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Phase 2a Medicine > Haematology > Flashcards

Haematology Flashcards

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1
Q

Where does myeloma start?

A

Plasma cell

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2
Q

Describe plasma cells

A
  1. Usually reside in bone marrow
  2. Fully differentiated B cell
  3. Easily recognisable
  4. Produce immunoglobulins
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3
Q

Describe the plasma cell in myeloma

A

Cloned malignant plasma cells all producing same immunoglobulin in massive quantities

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4
Q

What is MGUS?

A

Monoclonal gammopathy of undetermined significance

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5
Q

Name 3 plasma cell diseases

A
  1. Plasmocytomas
  2. Waldenstroms macroglobulinaemia
  3. MGUS
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6
Q

What does MGUS involve?

A

IgM

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7
Q

What is the end organ damage in myeloma?

A

CRAB

  1. Calcium
  2. Renal
  3. Anaemia
  4. Bone disease
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8
Q

Give 6 symptoms of myeloma

A
  1. Anaemia
  2. Fatigue
  3. Bone pain (esp. back)
  4. Hypercalcaemia
  5. High ESR
  6. Lytic bone lesions/CRAB
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9
Q

What is CRAB associated with?

A
  1. Infection
  2. Hyperviscosity
  3. Amyloidosis
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10
Q

What does myeloma look like under microscope?

A

Rouleaux (basophilic, accentuated nucleus)

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11
Q

What is the main cause of death in myeloma?

A

Infection

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12
Q

Why does hyperviscosity occur in myeloma?

A

Excessive protein in blood causes it to thicken

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13
Q

What are the causes of immune deficiency in myeloma?

A
  1. Immunoglobulin deficiency
  2. Neutropenia
  3. Chemo/steroids
  4. Immobility
  5. Renal failure
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14
Q

Which gene is most often associated with myeloma?

A

T(11;14)

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15
Q

What are the signs of amyloidosis?

A
  1. Swelling of limbs
  2. Nephrotic syndrome
  3. HF
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16
Q

What is the Tx aim for myeloma?

A

Achieve a plateau phase, control symptoms and supportive measures

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17
Q

What Tx are used for myeloma?

A
  1. Radiotherapy - spot welding
  2. Chemo/steroids/biphosphonates
  3. Palliative care
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18
Q

What are the 4 types of leukaemia?

A
  1. Acute myeloid leukaemia (AML)
  2. Chronic myeloid leukaemia (CML)
  3. Acute lymphoblastic leukaemia (ALL)
  4. Chronic lymphocytic leukaemia (CLL)
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19
Q

What are the common symptoms of leukaemia?

A
  1. Symptomatic anaemia e.g. fatigue
  2. Symptomatic thrombocytopenia e.g. bruising
  3. Symptomatic low WCC e.g. recurrent infections
  4. Symptomatic high WCC e.g. leukostasis or tumour lysis
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20
Q

What is the presentation of leukostasis?

A
  1. Seen on CXR lungs
  2. SOB
  3. Renal impairment
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21
Q

What is the presentation of tumour lysis?

A
  1. AKI
  2. Hyperkalaemia
  3. Hypophosphataemia
  4. Raised LDH
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22
Q

What is the DDx for leukaemia?

A
  1. Acute leukaemia
  2. Haematological disorder
  3. Severe sepsis
  4. Post-operative reactive changes
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23
Q

What % of cytopenias are blasts?

A

20%

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24
Q

What is the DDx for cytopenia?

A
  1. Haematinic deficiency
  2. Immune
  3. Consumption
  4. Infections
  5. Comorbidities e.g. renal impairment
  6. Bone marrow infiltration
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25
What is the investigation for leukaemia?
1. FBC, LFT, U&E | 2. Bone marrow aspirate and trephine biopsy (>20% blasts)
26
How is acute leukaemia classified?
Bone marrow contains >20% blasts/leukaemic cells
27
How is chronic leukaemia classified?
1. Clonal mature cells 2. High WCC 3. Pt. are less unwell at presentation
28
What is leukaemia?
Malignant proliferation of haematopoietic cells
29
How is leukaemia diagnosed?
1. Blood film 2. Bone marrow biopsy 3. Lymph node biopsy 4. Immunophenotyping 5. Genetics e.g. FISH, PCR
30
AML makes up what % of childhood leukaemia?
10-15%
31
What groups are at higher risk of AML?
1. Preceding haematological disorders 2. Prior chemo 3. Exposure to ionising radiation
32
What is the median age for AML?
85-89
33
What is the treatment for AML?
1. Supportive care 2. Chemo 3. Transplantation
34
What is the supportive Tx for AML?
1. HML 2. Blood product support 3. Prompt Tx of infections 4. Recognition of atypical/unusual infections
35
What must be considered prior to chemo?
1. Fertility cryopreservation 2. Clinical trial availability 3. Bystander damage to other organs
36
Name 2 chemotherapy drugs for AML
1. Anthracycline | 2. Cytarabine
37
Name 4 side effects of chemotherapy
1. Nausea/vomiting 2. Altered bowel habit 3. Reduced fertility 4. Loss of appetite
38
What non-curative Tx are available for AML?
1. Azacytidine | 2. Low dose SC cytarabine
39
What supportive measures are used for AML?
1. Red cell transfusion 2. Platelet transfusion 3. Abx
40
What personalised Tx can be used for leukaemia?
CAR-T (chimeric antigen receptor T cells)
41
What transplant is used for AML?
Allogenic haematopoietic stem cell transplantation
42
Name 4 post-transplant complications
1. Hickman line infection 2. Cutaneous graft vs host disease 3. Jaundice 4. Hormone dysfunction
43
What are the cure rates of AML?
20-60% depending on age
44
What is the usual age of onset in CML?
40-60yr
45
What are the clinical features of CML?
1. Splenomegaly 2. Metabolic features 3. High WCC 4. Film: left shift and basophilia
46
What gene is associated with CML?
Philadelphia chromosome: t(9;22)
47
What is the Tx for CML?
Tyrosine kinase inhibitors 1. Imatinib 2. Nilotinib
48
What are the complications of CML?
1. Risk of accelerated phase/blast crisis | 2. TKI binding site mutations
49
What is the most common paediatric malignancy?
ALL (3-7yr)
50
What is the presentation of ALL?
1. Bone marrow failure | 2. Organ infiltration (CNS)
51
What are the Tx phases for ALL?
1. Induction 2. Consolidation 3. Delayed intensification 4. Maintenance
52
What is the Tx for ALL?
1. CNS directed therapy | 2. Stem cell transplant
53
What is the most common leukaemia?
CLL
54
What is the pathophysiology of CLL?
Gradual accumulation of B lymphocytes
55
What are the clinical features of CLL?
1. Progressive lymphadenopathy 2. Haemolysis 3. Bone marrow failure 4. Hypogammaglobinaemia
56
What is the Tx for CLL?
1. Chemo 2. Monoclonal antibodies e.g. rituximab 3. Targeted therapy e.g. ibrutinib 4. Bone marrow transplant
57
What is lymphoma?
A malignant growth of white blood cells
58
What are the causes of lymphoma?
1. Primary immunodeficiency 2. Secondary immunodeficiency 3. Infection 4. Autoimmune disorders
59
What is the pathophysiology of lymphoma?
1. Impaired immunosurveillance of EBV infected cells | 2. Infected B cells escape regulation and proliferate autonomously
60
Give 5 symptoms of lymphoma
1. Enlarged lymph glands 2. Extranodal disease 3. Lymph oedema 4. Fever 5. Weight loss
61
How is lymphoma diagnosed?
1. Blood film 2. Bone marrow 3. Lymph node biopsy 4. Immunophenotyping - CD20 on B lymphocytes 5. Cytogenics e.g. FISH 6. PCR
62
What investigations are used to stage lymphoma?
1. Bloods 2. CT chest/abdo/pelvis 3. Bone marrow biopsy 4. PET
63
What are the lymphoma subtypes?
1. Hodgkin's | 2. Non-Hodgkin's
64
What is the presentation of Hodgkin's lymphoma?
1. Painless lymphadenopathy | 2. B symptoms e.g. sweats, weight loss
65
What confirms Hodgkin's lymphoma diagnosis?
Reed-Sternberg cell
66
What is the Tx for stage 1-2A lymphoma?
Short course combination chemo followed by radiotherapy
67
What is the Tx for stage 2B-4 lymphoma?
Combination chemo
68
What is the treatment in Hodgkin's lymphoma relapse?
Autologous bone marrow transplant
69
Give 4 complications of Hodgkin's lymphoma
1. Infertility 2. Bleomycin 3. Psychological issues 4. Anthracyclines
70
What is the Tx for indolent NHL?
1. Nothing 2. Alkylating agents 3. Chemo 4. Monoclonal antibodies 5. Bone marrow transplant
71
What is the Tx for early aggressive NHL?
Short course chemo + RT
72
What is the Tx for late aggressive NHL?
Combination chemo + monoclonal antibodies
73
Give an example of a monoclonal antibodies drug
Rituximab
74
What is anaemia?
Reduced red cell mass +/- reduced Hb conc.
75
When would a person get reduced Hb but increased RCM?
Third trimester pregnancy
76
What is high RBC called?
Cytopenia
77
What are the consequences of anaemia?
1. Reduced O2 transport 2. Tissue hypoxia 3. Compensatory changes for reduced Hb
78
What are the compensatory changes for reduced Hb?
1. Tachycardia 2. Increase tissue perfusion 3. Increase O2 transfer to tissues 4. Increase RBC production
79
What are the pathological consequences of anaemia?
1. Myocardial fatty change 2. Fatty change in liver 3. Aggravate angina 4. Spooning 5. CNS cell death
80
How is anaemia classified?
1. Microcytic 2. Normocytic 3. Macrocytic
81
What is the aetiology of microcytic anaemia?
1. Iron deficiency 2. Chronic disease 3. Thalassaemia
82
What are the investigations for iron deficiency?
1. Ferritin | 2. Iron studies
83
What are the causes of microcytic anaemia?
1. Cancer 2. Dietary 3. Parasites
84
What is the aetiology of normocytic anaemia?
1. Acute blood loss 2. Anaemia of chronic disease 3. Combined haematinic deficiency
85
What is the DDx of macrocytic anaemia?
1. Foetus (pregnancy) 2. Alcohol 3. Thyroid disease (hypothyroidism) 4. Reticulocytosis 5. B12 and folate deficiency 6. Cirrhosis and chronic liver disease
86
What are the haematological causes of macrocytic anaemia?
1. Antimetabolite therapy 2. Haemolysis 3. Bone marrow failure 4. Bone marrow infiltration
87
What are the investigations for B12 deficiency?
1. IF antibodies 2. Schilling test 3. Coeliac antibodies
88
What is the Tx for B12 deficiency?
1. B12 replacement | 2. Anti-parietal cell antibodies
89
Which anaemia needs haematology referral +/- bone marrow biopsy?
Macrocytic anaemia
90
What is the likely cause of combined haematinic deficiency?
Malabsorption
91
Why is reticulocyte count done?
To see if RBC are produced or destroyed too much
92
How can haemoglobinopathies be classified?
1. Disorders of quality | 2. Disorders of quantity
93
What is Hb S?
A variant haemoglobin arising because of a point mutation in the beta globin gene
94
What does HbS carriage offer protection against?
Falciparum malaria
95
What is sickle cell crisis?
Pain due to blockage of blood vessels inside bone, marrow swells up and is excruciatingly painful
96
What is the life expectancy in sickle cell disease?
50-60 years
97
What are the acute complications of sickle cell disease?
1. Painful crisis 2. Sickle chest syndrome 3. Stroke
98
What are the chronic complications of sickle cell disease?
1. Renal impairment 2. Pulmonary HT 3. Joint damage
99
What is the Tx for sickle cell disease?
1. Transfusion 2. Hydroxycarbamide 3. Stem cell transplant 4. Gene therapy and gene editing
100
What is thalassaemia?
Globin chain disorder resulting in diminished synthesis of one or more globin chains with consequent reduction in haemoglobin
101
What genetic lesions tend to affect alpha thalassaemia?
Deletions
102
What genetic lesions tend to affect beta thalassaemia?
Mutations
103
What are the classes of thalassaemia?
1. Thalassaemia major 2. Thalassaemia intermedia 3. Thalassaemia carrier
104
What is the age at presentation for beta thalassaemia major?
6-12 months
105
What are the symptoms of beta thalassaemia major?
1. Failure to feed 2. Listless 3. Crying 4. Pale
106
What is the diagnosis for beta thalassaemia major?
1. Low Hb, MCV, MCH 2. Large and small pale RBC on blood film 3. Hb F >90%
107
What is the Tx for thalassaemia major?
1. Regular transfusion 2. Iron chelation 3. Endocrine supplements
108
What is the monitoring for thalassaemia major?
1. Ferritin 2. Cardiac and liver MRI 3. Endocrine testing 4. Dexa scanning
109
Where is severe alpha thalassaemia found?
Eastern Mediterranean and Far East
110
What are membranopathies?
Deficiency of red cell membrane proteins caused by a variety of genetic lesions
111
What are the most common membranopathies?
1. Spherocytosis | 2. Elliptocytosis
112
What is the presentation of membranopathies?
1. Neonatal jaundice 2. Haemolytic anaemia 3. Gallstones splendid
113
What is the Tx for membranopathies?
1. Folic acid | 2. Splenectomy
114
What is the effect of parvovirus?
Reduced RBC production and lifespan
115
What is the result of enzymopathies?
Shortened red cell lifespan from oxidative damage
116
What are the common causes of enzymopathies?
1. G6PD deficiency | 2. Pyruvate kinase deficiency
117
How are enzymopathies diagnosed?
NADPH screening test
118
What are the clinical presentations of G6PD deficiency?
1. Haemolysis 2. Jaundice 3. Anaemia
119
What are 4 causes of microcytic anaemia?
1. Smoking 2. Lung disease 3. Altitude 4. Polycythaemia rubra vera (PRV)
120
What is PRV?
Myeloproliferative disorder
121
What mutation is associated with PRV?
JAK2
122
What is the presentation of PRV?
1. Plethoric appearance 2. Thrombosis 3. Itching 4. Splenomegaly 5. Abnormal FBC
123
What is the Tx for PRV?
1. Aspirin 2. Venesection 3. Bone marrow suppressive drugs e.g. hydroxycarbamide
124
What is neutrophilia?
Too many white blood cells
125
What are the causes of neutrophilia?
1. Infection 2. Inflammation 3. Malignancy 4. CML
126
What are the causes of lymphocytosis?
1. Infection 2. Inflammation 3. Malignancy 4. CLL
127
What is thrombocytopenia?
Not enough platelets
128
What are the causes of thrombocytosis?
1. Infection 2. Inflammation 3. Malignancy 4. Essential thrombocythaemia
129
What haemolytic condition is a major infection risk?
Severe neutropaenia
130
What are the causes of neutropaenia?
1. Marrow failure 2. Marrow infiltration 3. Marrow toxicity 4. Autoimmune 5. Felty's syndrome 6. Cyclical
131
What regulates platelet production?
Thrombopoietin
132
What is the lifespan of platelets?
7-10 days
133
What do platelets do to form a platelet plug?
Adhesion and aggregation
134
What activates platelets?
1. Adhesion to collagen via GPIa | 2. Adhesion to vWF via GPIb and IIb/IIIa
135
What happens when platelets are activated?
1. Release of alpha granules 2. Dense granules 3. Membrane phospholipids activate clotting factors II, V and X
136
What are the investigations for platelets disorders?
1. FBC 2. Blood film 3. PFA 4. Bleeding time 5. Surface proteins (flow cytometry)
137
What are the causes of bleeding?
1. Injury 2. Vascular disorders 3. Low platelets 4. Abnormal platelet function 5. Defective coagulation
138
What are the clinical features of platelet dysfunction?
1. Mucosal bleedings 2. Easy bruising 3. Petechiae, prupura 4. Traumatic haematomas
139
Give 5 causes of low platelets
1. Congenital 2. Drugs 3. Marrow suppression 4. EDTA induced clumping 5. Consumption
140
Give 5 causes of impaired platelet function?
1. von Willebrand disease 2. Uraemia 3. Anti-inflammatory drugs 4. Glanzmann disease 5. Storage pool disorders
141
What is thrombocytopaenia?
Altered platelet production
142
What is the pathophysiology of thrombocytopaenia?
Absent/ reduced/ malfunctioning megakaryocytes in BM
143
What are the results of thrombocytopaenia infiltrating bone marrow?
1. Leukaemia 2. Metastatic malignancy 3. Lymphoma 4. Myeloma 5. Myelofibrosis
144
Give 4 causes of reduced platelet production by bone marrow
1. Low B12/folate 2. Reduced TPO 3. MTX/chemo 4. Alcohol
145
What can cause dysfunction production of platelets in BM?
Myelodysplasia
146
What are the causes for thrombocytopenia?
1. Autoimmune 2. Hypersplenism 3. Drug related immune destruction 4. Consumption of platelets
147
What is a major autoimmune thrombocytopenia?
Immune thrombocytopaenia (ITP)
148
What are 3 causes of consumption of platelets?
1. Thrombotic thrombocytopenic purpura (TTP) 2. Disseminated intravascular coagulopathy (DIC) 3. Major haemorrhage
149
Name 3 drugs that can affect platelet function
1. Tirofiban 2. Clopidogrel 3. Aspirin
150
What is the pathophysiology of ITP?
1. IgG antibodies form to platelet and megakaryocytic surface glycoproteins 2. Opsonised platelets are removed by reticuloendothelial system
151
What is the cause of primary ITP?
Viral infection
152
What can cause secondary ITP?
1. CLL 2. HIV 3. Hep C
153
What are the investigations for ITP?
1. Underlying cause | 2. Diagnosis of exclusion
154
What is the Tx for ITP?
1. Immunosuppression 2. Platelets for bleeds 3. Tranexamic acid
155
What is the pathophysiology of DIC?
Cytokine release in response to systemic inflammatory response syndrome (SIRS)
156
How does DIC cause bleeding?
1. Systemic activation of clotting cascade 2. Consumption of platelets and clotting factors 3. Bleeding
157
How does DIC cause organ failure?
1. Systemic activation of clotting cascade 2. Microvascular thrombosis 3. Organ failure
158
What are the investigations for DIC?
1. Underlying cause 2. Thrombocytopenia 3. Prolonged PT and APTT 4. Low fibrinogen 5. High D-Dimer 6. Evidence of organ failure
159
What is the Tx for DIC?
1. Platelets 2. FFP 3. Cryoprecipitate
160
What is the pathophysiology of TTP?
1. Spontaneous platelet aggregation in microvasculature | 2. Reduction in a protease enzyme
161
What are the symptoms of TTP?
1. Microangiopathic haemolytic anaemia 2. Renal/CNS/cardiac impairment 3. Fever
162
What is the Tx for TTP?
1. Urgent plasma exchange | 2. Immunosuppression
163
Why are platelets NOT given in TTP Tx?
Increases thrombosis
164
What is polycythaemia?
Abnormal increase in RBC and Hb
165
What are the symptoms for polycythaemia?
1. Headaches 2. Blurred vision 3. Red skin 4. Tiredness 5. High BP
166
What are the investigations for polycythaemia?
1. High RBC number 2. High RBC in haematocrit 3. Elevated Hb 4. Low EPO
167
What is the Tx for polycythaemia?
1. Low dose aspirin 2. Therapy to reduce itching 3. Phlebotomy to remove blood 4. Droxia

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