE, trauma, DIC, haemolytic uraemic syndrome, liver disease
149
Presentation of Haemolytic Anaemia
Severe anaemia
| Gallstones, haemoglobinuria, splenomegaly
150
What is found on blood tests in Haemolytic Anaemia?
Low Hb
| High reticulocytes
151
Management of Haemolytic Anaemia
Folic acid
Discontinue causative drugs
Iron therapy
Splenectomy
152
What is the inheritance pattern of Hereditary spherocytosis?
Autosomal dominant
153
What is Hereditary spherocytosis?
Autosomal dominant defect of the RBC cytoskeleton
154
Presentation of Hereditary spherocytosis
FTT, jaundice, gallstones, splenomegaly, aplastic crisis, haemolysis
155
Investigations in Hereditary spherocytosis
Blood film- spherocytes
| Cryohaemolysis test + EMA binding
156
Management of Hereditary spherocytosis
Folate replacement + Splenectomy
157
What is the inheritance pattern of Sickle Cell Disease?
Autosomal recessive
158
Aetiology of Sickle cell disease
Forms abnormal Hb molecule
Sickled cells have reduced deformability and are easily destroyed --> occlusion of microcirculation + chronic haemolytic anaemia
159
In which region is Sickle Cell Disease most prevalent?
Sub-Saharan Africa
160
When does Sickle Cell Disease present?
Symptoms appear at 3-6 months when HbF is falling
161
Presentation of Sickle Cell Disease
Anaemia, jaundice, pallor, lethargy, growth restriction, infections, splenomegaly, delayed puberty, priapism
162
How is Sickle Cell Disease diagnosed?
Blood films, sickle solubility test, Hb analysis
163
How is Sickle Cell Disease screened for?
Neonatal blood spot, preconceptual, preop, prenatal
164
What genotype is Sickle cell trait?
Heterozygous HbAS
165
What genotype is Sickle cell anaemia?
Homozygous HbSS
166
How does Sickle cell trait present?
Usually asymptomatic
| Haematuria, renal papillary necrosis, splenic infarction, renal medullary cancer, exercise-related sudden death
167
How is Sickle cell trait diagnosed?
Presence of HbAS on Hb electrophoresis
168
Management of Sickle cell trait
Adequate hydration, avoid exertion/heat
169
Name the Sickle cell crises
- Vaso-occlusive crisis
- Aplastic crisis
- Sequestration crisis
- Acute chest syndrome
- Hyperhaemolytic crisis
170
Aetiology of Vaso-occlusive crisis in Sickle Cell Disease
Obstruction of micro-circulation by sickled cells
| Precipitated by cold, infection, dehydration, exertion, ischaemia
171
What can Vaso-occlusive crisis in Sickle Cell Disease be precipitated by?
Cold, infection, dehydration, exertion, ischaemia
172
Presentation of Vaso-occlusive crisis in Sickle Cell Disease
Swollen painful joints, tachypnoea, neuro signs, abdominal distension, pain, stroke, placental infarction
173
Aetiology of Aplastic crisis in Sickle cell disease
Temporary cessation of erythropoeisis
| Usually precipitated by Parvovirus 19
174
What is Aplastic crisis in Sickle cell disease usually precipitated by?
Parvovirus 19
175
Presentation of Aplastic crisis in Sickle cell disease
Severe anaemia
176
Aetiology of Sequestration crisis in Sickle cell disease
Sudden enlargement of spleen
| --> reduced Hb concentration, circulatory collapse and hypovolaemic shock
177
What is Acute chest syndrome in Sickle cell disease?
Vaso-occlusive crisis affecting the lungs
178
Management of Sickle Cell Disease
- Monitoring, educational, psychological
- Folic acid + zinc supplements
- Penicillin prophylaxis, pneumococcal vaccine, malaria chemoprophylaxis
- Blood transfusions
- Hydroxycarbamide to increase HbF
- Bone marrow transplant
- Annual transcranial doppler
179
What annual screening test needs to be done in Sickle cell disease?
Annual transcranial doppler
