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Phase 3B > Haematology - Other > Flashcards

Haematology - Other Flashcards

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
Q

What are the main presentations of lymphomas?

A

Painless cervical/mediastinal lymphadenopathy
B symptoms - weight loss, night sweats, fatigue, anorexia, fever
Hepatosplenomegaly

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26
Q

What are the main diagnostic techniques in lymphoma?

A 
Lymph node ultrasound and fine needle aspiration/biopsy
Bone marrow biopsy
FBC and blood films
U&Es, LFTs, LDH, uric acid
CT scan
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27
Q

What is the chemotherapy regimen used in Hodgkin’s lymphoma?

A

ABVD 2-8 cycles depending on stage

Doxorubicin, bleomycin, vinblastine, dacarbazine

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28
Q

What is the chemotherapy regimen used for B-cell lymphomas?

A

R-CHOP

Rituximab (not T cell), cyclophosphamide, doxorubicin, vincristine, prednisolone

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29
Q

What are two risk factors for Burkitt’s lymphoma and what is the main symptom?

A

EBV and AIDS

Jaw tumour

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30
Q

What staging system is used for lymphoma?

A

Ann Arbor

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31
Q

Give three risk factors for general lymphoma.

A

Smoking
EBV
HIV

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32
Q

What factors suggest a poor prognosis in lymphoma?

A 
Increasing age
Constitutional symptoms
Anaemia/leucopenia/leucocytosis
Increased ESR or low albumin
Male gender
Lymphocyte-depleted subtype
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33
Q

How is neutropenia managed in lymphoma patients?

A

Antibiotic prophylaxis

rhG-CSF

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34
Q

What is the general treatment of lymphoma?

A

High dose chemotherapy and autologous stem cell transplant

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35
Q

What are the risks of high dose chemotherapy?

A

Squamous cell carcinomas and other cancers

Immunesuppression and neutropenic sepsis

36
Q

What are three risk factors for ALL?

A

Genetics - Philadelphia chromosome
Trisomy 21
High dose radiation

37
Q

What are the main symptoms of leukaemia?

A 
Anaemia
Frequent infection
Bruising and petechiae
Lymphadenopathy
Hepatosplenomegaly
Orchidomegaly
Bone pain
38
Q

How is ALL diagnosed?

A

BM biopsy
FBC shows BM suppression but this is a late feature
Blood film - blast cells
Increased LDH and uric acid

39
Q

What percentage of serum/BM blasts are required for diagnosis of ALL?

A

> 20%

40
Q

Which type of leukaemia has Auer rods on blood film?

A

AML

41
Q

What is the treatment of ALL?

A

Stem cell transplant
Chemotherapy
Allopurinol

42
Q

What is the purpose of allopurinol in treatment of leukaemia?

A

Prevents tumour lysis syndrome

43
Q

What is Kymriah?

A

New ALL CAR-T cell therapy

44
Q

What is the management of ALL with CNS involvement?

A

CNS irradiation

Intrathecal methorexate

45
Q

How does CLL present?

A

Often asymptomatic; insidious onset.

46
Q

How is CLL diagnosed?

A

Lymphocytosis
BM infiltration with lymphocytes
Blood film - smudge cells (small lymphocytes w/o blasts)

47
Q

What are the three phases of CML?

A

Chronic phase
Accelerated phase
Blast phase

48
Q

What is CLL?

A

Uncontrolled proliferation of one or more cell lines: erythroid, platelet, or myeloid

49
Q

What is the extra treatment of CML?

A

Imatinib - tyrosine kinase inhibitor

50
Q

What is immune thrombocytopenic purpura?

A

Autoimmune destruction of platelets in response to an unknown stimulus

51
Q

How is lymphoma classified?

A

High grade and low grade

52
Q

Define the thrombocytopenia in ITP?

A

Platelets <100x10^9

53
Q

What investigations should be done in suspected ITP?

A 
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
Q

What triggers ITP in young children?

A

Viral infection or immunization

55
Q

What are the symptoms of ITP?

A 
Asymptomatic
Petechiae/bruising
Nosebleeds
Menorrhagia/GI bleed
Cranial bleed
56
Q

How is ITP managed?

A

Majority - monitoring only
Prednisolone/IVIG
Platelet transfusion if emergency

57
Q

When is splenectomy indicated in ITP?

A

Life threatening bleeding

Severe unremitting ITP

58
Q

How does ITP present in adults, compared to children?

A

No trigger

Less insidious onset

59
Q

What medication can be tried in unremitting ITP in adults?

A

Romiplostin - thrombopoietin receptor agonists

Increase platelet production

60
Q

What are the differentials for ITP?

A 
DIC
Leukaemia
Fanconi anaemia
von Willebrand disease
TTP
Aplastic anaemia
61
Q

What is Thrombotic Thrombocytopenic Purpura?

A

A rare thrombotic microangiopathy consisting of:

  • microangiopathic haemolysis
  • thrombocytopenia
  • fever
  • neurological abnormalities
  • renal dysfunction
62
Q

What is the main risk factor for TTP?

A

Pregnancy and postpartum

63
Q

What is the cause of TTP?

A

Deficiency of von Willebrand factor cleaving protein: ADAMTS13

64
Q

What is seen on examination in TTP?

A 
Jaundice
Splenomegaly
Fever
Hypertension
Petechiae/purpura
Signs of anaemia
65
Q

How is TTP diagnosed?

A

Massively increased LDH
Reticulocytes
Schistocytes
ADAMTS13 levels and anti-ADAMTS13 antibodies

66
Q

What is the main treatment of TTP?

A

Plasmaphresis

67
Q

Define DIC.

A

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
Q

What is the main pathophysiology of DIC?

A

Initial thrombosis

Followed by a bleeding tendency

69
Q

What are the risk factors for DIC?

A

Obstetric emergencies
Septicaemia
Malignant disease
Trauma

70
Q

How does DIC present/?

A

Shock
Bleeding from >3 sites including venepuncture sites
Widespread ecchymoses
Fever and confusion

71
Q

How is DIC diagnosis?

A 
PT, APTT, TT very prolonged
Decreased fibrinogen
Increase FDPs including D-dimer
Thrombocytopenia
Fragmented RBC on film
72
Q

What is myelodysplasia?

A

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
Q

What can myelodysplasia progress to?

A

Acute myeloid leukaemia

74
Q

What is the prevention and treatment of tumour lysis syndrome?

A

Prevention - allopurinol

Treatment - rasburicase

75
Q

Apart from the electrolyte abnormalities, what is required to diagnose tumour lysis syndrome?

A

Increased serum creatinine, a cardiac arrhythmia, or a seizure

76
Q

What are the symptoms of von Willebrand’s disease?

A

Epistaxis and menorrhagia

Behaves like a platelet disorder

77
Q

How is von Willebrand disease diagnosed?

A

Prolonged bleeding time

Prolonged APTT

78
Q

Diseases causing secondary haemostasis, such as Haemophilia, have symptoms such as…

A

Intramuscular and intra-articular bleeds

79
Q

Which conditions are associated with thymomas?

A

Myasthenia gravis
Red cell aplasia
Dermatomyositis
SLE

80
Q

Define end organ damage in myeloma.

A

Calcium normal
Hb normal
Creatinine normal
No bone lesions

81
Q

What is the diagnostic criteria for MGUS?

A

Presence of monoclonal antibody in serum and:

  • No end organ damage
  • Plasma cells less than 10% in BM
  • Serum paraprotein <30g/L
82
Q

What is the diagnostic criteria for smouldering myeloma?

A

Presence of monoclonal antibody in serum/urine and:

  • No end organ damage
  • Plasma cells >10% in BM
  • Serum paraprotein <30g/L
83
Q

What is the treatment of a patient with major bleeding who is taking warfarin?

A

Stop warfarin
Vitamin K
Prothrombin complex concentrates (FFP less effective)

84
Q

What is the treatment of polycythaemia?

A

Venesection aiming for haematocrit <45%
Low dose aspirin
Hydroxyurea

85
Q

What are the causes of polycythaemia?

A

Relative reduction in plasma volume (idiopathic)

Increase in circulating EPO

86
Q

What is the prognosis of polycythaemia?

A

Survival of 10 years or more

May transform to acute leukaemia or myelofibrosis

Phase 3B (20 decks)

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