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exam > 3 Anaemia and Leukemia > Flashcards

3 Anaemia and Leukemia Flashcards

1
Q

Main sites of haemopoiesis throughout life

A

Foetus:
First few weeks = yolk sac
2 - 6/7 months = liver and spleen
6/7 months = bone marrow (& liver/ spleen -> 2wks PP)

Infant: all bone marrow

Adult: central bone marrow and proximal femur (as 70% marrow replaced by fat)

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2
Q

What are the 3 fates of haemapoietic stem cells?

A

Apoptosis
Self-renewal
Differentiation

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3
Q

What are the 6 types of stromal cells and what do they produce (6)?

A 
Cells:
>Macrophages
>Epitheliod cells
>Fibroblasts
>Fat cells
>Reticulum cells
Produce:
>Fibronectin
>Haemonectin
>Collagen
>Laminin
>Proteoglycans
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4
Q

What is bone marrow environment composed of/ how does it support haemapoietic stem cells?

A

Stroma (produces proteins for growth/ differentiation and cell adhesion)
Extracellular matrix
Microvascular network

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5
Q

Difference between bone marrow aspirate and trephine

A 
Aspirate = small biopsy of cells
Trephine = core biopsy of 1-2cm and marrow structure is maintained
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6
Q

Define “clonal” proliferative disorder

A

Arise from a single ancestral cell

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7
Q

Define the Philadelphia chromosome, the condition in which it is present, and how it causes abnormality (3)

A

Present in CML - short chromosome 22
Due to reciprocal translocation between chromosomes 22 and 9

BCR-ABL gene (tyrosine kinase) constantly on > turns on downstream targets by phosphorylation > cell becomes malignant

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8
Q

What are the 3 main myeloproliferative disorders

A

Essential thrombocytosis (inc platelets)
Polycythemia rubra vera (inc Hb and RBC)
Myelofibrosis (inc fibrosis and scarring)

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9
Q

What is a myeloproliferative disorder

A

Abnormal clonal proliferation, leading to increased numbers of a mature myeloid blood cell type

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10
Q

What mutation are most myeloproliferative disorders associated with

A

JAK2- V617F

Calreticulin

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11
Q

Clinical features and classification of essential thrombocytosis

A

Thrombotic complications
Haemorrhagic complications
Splenomegaly (and hepatomegaly in myelofibrosis)

Progression to PRV/ myelofibrosis/ leukemia

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12
Q

Histological features of essential thrombocytosis (blood and marrow)

A

Blood - lots of clumps of platelets

Marrow - clumps of megakaryocytes

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13
Q 
Treatment of essential thrombocytosis in 
low risk
med risk
high risk
pregnancy
elderly
new options?
A

low risk - aspirin OR other antiplatelet (clopidogrel)
med risk - aspirin ± hydrocarbamide
high risk - aspirin + hydrocarbamide (1st) or anagrelide (2nd)

pregnancy - IFN-alpha
elderly - Busulphan/ radioactive phosphorous
new options - JAK2 inhibitors

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14
Q

What are myelodysplastic syndromes?

A

Dysplasia of one or more types of myeloid cells, leading to ineffective haemopoiesis

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15
Q

How do myelodysplastic syndromes present (3)?

A

20% Incidental on FBC
20% Bleeding and infection (WBC/plts)
Most anaemic/ tired (RBCs)

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16
Q

Main treatment options for myelodysplastic syndrome

A

Supportive care = blood/plasma transfusion, and consider iron chelation in younger patients

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17
Q

What is Fanconi anaemia?

A

Type of aplastic anaemia (pancytopenia) as a result of AR genetic bone marrow failure

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18
Q

Main features of Fanconi anaemia

A 
>Somatic abnormalities: Short stature, digital abnormalities, GI/GU malformations
> Chromosomal instability
> CNS: metal retardation, hydrocephalus
> Hearing problems
> Micropthalmia
> Cafe au lai spots (neurofibromas)

High malignancy risk

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19
Q

Main treatment/ management of Fanconi anaemia

A

Allogeneic stem cells transplant
Monitor for 2y tumours

Inc blood count - corticosteroids/androgens
Supportive care

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20
Q

2 types of stem cell transplant and their uses

A

Autologous: relapsed H lymphoma, NH lymphoma, Myeloma

Allogeneic: leukemias, relapsed lymphoma, aplastic anaemia and hereditary disorders

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21
Q

Types of allogeneic transplant donors (5)

A 
Syngeneic = identical twin
Allogeneic sibling - HLA identical 
Haplotype = 1/2 matched family member 
VUD/MUD = volunteer unmatched donor/ matched
Umbilical cord transplant
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22
Q

5 steps of autologous transplantation by aphaeresis

A

1) move stem cells from marrow to blood with G-CSF
2) remove pt blood and take out stem cells and put blood back in = aphaeresis
3) stem cells preserved by freezing
4) patient receives high dose chemo and radio
5) thawed stem cells rein fused to patient

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23
Q

Describe myeloablative full intensity vs reduced intensity “mini” stem cell transplants

A

Myeloablative:
>High dose chemo and radio (completely destroying all patient stem cells), then rescue with donor cells so patient is 100% donor

Mini:
>Low dose chemo with radio/immunosuppression - not intended to eradicate all patient cells/malignancy
> donor introduced and patient becomes mixed chimera, then progresses to full donor (sometimes with help of DLI)

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24
Q

Pros and cons of umbilical cord blood stem cell transplants

A

Pros:
>More rapidly available
>Requires less tissue matching as immune system still naive

Cons:
> small amounts - adult often require double transplants
> if relapse, can’t treat with DLI

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25
Q

Describe DLI

A

Donor lymphocyte infusion:
>Given after initial STC (which has the anti-tumour effect), to prevent remission by GvL
>Given in incremental doses as has a high risk of GvHD (to reduce risk)

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26
Q

Describe graft vs host disease

A

Donor cells recognise host cells as foreign and attack
Chronic = over 100 days post transplant
Acute = within 100 days

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27
Q

Describe graft vs leukemia

A

Positive of GvHD - graft also recognises leukemias cells (and myeloma/lymphoma) as foreign and attacks them

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28
Q

What enzyme in RBCis responsible for the conversion of Co2 & H2O -> HCO3- & H+

And how does HCO3- leave the RBC

A

Carbonic anhydrase

Chloride shift - chloride comes in as bicarb leaves

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29
Q

How much iron is in the body and where is it stored/used (4)?

A

about 4g

Most in RBCs/ erythroblasts (3g)
Reticuloendothelial cells (macrophages) - 500mg
Enzymes - 100mg
Myoglobin - 200-300mg

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30
Q

What is the iron transport glycoprotein and where is it produced?

A

Transferrin

Liver

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31
Q

What happens to iron in erythroblasts?

A

Taken in via transferrin receptor (TfR) and either stored as ferritin or put in haem

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32
Q

What happens to iron (and RBCs in general) in the reticuloendothelial system (macrophages)?

A

Macrophages digest dead RBCs

Globin -> amino acids - released
Haem -> bilirubin - liver for conjugation
Iron -> stirred as ferritin or released to transferrin

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33
Q

How much iron do males/ females loose/need daily?

A 
Females = 2mg
Males = 1mg
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34
Q

What is the difference in how haem/ non-haem iron is absorbed in the GIT

A 
Haem = readily absorbed (ferrous)
Non-haem = needs to be connected to ferrous (from ferrate) before absorption
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35
Q

What regulates the amount iron released from RBC into plasma and how?

A

Hepcidin (made in liver) and ferroportin

Ferroportin increases release of iron from RES and increased absorption
Hepcidin binds and degrades ferroportin, reducing plasma iron

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36
Q

Define hereditary haemochromatosis

A

Hereditary disease where the body absorbs too much iron, possibly due to decreased amounts of hepcidin (defects in HFE gene)

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37
Q

Anaemias producing microcytic RBCs

A 
Iron deficiency
Anaemia of chronic disease
Blood loss (longer term)
Sideroblastic
Thalassemia
38
Q

Clinical signs of IDA (4)

A

Koilonychia
Angular stomatitis
Atrophic glossitis
Oesophageal webs (Plummer Vinson syndrome)

39
Q

Describe 1st and 2nd stages of IDA

A

1st (latent iron def) - RBCs use up storage iron so Hb is normal but RES stores decrease
2nd - Hb and RES stores both decreased

40
Q

Causes of IDA from GI bleed (4)

And most likely GI cause of silent IDA (no symptoms)

A

Diverticular disease/ diverticulitis
Rectal carcinoma - stricure
Bleeding peptic ulcer
Caecal tumour - asymptomatic

41
Q

Until proven otherwise, most likely causes of IDA in:
> males/ post menopausal women
> young women

A

males/ post menopausal women = GI bleed

young women = menopausal bleeding

42
Q

Treatment of IDA

A

Replace iron - ferrous sulphate/ gluconate (GI upset)/

IV (intollerant/ compliance/ renal IDA on dialysis with EPO)

43
Q

Levels in IDA of:
RES iron stores
Ferritin
Transferrin

A

RES iron stores (dec)
Ferritin (dec)
Transferrin (inc)

44
Q

Levels in anaemia of chronic disease of:
RES iron stores
Ferritin
Transferrin

A

RES iron stores (inc)
Ferritin (dec)
Transferrin (dec)

45
Q

What other factor is raised in anaemia of chronic disease and what shape do RBCs form when this occurs

A

ESR - inflammation

Rouleaux

46
Q

Causes of anaemia of chronic disease (3)

A

Bone marrow failure to produce RBCs
Bone marrow reduced response to EPO
RES blockage - trapped in macrophages (?herceptin)

47
Q

How is B12 absorbed from GIT (5)

A

1) Ingested and released from food by enzymes
2) IF produced - parietal cells
3) IF binds B12
4) IF-B12 binds cubulin receptor- ileum
5) IF-B12 absorbed to blood - binds transcobalamin

48
Q

What is the B12/ folate transport proteins?

A

B12 = cobalamin

Folate - none

49
Q

What is the 2 main functions of B12 in cells?

A

1) Methylation of homocysteine > methionine

2) Methlymalonyl-CoA isomerisation

50
Q

What are the main dietary sources of B12 and folate, and where are they absorbed?

A 
B12 = meat (and dairy)
Folate = raw green veg
51
Q

How does B12/folate deficiency cause megaloblastic anaemia?

A

Affects downstream DNA synthesis = disparity in synthesis and upstream precursors
Makes abnormal large RBCs - prematurely destroyed in bone marrow before release

52
Q

What type of anaemia is:
Iron deficiency
Anaemia of chronic disease
B12/folate deficiency

A

Iron deficiency = microcytic hypochromic
Anaemia of chronic disease = microcytic hypochromic
B12/folate deficiency = megaloblastic macrocytic

53
Q

Other than anaemia, what other problems can be caused by B12/folate deficiency?

A

B12 - Dorsal column/spinal cord degeneration
Folate - Neural tube defects 1st 12 weeks of pregnancy

Both - thrombocytopenia, leucopenia, affect epithelial surfaces (GI/GU)

54
Q

Clinical symptoms/ signs of B12/folate deficiency (4)

A

Anaemia - Pale, tried, SOB
Mild jaundice - haemolysis (bilirubin)
Bruises - thrombocytopenia
CNS defects

55
Q

Causes of B12 deficiency (3)

A

Pernicious anaemia/ lack of IF
Gastrectomy - lack of IF/ acid
Terminal ileum problems - Chron’s, resection

56
Q

Causes of folate deficiency (3)

A

> Diet deficiency
Increased cell turnover (pregnancy, haemolysis, severe skin conditions e.g. psoriasis) - low stores
Small bowel problems - severe Chron’s/ coeliac

57
Q

Other causes of macrocytic cells (3)

A

> Reticulocytosis - increased reticulocyte production
Cell wall/ lipid abnormality - abnormal structure
Bone marrow failure syndromes - abnormal production

58
Q

How many alpha and beta Hb genes do we receive from each parent?
And what chromosome are they on?

A

4 alpha - chr 16

2 beta - chr 11

59
Q

What is the treatment for beta thalassemia major?

A

Transfusions from easy age > first few years

Consider iron chelation

60
Q

What is the genetic abnormality causing sickle cell disease?

A

Codon 6 substitution on chromosome 11

Glutamine -> valine

61
Q

SICKLED features of sickle cell anaemia

A

Splenomegaly
I Infarction (organs, osteonecrosis, stroke,)
C Crises - mesenteric, pulmonary,
K Kidneys
L Lungs/Liver (pul. hypertension, acute chest)
E Erection (maintained)/ Eyes (vascular retinopathy)
D Dactylitis

62
Q

Treatment of sickle cell disease

A

Prevent crisis - fluid/analgesia, folic acid, prophylactic vaccination/abx for splenectomy (Pv)

Early intervention of crisis - fluid/o2/Abx/analgesia, transfusion/RBC exchange

Bone marrow transplant

63
Q

Counts in haemolytic anaemia of:
Hb
Reticulocytes
Bilirubin

A

Hb - low
Reticulocytes - high
Bilirubin - high

64
Q

3 main classes of congenital haemolytic anaemias, and examples

3 types of acquired haemolytic anaemias, and examples

A

Congenital:

1) RBC membrane abnormalities - hereditary spherocytosis
2) Hamoglobinopathies - thalassemias, sickle cell
3) Exzyme abnormalities - pyruvate kinase, Glucose-6-phosphate dehydrogenase

Acquired:

1) autoimmune - cold/ warm (drug induced)
2) isoimmune - HDN
3) non autoimmune - fragmentation haemolysis

65
Q

3 main clinical signs of haemolytic anaemia

A

Jaundice
Fatigue/anaemia
Splenomegaly

66
Q

Blood film appearance of hereditary spherocytosis and why

A

Polychromatic spherocytic

67
Q

Treatment of hereditary spherocytosis and inheritance pattern

A

Autosomal dominant

None usually

If severe splenectomy with prophylactic penicillin V and vaccinations (pneumococcus, meningococcus, homophiles)

68
Q 
Pyruvate kinase deficiency haemolytic anaemia:
>Mechanisms 
>Acute/ chronic
>Intra/ extra vascular
>Inheritance
A

> Mechanisms - prevents ATP production, so all cells die
Acute/ chronic - chronic
Intra/ extra vascular - extra
Inheritance - autosomal recessive

69
Q 
Glucose-6-phosphate dehydrogenase deficiency haemolytic anaemia:
>Mechanisms 
>Acute/ chronic
>Intra/ extra vascular
>Inheritance
A

> Mechanisms - prevents NADP>NADPH, which normally protects from oxidative damage from drugs (triggers = drugs/ favism)
Acute/ chronic - acute, explosive episodes
Intra/ extra vascular - intra
Inheritance - X lined recessive

70
Q

Causes of fragmentation haemolysis (3)

A

VAD
Mechanical heart valve
E. Coli 0157 - haemolytic uremic syndrome

71
Q

Cold type AIHA antibody and causes/ associations

A

IgM + complement

Idiopathic
Lymphoproliferative disorders (lymphoma/CLL)
Mycoplasma pneumonia infection

72
Q

Warm type AIHA antibody and causes/ associations

A

IgG ± complement

Idiopathic
Lymphoproliferative disorders (lymphoma/CLL)
Other autoimmune - thyroid, SLE
Drug induced

73
Q

3 types/ methods of drug-induced AIHA

A

Hapten - drug binds RBC and attracts Abs
Immune complex - RBC is a bystander
Direct autoimmune - Drug causes Ab to attack RBC

74
Q

Describe direct coombs test and what it is for

A

HDN/ AIHA

Mix pt blood with Abs and if they glutamate, they have AI Abs in their blood (+ve)

75
Q

Describe indirect coombs test and what it is for

A

Transfusion

Mix pt plasma + transfusion RBCs +Abs, if they glutamate, the patient has Abs against the transfusion blood

76
Q

Treatment of warm and cold autoimmune haemolytic anaemia

A

Cold - keep patient warm (mycoplasma self limiting)

Warm - steroids/ immunosuppression/ splenectomy

77
Q

Describe how haemolytic disease of the newborn occurs

A

Mother Rhs -ve and foetus +ve (from father)
Fetal blood leaks into maternal blood and mother produces Abs against fatal blood
Abs cross placenta and attack RBCs

78
Q

Which leukemias are more common in children and adults?

A

ALL - children, under 20

AML - adults, over 60

79
Q

Clinical signs/ symptoms of acute leukemias

A 
Rapid onset
Anaemia - fatigue, pale
Thrombocytopenia - bleeding/ bruising
Leukopenia - infection
Bone pain
Gum swelling
Skin rash
Lymphadenopathy
80
Q

What is M3 AML and its main pathopneumonic histological feature on blood film?

A

Translocation on cr 17/15
Medical emergency, assoc. with DIC

Granules in large blast cells with auer rods

81
Q

What method is used to identify the cell types in acute leukemia?

What method is used to identify the genetic abnormalities in acute leukemia?

A

Cell types - flow cytometry

Genetic - cytogenetics, arrested in metaphase

82
Q

What chromosome translocations are present in M3 AML and M2 AML

A

M3 = 15/17

M2 = 8/21

83
Q

Drugs used in AML chemotherapy (2)

A

Cytarabine and anthracycline

84
Q

Side effects of AML chemotherapy

A

Hair loss
Bleeding/ infection
Infertility
Mucositis

85
Q

Presenting features of CLL (5)

A

1/3 asymptomatic

Weight loss/ night sweats/ fatigue
Abdo pain
Splenomegaly**

86
Q

Diagnostic methods for CLL (4) and describe what is being looked for

A

1- surface antigens - CD 5/19/23
2- flow cytometry
3- Binet staging - A (<3), B (>3/spleen/liver), C (thrombocytopenia/anaemia)
4- cytogenetics (interphase FISH) - 17pdel, 11qdel

87
Q

What are the main complications of CLL (2)?

A

Autoimmune - thrombocytopenia/ haemolytic anaemia

Infection - pulmonary

88
Q

CLL presenting features

A

Asymptomatic

Weight loss/ night sweats/ fatigue
Anaemia
Lymphadenopathy
Splenomegaly

89
Q

Diagnostic methods for CML (3)

A

1 - blood film/ test and history - clumping of cells
2- molecular testing for BCR-ABL
3- cytogenetics karyotype (translocation)

90
Q

Treatment of CML and CLL

A 
CML = imatinib
CLL= nothing unless symptomatic
91
Q

What are the main complications of CLM (2)?

A

Imatinib resistance/ intolerance

Accelerated phase/ blast crisis

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