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Phase 3B > Haematology - Other > Flashcards

Haematology - Other Flashcards

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1
Q

What is the cause of myeloma?

A

Genetic changes (c14 translocation, hyperdiploidy) that occur during the terminal differentiation of B lymphocytes into plasma cells.

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2
Q

What is a paraprotein?

A

A monoclonal antibody found in blood as a result of cancer

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3
Q

What are the paraproteins found in the serum in myeloma?

A

IgG most commonly

Then IgA

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4
Q

What is found in the urine in myeloma and how?

A

Bence-Jones protein (light chains)

Urine electrophoresis

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5
Q

What are the patient demographics of myeloma patients?

A

Median age 70y

Commoner in males and Black Africans

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6
Q

What are the main symptoms of myeloma?

A

C - hypercalcaemia
R - renal failure
A - anaemia
B - bone lesions

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7
Q

What are the symptoms of hypercalcaemia?

A

Polyuria and polydipsia
Constipation and nausea
Renal stones
Confusion

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8
Q

How does bone marrow failure result from myeloma?

A

Plasma cells infiltrate the bone marrow, leading to anaemia, neutropenia, and thrombocytopenia.

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9
Q

How does renal failure occur in myeloma?

A

Deposition of light chains in renal tubules

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10
Q

What causes the lytic lesions of myeloma?

A

Dysregulation of bone remodelling; unopposed osteolysis from increased osteoclast activity due to increased production of RANK ligand –> hypercalcaemia
Myeloma cells produce DKK1 which inhibit osteoblast activity

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11
Q

Where are lytic lesions commonly found in myeloma?

A

Vertebrae - back pain
Skull - pepperpot
Long bones and ribs

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12
Q

The paraprotein in myeloma can cause hyperviscosity; what are the symptoms?

A

Blurred vision
Dizziness
Epistaxis
Confusion

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13
Q

How is myeloma diagnosed, other than urine electrophoresis?

A 
FBC for BM failure
ESR high
High Ca2+
Rouleaux on blood film
Serum protein electrophoresis and immunofixation
BM aspirate
Skeletal survey - MRI
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14
Q

What are rouleaux?

A

4 red blood cells in a row from paraprotein

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15
Q

What is seen on radiological investigation in myeloma?

A

Lytic lesions

Plasmacytomas

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16
Q

What are the differentials for presence of monoclonal proteins in the blood?

A 
MGUS
Light chain amyloidosis
Plasmacytoma
CLL
B-cell lymphoma
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17
Q

What does MGUS stand for and what is it?

What percentage of patients progress to myeloma?

A

Monoclonal gammopathy of unknown significance. An isolated finding of paraprotein in the serum. 20% Progresses to multiple myeloma in 25 years (Rate = 1% per year)

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18
Q

Define smouldering/indolent myeloma and what is the rate of progression?

A

Asymptomatic myeloma: significant paraproteinaemia but no end organ damage.
Rate of progression is 10%/year

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19
Q

What protease inhibitor medication is used to induce remission in myeloma, as well as stem cell transplant if possible?

A

Bortezumib (protease inhibitor)/Thalidomide

+

Alkylating agent +/- dexamethasone

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20
Q

What are some alternative medications used for relapse of myeloma?

A

2nd stem cell transplant
Daratumumab
Ixazomib

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21
Q

Name three supportive treatments of multiple myeloma.

A

Bone pain - radiotherapy and bisphosphonates
Infection - flu vac
Anaemia - transfusion + EPO
Vertebral fractures - kyphoplasty

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22
Q

What is the main side effect of bortezomib?

A

Peripheral neuropathy

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23
Q

What is lymphoma?

A

A group of lymphoproliferative malignancies (neoplastic transformation of B or T cells)

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24
Q

What are Reed-Sternberg cells and in what condition are they found?

A

Neoplastic B cells with mirror image nuclei

Hodgkins’ lymphoma

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25
What are the main presentations of lymphomas?
Painless cervical/mediastinal lymphadenopathy B symptoms - weight loss, night sweats, fatigue, anorexia, fever Hepatosplenomegaly
26
What are the main diagnostic techniques in lymphoma?
``` Lymph node ultrasound and fine needle aspiration/biopsy Bone marrow biopsy FBC and blood films U&Es, LFTs, LDH, uric acid CT scan ```
27
What is the chemotherapy regimen used in Hodgkin's lymphoma?
ABVD 2-8 cycles depending on stage Doxorubicin, bleomycin, vinblastine, dacarbazine
28
What is the chemotherapy regimen used for B-cell lymphomas?
R-CHOP Rituximab (not T cell), cyclophosphamide, doxorubicin, vincristine, prednisolone
29
What are two risk factors for Burkitt's lymphoma and what is the main symptom?
EBV and AIDS Jaw tumour
30
What staging system is used for lymphoma?
Ann Arbor
31
Give three risk factors for general lymphoma.
Smoking EBV HIV
32
What factors suggest a poor prognosis in lymphoma?
``` Increasing age Constitutional symptoms Anaemia/leucopenia/leucocytosis Increased ESR or low albumin Male gender Lymphocyte-depleted subtype ```
33
How is neutropenia managed in lymphoma patients?
Antibiotic prophylaxis | rhG-CSF
34
What is the general treatment of lymphoma?
High dose chemotherapy and autologous stem cell transplant
35
What are the risks of high dose chemotherapy?
Squamous cell carcinomas and other cancers | Immunesuppression and neutropenic sepsis
36
What are three risk factors for ALL?
Genetics - Philadelphia chromosome Trisomy 21 High dose radiation
37
What are the main symptoms of leukaemia?
``` Anaemia Frequent infection Bruising and petechiae Lymphadenopathy Hepatosplenomegaly Orchidomegaly Bone pain ```
38
How is ALL diagnosed?
BM biopsy FBC shows BM suppression but this is a late feature Blood film - blast cells Increased LDH and uric acid
39
What percentage of serum/BM blasts are required for diagnosis of ALL?
>20%
40
Which type of leukaemia has Auer rods on blood film?
AML
41
What is the treatment of ALL?
Stem cell transplant Chemotherapy Allopurinol
42
What is the purpose of allopurinol in treatment of leukaemia?
Prevents tumour lysis syndrome
43
What is Kymriah?
New ALL CAR-T cell therapy
44
What is the management of ALL with CNS involvement?
CNS irradiation | Intrathecal methorexate
45
How does CLL present?
Often asymptomatic; insidious onset.
46
How is CLL diagnosed?
Lymphocytosis BM infiltration with lymphocytes Blood film - smudge cells (small lymphocytes w/o blasts)
47
What are the three phases of CML?
Chronic phase Accelerated phase Blast phase
48
What is CLL?
Uncontrolled proliferation of one or more cell lines: erythroid, platelet, or myeloid
49
What is the extra treatment of CML?
Imatinib - tyrosine kinase inhibitor
50
What is immune thrombocytopenic purpura?
Autoimmune destruction of platelets in response to an unknown stimulus
51
How is lymphoma classified?
High grade and low grade
52
Define the thrombocytopenia in ITP?
Platelets <100x10^9
53
What investigations should be done in suspected ITP?
``` FBC and blood film BM exam if uncertain Any investigation for secondary ITP Screen for HIV and Hep C Test Ig levels if over 60 ```
54
What triggers ITP in young children?
Viral infection or immunization
55
What are the symptoms of ITP?
``` Asymptomatic Petechiae/bruising Nosebleeds Menorrhagia/GI bleed Cranial bleed ```
56
How is ITP managed?
Majority - monitoring only Prednisolone/IVIG Platelet transfusion if emergency
57
When is splenectomy indicated in ITP?
Life threatening bleeding | Severe unremitting ITP
58
How does ITP present in adults, compared to children?
No trigger | Less insidious onset
59
What medication can be tried in unremitting ITP in adults?
Romiplostin - thrombopoietin receptor agonists | Increase platelet production
60
What are the differentials for ITP?
``` DIC Leukaemia Fanconi anaemia von Willebrand disease TTP Aplastic anaemia ```
61
What is Thrombotic Thrombocytopenic Purpura?
A rare thrombotic microangiopathy consisting of: - microangiopathic haemolysis - thrombocytopenia - fever - neurological abnormalities - renal dysfunction
62
What is the main risk factor for TTP?
Pregnancy and postpartum
63
What is the cause of TTP?
Deficiency of von Willebrand factor cleaving protein: ADAMTS13
64
What is seen on examination in TTP?
``` Jaundice Splenomegaly Fever Hypertension Petechiae/purpura Signs of anaemia ```
65
How is TTP diagnosed?
Massively increased LDH Reticulocytes Schistocytes ADAMTS13 levels and anti-ADAMTS13 antibodies
66
What is the main treatment of TTP?
Plasmaphresis
67
Define DIC.
A syndrome characterized by the systemic activation of blood coagulation, which generates intravascular fibrin, leading to thrombosis of small and medium sized vessels, and eventually organ dysfunction.
68
What is the main pathophysiology of DIC?
Initial thrombosis | Followed by a bleeding tendency
69
What are the risk factors for DIC?
Obstetric emergencies Septicaemia Malignant disease Trauma
70
How does DIC present/?
Shock Bleeding from >3 sites including venepuncture sites Widespread ecchymoses Fever and confusion
71
How is DIC diagnosis?
``` PT, APTT, TT very prolonged Decreased fibrinogen Increase FDPs including D-dimer Thrombocytopenia Fragmented RBC on film ```
72
What is myelodysplasia?
A form of bone marrow failure where a line of myeloid blasts are produced rapidly, do not mature, and usually die, causing a deficiency in that line of cells.
73
What can myelodysplasia progress to?
Acute myeloid leukaemia
74
What is the prevention and treatment of tumour lysis syndrome?
Prevention - allopurinol | Treatment - rasburicase
75
Apart from the electrolyte abnormalities, what is required to diagnose tumour lysis syndrome?
Increased serum creatinine, a cardiac arrhythmia, or a seizure
76
What are the symptoms of von Willebrand's disease?
Epistaxis and menorrhagia | Behaves like a platelet disorder
77
How is von Willebrand disease diagnosed?
Prolonged bleeding time | Prolonged APTT
78
Diseases causing secondary haemostasis, such as Haemophilia, have symptoms such as...
Intramuscular and intra-articular bleeds
79
Which conditions are associated with thymomas?
Myasthenia gravis Red cell aplasia Dermatomyositis SLE
80
Define end organ damage in myeloma.
Calcium normal Hb normal Creatinine normal No bone lesions
81
What is the diagnostic criteria for MGUS?
Presence of monoclonal antibody in serum and: - No end organ damage - Plasma cells less than 10% in BM - Serum paraprotein <30g/L
82
What is the diagnostic criteria for smouldering myeloma?
Presence of monoclonal antibody in serum/urine and: - No end organ damage - Plasma cells >10% in BM - Serum paraprotein <30g/L
83
What is the treatment of a patient with major bleeding who is taking warfarin?
Stop warfarin Vitamin K Prothrombin complex concentrates (FFP less effective)
84
What is the treatment of polycythaemia?
Venesection aiming for haematocrit <45% Low dose aspirin Hydroxyurea
85
What are the causes of polycythaemia?
Relative reduction in plasma volume (idiopathic) Increase in circulating EPO
86
What is the prognosis of polycythaemia?
Survival of 10 years or more | May transform to acute leukaemia or myelofibrosis

Phase 3B (20 decks)

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