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Phase 2a Medicine > Haematology > Flashcards

Haematology Flashcards

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
Q

What is the investigation for leukaemia?

A
  1. FBC, LFT, U&E

2. Bone marrow aspirate and trephine biopsy (>20% blasts)

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26
Q

How is acute leukaemia classified?

A

Bone marrow contains >20% blasts/leukaemic cells

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27
Q

How is chronic leukaemia classified?

A
  1. Clonal mature cells
  2. High WCC
  3. Pt. are less unwell at presentation
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28
Q

What is leukaemia?

A

Malignant proliferation of haematopoietic cells

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29
Q

How is leukaemia diagnosed?

A
  1. Blood film
  2. Bone marrow biopsy
  3. Lymph node biopsy
  4. Immunophenotyping
  5. Genetics e.g. FISH, PCR
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30
Q

AML makes up what % of childhood leukaemia?

A

10-15%

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31
Q

What groups are at higher risk of AML?

A
  1. Preceding haematological disorders
  2. Prior chemo
  3. Exposure to ionising radiation
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32
Q

What is the median age for AML?

A

85-89

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33
Q

What is the treatment for AML?

A
  1. Supportive care
  2. Chemo
  3. Transplantation
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34
Q

What is the supportive Tx for AML?

A
  1. HML
  2. Blood product support
  3. Prompt Tx of infections
  4. Recognition of atypical/unusual infections
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35
Q

What must be considered prior to chemo?

A
  1. Fertility cryopreservation
  2. Clinical trial availability
  3. Bystander damage to other organs
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36
Q

Name 2 chemotherapy drugs for AML

A
  1. Anthracycline

2. Cytarabine

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37
Q

Name 4 side effects of chemotherapy

A
  1. Nausea/vomiting
  2. Altered bowel habit
  3. Reduced fertility
  4. Loss of appetite
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38
Q

What non-curative Tx are available for AML?

A
  1. Azacytidine

2. Low dose SC cytarabine

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39
Q

What supportive measures are used for AML?

A
  1. Red cell transfusion
  2. Platelet transfusion
  3. Abx
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40
Q

What personalised Tx can be used for leukaemia?

A

CAR-T (chimeric antigen receptor T cells)

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41
Q

What transplant is used for AML?

A

Allogenic haematopoietic stem cell transplantation

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42
Q

Name 4 post-transplant complications

A
  1. Hickman line infection
  2. Cutaneous graft vs host disease
  3. Jaundice
  4. Hormone dysfunction
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43
Q

What are the cure rates of AML?

A

20-60% depending on age

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44
Q

What is the usual age of onset in CML?

A

40-60yr

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45
Q

What are the clinical features of CML?

A
  1. Splenomegaly
  2. Metabolic features
  3. High WCC
  4. Film: left shift and basophilia
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46
Q

What gene is associated with CML?

A

Philadelphia chromosome: t(9;22)

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47
Q

What is the Tx for CML?

A

Tyrosine kinase inhibitors

  1. Imatinib
  2. Nilotinib
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48
Q

What are the complications of CML?

A
  1. Risk of accelerated phase/blast crisis

2. TKI binding site mutations

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49
Q

What is the most common paediatric malignancy?

A

ALL (3-7yr)

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50
Q

What is the presentation of ALL?

A
  1. Bone marrow failure

2. Organ infiltration (CNS)

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51
Q

What are the Tx phases for ALL?

A
  1. Induction
  2. Consolidation
  3. Delayed intensification
  4. Maintenance
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52
Q

What is the Tx for ALL?

A
  1. CNS directed therapy

2. Stem cell transplant

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53
Q

What is the most common leukaemia?

A

CLL

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54
Q

What is the pathophysiology of CLL?

A

Gradual accumulation of B lymphocytes

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55
Q

What are the clinical features of CLL?

A
  1. Progressive lymphadenopathy
  2. Haemolysis
  3. Bone marrow failure
  4. Hypogammaglobinaemia
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56
Q

What is the Tx for CLL?

A
  1. Chemo
  2. Monoclonal antibodies e.g. rituximab
  3. Targeted therapy e.g. ibrutinib
  4. Bone marrow transplant
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57
Q

What is lymphoma?

A

A malignant growth of white blood cells

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58
Q

What are the causes of lymphoma?

A
  1. Primary immunodeficiency
  2. Secondary immunodeficiency
  3. Infection
  4. Autoimmune disorders
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59
Q

What is the pathophysiology of lymphoma?

A
  1. Impaired immunosurveillance of EBV infected cells

2. Infected B cells escape regulation and proliferate autonomously

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60
Q

Give 5 symptoms of lymphoma

A
  1. Enlarged lymph glands
  2. Extranodal disease
  3. Lymph oedema
  4. Fever
  5. Weight loss
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61
Q

How is lymphoma diagnosed?

A
  1. Blood film
  2. Bone marrow
  3. Lymph node biopsy
  4. Immunophenotyping - CD20 on B lymphocytes
  5. Cytogenics e.g. FISH
  6. PCR
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62
Q

What investigations are used to stage lymphoma?

A
  1. Bloods
  2. CT chest/abdo/pelvis
  3. Bone marrow biopsy
  4. PET
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63
Q

What are the lymphoma subtypes?

A
  1. Hodgkin’s

2. Non-Hodgkin’s

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64
Q

What is the presentation of Hodgkin’s lymphoma?

A
  1. Painless lymphadenopathy

2. B symptoms e.g. sweats, weight loss

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65
Q

What confirms Hodgkin’s lymphoma diagnosis?

A

Reed-Sternberg cell

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66
Q

What is the Tx for stage 1-2A lymphoma?

A

Short course combination chemo followed by radiotherapy

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67
Q

What is the Tx for stage 2B-4 lymphoma?

A

Combination chemo

68
Q

What is the treatment in Hodgkin’s lymphoma relapse?

A

Autologous bone marrow transplant

69
Q

Give 4 complications of Hodgkin’s lymphoma

A
  1. Infertility
  2. Bleomycin
  3. Psychological issues
  4. Anthracyclines
70
Q

What is the Tx for indolent NHL?

A
  1. Nothing
  2. Alkylating agents
  3. Chemo
  4. Monoclonal antibodies
  5. Bone marrow transplant
71
Q

What is the Tx for early aggressive NHL?

A

Short course chemo + RT

72
Q

What is the Tx for late aggressive NHL?

A

Combination chemo + monoclonal antibodies

73
Q

Give an example of a monoclonal antibodies drug

A

Rituximab

74
Q

What is anaemia?

A

Reduced red cell mass +/- reduced Hb conc.

75
Q

When would a person get reduced Hb but increased RCM?

A

Third trimester pregnancy

76
Q

What is high RBC called?

A

Cytopenia

77
Q

What are the consequences of anaemia?

A
  1. Reduced O2 transport
  2. Tissue hypoxia
  3. Compensatory changes for reduced Hb
78
Q

What are the compensatory changes for reduced Hb?

A
  1. Tachycardia
  2. Increase tissue perfusion
  3. Increase O2 transfer to tissues
  4. Increase RBC production
79
Q

What are the pathological consequences of anaemia?

A
  1. Myocardial fatty change
  2. Fatty change in liver
  3. Aggravate angina
  4. Spooning
  5. CNS cell death
80
Q

How is anaemia classified?

A
  1. Microcytic
  2. Normocytic
  3. Macrocytic
81
Q

What is the aetiology of microcytic anaemia?

A
  1. Iron deficiency
  2. Chronic disease
  3. Thalassaemia
82
Q

What are the investigations for iron deficiency?

A
  1. Ferritin

2. Iron studies

83
Q

What are the causes of microcytic anaemia?

A
  1. Cancer
  2. Dietary
  3. Parasites
84
Q

What is the aetiology of normocytic anaemia?

A
  1. Acute blood loss
  2. Anaemia of chronic disease
  3. Combined haematinic deficiency
85
Q

What is the DDx of macrocytic anaemia?

A
  1. Foetus (pregnancy)
  2. Alcohol
  3. Thyroid disease (hypothyroidism)
  4. Reticulocytosis
  5. B12 and folate deficiency
  6. Cirrhosis and chronic liver disease
86
Q

What are the haematological causes of macrocytic anaemia?

A
  1. Antimetabolite therapy
  2. Haemolysis
  3. Bone marrow failure
  4. Bone marrow infiltration
87
Q

What are the investigations for B12 deficiency?

A
  1. IF antibodies
  2. Schilling test
  3. Coeliac antibodies
88
Q

What is the Tx for B12 deficiency?

A
  1. B12 replacement

2. Anti-parietal cell antibodies

89
Q

Which anaemia needs haematology referral +/- bone marrow biopsy?

A

Macrocytic anaemia

90
Q

What is the likely cause of combined haematinic deficiency?

A

Malabsorption

91
Q

Why is reticulocyte count done?

A

To see if RBC are produced or destroyed too much

92
Q

How can haemoglobinopathies be classified?

A
  1. Disorders of quality

2. Disorders of quantity

93
Q

What is Hb S?

A

A variant haemoglobin arising because of a point mutation in the beta globin gene

94
Q

What does HbS carriage offer protection against?

A

Falciparum malaria

95
Q

What is sickle cell crisis?

A

Pain due to blockage of blood vessels inside bone, marrow swells up and is excruciatingly painful

96
Q

What is the life expectancy in sickle cell disease?

A

50-60 years

97
Q

What are the acute complications of sickle cell disease?

A
  1. Painful crisis
  2. Sickle chest syndrome
  3. Stroke
98
Q

What are the chronic complications of sickle cell disease?

A
  1. Renal impairment
  2. Pulmonary HT
  3. Joint damage
99
Q

What is the Tx for sickle cell disease?

A
  1. Transfusion
  2. Hydroxycarbamide
  3. Stem cell transplant
  4. Gene therapy and gene editing
100
Q

What is thalassaemia?

A

Globin chain disorder resulting in diminished synthesis of one or more globin chains with consequent reduction in haemoglobin

101
Q

What genetic lesions tend to affect alpha thalassaemia?

A

Deletions

102
Q

What genetic lesions tend to affect beta thalassaemia?

A

Mutations

103
Q

What are the classes of thalassaemia?

A
  1. Thalassaemia major
  2. Thalassaemia intermedia
  3. Thalassaemia carrier
104
Q

What is the age at presentation for beta thalassaemia major?

A

6-12 months

105
Q

What are the symptoms of beta thalassaemia major?

A
  1. Failure to feed
  2. Listless
  3. Crying
  4. Pale
106
Q

What is the diagnosis for beta thalassaemia major?

A
  1. Low Hb, MCV, MCH
  2. Large and small pale RBC on blood film
  3. Hb F >90%
107
Q

What is the Tx for thalassaemia major?

A
  1. Regular transfusion
  2. Iron chelation
  3. Endocrine supplements
108
Q

What is the monitoring for thalassaemia major?

A
  1. Ferritin
  2. Cardiac and liver MRI
  3. Endocrine testing
  4. Dexa scanning
109
Q

Where is severe alpha thalassaemia found?

A

Eastern Mediterranean and Far East

110
Q

What are membranopathies?

A

Deficiency of red cell membrane proteins caused by a variety of genetic lesions

111
Q

What are the most common membranopathies?

A
  1. Spherocytosis

2. Elliptocytosis

112
Q

What is the presentation of membranopathies?

A
  1. Neonatal jaundice
  2. Haemolytic anaemia
  3. Gallstones
    splendid
113
Q

What is the Tx for membranopathies?

A
  1. Folic acid

2. Splenectomy

114
Q

What is the effect of parvovirus?

A

Reduced RBC production and lifespan

115
Q

What is the result of enzymopathies?

A

Shortened red cell lifespan from oxidative damage

116
Q

What are the common causes of enzymopathies?

A
  1. G6PD deficiency

2. Pyruvate kinase deficiency

117
Q

How are enzymopathies diagnosed?

A

NADPH screening test

118
Q

What are the clinical presentations of G6PD deficiency?

A
  1. Haemolysis
  2. Jaundice
  3. Anaemia
119
Q

What are 4 causes of microcytic anaemia?

A
  1. Smoking
  2. Lung disease
  3. Altitude
  4. Polycythaemia rubra vera (PRV)
120
Q

What is PRV?

A

Myeloproliferative disorder

121
Q

What mutation is associated with PRV?

A

JAK2

122
Q

What is the presentation of PRV?

A
  1. Plethoric appearance
  2. Thrombosis
  3. Itching
  4. Splenomegaly
  5. Abnormal FBC
123
Q

What is the Tx for PRV?

A
  1. Aspirin
  2. Venesection
  3. Bone marrow suppressive drugs e.g. hydroxycarbamide
124
Q

What is neutrophilia?

A

Too many white blood cells

125
Q

What are the causes of neutrophilia?

A
  1. Infection
  2. Inflammation
  3. Malignancy
  4. CML
126
Q

What are the causes of lymphocytosis?

A
  1. Infection
  2. Inflammation
  3. Malignancy
  4. CLL
127
Q

What is thrombocytopenia?

A

Not enough platelets

128
Q

What are the causes of thrombocytosis?

A
  1. Infection
  2. Inflammation
  3. Malignancy
  4. Essential thrombocythaemia
129
Q

What haemolytic condition is a major infection risk?

A

Severe neutropaenia

130
Q

What are the causes of neutropaenia?

A
  1. Marrow failure
  2. Marrow infiltration
  3. Marrow toxicity
  4. Autoimmune
  5. Felty’s syndrome
  6. Cyclical
131
Q

What regulates platelet production?

A

Thrombopoietin

132
Q

What is the lifespan of platelets?

A

7-10 days

133
Q

What do platelets do to form a platelet plug?

A

Adhesion and aggregation

134
Q

What activates platelets?

A
  1. Adhesion to collagen via GPIa

2. Adhesion to vWF via GPIb and IIb/IIIa

135
Q

What happens when platelets are activated?

A
  1. Release of alpha granules
  2. Dense granules
  3. Membrane phospholipids activate clotting factors II, V and X
136
Q

What are the investigations for platelets disorders?

A
  1. FBC
  2. Blood film
  3. PFA
  4. Bleeding time
  5. Surface proteins (flow cytometry)
137
Q

What are the causes of bleeding?

A
  1. Injury
  2. Vascular disorders
  3. Low platelets
  4. Abnormal platelet function
  5. Defective coagulation
138
Q

What are the clinical features of platelet dysfunction?

A
  1. Mucosal bleedings
  2. Easy bruising
  3. Petechiae, prupura
  4. Traumatic haematomas
139
Q

Give 5 causes of low platelets

A
  1. Congenital
  2. Drugs
  3. Marrow suppression
  4. EDTA induced clumping
  5. Consumption
140
Q

Give 5 causes of impaired platelet function?

A
  1. von Willebrand disease
  2. Uraemia
  3. Anti-inflammatory drugs
  4. Glanzmann disease
  5. Storage pool disorders
141
Q

What is thrombocytopaenia?

A

Altered platelet production

142
Q

What is the pathophysiology of thrombocytopaenia?

A

Absent/ reduced/ malfunctioning megakaryocytes in BM

143
Q

What are the results of thrombocytopaenia infiltrating bone marrow?

A
  1. Leukaemia
  2. Metastatic malignancy
  3. Lymphoma
  4. Myeloma
  5. Myelofibrosis
144
Q

Give 4 causes of reduced platelet production by bone marrow

A
  1. Low B12/folate
  2. Reduced TPO
  3. MTX/chemo
  4. Alcohol
145
Q

What can cause dysfunction production of platelets in BM?

A

Myelodysplasia

146
Q

What are the causes for thrombocytopenia?

A
  1. Autoimmune
  2. Hypersplenism
  3. Drug related immune destruction
  4. Consumption of platelets
147
Q

What is a major autoimmune thrombocytopenia?

A

Immune thrombocytopaenia (ITP)

148
Q

What are 3 causes of consumption of platelets?

A
  1. Thrombotic thrombocytopenic purpura (TTP)
  2. Disseminated intravascular coagulopathy (DIC)
  3. Major haemorrhage
149
Q

Name 3 drugs that can affect platelet function

A
  1. Tirofiban
  2. Clopidogrel
  3. Aspirin
150
Q

What is the pathophysiology of ITP?

A
  1. IgG antibodies form to platelet and megakaryocytic surface glycoproteins
  2. Opsonised platelets are removed by reticuloendothelial system
151
Q

What is the cause of primary ITP?

A

Viral infection

152
Q

What can cause secondary ITP?

A
  1. CLL
  2. HIV
  3. Hep C
153
Q

What are the investigations for ITP?

A
  1. Underlying cause

2. Diagnosis of exclusion

154
Q

What is the Tx for ITP?

A
  1. Immunosuppression
  2. Platelets for bleeds
  3. Tranexamic acid
155
Q

What is the pathophysiology of DIC?

A

Cytokine release in response to systemic inflammatory response syndrome (SIRS)

156
Q

How does DIC cause bleeding?

A
  1. Systemic activation of clotting cascade
  2. Consumption of platelets and clotting factors
  3. Bleeding
157
Q

How does DIC cause organ failure?

A
  1. Systemic activation of clotting cascade
  2. Microvascular thrombosis
  3. Organ failure
158
Q

What are the investigations for DIC?

A
  1. Underlying cause
  2. Thrombocytopenia
  3. Prolonged PT and APTT
  4. Low fibrinogen
  5. High D-Dimer
  6. Evidence of organ failure
159
Q

What is the Tx for DIC?

A
  1. Platelets
  2. FFP
  3. Cryoprecipitate
160
Q

What is the pathophysiology of TTP?

A
  1. Spontaneous platelet aggregation in microvasculature

2. Reduction in a protease enzyme

161
Q

What are the symptoms of TTP?

A
  1. Microangiopathic haemolytic anaemia
  2. Renal/CNS/cardiac impairment
  3. Fever
162
Q

What is the Tx for TTP?

A
  1. Urgent plasma exchange

2. Immunosuppression

163
Q

Why are platelets NOT given in TTP Tx?

A

Increases thrombosis

164
Q

What is polycythaemia?

A

Abnormal increase in RBC and Hb

165
Q

What are the symptoms for polycythaemia?

A
  1. Headaches
  2. Blurred vision
  3. Red skin
  4. Tiredness
  5. High BP
166
Q

What are the investigations for polycythaemia?

A
  1. High RBC number
  2. High RBC in haematocrit
  3. Elevated Hb
  4. Low EPO
167
Q

What is the Tx for polycythaemia?

A
  1. Low dose aspirin
  2. Therapy to reduce itching
  3. Phlebotomy to remove blood
  4. Droxia

Phase 2a Medicine (15 decks)

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