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Year 5 Pathology > Haematology > Flashcards

Haematology Flashcards

1
Q

Anticoagulant molecules expressed by the vessel wall

A

Thrombomodulin
Endothelial protein C receptor
Tissue factor pathway inhibitor
Heparans

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2
Q

Antiplatelet factors expressed by the vessel wall

A

Prostacyclin

Nitrous Oxide

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3
Q

Effects of inflammation which make vessel wall prothrombotic

A

Downregulation of anticoagulant molecules
Upregulation of adhesion moiecules
Expression of tissue factor
Reduced prostacyclin production

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4
Q

Effects of stasis (of blood flow) that create a prothrombotic environment

A

Accumulation of activated factors
Promotes platelet adhesion
Promotes leukocyte adhesion and transmigration
Hypoxia produces inflammatory effect on endothelium

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5
Q

Causes of stasis (of blood flow)

A

Immobility: surgery, paraparesis, travel
Compression: Tumour, pregnancy
Viscosity: Polycythaemia, paraprotein
Congenital: Vascular abnormalities

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6
Q

Clotting factor increased in pregnancy:

A

Factor VIII

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7
Q

Bence Jones proteins are Ig…

A

IgG

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8
Q

Multiple myeloma is a neoplasia of which cells?

A

Plasma cells (effector B cells)

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9
Q

B cell differentiation and maturation (in germinal centre). Name cells starting with antigen activated B cell to mature fully differentiated plasma cell

A

Antigen activated B cell
Centroblast
Plasmablast
Plasma cell

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10
Q

The premalignant state of multiple myeloma is…

A

Monoclonal gammopathy of undetermined significance (MGUS)

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11
Q

Monoclonal gammopathy of undetermined significance (MGUS) is…

A

The premalignant state of multiple myeloma. It carries most of the key genetic abnormalities of MM such as translocations but the cells do not do much harm. Sit in the bone marrow and secrete.

(The older we are the more likely we have it)

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12
Q

Chromosomal abnormalities common in multiple myeloma (2)

A

Translocations between chromosome 14 at locus 32 and an oncogene (seen in 50%)
Deletions of parts of chromosome 13 (seen in 50%)

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13
Q

Key clinical features of myeloma

A

Calcium elevated: thirst, bones, moans, stones, groans,
Renal failure (plus amyloidosis and nephrotic syndrome)
Anaemia (and pancytopenia): fatigue, infections
Bones: pain, osteoporosis, osteolytic lesions, wedge compression fractures (back pain), pepper pot skull (more correct: raindrop skull), hyperviscosity syndrome.

Infections

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14
Q

Key investigations (and results) for multiple myeloma

A 
Serum electrophoresis: Dense narrow band
Blood film: Rouleaux 
Urine: Bence-Jones protein 
ESR: Very high 
Bone marrow: >10% plasma cells in bone marrow 
Monoclonal plasma cells
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15
Q

Staging system of multiple myeloma

A

Durie-salmon

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16
Q

Criteria for MGUS

A

Monoclonal serum protein 70y)

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17
Q

Multiple myeloma:

a) median age at diagnosis
b) Most common in which racial group?

A

65-70

Black people

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18
Q

Multiple myeloma immunophenotypes:

a) MM cells are typically positive for
b) MM cells are typically negative for

A

a) CD38, CD138, CD56/58, monotypic cytoplasmic Ig

b) CD19, CD20, surface Ig, light chain restriction

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19
Q

Features of “smouldering myeloma”

A

> 10% plasma cells in BM but no CRAB/organ/tissue involvement.

CRAB= raised calcium, renal failure, anaemia, bone pathology

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20
Q

Features of myeloma bone disease:

A 
Lytic lesions 
Low bone density 
Pathological fractures 
Spinal cord compression (paralysis) 
Hypercalcaemia (renal failure) 
Bone pain
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21
Q

Explain relationship between multiple myeloma and bone disease

A

Plasma cells secrete cytokines that activate osteoclasts and cytokines that inhibit osteoblasts. Osteoclasts stimulate osteoclasts. So treating myeloma bone disease is very important.

Osteoclast activating: RANK-L, MIP1-alpha, TNFalpha. IL-6, IL-3

Osteoblast inhibiting: Dkk-1, sFRP3, HGF, TGF-beta1, sclerostin

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22
Q

Briefly describe pathogenesis of myeloma nephropathy

A

Light chains of paraproteins precipitate in the kidneys, they form a glue and block normal flow. Induces an inflammatory response that leads to kidney failure.

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23
Q

Treatment of multiple myeloma

A 
Steroids 
Classical cytostatic drugs e.g. melphalan 
Proteosome inhbitors 
IMIDs: e.g. thalidomide 
Supportive treatment for CRAB

Autologous stem cell transplantation (makes use of high dose melphalan)

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24
Q

Mechanism of action of melphalan

A 
Alkylating agent (nitrogen mustard type). 
Adds alkyl group to DNA (guanine) forming crosslinks and therefore blocks DNA replication.
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25
Q

Mechanism of action of proteosome inhibitors

A

Proteosome in the cell degrades damaged/unnecessary proteins into amino acids ready to reenter protein production.

Misfolding of (large proteins happens when you have to fold a large amount of protein. The proteins are non-functional and precipitate easily and clog up the ER killing the cell. The proteins are exported and degraded by the ER. If the proteosome is inhibited you get a backlog of this protein, increasing the chance of it clogging the ER and killing the cell. Also causes a shortage of amino acids to create new protein.

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26
Q

Examples of proteosome inhbitors

A

Bortezomib, carfilzomib, and ixazomib

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27
Q

% of multiple myeloma patients with lytic lesions or low bone density

A

80-90%

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28
Q

Features of Waldenstrom’s macroglobuinaemia

Histology, clinical,

A

AKA lymphoplasmacytoid lymphoma

Increased risk in elderly men
Lymphoplasmacytoid cells produce monoclonal iGM that infiltrates lymph nodes and bone marrow
Weight loss, fatigue, hyperviscosity (visual problems, confusion, CCF, muscle weakness)

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29
Q

Treatment of Waldenstrom’s macroglobuinaemia

A

Plasmaphoresis for hyperviscosity

Chlorambucil, cyclophosphamide and other chemo

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30
Q

FBC changes in pregnancy

A

Mild anaemia (dulutional effect)
Macrocytosis (but beware folate deficiency)
Neutrophilia
Thrombocytopenia (increased platelet size as younger platelets are released)

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31
Q

Consequences of iron deficiency in pregnancy

A

Iron deficiency may cause IUGR, prematurity, postpartum haemorrhage

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32
Q

The recommended daily allowance of iron in pregnancy is

A

30mg

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33
Q

WHO recommendations for iron and folate supplementation in pregnancy

A

60mg iron

400mcg folic acid

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34
Q

Folic acid should be taken in pregnancy until at least… weeks

A

12

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35
Q

Causes of reduced platelet count in preganancy

A

Physiological: ‘gestational’/incidental thrombocytopenia (most likely if plt between 100-150)
Pre-eclampsia
Immune thrombocytopenia (ITP)
Microangiopathic syndromes
All other causes: bone marrow failure, leukaemia, hypersplenism, DIC etc.

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36
Q

Mangement of ITP in pregnancy

A

IVIG
Steroids
Anti-D (where Rh-D +ve)
Avoid ventouse delivery due to effect of ITP on baby (bleeding risk)

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37
Q

Features of microangiopathic haemolytic anaemia on blood film

A

Thrombocytopenia
Schistocytes(red cell fragment)
Anaemia

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38
Q

Brief pathophysiology of microangiopathic haemolytic anaemia

A

Formation of a fibrin/platelet mesh in small vessels. Damage to RBCs as they are forced through (form schistocytes)

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39
Q

Causes of microangiopathic haemolytic anaemia

A 
Autoimune: Thrombotic thrombocytopaenic purpura  
Haemolytic uraemic syndrome
DIC
Pre-eclampsia 
Eclampsia
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40
Q

What is HELLP syndrome

A

A variant of pre-eclampsia. Abbreviation of 3 main characteristics
Hemolysis
Elevated Liver enzymes
Low Platelet count

Usually begins in 3rd trimester
High fetal/infant mortality

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41
Q

Causes of thrombocytopenia in pregnancy.
Which are definitively treated by delivery of the baby

TTP
HUS
HELLP
Pre-eclampsia

A

HELLP

Pre-eclampsia

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42
Q

Coagulation changes in pregnancy (changes in coagulation factors)

A 
Factor VIII and vWF 	increase  3-5 fold
Fibrinogen 			increases 2 fold
Factor VII 			increases 0.5 fold
(Factor X)
RESULT IN HYPERCOAGULABLE STATE

Protein S falls to half basal
PAI-1 increase 5 fold
PAI-2 produced by placenta

RESULT IN HYPOFIBRINOLYTIC STATE

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43
Q

DVT in pregancy is more common on which side

A

Left

Because of reduced venous return

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44
Q

Risk factors for DVT in pregnancy

A 
Hyperemesis/dehydration
 Bed rest
 Obesity
- BMI>29 3x risk of PE
Pre-eclampsia
Operative delivery
Previous thrombosis/thrombophilia
Age
Parity
Multiple pregnancy
Other medical problems: 
-HbSS, nephrotic syndrome
IVF: ovarian hyperstimulation
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45
Q

Warfarin is most teratogenic in which trimester

A

1st

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46
Q

Complications in pregnancy associated with thrombophilia

A 
Fetal growth restriction (IUGR)
Recurrent miscarriage
Late fetal loss
Placenetal abruption
Severe pre-eclampsia

Possibly due to impaired placental circulation

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47
Q

Heparin and aspirin can prevent complications in pregnancy associated with which thrombophilia?

A

Antiphospholipid syndrome

in women with recurrent pregnancy loss

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48
Q

Post partum haemorrhage is defined as…

A

> 500ml blood loss

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49
Q

Haematological factors affecting risk of post-partum haemorrhage

A

Dilutional coagulopathy
DIC in abruption
Amniotic fluid embolism

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50
Q

DIC in pregnancy can be triggered by…

A 
Amniotic fluid embolism
Placental abruption 
Retained dead fetus
Preeclampsia (severe) 
Sepsis
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51
Q

Signs associated with amniotic fluid embolism

A

Sudden onset shivers, vomiting, shock. DIC

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52
Q

Haemoglobinopathy associated with hydrops fetalis

A

Alpha 0 thalassaemia

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53
Q

Complications in pregnancy associated with sickle cell disease

A 
Fetal growth restriction
Miscarriage
Preterm labour
Pre-eclampsia 
Venous thrombosis

Increased frequency of vaso-occlusive crises

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54
Q

Managament of sickle cell disease in pregnancy

A

Red cell transfusion (top up or exchange)

Prophylactic transfusion:
reduces number of vaso-occlusive episodes
Not clear whether affects fetal or maternal outcome

Alloimmunisation -extended phenotype: Rh D c E, Kell

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55
Q

RBC count in:

a) iron deficiency anaemia
b) Thalassaemia trait

A

a) Low or normal

b) Increased

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56
Q

Causes of anaemia with low MCV

A

Iron deficiency
Thalassaemia trait
Anaemia of chronic disease

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57
Q

Presence of poikilocytes and anaemia suggests…

A

Iron deficiency

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58
Q

Anisopoikilocytosis and anaemia suggests…

A

iron deficiency

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59
Q

Basophilic stippling and anaemia suggests

A

Beta thalassaemia trait
Lead poisoning
Alcoholism
Sideroblastic anaemia

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60
Q

Neutrophils should contain a maximum of… segments

A

Five

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61
Q

Target cells are also known as

A

codocytes

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62
Q

Presence of target cells suggests

A

Iron deficiency
Thalassaemia
Hyposplenism
Liver disease

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63
Q

Howell-Jolly bodies are seen in

A

Hyposplenism

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64
Q

Causes of a poorly functioning spleen include…

A

Inflammatory bowel disease
Coeliac disease
Sickle cell disease
SLE

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65
Q

B12 is absorbed from the…

A

terminal ileum

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66
Q

Should be measured before starting a transfusion of blood products

A

Baseline temp, pulse, respiratory rate,BP

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67
Q

Most acute transfusion reactions will occur in within the first…. (duration) of a transfusion

A

15 minutes

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68
Q

Probable cause?

During or soon after transfusion (blood or platelets), rise in temperature of 1 degree, chills, rigors.

A

Febrile non-haemolytic transfusion reaction

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69
Q

Cause of febrile non-haemolytic transfusion reaction

A

White cells in blood products. The patient forms antibodies against them.

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70
Q

Treatment of febrile non-haemolytic transfusion reactions

A

Have to stop or slow transfusion
Treat with paracetamol
Can restart transfusion

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71
Q

Symptoms and signs of acute intravascular haemolysis

A

Restless, chest/ loin pain, fever, vomiting, flushing, collapse, haemoglobinuria (later)

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72
Q

The intravascular haemolysis due to ABO incompatible blood is mediated by….

A

complement

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73
Q

Antibodies involved in intravascular haemolysis

A

IgM

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74
Q

Cause of delayed haemolytic transfusion reaction.

A

Initially alloimmunisation occurs: the patient develops an immune antibody to the foreign antigen in the product.
Then if they are exposed to it again through another transfusion the antibodies will trigger extravascular haemolysis. The haemolysis is driven by phagocytes.

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75
Q

Clinical features of a delayed haemolytic transfusion reaction

A 
Increased bilirubin 
Increased reticulocytes 
Decreased Hb 
Haemoglobinuria 
Can cause renal failure 
May require additional transfusion
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76
Q

Treatment of delayed haemolytic transfusion reaction

A

Repeat cross match
Treat renal failure
May require another transfusion

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77
Q

3 causes of anaphylactic transfusion reaction

A

Previous exposure to an antigen, develop IgE antibody and react on next exposure (classically IgA deficiency)

IgE antibody passively transferred by transfusion

Antigen passively transferred by transfusion and patient has IgE antibody

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78
Q

Requirements for a diagnosis of transfusion associated circulatory overload

A

Any FOUR of the following that occur within SIX HOURS of transfusion:

Acute respiratory distress
Tachycardia
Increased blood pressure
Acute or worsening pulmonary oedema
Evidence of a positive fluid balance
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79
Q

What is TR-ALI

A

Transfusion associated acute lung injury:

Acute dyspnoea with hypoxia and bilateral pulmonary infiltrates during or within 6 hours of transfusion, not due to circulatory overload or other likely causes

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80
Q

Pathogenesis of Transfusion associated acute lung injury

A

Donor anti-leucocyte antibodies (HLA or anti-granulocyte Abs)
Interact with patient’s leucocyte antigens
Aggregates of white blood cells get stuck in the pulmonary small capillaries
Release neutrophil proteolytic enzymes and toxic oxygen metabolites causes lung damage

Mechanism not fully understood, antibodies do not always cause problems

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81
Q

How do we prevent transfusion associated acute lung injury?

A

Don’t give plasma from female donors:
Most FFP is male donor
If platelets are pooled from 4 donors, the plasma they are resuspended in is from a male donor
Virally inactivated FFP (pooled, solvent detergent treated) does not cause TRALI

Stop unnecessary use of FFP:
Use vitamin K or PCC/Octaplex for reversing warfarin

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82
Q

Which group of patients are most susceptible to transfusion related GvHD and how is it prevented?

A

Immunosupressed patients
or
If donor HLA matched or HLA-similar to the recipient

Prevention: Irradiate donor blood

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83
Q

What is Post Transfusion Purpura?

A

Purpura appears 7-10 days after transfusion of blood or platelets and usually resolves in 1 to 4 weeks but can cause life threatening bleeding

Affects HPA -1a negative patients
(HPA is human platelet antigen)

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84
Q

Treatment of post transfusion purpura

A

IVIG

and maybe HPA-1a negative platelets

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85
Q

Pathogenesis of haemolytic disease of the foetus and newborn

A

RhD negative mother pregnant with RhD positive foetus, foetal blood crosses placenta.

Mother develops antibodies against RhD 6 months later

Pregnant again with RhD positive foetus, the antibodies against RhD cross placenta into the foetus.

The antibodies coat the RhD positive foetal red cells and destroy them in the foetal spleen and liver.

Note: only IgG can cross placenta

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86
Q

Clinical features of haemolytic disease of the foetus and newborn

A

Fetal anaemia (haemolytic)

Haemolytic disease of newborn (anaemia plus high bilirubin - which builds up after birth as no longer removed by placenta)

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87
Q

Treatment of pregnancy when mother is alloimmunised to RBC antigens

A

All pregnant women Group and Antibody screen at around 11 weeks (booking) and again at 28 weeks to check for RBC antibodies
If RBC antibody present, quantify, check partner and monitor level of antibody (high or rising - more likely to affect fetus)
Monitor fetus for HDN – MCA Doppler ultrasound
Deliver baby early, as HDN gets a lot worse in last few weeks of pregnancy

If necessary, intra-uterine transfusion can be given to fetus

At delivery - monitor baby’s Hb and bilirubin for several days as HDN can get worse for few days

Can give exchange transfusion to baby if needed to bilirubin and Hb; plus phototherapy to bilirubin
Note: subsequent pregnancies usually worse

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88
Q

Mechanism of action of prophylactic anti-D Immunoglobulin

A

RhD positive (fetal) red cells get coated with anti-D Ig and then they get removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother to produce anti-D antibodies

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89
Q

Times when fetomaternal bleed likely to occur

A

spontaneous miscarriages if surgical evacuation needed and therapeutic abortions
amniocentesis and chorionic villous sampling
abdominal trauma (falls and car accidents)
external cephalic version (turning the fetus)
stillbirth or intrauterine death

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90
Q

Doses of anti-D used after events likely to cause fetomaternal bleed

A

At least 250 iu - for events before 20 weeks of pregnancy
At least 500 iu - for events after 20 weeks of pregnancy
and at delivery

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91
Q

Doses (and timing) of anti-D given as prophylaxis during pregancy

A

At least 500 iu anti-D Ig at 28 and 34 weeks or 1500 iu anti-D Ig at 28-30 weeks

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92
Q

Antibodies that can cause severe haemolytic disease of the newborn

A

Anti-D
Anti-c
Anti-Kell

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5
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93
Q

Effects of anti-Kell antibodies on a foetus

A

Haemolysis

Reticulocytopenia

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94
Q

Risk factors for lymphoma

A

Constant antigenic stimulation
Infection (viral infection of cells)
Immunosupression (HIV and immunosupressants)

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95
Q

Examples of conditions in which chronic antigenic stimulation leads to lymphoma

A

H. Pylori: Gastric MALT
Coeliac disease: Small bowel T cell lymphoma
Sjogren’s syndrome: Parotid lymphoma
Hashimoto’s thyroiditis: Thyroid marginal zone lymphoma

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96
Q

Viral infections that increase lymphoma risk

A

EBV infects B cells, carrier state regulated by T cells. T cells supressed by immunosupressants.
HIV: EBV infects B cells, HIV leads to loss of T cell regulation of infected B cells
HTLV1: Direct viral integration. Infects T cells by vertical transmission. May develop adult T cell leukaemia

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97
Q

Lymphoma associated translocations involve which locus

A

Ig promoter

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98
Q

Within a lymohoid follicle the mantle zone contains…

A

Naive unstimulated B cells

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99
Q

Most common type of non-hodgkin lymphoma

A

B cell

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100
Q

Types of Hodgkin lymphoma

A

Classical

Lymphocyte predominant

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101
Q

Types of Non-Hodgkin lymphoma

A

B cell
Precursor B cell neoplasms
Peripheral B cell neoplasms (high and low grade)

T cell
Precursor T cell neoplasms
Peripheral T cell neoplasms

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102
Q

Types of lymphoma that begin in the germinal centre

A

Follicular lymphoma
Burkitt’s lymphoma
Diffuse large B cell lymphoma
Hodgekin lymphoma

(also multiple myeloma)

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103
Q

Types of lymphoma that begin in the mantle centre

A

Mantle cell lymphoma

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104
Q

Types of lymphoma that begin in the marginal zone

A

Diffuse large B cell lymphoma
Marginal zone lymphoma
Small lymphocytic lymphoma
Chronic lymphocytic lymphoma

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105
Q

Differentiating between B and T cells. B cells express CD… T cells express CD…

A

B cells: CD20

T cells: CD3 and CD5

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106
Q

High grade non-hodgkin lymphomas

A

Diffuse large B cell lymphoma

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107
Q

Low grade non-hodgkin lymphomas

A

Follicular lymphoma
Marginal zone lymphoma
Mantle zone lymphoma
Small lymphocytic lymphoma/chronic lymphocytic leukaemia

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108
Q

Key clinical features of follicular lymphoma

A

Middle age/ old age

Lymphadenopathy

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109
Q

Key histological features of follicular lymphoma

A

Follicular pattern
Germinal centre origin
CD10, bcl2

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110
Q

Translocation seen in follicular lymphoma

A

14;18 translocation involving bcl2 gene

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111
Q

Key clinical features of small lymphocytic lymphoma

A

Middle age/ elderly

Nodes or blood

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112
Q

Key histological features of small lymphocytic lymphoma

A

Small lymphocytes
Naive or post germinal centre memory B cell
Express CD5 and CD23

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113
Q

MALT lymphoma affects which cells

A

Post germinal centre memory B cells

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114
Q

Key clinical features of mantle cell lymphoma

A

Male predominance
Lymph nodes and GI tract
Disseminated disease at presentation

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115
Q

Key histological features of mantle cell lymphoma

A

Located in mantle zone
Pre-germinal centre naive B cells
Aberrant CD5 and cyclin D1 expression
Cyclin D1 overexpression

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116
Q

Clinical features of Burkitt’s lymphoma

A

Seen in children and young adults
Endemic type (equatorial Africa, EBV associated)
Sporadic type (outside Africa, EBV associated),
Immune deficiency type (Non-EBV associated, HIV/post transplant)
Associated with EBV

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117
Q

Key histological features of Burkitt’s lymphoma

A

Germinal centre cell origin

Starry sky appearance

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118
Q

Translocation seen in Burkitt’s lymphoma

A

c-myc translocations

8: 14
2: 8
8: 22

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119
Q

Key clinical features of diffuse large B cell lymphoma

A

Middle age/ elderly

lymphadenopathy

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120
Q

Key histological features of diffuse large B cell lymphoma

A

Germinal centre or post-germinal centre B cell
Sheets of large lymphoid cells

Germinal centre phenocyte= good prognosis
P53 positive, high proliferation fraction= poor prognosis

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121
Q

Enteropathy associated T cell lymphoma is associated with…

A

Coeliac disease

122
Q

Features of peripheral T cell lymphomas

A 
Middle age/ elderly
Lymphadenopathy and extranodal sites  
Large T cells
Often associated with reactive cell population e.g. eosinophils 
Aggressive
123
Q

Most common form of cutaneous T cell lymphoma

A

Mycosis fungoides

also known as Alibert-Bazin syndrome

124
Q

Key features of anaplastic large cell lymphoma

A

Clinical:
children and young adults
Lymphadenopathy

Histology
Large epithelioid lymphocytes
T cell or null phenotype

Molecular
t (2;5) translocation
Alk-1 protein expression (better prognosis if positive)

Aggressive

125
Q

Key differences between Hodgkin and NH lymphoma

A

Spread:
Hodgkin spreads contigiously to adjacent lymph nodes
NHL spreads discontinuously

Locations:
HL: more often localised to a single nodal site
NHL: More often involves multiple lymph node sites

126
Q

Key clinical features of classical Hodgkin lymphoma

A 
Young and middle aged 
Male predominance 
Often involves single lymph node group
EBV associated
Moderately aggressive
127
Q

Key histological features of classical Hodgkin lymphoma

A

Germinal centre/post germinal centre B cell origin
Sclerosis
Mixed cell population with scattered Reed-Sternberg and Hodgkin cells with eosinophils

128
Q

Key clinical features of nodular lymphocyte predominant Hodgkin lymphoma

A

Isolated lymphadenopathy

NO association with EBV

129
Q

Key histological features of nodular lymphocyte predominant Hodgkin lymphoma

A

Germinal centre B cell

B cell rich nodules with lymphocytic & histiocytic cells

130
Q

Clinical features/presentation of Hodgkin lymphoma

A 
Male predominance 
Bimodal age incidence: 20-29 and >60 
Painless lymphadenopathy (asymmetrical) 
Constitutional symptoms: fever, weight loss, night sweats, pruritus, fatigue 
Pel-Ebstein fever (cyclical 1-2 week) 
Pain in affected nodes after alcohol
131
Q

Staging of Hodgkin lymphoma

A

Stage 1: one lymph node region (can include spleen)
Stage 2: two or more LN regions on same side of diaphragm
Stage 3: two or more LN regions on opposite sides of the diaphragm
Stage 4: extranodal sites (liver, BM)

A: No constitutional symptoms (fever, unexplained weight loss, night sweats)
B: Constitutional symptoms

132
Q

What is a Reed-sternberg cell

A

Bi-nucleate/multinucleate (owl eyed) cell on a background of lymphocytes and reactive cells.
Associated with Hodgkin Lymphoma

133
Q

Imaging used in Hodgkin lymphoma

A

CT/PET

134
Q

Chemotherapeutic combination used in Hodgkin lymphoma

A

Adriamycin (doxorubicin)
Bleomycin
Vincristine
Dacarbazine/DTIC

Every 4 weeks

135
Q

Long term adverse affects of chemotherapy used to treat Hodgkin lymphoma

A

Pulomary fibrosis
Cardiomyopathy

(Preserves fertility)

136
Q

Secondary malignancies seen after radiotherapy for Hodgkin lymphoma

A

Breast
Leukaemia
Lung
Skin

137
Q

Hodgkin lymphoma:
Over…% of patients with stage 1 or 2 disease are cured
Around…. % of patients with stage 4 are cured

A

80%

50%

138
Q

Clinical features/presentation of NH lymphoma

A

Painless lymphadenopathy often involving multiple sites
Constitutional symptoms (fever, weight loss, night sweats, etc)
NO pain after alcohol

139
Q

Very aggressive Non-hodgkin lymphomas

A

Burkitt’s

140
Q

Treatment of diffuse large B cell lymphoma

A 
Rituximab
Cyclophosphamide
Doxorubicin 
Vincristine
Prednisolone
141
Q

Follicular Non-Hodgkin lymphoma prognosis

A

Incurable

Survival median 12-15 years (with chemo)

142
Q

What is bcl2?

A

Anti-apoptosis protein

143
Q

Laboratory findings in CLL

A

Lymphocytosis between 5 and 300 x 109/l
Smear cells
Normocytic normochromic anaemia
Thrombocytopenia

Bone marrow: Lymphocytic replacement of normal
marrow elements

Proliferation of mature B cells (CD19) co-expressing CD5

144
Q

CD35 expressed by which type of B cell

A

Plasma cell

145
Q

Name 2 systems used for staging CLL

A

Rai

Binet

146
Q

Outline Rai staging system

A

Used to stage CLL
Stage 0 Lymphocytosis only

Stage 1 lymphocytosis plus lymphadenopathy

Stage 2 lymphocytosis plus hepatosplenomegaly +/- lymphadenopathy

Stage 3 lymphocytosis plus anaemia with or without lymphadenopathy, hepatomegaly, or splenomegaly

Stage 4 lymphocytosis + thrombocytopenia

147
Q

Prophylaxis against infections in CLL patients

A

Aciclovir
PCP prophylaxis for those receiving fludarabine or alemtuzumab (Campath)
IVIG is recommended for those with hypogammaglobulinemia and recurrent bacterial infections
Immunisation against pneumococcus, and seasonal flu

148
Q

50% of CLL deaths are due to

A

Infection

149
Q

Treatment of autoimmune phenomena in CLL

A

1st line: steroids

2nd line: Rituximab

150
Q

Indications for treating CLL (instead of watching and waiting)

A

Progressive lymphocytosis:
>50% increase over 2 months
lymphocyte doubling time

151
Q

Treatment of CLL with 17p deletion

A

BCR kinase inhibitor

152
Q

Treatment of CLL (if not 17p deletion)

A

Rituximab+ Fludarabine+ Cyclophosphamide (FCR)

Add bendamustine and BCR inhibitor of relapse

153
Q

Transformation of low grade to high grade lymphoma is known as

A

Richter transformation

154
Q

Treatment of Richter’s syndrome

A 
Rituximab
Cyclophosphamide
Doxorubicin 
Vincristine
Prednisolone
155
Q

Outline Binet staging system

A

Clinical staging system for CLL
A: Less than 3 lymphoid areas
B: More than 3 lymphoid areas
C: Anaemia / low platelets

156
Q

Causes of a relative polycthaemia

A

Alcohol
Diuretics
Obesity

157
Q

Causes of APPROPRIATE raised EPO

A

High altitude
Hypoxic lung disease
Cyanotic heart disease
High affinity haemoglobin

158
Q

Causes of INAPPROPRIATE raised EPO

A 
Renal disease (cysts, tumours inflammation)
uterine myoma
other tumours (liver, lung1)
159
Q

Mutations associated with polycythaemia vera

A 
JAK2 gene (acquired point mutations)
Calreticulin gene (acquired insertions and deletions, which activate STAT5 by unknown mechanism)
160
Q

Average age of polycythaemia vera diagnosis

A

60

Also slightly more common in males

161
Q

Presentation of polycythaemia vera

A

Incidental diagnosis on routine blood testing

Symptoms of increased hyper viscosity:
Headaches, light-headedness, stroke, Thrombosis, retinal vein engorgement
Visual disturbances
Fatigue, dyspnoea

Increased histamine release:
Aquagenic pruritus
Severe burning pain in the hands and feet with a reddish or bluish skin discolouration
Peptic ulceration

Plethora
Gout: due to red cell turnover and overproduction of uric acid
Splenomegaly

162
Q

Treatment of polycythaemia

A

Reduce viscosity: venesection, hydroxycarbamide

Reduce risk of thrombosis: aspirin (keep platelets below 400)

163
Q

Epidemiology (age and sex) of polycythaemia vera

A

Mean age two peaks 55 years and minor peak 30 years

Females :males equal first peak but females predominate second peak

164
Q

Presentation of essential thrombocythaemia

A

Incidental finding in half the patients

Thrombosis: arterial or venous, so:
CVA, gangrene, TIA
DVT or PE

Bleeding: mucous membrane and cutaneous
Minor: headaches, dizziness visual disturbances
Splenomegaly usually modest

165
Q

Treatment of essential thrombocythaemia

A

Aspirin: to prevent thrombosis
Anagrelide: specific inhibition of platelet formation from megakaryocytes, side effects include palpitations and flushing (Possible myelofibrosis risk?)
Hydroxycarbamide: antimetabolite. Suppression of other cells as well. Possible mildly leukaemogenic

166
Q

Essential thrombocythaemia is associated with mutation of…

A

JAK2 gene

167
Q

Long term complications of essential thrombocythaemia

A

Risk of myelofibrosis development

Leukaemic transformation in about 5% after >10 years

168
Q

Chronic idiopathic myelofibrosis involves proliferation of which cells?

A

Mainly of megakaryocytes and granulocytic cells

169
Q

Myelofibrosis can be secondary. A progression from

A

Essential thrombocythaemia or polycythaemia vera

170
Q

Myelofibrosis (idiopathic) usually develops at what age

A

7th decade

171
Q

Classical triad of Budd-Chiari syndrome

A

Abdominal pain
Ascites
Liver enlargement

172
Q

Presentation of idopathic myelofibrosis

A

Incidental in 30%

Cytopenias: anaemia or thrombocytopenia
Thrombocytosis
Splenomegaly: may be massive
Budd-Chiari syndrome
Hepatomegaly
Hypermetabolic state:
Weight loss
Fatigue and dyspnoea
Night sweats
Hyperuricaemia
173
Q

Budd-Chiari syndrome is caused by….

A

Occlusion of the hepatic vein

174
Q

Investigations and diagnosis of myelofibrosis

A

Blood film: tear-drop poikilocytes (dacrocytes) and leukoerythroblasts.
Giant platelets
Circulating megakaryocytes

Bone Marrow: dry tap
Trephine biopsy:
Increased reticulin/collagen fibrosis. Megakaryocyte hyperplasia and clustering. New bone formation.

Liver and spleen:
Extramedullary haemopoiesis in spleen and liver

175
Q

Treatment of myelofibrosis (and problems)

A

Blood products:
Platelet transfusions often ineffective
Splenomegaly makes RBC transfusions increasingly difficult
Splenectomy: often hazardous and can lead to worsening of the condition

Hydroxycarbamide: may lead to worsening of anaemia
Ruxolotinib: a JAK2 inhibitor
, thalidomide, steroids,
allogenic stem cell transplant: may be curative. Young patients only. Experimental.

176
Q

Key features of pre-fibrotic and fibrotic stage of myelofibrosis

A

Pre-fibrotic: blood changes mild and may be confused with essential thrombocythaemia. Hypercellular marrow.

Fibrotic: Splenomegaly and blood changes. Dry BM tap. Prominent collagen fibrosis. Later Osteosclerosis

177
Q

Ruxolotinib is…

A

JAK 2 inhibitor.

Used in myelofibrosis

178
Q

Clinical features of CML

A

M:F 1.4:1

  • 40-60 years
  • Weight loss, lethargy, night sweats
  • Splenomegaly
  • Features of anaemia
  • Bruising/bleeding
  • Gout
179
Q

Stages of maturation from blast cell to neutrophil

A

Myeloblast, promyelocyte, metamyelocyte, Band cell, neutrophil

180
Q

Laboratory features of CML

A 
•Leucocytosis between 50 – 500x109/l
Mature myeloid cells
Bi phasic peak Neutrophils and myelocytes
Basophils
No excess (
181
Q

Genetic mutation found in large proportion of CML patients

A

translocation 9;22

Translocation of part of long arm of chromosome 22 to chromosome 9 and reciprocal translocation of part of chromosome 9 to chromosome 22.

The latter involves transfer of the ABL oncogene to a breakpoint cluster (BCR) region of chromosome 22. This creates the Philadelphia chromosome, and leads to creation of a fusion gene that leads to synthesis of abnormal ABL protein with tyrosine kinase activity higher than normal.

182
Q

Phases of CML

A

Chronic phase
Accelerated phase
Blast phase

183
Q

% of blood and BM made up of blast cells in CML:
Chronic phase
Accelerated phase
Blast phase

A

10%

>20%

184
Q

Duration of CML chronic phase (natural history)

A

Months to 4-5 years

185
Q

1st generation tyrosine kinase inhibitor

A

Imatinib

186
Q

2nd generation tyrosine kinase inhibitor

A

Dasatanib, and Nilotinib

187
Q

Treatment of CML chronic phase

A

Disease control: Imatinib 1st line
2nd line: dasatinib/nilotinib.

Potential cure with stem cell transplantation (usually young people)

Reduce symptoms with chemotherapy with: hydroxyurea, busulfan, omacetaxine, or interferon alpha with or without cytarabine. These used to be used for disease management, shorter chronic phase than with imatinib.

188
Q

In context of CML what is a complete cytogenic response?

A

0% philadelphia chromosome positive cells on cytogenic analysis (20 metaphases)

189
Q

Side effects imatinib

A

fluid retention

pleural effusions

190
Q

What is Pelger-Huet anomaly?

A

dumbel shaped bilobed neutrophils. Associated with lamin B receptor

191
Q

Myelokathexis is…

A

Congenital disorder of the white blood cells that causes severe, chronic leukopenia (a reduction of circulating white blood cells) and neutropenia (a reduction of neutrophil granulocytes). The neutrophils are retained in the bone marrow.

The disorder is believed to be inherited in an autosomal dominant manner.

192
Q

What is congenital dyserythropoietic anaemia?

A

Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood.

There are 4 types

193
Q

What is sideroblastic aneamia

A

In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently.

Ring sideroblasts are named so because iron-laden mitochondria form a ring around the nucleus. To count a cell as a ring sideroblast, the ring must encircle a third or more of the nucleus and contain five or more iron granules

194
Q

What are Auer rods?

A

Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts

195
Q

List subtypes of myelodysplastic syndrome (WHO classificiation)

A

Refractory anaemia without ringed sideroblasts
Refractory anaemia with ringed sideroblasts
Refractory cytopenia with multilineage dysplasia
Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
Refractory anaemia with excess of blasts 1
Refractory anaemia with excess of blasts 2
5q deletion syndrome/myelodysplastic syndrome with 5q deletion
Myelodysplastic syndrome unclassified: MDS with fibrosis, childhood MDS, others

196
Q

Refractory anaemia without ringed sideroblasts
Blood features
Bone marrow features

A

Anaemia and no blasts

Erythroid dysplasia with

197
Q

Refractory anaemia with ringed sideroblasts
Blood features
Bone marrow features

A

Anaemia and no blasts

Erythroid dysplasia with over 15% ringed sideroblasts
Less than 5% blasts

198
Q

Refractory cytopenia with multinlineage dysplasia
Blood features
Bone marrow features

A

Cytopenia in 2 or more cell lines

Dysplasia in over 10% cells in over 2 cell lines
Less than 5% blasts

199
Q

Mean age of onset of myelodysplastic syndromes

A

68 years

200
Q

Refractory cytopenia with multinlineage dysplasia and ringed sideroblasts
Blood features
Bone marrow features

A

Cytopenia in 2 or more cell lines

Dysplasia in over 10% cells in over 2 cell lines
Over 15% ringed sideroblasts
Less than 5% blasts

201
Q

Refractory aneamia with excess blasts 1
Blood features
Bone marrow features

A

Cytopenias, less than 5% blasts, no Aeur rods

Dysplasias and 5-9% blasts

202
Q

Refractory anaemia with excess blasts 2
Blood features
Bone marrow features

A

Cytopenias or 5-19% blasts, or Aeur rods.

Dysplasias, 10-19% blasts or Aeur rods

203
Q

Myelodysplastic syndrome with 5q deletions
Blood features
Bone marrow features

A

Anaemia, normal or increased platelets.

Megakaryocytes with hypolobulated nuclei and less than 5% blasts

204
Q

Myelodysplastic syndrome unclassified

A

Complex- cytopenias, no Aeur rods, no blasts

Complex- myeloid or megakaryocytic dysplasia, less than 5% blasts

205
Q

Causes of death among patients with myelodysplastic syndromes

A

1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia

206
Q

Myelodysplastic syndromes develop into… in half of patients

A

AML

207
Q

Treatment of myelodysplastic syndromes

A

Prolonging survival:
Stem cell transplant
Intensive chemotherapy

Supportive care:
Blood product support
Antimicrobial therapy
Growth factors (Epo, G-CSF)

Biological modifiers
Immunosuppressive therapy
Azacytidine
Lenalidomide

Oral chemotherapy:
Hydroxycarbamide

Low dose chemotherapy:
Subcutaneous low dose cytarabine

Intensive chemotherapy/ stem cell transplant
AML type regimens
Allo/VUD standard/ reduced intensity

208
Q

All patients with myelodysplastic syndromes have less than….% blasts

A

20%

Over 20% is acute leukaemia

209
Q

Clinical features of myelodysplastic syndromes

A 
BM failure and cytopenias with expected effects (infection, bleeding, fatigue) 
Hypercellular BM 
Defective cells e.g.: 
Ring sideroblasts (RBC)
Hypogranulation (in WBC)
Micromegakaryocytes
210
Q

Which type of myelodysplastic syndrome affects platelets

A

MDS with 5q deletion

211
Q

Which type of myelodysplastic syndrome affects WBCs

A

Refractory cytopenia with multilineage dysplasia

212
Q

Basic classification of aplastic anaemia

A

Severe aplastic anaemia (SAA)

Non-severe aplastic anaemia (NSAA)

213
Q

Camitta criteria for SEVERE aplastic anaemia

A

2 out of 3 peripheral blood features

An absolute neutrophil count (ANC) of less than 0.5×109/L

A platelet count (PLT) of less than 20×109/L,

A corrected reticulocyte count (CRC) of less than 1%.

214
Q

Specific (non-supportive) treatment of idiopathic aplastic anaemia

A

Based on:
Severity of illness
Age of patient
Potential sibling donor

	A. 	Immunosuppressive therapy – older patient
			Anti-Lymphocyte Globulin (ALG)
			Ciclosporin
	B.	Androgens – oxymethalone
	C.	Stem cell transplantation
			Younger patient with donor (80% cure)
			VUD/MUD for > 40 yrs (50% survival)
215
Q

Late complications following immunosuppressive treatment for aplastic anaemia

A
  1. Relapse of AA (35% over 15 yrs)
  2. Clonal haematological disorders
    Myelodysplasia
    Leukaemia
    ~ 20% risk over 10 yrs
    PNH (paroxysmal nocturnal haemoglobinuria)
    May be a transient phenomenon
  3. Solid tumours ~ 3% risk
216
Q

Which patients with aplastic anaemia have immunosuppressive therapy

A

Older patients

217
Q

Most common form of inherited aplastic anaemia

A

Fanconi anaemia

218
Q

Mode of inheritance of Fanconi anaemia

A

X-linked or autosomal recessive

219
Q

Genes responsible for Fanconi anaemia contribute to…

A

Genomic stability

220
Q

Androgen used in aplastic anaemia

A

Oxymethalone

221
Q

Age of onset of pancytopenia in Fanconi anaemia

A

5-10 years

222
Q

10% of Fanconi anaemia cases terminate in…

A

Acute leukaemia

223
Q

Features of Fanconi anaemia include pancytopenia and…

A 
Short Stature
Hypopigmented spots and café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Hyogonadism
Developmental delay

(Congenital malformations may occur in 60-70% of children with FA)

224
Q

% of patients with Fanconi anaemia who develop aplastic anaemia

A

90%

225
Q

% of patients with Fanconi anaemia who develop myelodysplasia

A

32% (30% approx)

226
Q

Complications of Fanconi anaemia

A 
Aplastic anaemia 
Myelodysplasia
Leukaemia 
Liver disease 
Epithelial cancer
227
Q

Skin pigmentation
Nail dystrophy
Leukoplakia
A classical triad seen in….

A

Dyskeratosis congenita

Also get BM failure!!

228
Q

Features of dyskeratosis congenita

A

Classical triad:
Nail dystrophy
Leukoplakia
Skin pigmentation

BM failure (85%)

229
Q

What it dyskeratosis congenita

A

Inherited disorder characterised by:
Marrow failure
Cancer predisposition
Somatic abnormalities

Classical triad of:
Hairy leukoplakia
Skin pigmentation
Nail dystrophy

85% get BM failure

230
Q

Somatic abnormalities/complications of dyskeratosis congenita

A 
Epiphora						
Learning difficulties/development/mental retardation	Pulmonary disease		
Short stature					
Extensive dental caries/loss		
Oesophageal stricture

Malignancy
Intrauterine growth retardation
Liver disease/peptic ulceration/enteropathy
Ataxia Hypogonadism/undescended testes
Microcephaly
Urethral stricture/phimosis
Osteoporosis/aseptic necrosis/scoliosis

231
Q

Mode of inheritance of dyskeratosis congenita

A

X-linked
Autosomal dominant
Autosomal recessive

232
Q

The genes involved in dyskeratosis congenita

A

DKC1 gene which results in defective telomerase function
TERC gene, which encodes the RNA component of telomerase
Additional recessive unidentified gene

233
Q

Dyskeratosis congenita has 3 patterns of inheritance. All affect…

A

Telomeric structure and function

234
Q

Management of severe aplastic anaemia: 1st line if:

a) acquired/idiopathic
b) Inherited/constitutional

A

a) Sibling stem cell transplant if under 40
Immunosuppressive therapy if over 40

b) Oxymethalone

235
Q

Drugs used for immunosuppressive therapy in aplastic anaemia

A

Anti-Lymphocyte Globulin (ALG)

Ciclosporin

236
Q

Philadelphia chromosome positive myeloproliferative disorder

A

CML

237
Q

Bone marrow maximum tolerated irradiation dose

A

12Gy

238
Q

Autologous bone marrow transplant can be used to treat

A

Acute leukaemia
Lymphoma
Solid tumours

239
Q

BMT: After infusion of stem cells engraftment takes and immune recovery takes…

A

14-28 days

6-12 months

240
Q

Organs affected by acute GvHD

A

skin, gastrointestinal tract and liver

241
Q

Organs affected by chronic GvHD

A

skin, mucosal membranes, lungs, liver, eyes, joints

242
Q

Risk factors for GvHD

A 
Degree of HLA disparity
Recipient  (and donor) age (older=higher risk) 
Conditioning regimen
R/D gender combination
Stem cell source
Disease phase (late is worse) 
Viral infections
243
Q

Treatments for GvHD

A 
Corticosteroids
Cyclosporin A
FK506
Mycophenylate mofetil
Monoclonal antibodies
Photopheresis
Total lymphoid irradiation
244
Q

Donor lymphocyte infusions induce remission via process called…

A

Graft vs tumour effect

245
Q

Donor lymphocyte infusions are used when?

A

Patient has relapsed after a bone marrow transplant.

246
Q

A non-myeloablative haematopietic stem cell transplant involves…

A

Preparative regiment followed by
Stem cell transplant followed by
Donor lymphocyte infusion

247
Q

HLA genes are found on which chromosome

A

6 (short arm)

248
Q

Disadvantages of using unrelated donor for stem cell transplant (compared to sibling)

A 
Rejection+++
GvHD+++
More toxicity+++
Delayed immunoreconstitution +++
All worse than with sibling transplant
249
Q

What are killer-cell immunoglobulin-like receptors (KIRs)?

A

Transmembrane receptors expressed on the surface of NK cells and a minority of T cells. They interact with MHC class 1 molecules and can differentiate between allelic variants. This allows them to recognise virally infected or transformed cells. They regulate the activity of their cells.

Most are inhibitory. Recognition of a healthy self cell leads to inhibition of of the NK cell cytolytic function.

250
Q

Advantage of BMT from donor with alloreactive NK cells

A

Alloreactive NK cells won’t be recognised by host KIRs (and therefore won’t be inhibited). Advantages:

Alloreactive NK cells kill patient’s DC thus preventing priming of allogeneic T cells and, thus, GvHD

Alloreactive NK cells kill patient’s T lymphocytes. This facilitates engraftment

Alloreactive NK cells kill leukaemic cells. This may reduce leukaemic relapse.

251
Q

Role of host dendritic cells in GvHD

A

Prime donor T cells (after initial tissue damage)

252
Q

Leukaemia

Features of bone marrow failure

A

Anaemia: fatigue, pallor, breathlessness
Neutropenia: infections
Thrombocytopenia: bleeding

253
Q

AML epidemiology (key points)

A

Increases with age
Prognosis worse with increasing age
40% of adults cured

254
Q

Chromosomal inversion inv(16)/t(16;16) is found in which condition

A

AML

Good prognosis

255
Q

Risk factors for AML

A

Familial or constitutional predisposition
Irradiation
Anticancer drugs
Cigarette smoking

256
Q

The 2 types of genetic abnormality seen in acute leukaemia

A

Type 1 abnormalities
promote proliferation & survival

Type 2 abnormalities
block differentiation (which would normally be followed by apoptosis)
257
Q

Examples of genetic abnormalities that lead to core binding factor leukaemias

Special feature of these leukaemias

A

Translocation 8;21
Inv(16)

There is some maturation. Not all cells produced are blasts

258
Q

Core binding factor is…

A

dimeric transcription factor

master controller of haematopoiesis

259
Q

Genetic abnormality found in 12% of adult AML

A

Inv(16) , t(16;16)

260
Q 
Key features of acute promyelocytic leukaemia 
Including genetic abnormality
Key presenting feature
Key features of affected cells 
Treatment
A
  • The retinoic acid receptor alpha gene (RARA) on chromosome 15 is translocated (reciprocally) with the promyelocytic leukaemia (PML) gene on chromosome 17. The translocation is denoted as t(15; 17)(q22;q21).
  • The fusion gene produced binds with strong affinity to DNA blocking transcription and differentiation of granulocytes (stops maturation at later stage than other acute leukaemias).
  • There is an excess of promyelocytes, which contain large granules that can be released into peripheral blood.
  • Often patients present with DIC
  • Myeloblasts seen in peripheral blood:
  • Large cells with large nucleus and relatively little cytoplasm
  • Nucleoli present
  • Sets of granules forming elongated needles (Auer rods) that are only seen in myeloblasts
  • The initial translocation initiates the process but additional mutations are needed for leukaemia to develop.
  • Can treat with retinoic acid
261
Q

Treatment pf acute promyelocytic leukaemia

A

Retinoic acid

262
Q

Genetic abnormality seen in 90% of patients with promyeloctyic leukaemia

A

t(15; 17)(q22;q21).

263
Q

Clinical features of AML

A

Bone marrow failure:
Anaemia
Neutropenia
Thrombocytopenia

Local infiltration:
Splenomegaly
Hepatomegaly
Gum infiltration (if monocytic)
Lymphadenopathy (only occasionally)
Skin, CNS or other sites

Hyperviscosity if WCC is high:
retinal haemorrhages and exudates

264
Q

AML:

CNS disease is more common with…

A

Monocytic differentiation

265
Q

AML:

Cytogenic studies, molecular studies and FISH. Which applies to all patients?

A

Cytogenic studies

266
Q

Treatment of AML

A

Supportive care
Red cells
Platelets
Fresh frozen plasma/ cryoprecipitate if DIC
Antibiotics
Long line
Allopurinol, fluid and electrolyte balance

Chemotherapy

267
Q

Basis of selective toxicity in AML chemotherapy

A

Normal stem cells:
often quiescent
checkpoints allow repair of DNA damage

Leukaemia cells:
continuously dividing
lack of cell cycle checkpoint control

268
Q

Why have results of treatment of AML improved?

A

Better supportive care
Identification of bad prognosis groups for more intensive treatment (more intensive chemotherapy or transplantation)
Specific treatment for acute promyelocytic leukaemia

269
Q

ALL epidemiology

A

Peak incidence in childhood
Most common childhood malignancy
85% of children cured
Prognosis worse with increasing age

270
Q

Clinical features of ALL

A

Bone marrow failure:
Anaemia
Neutropenia
Thrombocytopenia

Local infiltration:
Lymphadenopathy (± thymic enlargement)
Splenomegaly
Hepatomegaly
Testes, CNS, kidneys or other sites
Bone (causing pain)

Lymohadenopathy, CNS infiltration and testicular infiltration more common than in AML

271
Q

ALL features in peripheral blood

A 
Peripheral blood
Anaemia
Neutropenia
Thrombocytopenia
Usually lymphoblasts
272
Q

ALL features in bone marrow

A

Lymphoblast infiltration

Lymphoblasts may be B-lineage or T-lineage

273
Q

Impact of translocation t(9;22) on ALL treatment

A

t(9;22) — improved prognosis with tyrosine kinase inhibitors e.g. imatinib

274
Q

Example of tyrosine kinase inhibitor

A

Imatinib

275
Q

Imatinib is a…

A

Tyrosine kinase inhibitor

276
Q

Treatment of ALL (general principles)

A

Specific therapy:
systemic chemotherapy
CNS-directed therapy

Supportive care:
blood products
antibiotics
general medical care

277
Q

Supportive treatment used in ALL

A

Central venous catheter

Red blood cell and platelet transfusions

Broad spectrum antibiotics for fever

Prophylaxis for Pneumocystis jirovecii infection

Hyperuricaemia: hydration, urine alkalinization and allopurinol or rasburicase

Hyperphosphataemia; aluminum hydroxide, calcium

Hyperkalemia: fluids, diuretics

Extreme leukocytosis (WBC > 200 × 109/l): leukapheresis

Sometimes haemodialysis

278
Q

3 (unique) Causes of polycythaemia in neonates

A

Twin-to-twin transfusion
Intrauterine hypoxia
Placental insufficiency

279
Q

Unique causes of anaemia in the neonate

A

Twin-to-twin transfusion
Fetal-to-maternal transfusion
Parvovirus infection (virus not cleared by immature immune system)
Haemorrhage from the cord or placenta

280
Q

Congenital leukaemia is particularly common in

A

Down syndrome

Note: This specific type of neonatal leukaemia (also sometimes called transient abnormal myelopoiesis or TAM) differs greatly from leukaemia in older infants or children

281
Q

Key features of neonatal leukaemia

A

The leukaemia is myeloid with major involvement of the megakaryocyte lineage

It usually remits spontaneously and relapse one to two years later occurs in only about a quarter of infants

282
Q

FBC:

Newborn babies, in contrast to adults, have…

A

Higher Hb

283
Q

Globin chains that form:

HbA
HbA2
HbF

A

α2β2

α2δ2

α2γ2

284
Q

HbSS

Red cells become sickle shaped in what sitatuon

A

Hypoxic conditions

285
Q

Which type of marrow is more susceptible to infarction in sickle cell disease?

A

Red marrow

286
Q

Sickle cell anaemia:

Why does splenic sequestration not occur commonly i older children and adults

A

Recurrent infarction has left the spleen small and fibrotic

287
Q

Cause of hyposplenism in sickle cell anaemia

A

Recurrent infarction has left the spleen small and fibrotic reducing its ability to filter out bacteria and parasites.

288
Q

Why does folic acid matter more in a child with sickle cell disease than in a normal child or an adult?

A

Hyperplastic erythropoiesis requires folic acid
Growth spurts require folic acid
Red cell life span is shorter so anaemia can rapidly worsen

289
Q

When does beta thalassaemia manifest (age)?

A

First 3‒6 months of life

290
Q

Clinical effects of poorly treated thalassaemia major

A

Anaemia leadfing to heart failure, growth retardation

Erythropoietic drive leading to bone marrow expansion, hepatomegaly, and splenomegaly

Iron overload leading to heart failure, gonadal failure

291
Q

Most inherited haemolytic anaemias are due to defects in…

A

Red cell membrane
Haemoglobin molecule
Red cell enzymes—glycolytic pathway
Red cell enzymes—pentose shunt

292
Q

Haemolytic anaemias in children:

A

Red cell membrane defects
Hereditary spherocytosis
Hereditary elliptocytosis

Haemoglobin defects
Sickle cell anaemia

Glycolytic pathway defects
Pyruvate kinase deficiency

Pentose shunt defects
G6PD deficiency

293
Q

Features of G6PD deficiency in the blood film

A

Heinz bodies, which are denatured haemoglobin

Bite cells (cells with Heinz bodies that pass through the spleen have part of the membrane removed).

294
Q

Causes of crises in G6PD deficiency

A

Illness (especially infections)
Certain drugs
Certain foods, most notably broad beans
Certain chemicals

295
Q

Mode of inheritance of g6pd deficiency

A

X-linked recessive

296
Q

G6PD deficiency affects which pathway

A

Pentose phosphate pathway

297
Q

Importance of the pentose phosphate pathway

A

Production of NADPH

One of the uses of NADPH in the cell is to prevent oxidative stress. It reduces glutathione via glutathione reductase, which converts reactive H2O2 into H2O by glutathione peroxidase.

If absent, the H2O2 would be converted to hydroxyl free radicals by Fenton chemistry, which can attack the cell.

Erythrocytes, for example, generate a large amount of NADPH through the pentose phosphate pathway to use in the reduction of glutathione.

298
Q

Autoimmune haemolytic anaemia is characterised by (lab results)

A

Spherocytosis

Positive direct antiglobulin test (Coombs’ test)

299
Q

Which is more common?
Haemophilia A
Haemophulia B

A

Haemophilia A (5 times more common)

300
Q

Presentation of autoimmune thrombocytopenic purpura

A

Petechiae
Bruises
Blood blisters in mouth

Year 5 Pathology (7 decks)

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