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Bateman - Phase 2a COPY > Haematology > Flashcards

Haematology Flashcards

1
Q

What is multiple myeloma?

A

Cancer of differentiated B lymphocytes, known as plasma cells.

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2
Q

What happens in multiple myeloma?

A

The accumulation of malignant plasma cells in the bone marrow leading to progressive bone marrow failure
The production of a characteristic paraprotein
Renal failure
Destructive bone disease and hypercalcaemia

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3
Q

How does multiple myeloma occur?

A

Mechanisms include an increase in bone resorption, decrease in bone formation and an uncoupling of resorption and formation leading to rapid bone loss.

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4
Q

What are some osteoclast activating factors?

A

RANKL
MIP 1-α
Il-3.

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5
Q

What are some osteoblast inhibitory factors?

A

Dkk-1
sFRP-3
HGF
TGF-β1.

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6
Q

What happens to the amount of osteoclasts in myeloma?

A

Increase.

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7
Q

What is CRAB in relation to myeloma?

A

A diagnostic indicator of multiple myeloma.

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8
Q

What does CRAB stand for?

A

C - ad Ca>0.25mmol/l above upper limit of normal or >2.75mmol/l
R – renal impairment, creatinine>173mmol/l (40% pts at Δ have some degree of RF; 10% req dialysis Dimopolous et al, 2008, Leukaemia, 22, 1485-1493 Pathogenesis and treatment of renal failiure in multiple myeloma)
A – anaemia 2g

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9
Q

What screening tests can you do for myeloma?

A 
FBC
ESR or PV
U&E, Ca, albumin
Serum and urinary EP
Quantification of polyclonal Igs
XR of suspect areas
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10
Q

What is ROTI?

A

Myeloma associated organ impairment.

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11
Q

What tests can you do to establish diagnosis in myeloma?

A

Bone marrow aspirate & trephine (20mm)
Immunofixation of serum and urine
Skeletal survey

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12
Q

What tests can you do to assess ROTI?

A

FBC
PV
U&E, CrCl, Ca.

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13
Q

What imaging studies can you do in a myeloma?

A

skeletal survey using plain radiographs firstline screen
MRI, CT or PET/CT to clarify ambiguous lesions
MRI to assess spinal cord compression .

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14
Q

What shows up during electrophoresis of myeloma patients vs normal?

A

Abnormal monoclonal IgG spike.

Normal only has polyclonal Ig’s.

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15
Q

What does myeloma produce?

A

Myeloma cells usually produce both an intact immunoglobulin product - IgG (2/3), IgA (1/3) or rarely IgD (1.8%), IgM (0.4%) or IgE and monoclonal free light chains (FLC) (90% of cases); in a minority of cases, myeloma cells produce FLC only (15%) termed ‘free light chain myeloma’

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16
Q

What is the difference between symptomatic and asymptomatic myeloma?

A 
Asymptomatic myeloma (aMM) - >30g/l and/or >10% plasma cells in BM, no ROTI
Symptomatic myeloma (sMM) – paraprotein**, clonal plasma cells in BM or Bx proven plasmacytomata, ROTI nb CRAB
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17
Q

How is the electrophoresis carried out?

A

Electrophoresis of serum and urine is performed, followed by immunofixation to confirm and type any M-protein present.
Immunofixation repeats electrophoresis but adds anti sera to IgG, IgA, IgM and κ or λ ie will detect IgG κ or IgG λ or IgA κ or IgA λ or IgM κ or IgM λ or κ FLC or λ FLC
A densitometry scan is then performed on the electrophoresis to quantify the paraprotein

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18
Q

Where do Ig’s end up in the electrophoresis area?

A

Gamma region.

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19
Q

What are the different steps for identifying immunoglobulins in myeloma?

A
  1. Electrophoresis - If a discrete additional band seen or bands fuzzy or suppressed, proceed to immunofixation
  2. Immunofixation repeats the electrophoresis plus identifies monoclones via the addition of specific antibodies. A second immunofixation is sometimes required if a rare band expected eg IgD or IgE; performed at diagnosis and at other key intervals eg relapse
  3. Densitometry scan performed on 1. or 2. to quantify the monoclone
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20
Q

What is the course of myeloma?

A

Asymptomatic
MGUS or smouldering myeloma.

Symptomatic
Active myeloma - 1st line of treatment
plateau remission
relapse -2nd line of treatment
plateau remission - 3rd line of treatment
refractory relapse.
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21
Q

How long is the plateau remission?

A

Unable to tell how long this will last.

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22
Q

What are the three aims of myeloma treatment?

A
  1. Anti-myeloma treatment
    combination chemotherapy e.g. CTD, MPT, HD-ASCT
  2. Prevention and treatment of bone and tissue damage
    Bisphosphonates, renal dialysis, MSCC treatment (radiotherapy, surgery), pain
  3. Improve quality of life and survival
    Infection prophylaxis and treatment, anaemia (EPO, transfusion).
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23
Q

What happens when diagnosing myeloma?

A

Asymptomatic
Regular monitoring

Symptomatic 
Clinical study
or candidate for stem cell transplant 
induction treatment, stem cell transplant.
or non-intensive drug treatment.
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24
Q

What is step 1 of treatment for myeloma for a patient in addition to a stem cell transplant?

A 
Thalidomide-based
CTD
	Cyclophosphamide
	Thalidomide
	Dexamethasone
Velcade-based
PAD
  Velcade
	Adriamycin
	Dexamethasone
Supportive
Bisphosphonates
	Zometa, pamidronate, Bonefos
Blood transfusions/EPO
Pain-killers
Anti-thrombotic
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25
Q

What is step 2 of treatment for myeloma?

A

Stem cell mobilisation.
Stem cell collection.
High-dose Melphalan.
Stem cell transplant.

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26
Q

What is the treatment of myeloma for a patient who cannot have a stem cell transplant?

A 
Thalidomide-based
CTD
	Cyclophosphamide
	Thalidomide
	Dexamethasone

MPT
Melphalan
Prednisolone
Thalidomide

Velcade-based
VMP
  Velcade
	Melphalan
	Prednisolone
Supportive
Bisphosphonates
	Zometa, pamidronate, Bonefos
Blood transfusions/EPO
Pain-killers
Anti-thrombotic
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27
Q

What is the treatment of myeloma at first relapse?

A

Velcade. Also known as bortezomib.

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28
Q

What are the side effects for Velcade?

A

Weakness, fatigue

- Peripheral neuropathy
- Low blood counts especially platelets
- Nausea, diarrhoea or constipation
- Postural hypotension
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29
Q

What is another option apart from Velcade in first remission of myeloma?

A

Same treatment again if first remission
lengthy
Second transplant if first transplant
remission >2yrs

Enter a clinical study

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30
Q

What is the treatment for myeloma at the second relapse?

A

Revlimid. Also known as lenalidomide.

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31
Q

What are the side effects of Revlimid?

A 
Less constipation and neuropathy
  than thalidomide
 Neutropenia and thrombocytopenia
 Increased risk of blood clots
 Fatigue
 Muscle cramp.
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32
Q

What are some anti myeloma drugs for multiple relapses?

A

Pomalidomide – alternative immuno-modulatory agent related to thalidomide
Bendamustine – mixed purine analogue and alkylating agent
Kyprolis (carfilzomib) – next generation proteasome inhibitor (cf bortezomib)
MLN 9708 – oral proteasome inhibitor
Elotuzumab – monoclonal antibody to CS1 antigen expressed by plasma cells
Daratumumab – monoclonal antibody to CD38 antigen expressed by plasma cells
Panobinostat – histone deacetylator inhibitor

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33
Q

What is lymphoma?

A 
Basically a malignant growth of white blood cells
Predominantly in lymph nodes
But also
Blood, bone marrow
Liver, spleen
Anywhere.
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34
Q

Where does lymphoma come from?

A

impaired immunosurveillance of EBV infected cells
infected B cells escape regulation and proliferate autonomously

Most cases unknown

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35
Q

How can you diagnose lymphoma?

A 
Blood film & bone marrow
Lymph node biopsy
Immunophenotyping
Cytogenetics
-Karyotype analysis
-FISH
Molecular techniques
-PCR
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36
Q

How can you stage lymphoma?

A 
Staging investigations
Blood tests
CT Scan chest/abdo/pelvis
Bone marrow biopsy 
PET
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37
Q

What are the two different types of lymphoma?

A

Hodgkin’s

NHL.

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38
Q

What are some example of NHL?

A

Low grade e.g. Follicular Lymphoma
High grade e.g. Diffuse Large B Cell Lymphoma
Very high grade e.g. Burkitt’s Lymphoma

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39
Q

How does Hodgkins lymphoma present?

A

Painless lymphadenopathy
B symptoms
Sweats, weight loss

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40
Q

How do you diagnose Hodgkins lymphoma?

A

Reed-Sternberg cell
4 histological subtypes.
Different giant cells.

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41
Q

How many stages does Hodgkin’s lymphoma have?

A

Four.

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42
Q

What is the treatment for Hodgkin’s lymphoma with a stage 1-2A?

A

Stage 1-2A
Short course combination chemotherapy followed by radiotherapy
70-80% prolonged disease free survival

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43
Q

What is the treatment for Hodgkin’s lymphoma with a stage 2B-4?

A

Combination chemotherapy
50-70% prolonged disease free survival
ABVD
Adriamycin, Bleomycin, Vinblastine and Dacarbazine

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44
Q

What the common late effects of treatment for lymphoma?

A 
E.g. infertility
Anthracyclines –cardiomyopathy
Bleomycin –lung damage
Vinca alkaloids –peripheral neuropathy
Second cancers
Psychological issues.
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45
Q

What is NHL?

A 
-Presentation
More varied
-Subtypes
More categories
-Treatments used
Wide variety
-Outcomes
More varied
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46
Q

What is the treatment for NHL?

A 
Do nothing!
Alkylating agents
Combination chemotherapy
Purine analogues
Monoclonal antibodies
Radio-immunoconjugates
New oral targeted agents
Radiotherapy
Bone marrow transplant
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47
Q

What is the outcome of indolent NHL on a graph of survival?

A

Linear graph down.

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48
Q

What is indolent NHL?

A 
e.g. Follicular Lymphoma
Slow growing
Usually advanced at presentation
Incurable
Median survival 9-11 years
Wide range of treatments used
?optimal sequence of treatment
?maintenance treatment.
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49
Q

What is high grade or aggressive NHL?

A 
e.g. Diffuse Large B Cell Lymphoma
Usually nodal presentation
1/3 cases have extranodal involvement
Patient usually unwell
Often short history.
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50
Q

What is the treatment for aggressive NHL?

A

Early
Short course chemotherapy + RT
e.g. 3# R-CHOP & IFRT

Advanced
Combination chemotherapy + monoclonal antibodies
e.g. 6# R-CHOP

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51
Q

What is the outcome for aggressive NHL?

A

Steep drop within the first year and then plateau.

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52
Q

What is an example of a monoclonal antibody for lymphoma treatment?

A

Rituximab.

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53
Q

What does Rituximab do?

A 
Monoclonal antibody 
Anti CD-20
Targets CD20 expressed on cell surface of B-cells
Chimeric mouse/human protein
Minimal side-effects.
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54
Q

What is an example of a T cell engaging therapy?

A

Blinatumomab

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55
Q

What does Blinatumomab do?

A

bi-specific Antibody
Targets CD19 on B cells
And CD3 on T cells
Directs own immune system.

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56
Q

What are some different types of leukaemia?

A

Acute Myeloid leukaemia (AML)
Chronic Myeloid Leukaemia (CML)

Acute Lymphoblastic Leukaemia (ALL)
Chronic Lymphocytic Leukaemia (CLL).

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57
Q

What is leukaemia?

A

Malignant proliferation of haemopoietic cells.

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58
Q

What is acute myeloid leukaemia a disease of?

A

Myeloblasts.

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59
Q

What is chronic myeloid leukaemia a disease of?

A

Basophils, Neutrophils and Eosinophils.

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60
Q

What is acute lymphoblastic leukaemia a disease of?

A

Lymphoblast.

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61
Q

What is chronic lymphocytic leukaemia a disease of?

A

B lymphocytes.

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62
Q

What techniques can you use to diagnose leukaemia?

A 
Blood film.
Bone marrow biopsy.
Lymph node biopsy.
Immunophenotyping.
-classifying tumour cells by antigen expression profile.
Genetics.
Cytogenetics:
-Karyotyping 
-FISH
Molecular genetics:
-PCR
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63
Q

What happens in acute myeloid leukaemia? What is the aetiology?

A

Incidence increases with age.
10-15% of childhood leukaemia

Aetiology usually not obvious but risk increased in
Preceeding Haematological disorders
Prior chemotherapy
Exposure to ionising radiation

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64
Q

What is the treatment for acute myeloid leukaemia?

A 
Supportive care
HML
Blood product support
Prompt treatment of infections
Recognition of atypical/unusual infections

Chemotherapy
Curative vs palliative

Transplantation.

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65
Q

What is acute promyelocytic leukaemia?

A

5-8% of AML in adults
Blocks differentiation of promyelocyte to mature granulocyte
Haematological emergency – DIC
90% remission rate

Targeted treatment ATRA

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66
Q

What are the properties of chronic myeloid leukaemia?

A 
Usually 40-60yrs age
Slow onset
Sometimes incidental finding
Splenomegaly
Metabolic features.
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67
Q

What the results of a blood count test and a blood film on chronic myeloid leukaemia?

A

FBC: High WBC
Film: Left shift + basophilia

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68
Q

What is the key diagnostic feature of chronic myeloid leukaemia?

A 
Key diagnostic feature:
Philadelphia Chromosome
t(9;22)
Resulting in 210-kDa fusion protein 
Activated tyrosine kinase
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69
Q

What is the treatment for chronic myeloid leukaemia?

A

Target molecular therapy:
Tyrosine kinase inhibitors
Imatinib (Glivec)
Nilotinib, Dasatinib, Ponatinib.

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70
Q

What is the outcome for chronic myeloid leukaemia patients?

A

Survival >90% at 5 years

Risk of accelerated phase/ blast crisis
TKI binding site mutations.

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71
Q

What does acute lymphoblastic leukaemia present as and who gets it?

A 
Most common paediatric malignancy
Esp. age 3-7yrs
Rarer in adults
Acute presentation
Bone marrow failure
Organ infiltration (CNS).
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72
Q

What is the diagnosis for acute lymphoblastic leukaemia?

A

Diagnosis:
As for AML
Cytogenetics:
Philadelphia chromosome = poor prognosis if present.

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73
Q

How do you treat acute lymphoblastic leukaemia?

A

Treatment phases

  • Induction
  • Consolidation
  • Delayed intensification
  • Maintenance

CNS directed therapy

Stem cell transplant

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74
Q

What are the outcomes of acute lymphoblastic leukaemia?

A

Children majority cured
TYA (16-25yrs) most cured with Paediatric style treatment
Adults up to ½ cured

Depends critically on age and cytogenetics.

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75
Q

What is chronic lymphocytic leukaemia? Who does it affect?

A 
Most common leukaemia
Gradual accumulation of B lymphocytes
Blood / bone marrow
Lymph glands (incl spleen)
Often incidental finding on FBC
Generally elderly but 20% <55yrs
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76
Q

What is the course of chronic lymphocytic leukaemia?

A 
Variable
Progressive lymphadenopathy / hepatosplenomegaly
Auto-immune
Haemolysis, ITP
Bone marrow failure
Due to marrow replacement
Hypogammaglobulinaemia &amp; infection.
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77
Q

What are the different stages of chronic lymphocytic leukaemia?

A 
Stage A
Lymphocytosis.
10-15 yrs
Stage B
Nodes.
5-7yrs
Stage C
Anaemia and/or thrombocytopenia.
2-3yrs
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78
Q

What is the treatment for chronic lymphocytic leukaemia?

A

Do nothing!
Chemotherapy
Monoclonal antibodies (eg anti-CD20 - rituximab)
Targeted therapy (eg bruton kinase inhibitors - ibrutinib)
Bone marrow transplant.

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79
Q

What does a bone marrow transplant involve?

A

Bone marrow or peripheral blood stem cells

Autologous = own

Allogeneic = from someone else

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80
Q

What are the properties of autologous stem cell transplantation?

A

Enables escalation of chemo with stem cell “rescue”
Relatively straightforward
Mortality 2%

81
Q

What are the properties of allogenic stem cell transplantation?

A 
Much more toxic 
Mortality ~15-30%
Stem cells attack residual tumour (GVL)
Stem cells also attack recipient (GVHD)
Used in acute and chronic leukaemias.
82
Q

What are some examples of different haemoglobinopathies?

A

Disorders of quality (abnormal molecule or variant haemoglobins)
Sickle cell disease
Disorders of quantity (reduced production)
a or b thalassaemia

83
Q

What does normal haemoglobin contain and foetal?

A

Normal Hb 2xa, 2xb

Foetal Hb 2xa, 2xg

84
Q

What does haemoglobin change from to during development?

A

Haemoglobin F to haemoglobin A.

85
Q

What is haemoglobin S?

A

Variant haemoglobin arising because of a point mutation in the b globin gene.

86
Q

What happens with a carrier or sickle cell disease?

A

Carriers of HbS are symptom free
Carriage offers protection against falciparum malaria
Sickle cell diseases arise in the homozygous state (SS) or in combined heterozygotes (SC or Sb thalassaemia).

87
Q

How does sickle cell happen?

A

Thiamine for adenine in 6th codon of b globin gene results in single amino acid change of valine for glutamine.

88
Q

What are some common complications of sickle cell disease?

A 
-Acute complications
Painful crisis
Sickle chest syndrome
Stroke
-Chronic complications
Renal impairment
Pulmonary hypertension
Joint damage
89
Q

What are some disease modifying treatments?

A

Transfusion
Hydroxycarbamide
Stem cell transplant.

90
Q

What is thalassaemia?

A

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

Heterogeneous disorders of world wide distribution.

91
Q

What are the different types of Thalassaemia? What different treatments do they require?

A

Thalassaemia Major
Transfusion dependent

Thalassaemia Intermedia
Less severe anaemia and can survive without regular blood transfusions

Thalassaemia Carrier/heterozygote
Asymptomatic.

92
Q

When does Beta Thalassaemia Major present? What are the signs?

A

Age at presentation: 6-12 months

Clinical presentation with severe symptoms: failure to feed, listless, crying, pale.

93
Q

What are the blood results of a patient with thalassaemia?

A

HB 40-70 g/l, MCV & MCH very low
Blood film: large and small (irregular) very pale red cells, NRBC
Hb F > 90% (neonatal sample)
Ferritin normal

94
Q

What is the treatment for thalassaemia major?

A 
Regular transfusion
Iron chelation
Endocrine supplementation
(fertility)
Bone health
Psychological support.
95
Q

How do you monitor patients with thalassaemia major?

A 
Ferritin
Cardiac and Liver MRI
Endocrine testing
Gonadal function
Diabetes screening
Growth  &amp; puberty
Vit D, Calcium, PTH
Thyroid
Dexa scanning.
96
Q

What happens when a child with Thalassaemia major has treatment by continuous blood transfusions?

A

Children who are afflicted with thalassemia major require lifelong blood transfusions if they are to grow and develop to adulthood. The unfortunate consequence of the transfusions is an inevitable progressive increase in body iron load. As there is no natural means for the body to eliminate the excessive iron, these patients inexorably develop a clinically worsening hemosiderosis. The excessive iron is deposited mainly in the liver and spleen, leading to liver fibrosis and cirrhosis. The excessive iron is also deposited in the endocrine glands and the heart, resulting in diabetes, heart failure and premature death. Death ultimately occurs, mainly due to cardiac hemosiderosis.

97
Q

What does degree of symptoms depends of in alpha Thalassaemia?

A

The amount of genes that are detailed which code for the alpha genes.

98
Q

What is the progression of symptoms?

A

Normal

Normal or minimal change to Hb, MCV and MCH
More marked changes. MCH<25pg
Moderately severe Hb 3-10g/dl, MCH 15-20pg
Hydrops foetalis

99
Q

What are membranopathies?

A

Autosomal dominant conditions.

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

100
Q

What are some examples of membranopathies?

A

Spherocytosis & elliptocytosis most common.

Neonatal jaundice.

101
Q

What are some complications of membranopathies?

A

Mild to moderate haemolytic anaemia with occasional exacerbations during infection
Gallstones
Folic acid and splenectomy in selected cases.

102
Q

What is Elliptocytosis? What causes this?

A

Where the red blood cells are shaped elliptically.

Horizontal interactions.

103
Q

What is Spherocytosis? What causes this?

A

Where the red blood cells are shaped spherically.

Vertical interactions.

104
Q

What are parvovirus and haemolytic anaemias?

A 
Common infection in children
Occurs in epidemics
“slapped cheek syndrome”
Leads to decreased RBC production
Dramatic Hb drop in patients who already have reduced red cell lifespan.
105
Q

What happens in anaemia in virological events?

A

Virus enters and then specific IgM produced.

106
Q

What happens in haematological events in anaemia?

A

Reticulocytes and leukocytes drops then haemoglobin drops whilst the other two rise above average.

107
Q

What are enzymopathies?

A

Provides the fuel for the red cell
Generates redox capacity to protect red cell
Inherited enzyme deficiencies lead to shortened red cell lifespan from oxidative damage.

108
Q

What is the most common enzymopathy?

A

G6PD deficiency and pyruvate kinase deficiency most common.

109
Q

What is Glucose 6 phosphate dehydrogenase deficiency?

A

Caused by a wide variety of mutations within G6PD gene
Most asymptomatic
X linked but women may also be affected

110
Q

How is Glucose 6 phosphate dehydrogenase deficiency diagnosed?

A

Diagnosed by screening test for NADPH.

111
Q

What does Glucose 6 phosphate dehydrogenase deficiency look like?

A

Crises characterised by haemolysis, jaundice, anaemia.
Precipitated by Broad beans, infection, drugs
Usually self limiting
Symptomatic patients rare.

112
Q

What are platelets and how are they formed?

A

Anucleate cells
formed by fragmentation of megakaryocyte
(MK) cytoplasm in bone marrow.

113
Q

What is important about platelets shape? What is their primary function?

A

Disc shape allows them to flow close to endothelium

Important role in primary haemostasis

114
Q

How are old platelets recycled and after how long?

A

Life span 7-10 days

Old platelets are phagocytosed by splenic macrophages in red pulp.

115
Q

What does thrombopoietin do?

A

Stimulates production of platelets by megakaryocytes

Binds to platelet and MK receptors

↓plts = less bound TPO = ↑ free TPO able to bind to MK = ↑ Plt prodn.

116
Q

Where is thrombopoietin produced?

A

Liver.

117
Q

What happens after damage to the endothelium is done?

A

1) Platelets adhere to vascular endothelium via collagen & vWF (von Willebrand factor)
2) Binding of platelets to collagen stimulates cytoskeleton shape change within the platelets, and they ‘spread’ out
3) This increases their surface area and results in their activation, leading to the release of platelet granule contents including ADP, fibrinogen, thrombin and calcium. These components facilitate the clotting cascade ending with the production of fibrin.
4) Aggregation of platelets then occurs, which involves the cross-linking of activated platelets by fibrin
5) Activated platelets also provide a negatively charged phospholipid surface, which allows coagulation factors to bind and enhance the clotting cascade.

118
Q

What do platelet granules contain?

A

contents that help the formation of fibrin, and provide a surface for clotting factors Va and Xa to function better.

119
Q

What is Thromboxane A2 (TXA2)?

A

synthesized from Arachidonic acid in platelets via cyclooxygenase (COX)-1
induces platelet aggregation & vasoconstriction.

120
Q

What is P2Y12?

A

receptor on platelets activated by ADP

amplifies activation of platelets & helps activate Gp IIbIIIa.

121
Q

What is Gp IIbIIIa?

A

acts as a receptor for fibrinogen and vWF

aids platelet adherence and aggregation.

122
Q

What does Clopidogrel inhibit?

A

P2Y12.

123
Q

What does Tirofiban inhibit?

A

Bp IIbIIIa.

124
Q

What does Aspirin inhibit?

A

COX-1.

125
Q

What is COX-1 needed to make?

A

Thromboxane A2 from prostaglandin H2.

126
Q

What is needed to make Arachidonic acid?

A

P2Y12 and Gp IIbIIIa.

127
Q

What is the platelet dysfunction: clinical features?

A 
Mucosal bleeding
Epistaxis, gum bleeding, menorrhagia
Easy bruising
Petechiae, purpura
Traumatic haematomas (inc subdural).
128
Q

What are some causes of platelet dysfunction?

A

Reduced platelet number (thrombocytopenia).

  • Decrease in production.
  • Increase in destruction.
Normal numbers but reduced function.
- Congenital abnormality in platelet function
- Medication e.g aspirin
- von Willebrand disease 
(reduced VWF activity)
- Uraemia
129
Q

What is thrombocytopenia?

A

Decreased platelet production.

130
Q

What are the different types of thrombocytopenia?

A

Congenital thrombocytopenia
Absent / reduced / malfunctioning megakaryocytes in BM

Infiltration of bone marrow
Leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis.

131
Q

What can cause a decreased production of platelets?

A 
Reduced platelet production by bone marrow
Low B12 / folate
Reduced TPO (e.g. liver disease)
Medication: Methotrexate, chemotherapy 
Toxins: e.g. Alcohol
Infections: e.g. viral (e.g. HIV) TB 
Aplastic anaemia (auto immune)

Dysfunctional production of platelets in BM
Myelodysplasia.

132
Q

What are some caused of increased destruction of platelets?

A

Autoimmune:
Immune thrombocytopenia (ITP)
Primary, or secondary

Hypersplenism:
Portal hypertension, splenomegaly

Drug related immune destruction:
E.g. Heparin induced thrombocytopenia.

133
Q

What are some diseased which increase destruction of platelets?

A

Disseminated intravascular coagulopathy (DIC)

Thrombotic thrombocytopenic purpura (TTP)

Haemolytic uraemic syndrome (HUS)

Haemolysis, elevated liver enzymes and low platelets (HELLP)

Major haemorrhage

134
Q

What is immune thrombocytopenia?

A

IgG antibodies form to platelet and megakaryocyte surface glycoproteins

Opsonized platelets are removed by reticuloendothelial system
Primary:
May follow viral infection / immunisation esp in children
Secondary:
Occurs in association with some
Malignancies, such as Chronic Lymphocytic Leukaemia (CLL)
Infections e.g. HIV / Hep C

135
Q

How does immune thrombocytopenia present?

A

Hb 130 Plt 6 Wbc 5.2 U+E normal LFTs normal Clotting normal
Examination: bruises but no LN or hepatosplenomegaly
Blood film: reduced platelets but nil else

136
Q

What is immune thrombocytopenia in relation to platelets?

A

Increased destruction of platelets.

137
Q

How do you treat immune thrombocytopenia?

A

Immunosuppression e.g. steroids / IVIG

Treat underlying cause

If bleeding – give platelets - but will disappear quickly

Tranexamic acid

Inhibits breakdown of fibrin

Good for mucosal bleeding but NOT if urinary tract bleeding (clot retention)

138
Q

How does acute lymphoblastic leukaemia present?

A

Hb 80 Plt 6 Wbc 2 Neut 0.3
Clotting / LFTs / UE normal
Small cervical lymph nodes palpable
Widened mediastinum on CXR.

139
Q

What is acute lymphoblastic leukaemia in relation to platelets?

A

Reduced production of platelets.

140
Q

How does disseminated intravascular coagulation present?

A

Hb 102 Plt 54 Wbc 28 Neut 22 Crp 380
PT 18 APTT 40 Fib 0.9 D-dimer 50,000
Blood film: ‘toxic’ neutrophils.

141
Q

What is disseminated intravascular coagulation in relation to platelets?

A

Increased consumption.

142
Q

What is DIC? What does this produce?

A

Cytokine release in response to SIRS
(Sepsis, trauma, pancreatitis, obstetric emergency, malignancy)

-Systemic activation of clotting cascade.
-Consumption of platelets and
clotting factors.
-Bleeding

  • Systemic activation fo clotting cascade.
  • Microvascular thrombosis.
  • Organ failure.
143
Q

How do you treat DIC?

A

Treat underlying cause

Supportive provision of:
Platelets
FFP: contains clotting factors
Cryoprecipitate: contains fibrinogen and some clotting factors.

144
Q

How does Heparin induced thrombocytopenia present?

A

Hb 105 Plt 46 Wbc 10 Clotting normal
Crp 50 Creatinine 120 LFTs normal

Noted to have a new swollen left leg: DVT found.

145
Q

What is Heparin induced thrombocytopenia in relation to platelets?

A

Increased destruction.

146
Q

What happens in heparin induced thrombocytopenia?

A

Development of an IgG antibody against a complex formed between

Platelets + Heparin

IgG/PF4/Heparin complexes bind to and activate platelets

Platelet consumption

Thrombosis (arterial or venous), skin necrosis.

147
Q

What is the presentation of heparin induced thrombocytopenia at the platelet level?

A

Usual presentation:

Sharp fall in platelets 5-10 days after starting Heparin treatment

Life threatening – need to stop UFH / LMWH Heparin immediately

Alternative anticoagulation (even if platelets low)

Never re-expose patient to Heparin.

148
Q

How can a neutrophil destroy bacteria?

A 
Phagocytosis
Degranulation
-ROS
-NOS
NETs
Cytokine release.
149
Q

What is Febrile Neutropenia?

A

Temperature recorded >38°C in a patient with absolute neutrophil count <1.0 x 10^9/L.

150
Q

How do you treat Febrile Neutropenia?

A

Thorough history & examination- top to toe!
Full septic screen:
Bloods
Line & peripheral cultures
Urine MC&S, viral & bacterial throat swab, stool MC&S, CXR, line swabs
Cannula & antibiotics WITHIN 1 HOUR
IV fluids- low threshold for senior input/ITU if haemodynamically unstable
Do not catheterize if neutropenic

151
Q

How does Febrile Neutropenia present?

A 
Pyrexia >38°C/rigors
Generally unwell
Infective symptoms
Signs of deterioration:
Confusion/ less responsive
Hypotensive, tachycardic, tachypnoeic 
May not have a temperature/rigors due to inability to amount immune response.
152
Q

Who is at risk of Febrile Neutropenia?

A

Any patient that has had chemotherapy <6 weeks ago
Any patient who has had a stem cell transplant or high dose chemotherapy within last year
Any haematological condition causing neutropenia:
Myelodysplasia, Aplastic anaemia, Autoimmune disease, Leukaemia
Other drugs- Methotrexate, Carbimazole, Clozapine
Bone marrow infiltration

153
Q

What can cause malignant spinal cord compression?

A

Any malignancy can cause spinal cord compression
Bone metastasis and vertebral collapse
Local tumour extension
Deposition of malignant cells within cord
In Haematology mainly seen in
Myeloma
Lymphoma.

154
Q

How does malignant spinal cord compression present?

A 
Back pain
Weakness/numbness in legs
‘Off legs’
Inability to control bladder/bowel
Saddle paraesthesia.
155
Q

How does malignant spinal cord compression present on compression/

A 
Uni/bilateral leg weakness
Paraesthesia- may be sensory level
Decreased perineal sensation
Decreased anal tone
In acute cord compression, tone and reflexes will be reduced.
156
Q

How do you treat malignant spinal cord compression?

A 
Strict bed rest
High dose steroid
Analgesia
Urgent MRI whole spine
Bladder/bowel care
If Spinal Cord Compression confirmed
 speak to the Spinal Surgeons
If not for surgery, discuss with Oncologists to arrange radiotherapy
157
Q

When is hypercalcaemia seen?

A

In Haematology, mostly seen in Multiple Myeloma

158
Q

What does hypercalcaemia present with?

A

Presents with confusion, bone pain, constipation, nausea, polyuria and polydipsia, abdominal pain, anorexia, renal stones

159
Q

What do patients with hypercalcaemia have?

A

Patients can get shortening of QT interval and suffer cardiac arrest

160
Q

What is the treatment of hypercalcaemia?

A

Treatment:
IV hydration (3-4L/day including PO fluid)
Bisphosphonates.

161
Q

What is anaemia?

A

Reduced red cell mass

+/- reduced haemoglobin concentration

162
Q

What is the normal haemoglobin range?

A

Male Hb = 131 – 166 g/L

Female Hb = 110 – 147 g/L

163
Q

What are the physiological consequences of anaemia?

A 
Reduced O2 transport
Tissue hypoxia
Compensatory changes
-Increase tissue perfusion
-Increase O2 transfer to tissues
-Increase red cell production
164
Q

What are some pathological consequences of anaemia?

A 
Myocardial fatty change
Fatty change in liver
Aggravate angina/claudication
Skin and nail atrophic changes
CNS cell death (Cortex and basal ganglia)
165
Q

Where are red blood cells produced?

A

Bone marrow.

166
Q

Where are red blood cells removed?

A

Spleen.
Liver.
Bone marrow.
Blood loss.

167
Q

How long do red blood cells last?

A

120 days.

168
Q

What are the different types of anaemias?

A

Bone marrow problems
Hypoplastic anaemias.
Post haemorrhage.

Breakdown problems
Dyshaemopoietic anaemias.
Haemolytic.

169
Q

What are some hypoplastic anaemias?

A 
Renal failure
Endocrine
PRCA
Aplastic anaemia
   -Inherited
   -Acquired
      -Idiopathic
      -Chemical/drug
      -Viral
      -Radiation
170
Q

What are some dyshaemopoietic anaemias?

A 
Multiple mechanisms
   e.g. ACD
Defective Hb synthesis
   Globin 
      e.g. thalassaemia
   Haem   
      e.g. iron def
Defective DNA synthesis
   e.g. Folic acid,  B12
171
Q

What are some post haemorrhage anaemias?

A

Intrinsic RBC abnormalities
Acquired
e.g. PNH

Hereditary
   membrane disorders 
      e.g. HS
   enzyme disorders
      e.g. PK
   Hb disorders
      e.g. HbSS
172
Q

What are some haemolytic anaemias?

A 
Extrinsic abnormalities
   Antibody mediated
      e.g. AIHA
   Mechanical trauma
      e.g. DIC
   Infections
      e.g. Malaria
   Chemicals
     e.g. lead poisoning
   Sequestration
      e.g. hypersplenism
173
Q

What are the different types of anaemias?

A

Microcytic.
Normocytic.
Macrocytic.

174
Q

What are the causes of microcytic anaemia?

A

Iron deficiency.
Chronic disease.
Thalassaemia.

Rarely
Congenital sideroblastic anaemia.
Lead poising.

175
Q

How can you investigate iron deficiency?

A

Ferritin.
Iron studies.
Tests of causes.
Treatment.

176
Q

What does an elevated ferritin show?

A

Inflammation.

177
Q

What is a low ferritin?

A

Iron deficiency.

178
Q

What does chronic disease anaemia show?

A

Renal failure
Clinical investigation.
Labatory investigation.

179
Q

What is normocytic anaemia caused by?

A

Acute blood loss.
Anaemia of chronic disease.
Combined haematinic deficiency.

180
Q

What is microcytic anaemia caused by?

A 
B12/folate deficiency 
Alcohol excess/liver disease.
hypothyroid.
HAEMATOLOGICAL
Antimetabolite therapy
Haemolysis
Bone marrow failure
Bone marrow infiltration.
181
Q

How can you investigate B12 deficiency?

A

IF antibodies
Schilling test
Coeliac antibodies

B12 replacement

182
Q

What does polycythaemia mean?

A

Too many red blood cells.

183
Q

What is the haematicrit?

A

Cells that sink to the bottom of a tube when centrifuged.

184
Q

What are the causes of polycythaemia?

A 
Reactive/Secondary
Smoking
Lung disease
Cyanotic heart disease
Altitude
Epo/Androgen excess

Primary/Proliferative
Polycythaemia Rubra Vera.

185
Q

What is a reactive cause?

A

Body response to a cause.

186
Q

What is polycythaemia Rubra Vera?

A

Deficiency of the bone marrow, produces too many red blood cells.
Genetic disorder.

187
Q

What is Myeloproliferative disorder?

A

Overactive bone marrow, predominately of red cells but also WBC’s and platelets too.

188
Q

How does PRV present like?

A 
Plethoric appearance
Thrombosis
Itching
Splenomegaly
Abnormal FBC
189
Q

How can you treat PRV?

A

Aspirin
Venesection
Bone marrow suppressive drugs (e.g. Hydroxycarbamide).

190
Q

What is neutrophilia?

A

Too many white blood cells.

Neutrophils.

191
Q

What are the causes of neutrophilia?

A

Reactive
Infection
Inflammation
Malignancy

Primary
CML (chronic myeloid leukaemia)

192
Q

What is too many white blood cells?

A

Lymphocytosis.

193
Q

What are the causes of increased white blood cells?

A

Reactive
Infection
Inflammation
Malignancy

Primary
CLL (chronic lymphocytic lymphoma)

194
Q

What is not enough platelets?

A

Thrombocytopaenia.

195
Q

What is too many platelets?

A

Thrombocytosis.

196
Q

What are the causes of thrombocytosis?

A

Reactive
Infection
Inflammation
Malignancy

Primary
Essential Trombocythaemia.

197
Q

What is not enough neutrophils?

A

Neutropaenia.

198
Q

What are the causes for neutropaenia?

A

Underproduction
Marrow failure
Marrow infiltration
Marrow toxicity e.g. drugs

Increased removal
Autoimmune
Felty’s syndrome
Cyclical

Bateman - Phase 2a COPY (15 decks)

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