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Phase 2a > Haem > Flashcards

Haem Flashcards

1
Q

production v removal -> aneamia?

A
  • Test to determine if bone marrow production is the issue is to look at the
    RETICULOCYTE COUNT which is a count of immature RBC’s in the bone
    marrow
  • If production is the issue then the reticulocyte count will be low
  • If removal is the issue then the reticulocyte count will be high
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2
Q

3 types of MCV?

A

Hypochromic (pale) MICROCYTIC - low MCV

  • Normochromic NORMOCYTIC - normal MCV
  • MACROCYTIC - high MCV
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3
Q

microcytic anaemia?

A

low MCV

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4
Q

aetiology of microcytic anaemia?

A

Iron deficiency anaemia - the MOST COMMON CAUSE WORLDWIDE
• Anaemia of chronic disease
• Thalassaemia (see inherited red cell disorders)

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5
Q

formation of haem -> haemoglobin using iron?

A

Iron is required for the formation of the haem part of haemoglobin
• Iron ions are actively transported into the duodenal intestinal epithelial cells
by the intestinal haem transporter (HCP1) which is highly expressed in the
duodenum and some is incorporated into FERRITIN (protein-iron complex) that
acts as an intracellular store for iron
• Absorbed iron that does not bind to ferritin is released into the blood where it
is able to circulate around the body bound to the plasma protein
TRANSFERRIN
• Transferrin transports iron in the blood plasma to the bone marrow to be
incorporated into new erythrocytes
• The majority of iron is incorporated into haemoglobin
• The rest is stored in reticuloendothelial cells, hepatocytes and skeletal
muscle cells either as FERRITIN (majority - more easily mobilised than
haemosiderin for Hb formation, found in small amounts in plasma and in
most cells especially liver, spleen and bone marrow) or HAEMOSIDERIN
(found in macrophages in the bone marrow, liver and spleen)

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6
Q

epidemiology of iron deficient anaemia?

A
  • 14% in menstruating women
  • premature infants
  • undeveloped countries
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7
Q

aetiology of iron deficient anaemia?

A
  • blood loss; menorrhagia, GI bleeding or hookworm
  • poor diet
  • pregnancy
  • malabsorption
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8
Q

pathophysiology of iron deficient anaemia?

A

Less iron is available for haem synthesis - crucial for haemoglobin
production thus reduction in iron will result in a decrease in haemoglobin
and thus smaller RBC’s resulting in microcytic anaemia

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9
Q

clinical presentation or iron deficient anaemia?

A
  • brittle hair and nails
  • spoon shaped nails - koilonychia
  • atrophy of papillae of tongue
  • ulcerations of corners of mouth (angular stomatitis)
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10
Q

investigation of iron deficient anaemia?

A
  • FBC; haematocrit and haemoglobin, serum ferritin (low), serum iron (low)
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11
Q

treatment of iron deficient anaemia?

A
  • oral ferrous sulphate (SE; constipation and nausea)
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12
Q

anaemia of chronic diseases, what is this?

A

Essentially this is anaemia that is secondary to a chronic disease, can think of
it as if the body is sick then the bone marrow will be too, resulting in anaemia
• RBC’s are often NORMOCYTIC but they can be MICROCYTIC, especially in
rheumatoid arthritis and Crohn’s disease

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13
Q

epidemiology of anaemia of chronic disease?

A
  • most common in hospital patients

- in people with chronic infections; crohns, RA, SLE and TB

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14
Q

pathophysiology of anaemia of chronic disease?

A

There is decreased release of iron from the bone marrow to developing
erythroblasts (early RBC, before reticulocyte)
- An inadequate erythropoietin response (cytokine which increases RBC
production) to anaemia
- Decreased RBC survival

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15
Q

clinical presentations of anaemia of chronic disease?

A
  • fatigue
  • SOB
  • anorexia
  • intermittent claudication
  • palpitations
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16
Q

investigations of anaemia of chronic diseases?

A
  • FBC; serum iron (low), serum ferritin (normal or raised due to inflammation), low Hb
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17
Q

treatment of anaemia of chronic causes?

A

Erythropoietin is effective in raising the haemoglobin level and is used in
anaemia of renal disease and inflammatory disease e.g. rheumatoid
arthritis and inflammatory bowel disease

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18
Q

causes of normal MCV anaemia?

A
  • acute blood loss
  • anaemia of chronic disease
  • endocrine disorders
  • renal failure
  • pregnancy
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19
Q

investigation of normlytic anaemia?

A
  • B12 and folate -> normal
  • raised reticulocytes
  • Hb low
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20
Q

macrolytic anaemia, sub types?

A

Megaloblastic:
- Presence of erythroblasts with delayed nuclear maturation because of
delayed DNA synthesis - these are megaloblasts, they are large (i.e.
high MCV) and have no nuclei
• Non-megaloblastic:
- Where the erythroblasts are normal i.e. normoblastic

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21
Q

main causes of macrolytic anaemia?

A
  • megaloblastic -> B12 and folate deficiency

- non-megaloblastic; alcohol, liver disease, hypothyroidism, haemoloysis, myeloma, aplastic anaemia

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22
Q

B12 physiology?

A

B12 is absorbed by binding to INTRINSIC FACTOR produced by the
PARIETAL CELLS of the stomach then being absorbed in the TERMINAL
ILEUM of the small intestines
- B12 is essential for thymidine and thus DNA synthesis
- Thus in B12 deficiency there is an impairment of DNA synthesis resulting in
delayed nuclear maturation resulting in large RBCs as well as decreased
RBC production in the bone marrow
- This DNA impairment will affect all cells, but bone marrow is most affected
since its the most active in terms of cell division

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23
Q

pernicious anaemia?

A

AUTOIMMUNE DISORDER in which the parietal
cells of the stomach are attacked resulting in atrophic gastritis and the loss
of intrinsic factor production and thus vitamin B12 malabsorption

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24
Q

pernicious anaemia epidemiology?

A
  • elderly
  • blood type A
  • F>M
  • caucasian
  • other autoimmune diseases; thyroid and Addisons
  • vegan diet
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25
Q

pernicious anaemia pathophysiology?

A

Parietal cell antibodies are present in the serum in 90% of patients with
pernicious anaemia - and also in 10% of normal individuals
- However, intrinsic factor antibodies, although found in only 50% of patients
with pernicious anaemia are SPECIFIC for DIAGNOSIS
- Autoimmune gastritis affecting the fundus with plasma cell and lymphoid
infiltration
- The parietal and chief cells are replaced by mucin-secreting cells
- There is achlorhydria (reduced HCL acid production) and of course the absent
secretion of intrinsic factor

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26
Q

clinical presentations of pernicious anaemia?

A
  • fatigue
  • palpitations
  • lemon-yellow skin colour (jaundice -> due to fact that
    body will try to remove defective large RBCs)
  • glossitis and angular stomatitis
  • symmetrical parasthesia
  • weakness
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27
Q

diagnosis of pernicious anaemia?

A
  • FBC; Hb low, serum b12 low, serum bilirubin maybe raised
  • macrocytic RBC
  • IF antibodies - diagnostic but low sensitivity
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28
Q

treatment for pernicious anaemia?

A
  • if dietary -> oral B12

- IM hydroxocobalamin

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29
Q

epidemiology of folate deficiency?

A
  • elderly
  • poverty
  • alcoholic
  • pregnant
  • cronhs/coeliac disease
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30
Q

folate physiology?

A

Absorbed by the duodenum/proximal jejunum
- Folate is also essential for DNA synthesis
- Thus in folate deficiency there is an impairment of DNA synthesis resulting in
delayed nuclear maturation resulting in large RBCs as well as decreased
RBC production in the bone marrow
- This DNA impairment will affect all cells, but bone marrow is most affected
since its the most active in terms of cell division
- Folate is also essential for fetal development - deficiency can result in neural
tube defects

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31
Q

clinical presentation of folate deficiency?

A
  • asymptomatic
  • symptoms of anaemia;pallor, fatigue, dyspnoea,
    anorexia and headache
  • Glossitis (red sore tongue) can occur
  • NO NEUROPATHY unlike B12 deficiency - how you can differentiate
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32
Q

investigations of folate deficiency?

A
  • blood smear; megaloblastic
  • FBC; serum folate is low
  • serum bilirubin may be raised
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33
Q

treatment of folate deficiency?

A
  • folic acid tablets

- never given without B12

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34
Q

haemolytic anaemia, normacytic or macrocytic?

A

RBCs can be either NORMOCYTIC or if there are many young RBC’s (which are
larger) due to excessive destruction of old RBCs then MACROCYTIC

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35
Q

compensated haemolytic disease?

A

If the red cell loss can be contained within the marrow’s capacity for
increased output, then a haemolytic state can exist without anaemia

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36
Q

main causes of haemolytic anaemia?

A

RBC membrane defects:
• Hereditary spherocytosis

Enzyme defects:
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Haemoglobinopathies:
• B Thalassaemia
• A Thalassaemia
• Sickle cell disease
- Autoimmune haemolytic anaemia
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37
Q

features of haemolytic anaemia?

A

High serum UNCONJUGATED BILIRUBIN

  • High urinary UROBILINOGEN
  • High faecal STERCOBILINOGEN
  • Splenomegaly
  • Bone marrow expansion
  • Reticulocytosis - increased reticulocytes
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38
Q

HEREDITARY SPHEROCYTOSIS, epidemiology?

A
  • northern europeans

- autosomal dominant

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39
Q

HEREDITARY SPHEROCYTOSIS, pathophysiology?

A

Caused by defects in the red cell membrane resulting in RBC’s losing part of
the cell membrane as they pass through the spleen

The abnormal cell membrane is associated functionally with an increased
permeability to Na+ requiring an increased rate of active transport of Na+
OUT of the cells, which is dependent on ATP produced by glycolysis
- The surface to volume ratio decreases and the cells become SPHEROCYTIC
- SPHEROCYTES are more RIGID and less deformable than normal red cells
- They are unable to pass through the splenic microcirculation so they become
trapped in the spleen and thus have a shortened lifespan and are destroyed
via extravascular haemolysis

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40
Q

clinical presentations of HEREDITARY SPHEROCYTOSIS?

A
  • jaundice
  • splenomegaly
  • ulcers of leg
  • gallstone
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41
Q

investigations of HEREDITARY SPHEROCYTOSIS?

A
  • blood film; spherocytes
  • FBC; low Hb and increased reticulocytes
  • raised bilirubin and urinary urobillnogen
  • negative direct antiglobulin (Coombs) test to rule out autoimmune haemolytic anaemia
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42
Q

treatment for Hereditary spherocytosis?

A
  • splenectomy
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43
Q

G6PD, epidemiology?

A
  • M>F

- common in Africa, Mediterranean, SE Asia and Middle East

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44
Q

pathophysiology of G6PD?

A

-G6PD is vital for a reaction that is
necessary for RBC’s by providing a
NADPH which is used with glutathione
to PROTECT the RBC from OXIDATIVE DAMAGE from compounds such as hydrogen peroxide
- This inherited enzyme deficiency thus results in reduced RBC lifespan due to
oxidant damage
- Gene for G6PD is localised to chromosome Xq28 near the factor VIII gene

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45
Q

clinical presentation of G6PD?

A
  • asymptomatic but may get oxidative crisis due to reduction in glutathione production and can be precipitated by drugs (aspirin, antimalarials and fava beans )
  • neonatal jaundice
  • pallor
  • dark urine
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46
Q

investigations fo G6DP?

A
  • FBC
  • blood film during attacks
  • urinalysis
  • G6DP enzyme levels (low bur immediately after an attack maybe normal)
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47
Q

treatment of G6DP?

A
  • stop offending drugs

- blood transfusions

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48
Q

normal hb composition?

A

heam + 2 alpha + 2 beta chains

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49
Q

foetal Hb composition?

A

haem + 2 alpha + 2 gamma chains

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50
Q

thalassaemias?

A

genetic disease of unbalance Hb synthesis, with under production (or
no production) of one globin chain
• The precipitation of the imbalance globin chains within red cell precursors
results in cell damage and death of precursors in bone marrow i.e INEFFECTIVE
ERYTHROPOIESIS
• The precipitation of these imbalanced globin chains in mature red cells leads to
HAEMOLYSIS

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51
Q

the 2 types of thalassaemia?

A
  • beta -> reduced B chain synthesis

- alpha -> reduced A chain

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52
Q

beta thalassaemia, epidemiology?

A
  • Mediterranean and Far East
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53
Q

beta thalassemia, pathophysiology?

A
  • point mutations
  • The mutations result in defects in transcription, RNA splicing and
    modification, translation via frame shifts and nonsense codons producing
    highly UNSTABLE B-GLOBIN which cannot be utilised
  • In heterozygous beta-thalassaemia there is usually asymptomatic
    microcytosis with or without MILD ANAEMIA
  • excess alpha chains combine with delta and gamma chains
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54
Q

beta thalassaemia, clinical presentations?

A 
SPLIT INTO 3 
minor (trait/carrier)
- asymptomatic 
- anaemia is mild or absent
- RBC are hypo chromic and microcytic 
- can be confused with iron deficiency but serum ferritin and iron stores are normal

intermediate

  • moderate anaemia
  • splenomegaly
  • bone deformities
  • gall stones

major

  • presents in children with homozygous in first year of life; recurrent bacterial infections, severe anaemia, hepatospenomegaly
  • need transfusion
  • bone abnormalities
  • microcytic
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55
Q

diagnosis, beta thalassemia?

A
  • FBC; raised reticulocyte count
  • film; Hypochromic microcytic anaemia
  • Haemoglobin electrophoresis shows increase HbF (gamma) and absent or
    less HbB (normal)
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56
Q

treatment of beta thalassaemia?

A
  • Regular (every 2-4 weeks) life-long transfusions to keep Hb above 90g/L
  • Iron-chelating agents to prevent iron overload; oral DEFERIPRONE & SC
    DESDERRIOXAMINE:
  • Large doses of ASCORBIC ACID to increase urinary excretion of iron
  • Splenectomy if hypersplenism persists with increasing transfusion
    requirements - but do after childhood to reduce infection risks
  • Bone marrow transplant
  • Long term folic acid
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57
Q

alpha thalassaemia, pathophysiology?

A

alpha-thalassaemia is often caused by
gene deletions
- The gene for alpha-globin chains is duplicated on both chromosomes 16
- The deletion of one alpha chain or both alpha-chain genes on each
chromosome 16 may occur (deletion of one alpha chain is most common)

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58
Q

clinical presentation of alpha thalaessemia?

A

FOUR GENE DELETION

  • no alpha chain synthesis
  • Hb barts (4 gamma chains) cannot carry o2 and baby often are stillborn or die after birth
THREE GENE DELETION
- Severe reduction in alpha chain synthesis results in HbH disease, which
is common in parts of Asia
• HbH has 4 beta-chains
• Moderate anaemia and splenomegaly

Two gene deletion (alpha-thalassaemia trait - carrier):
• There is MICROCYTOSIS with or without mild anaemia

  • Once gene deletion:
    • Usually a normal blood picture

-

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59
Q

sickle cell anaemia, epidemiology?

A

Commonest in Africans but also in India, Middle
East and southern Europe
- AUTOSOMAL RECESSIVE disorder causing the
production of abnormal Beta globin chains
- 1 in 4 chance of disease
- 50% chance of being a carrier
- 1 in 4 chance of being disease free

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60
Q

pathophysiology, sickle cell?

A

Sickle cell haemoglobin (HbS) results from a SINGLE-BASE MUTATION of
ADENINE to THYMINE which produces a substitution of VALINE for
GLUTAMIC ACID at the SIXTH CODON of the beta-globin chain

-Since the synthesis of HbF (gamma or fetal) is normal, the disease does not
manifest itself until the HbF decreases to adult levels at about 6 months of age
- Sickle cell haemoglobin (HbS) is insoluble and polymerises when
deoxygenated
- The flexibility of the cells is decreased and they become rigid and take up
their characteristic sickle appearance
- This process is initially reversible but, with repeated sickling, the cells
eventually lose their membrane flexibility and become IRREVERSIBLY
SICKLED
- This irreversibly sickled cells are dehydrated and dense, and will not return
to normal when oxygenated
- HbS releases its oxygen to the tissues more readily than normal RBCs and
patients thus feel well despite being anaemic (except during crises or
complications)

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61
Q

clinical presentation of sickle cell?

A

Heterozygous sickle cell trait:
• Symptom free with no disability expect in hypoxia e.g. in unpressurised
aircraft or anaesthesia when vaso-occlusive events may occur
• Carriage offer protection against FALCIPARUM MALARIA

Homozygous sickle cell

  • pulmonary hypertension
  • anaemia
  • low growth and development
  • bone issues
  • neurological
  • chronic hepatomegaly
  • visual floaters
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62
Q

investigations for sickle cell?

A

Blood count:
• Level of Hb is in the range of 60-80 g/L
• RAISED RETICULOCYTE COUNT

Blood films:
• Sickled erythrocytes shown

Sickle solubility test will be POSITIVE

Hb electrophoresis:
• Confirms diagnosis
• Shows 80-95% HbS and absent HbA
• Aim for diagnosis at birth (cord blood) to aid prompt pneumococcal
prophylaxis
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63
Q

treatment for sickle cell?

A
  • attacks; analgesia, oxygen

- anaemia; blood transfusion and ORAL HYDROXYCARBAMIDE

64
Q

aplastic anaemia epidemiology?

A
  • rare stem cell disorder
  • inherited
  • idiopathic
  • bezene or glue sniffing
  • chemotherapeutic drugs
  • infections
  • antibiotics
65
Q

pathophysiology of aplastic anaemia?

A

Due to a reduction in the number of pluripotent stem cells, together with a
fault in those remaining or an immune reaction against them so that they are
unable to repopulate the bone marrow

66
Q

symptoms of aplastic anaemia?

A

Symptoms result because of RBC, WBC and platelet deficiency:
• Anaemia
• Increased susceptibility to infection
• Bleeding
• Bleeding gums, bruising with minimal trauma and blood blisters in
mouth

67
Q

investigations of aplastic anaemia?

A
  • blood count; low reticulocyte count

- bone marrow examination

68
Q

treatment of aplastic anaemia?

A
  • treat cause
  • antibiotic
  • RBC and platelet transfusion
  • bone marrow transplant
69
Q

polycthamia?

A

blood cell mass, whereas polycythaemia refers to any increase in RBC’s
• Defined as an INCREASE in haemoglobin, packed cell volume (PCV) known as
HAEMATOCRIT and red cell count

70
Q

types of polycthaemia?

A
  • absolute; primary (PV and mutations in erythropoietin receptor) and secondary (hypoxia)
  • relative (decreased plasma volume and normal RBC mass) -> dehydration
71
Q

polycythamia vera, epidemiology?

A

Over 95% of patients have acquired mutations of the gene Janus kinase 2
(JAK2)
- In the vast majority of cases there is a point mutation that causes the
substitution of phenylalanine for valine at position 617
- JAK2 is a cytoplasmic tyrosine kinase that transduces signals, especially
those triggered by haemopoietic growth factors such as erythropoietin
- Commoner if over 60

72
Q

pathophysiology of polycthamia vera?

A

A clonal stem cell disorder resulting in a malignant proliferation of a clone
derived from one pluripotent marrow stem cell
- The erythroid progenitor offspring are unusual in NOT NEEDING
ERYTHROPOIETIN to avoid apoptosis
- This results in the excess proliferation of RBCs, white blood cells and
platelets which causes a raised haematocrit (packed cell volume) resulting in
hyperviscosity and thrombosis

73
Q

clinical presentations of polycythaemia vera?

A
  • headache
  • itching
  • tinnitus
  • burning sensation in fingers and toes
  • gout
  • hypertension
  • intermediate claudication
  • hepatosplenomaglay
74
Q

investigations for polycythaemia vera?

A

Blood count:
• Raised white cell count (WCC) and platelets = distinguishes PV from
other secondary causes
- Raised Hb (major criteria)
- Presence of JAK2 mutation on genetic screen (major criteria)
- Bone marrow biopsy showing prominent erythroid, granulocytic and
megakaryocytic proliferation (minor criteria)
- Serum erythropoietin low (minor criteria)

75
Q

treatment for polycythaemia vera?

A
  • venesection
  • chemotherapy; hydroxycarbamide
  • low dose aspirin
  • allopurinol
76
Q

arterial circulation v venous circulation?

A

Arterial circulation:
• High pressure and platelet rich
- Venous circulation:
• Low pressure and fibrin rich

77
Q

platelet characteristics?

A

Platelets are anucleate cells formed by fragmentation of megakaryocytic (MK)
cytoplasm in bone marrow

Life span of 7-10 days

78
Q

thrombopoietin?

A

• Prodcued mainly by the liver thus if liver damage then there will be
reduced thrombopoietin and thus decreased platelets
• Stimulates the production of platelets by megakaryocytes (MKs)
• Binds to platelet and MK receptors
• Decrease in platelets = less bound TPO = more TPO able to bind to MK
= increased platelet production

79
Q

thromboxane A2?

A

Synthesised from arachidonic acid in platelets via cyclooxygenase
(COX-1)
• Induces platelet aggregation and vasoconstriction

80
Q

P2Y12?

A
  • Receptor on platelets that is activated by ADP

* Amplifies activation of platelets and helps activate glycoprotein IIb/IIIa

81
Q

GP2B/3A?

A

Acts as a receptor for fibrinogen and von Willebrand Factor (vWF)
• vWF is a clotting factor that is essential for platelets to adhere to
damaged blood vessels
• Aids platelet adherence and aggregation

82
Q

what can causes decreased production of protein?

A
  • congenital thrombocytopenia
  • infiltration of bone marrow (leukemias)
  • reduced platelet production by bone marrow
83
Q

what can cause increase destruction of platelets?

A
  • autoimmune -> ITP
  • hypersplenism
  • drug related
84
Q

what is immune thrombocytopenia Purpura?

A
  • immune destruction of platelets
  • The antibody-coated platelets are removed following binding to Fc receptors on
    macrophages
    • IgG antibodies form to platelets and megakaryocytes
85
Q

acute ITP in children?

A

Occurs most commonly in the 2-6 year age group
- Has an acute onset with muco-cutaneous
bleeding and there may be a history or recent viral
infection including varicella zoster (chickenpox) or
measles
- May also follow immunisation
- Although bleeding may be severe, life-threatening
haemorrhage is rare
- Sudden self-limiting purpura (red or purple spots
on the skin caused by bleeding underneath skin)

86
Q

secondary ITP in adults?

A

Usually is less acute than in children
- Characteristically seen in WOMEN and may be associated with other
autoimmune disorders such as SLE, thyroid disease and autoimmune
haemolytic anaemia
- It is also seen in patients with chronic lymphocytic leukaemia (CLL) and solid
tumours, and after infections with viruses like HIV or Hep C
- Platelet autoantibodies are detected in about 60-70% of patients, and are
presumed to be present, although not detectable in the remaining patients;
the antibodies often have specificity for platelet membrane glycoproteins
IIb/IIIa and/or Ib

87
Q

clinical presentations of immune thrombocytopenia Purpura?

A
  • easy bruising
  • nose bleeding
  • menorrhagia
  • purpura
  • gum bleeding
88
Q

diagnosis of immune thrombocytopenia Purpura?

A

Bone marrow examination:
• Shows thrombocytopenia with increased or normal megakaryocytes in
the marrow
- Platelet autoantibodies (present in 60-70%) - not needed for diagnosis

89
Q

treatment for immune thrombocytopenia Purpura?

A
  • first line -> corticosteroids and IV IgG (raise platelet count)
  • secondline -> splenectomy or immunosuppression
90
Q

thrombotic thrombocytopenia Purpura?

A

Widespread adhesion and aggregation of platelets leads to microvascular
thrombosis and thus consumption of platelets and thus profound
thrombocytopenia
• Occurs due to a reduction in ADAMTS-13 (which are attacked by the immune
system) - a protease that is normally responsible for the degradation of vWF
• Large multimers of vWF form resulting in platelet aggregation and fibrin
deposition in small vessels leading to microthrombi

91
Q

causes of TTP? thrombotic thrombocytopenia Purpura

A
  • autoimmune
  • cancer
  • pregnancy
92
Q

presentation of thrombotic thrombocytopenia Purpura?

A
  • fever

- fluctuating cerebral dysfunction

93
Q

investigation of thrombotic thrombocytopenia Purpura?

A
  • coagulation screen
  • lactate dehydrogenase is raised due to haemolysis
  • platelet count
94
Q

treatment for thrombotic thrombocytopenia Purpura?

A

Plasma exchange to remove antibody to ADAMTS-13 as well as provide a
source of ADAMTS-13
- IV METHYLPREDNISOLONE
- IV RITUXIMAB

95
Q

disseminated IV coagulation?

A

DIC arises because of systemic activation of coagulation either by release of
procoagulant material, such as tissue factor or via cytokine pathways as
part of the inflammatory response
- Such systemic activation leads to widespread generation of fibrin and
depositing in the blood vessels, leading to thrombosis and multiorgan
failure
- Also results in the consumption of platelets and clotting factors with
increased risk of bleeding

96
Q

cause of disseminated IV coagulation?

A

Massive activation of the coagulation cascade
• Initiating factors are:
- Extensive damage to vascular endothelium thereby exposing
tissue factor
- Enhance expression of tissue factor by monocytes in response to
cytokines
• Sepsis
• Major trauma and tissue destruction
• Advanced cancer
• Obstetric complications

97
Q

pathophysiology of disseminated IV coagulation?

A
  • Cytokine release in response to SIRS (systemic inflammatory response
    syndrome) - usually caused by sepsis, trauma, pancreatitis, obstetric
    emergency or malignancy
  • Widespread systemic generation of fibrin within blood vessels caused by the
    initiation of the coagulation pathway
  • Either cause microvascular thrombosis and thus organ failure OR
  • The consumption of platelets and coagulation factors, leading to bleeding by
    inhibiting fibrin polymerisation (thus fibrin cannot polymerise)
98
Q

clinical presentation of disseminated IV coagulation?

A
  • bleeding
  • confusion
  • bruising
99
Q

investigation of disseminated IV coagulation?

A
  • FBC; severe thrbocytopenia o
99
Q

investigation of disseminated IV coagulation?

A
  • FBC; severe thrombocytopenia
  • decreased fibrinogen
  • D dimer test -> increased
  • blood film
  • prolonged prothrombin time
100
Q

treatment for disseminated IV coagulation?

A
  • replace platelets

- FFP to replace coagulation factors

101
Q

heparin induced thrombocytopenia pathophysiology?

A

Development of an IgG antibody against a complex formed between platelets and
Heparin
• Heparin binds to a protein in the blood called Platelet Factor 4 (PF4), forming a
complex - PF4/Heparin
• IgG then binds to this complex forming IgG/PF4/Heparin which in turn then binds
and activates platelets
• This results in platelet consumption and thus THROMBOCYTOPENIA
• Also results in thrombosis (arterial or venous) as well as skin necrosis
• Most at risk are those after cardiac bypass surgery (since lots of Heparin used)
and those on unfractionated Heparin treatment
• Typically seen as a sharp fall in platelets around 5-10 days starting Heparin
treatment

102
Q

treatment of heparin induced thrombocytopenia?

A

Can be life-threatening and need to stop Heparin immediately and try alternative
anticoagulation even if platelets are low
• NEVER RE-EXPOSE PATIENT to Heparin

103
Q

4 subtypes of leukaemia’s?

A
  • ALL
  • AML
  • CML
  • CLL
104
Q

problems associated with leukaemia’s?

A
  • rapidly dividing leukaemia cells waste energy so there is less energy in the bone marrow to make normal functioning cells
  • rapidly replicating cells take a lot of space in the bone marrow so there is little space for other cells to grow also when there is no longer any space in the BM, the leukaemia cells present in the blood
105
Q

epidemiology of ALL?

A
  • age 2-4
    most common cancer in childhood
  • genetic susceptibility + environmental trigger
  • associated with X-rays during pregnancy and Down Syndrome
106
Q

pathophysiology of ALL?

A

Malignancy of immature lymphoid cells (gives rise to T cells and B cells)
- Affects B or T lymphocyte cell lines, arrests the maturation and promotes
uncontrolled proliferation of immature blast cells (immature precursor of
myeloid cells (myeloblasts) or lymphoid cells (lymphoblast))
- Majority of cases derive from B-cell precursors
- There is increased proliferation of immature lymphoblast cells (B or T cell
precursors) in the bone marrow:
• If all B cells = CHILDREN
• If all T cells = Adults

107
Q

clinical presentation of ALL?

A
  • anaemia (low Hb) -> SOB, fatigue, claudication
  • infection (low WBC)
  • bleeding (low platelets)
  • hepatosplenomegaly
  • headache and cranial nerve palsies
108
Q

investigations for ALL?

A
  • FBC and blood film (WCC high)
  • CXR and CT for mediastinal and abode lymphadenopathy
  • lumbar puncture for CNS involvement
109
Q

treatment for ALL?

A
  • blood and platelet transfusion
  • allopurinol -> prevent tumour lysis syndrome
  • chemo
  • marrow transplantation
110
Q

AML, epidemiology?

A
  • common acute leukaemia in adults

- associated with radiation and downs syndrome

111
Q

AML pathophysiology?

A

The neoplastic proliferation of blast cells derived from marrow myeloid
(gives rise to basophils, neutrophils and eosinophils) elements
- Progresses rapidly with death in 2 months if untreated

112
Q

clinical presentation of AML?

A
  • anaemia
  • infection
  • bleeding
  • hepatomegaly and splenomegaly
  • DIC
113
Q

investigations of AML?

A
  • FBC
  • blood smear
  • microscopy
  • immunophenotyping
114
Q

treatment of AML?

A
  • blood and platelet transfusion
  • allopurinol -> TLS
  • chemo
  • bone marrow transplant
115
Q

CML, epidemiology?

A
  • adults
  • 40-60 yrs
  • male dominance
  • More than 80% have the Philadelphia chromosome which forms a fusion
    gene BCR/ABL on chromosome 22, which has tyrosine kinase activity -
    stimulates cell division
116
Q

what is CML?

A
  • uncontrolled clonal proliferation of myeloid cells
117
Q

clinical presentations of CML?

A
  • symptomatic anaemia
  • splenomegaly -> abdo discomfort
  • weight loss
  • tiredeness
  • fever
  • gout -> purine breakdown
118
Q

investigations of CML?

A
  • FBC; high WCC, low Hb and platelets can be low, normal or raised
  • bone marrow aspirate -> hypercellualar
119
Q

treatment for CML?

A
  • oral IMATINIB -> specific BCR/ABL tyrosine kinase inhibitor
  • stem cell transplant
120
Q

CLL, epidemiology?

A
  • most common leukaemia
  • in later life
  • pneumonia may be triggering event
121
Q

what is CLL?

A

accumulation of mature B cells that have escaped programmed cell
death and undergone cell-cycle arrest

122
Q

clinical presentations of CLL?

A
  • asymptomatic
  • symptoms of anaemia
  • severe -> weight loss, heptasplenomenagly and enlarged non tender nodes
123
Q

investigations of CLL?

A
  • FBC; normal or low Hb, raised WCC

- blood film; smudge cells

124
Q

complications of CLL?

A
  • autoimmune haemolysis

- increased infection risk due to hypogammaglobulinaemia (low IgG)

125
Q

treatment for CLL?

A
  • blood transfusions
  • human IV immunoglobulins
  • chemo and radiotherapy
  • stem cell transplant
126
Q

what are lymphomas?

A

disorders caused by malignant proliferations of lymphocytes
• These accumulate in the lymph nodes causing LYMPHADENOPATHY (enlarger
lymph nodes), but may also be found in the peripheral blood or infiltrate organs

127
Q

what are the types of lymphomas?

A
  • hodgkin (characteristic cells with mirror-image nucleus)

- non hodkin (low, high and very high grade)

128
Q

hodgkin lymphoma, epidemiology?

A
  • common in men
  • occur in teens and elderly
  • EBV may be have role
129
Q

divisions of Hodgkin lymphoma?

A
  • classical -> REED-STERNBERG cells (955)

- nodular -> REED STERNBERG VARIANT -> popcorn cell

130
Q

aetiology of Hodgkin lymphoma?

A
  • genetic
  • EBV
  • SLE
  • post transplantation
131
Q

clinical presentation of Hodgkin lymphoma?

A
  • rubbery painless cervical lymphadenopathy
  • cough
  • heptaosplenomagaly
  • weight loss/fever
  • increased JVP
132
Q

investigations for Hodgkin lymphoma?

A
  • CXR
  • bone marrow biopsy
  • FBC; high ESR, low Hb and high serum lactate dehydrogenase
  • immunophenotyping
133
Q

Ann Arbor classification?

A 
I - Confined to single lymph node region
 II - Involvement of two or more nodal
areas on the same side of the diaphragm
III - Involvement of nodes on both sides
of the diaphragm
IV - Spread beyond the lymph nodes e.g.
liver or bone marrow
134
Q

treatment for Hodgkin lymphoma?

A

ABVD

  • Adriamycin
  • Bleomycin
  • Vinblastine
  • Darcabazine
135
Q

non Hodgkin lymphoma, epidemiology?

A
  • strong like to EBV and BURKITTS LYMPHOMA

- family risk

136
Q

non Hodgkin lymphoma pathophysiology?

A

Includes all lymphomas without Reed-Sternberg cells
- Around 80% is of B-cell origin (MAJORITY), diffuse large B-cell lymphoma
(DLBCL) is commonest
- Around 20% is of T-cell origin
- Generally more varied in terms of presentation, sub-types, treatments and
outcomes

137
Q

clinical presentation of non Hodgkin lymphoma?

A
  • 75% nodes
  • fever, night sweats and weight loss
  • pancocyopenia
138
Q

low grade v high grade non Hodgkin lymphoma?

A
  • low grade -> slow growing, advanced presentation

- high grade -> nodal presentation

139
Q

investigation of non Hodgkin lymphoma?

A
  • raised lactose dehydrogenase
  • bone marrow biopsy
  • CTI/MRI
  • immunophenotyping
140
Q

treatment of non-hodgkin lymphoma?

A 
R-CHOP
R - RITUXIMAB (monoclonal antibody - minimal side effects)
• C - CYCLOPHOSPHAMIDE
• H - HYDROXY-DAUNORUBICIN
• O - VINCRISTINE (Oncovin brand name)
• P - PREDNISOLONE
141
Q

myeloma, epidemiology?

A
  • peak age 70 yrs

- more common in afro-caribbeans

142
Q

myeloma, pathophysiology?

A

Cancer of differentiated B lymphocytes known as PLASMA CELLS (produce
antibodies)
- The accumulation of malignant plasma cells in the bone marrow leads to
progressive bone marrow failure
- Normal plasma cells produce a wide range of immunoglobulins (antibodies)
such as IgG,IgA,IgM & IgD
- However in myeloma the malignant plasma cells just produce an EXCESS of
one type of immunoglobulin this is known as monoclonal paraprotein:
• IgG (55%)
• IgA (20%)
• Rarely IgM and IgD
- Other immunoglobulin levels are low resulting in immunoparesis resulting in
increased susceptibility to infections

143
Q

clinical presentation, myeloma?

A

OLD CRAB

  • old age
  • calcium elevated
  • renal failure (deposited raised immunoglobulins)
  • anaemia
  • bone lytic lesions -> back pain
144
Q

investigations of myeloma?

A
  • FBC; low Hb, raised ESR
  • U&E; high calcium and ALP
  • XRAY
  • bone marrow
  • serum and urine electrophoresis
  • urine bence-jones protein test
145
Q

treatment of myeloma/

A
  • analgesia
  • bisphosphpnate
  • blood transfusion and EPO
  • renal dialysis
  • chemo
146
Q

febrile neutropenia?

A

Temperature recorded as above 38°C in a patient with absolute neutrophil
count <1.0x109/L

147
Q

risk factors of febrile neutropenia?

A

Any patient that has had chemotherapy less than 6 weeks ago
- Any patient who has had a stem cell transplant or high dose chemotherapy
within the last year
- Any haematological condition resulting in neutropenia:
• Aplastic anaemia - bone marrow failure syndrome
• Autoimmune disease
• Leukaemia

148
Q

clinical presentation of febrile neutropenia?

A
  • pyrexia
  • sweats
  • cough
  • tachycardia
  • hypotension
149
Q

management of febrile neutropenia?

A
  • IV broad spectrum antibiotics
149
Q

management of febrile neutropenia?

A
  • IV broad spectrum antibiotics
150
Q

malignant spinal cord compression?

A
  • seen in myeloma and lymphoma
  • causes back pain, weakness, inability to control bladder
  • high dose steroid -> treatment
151
Q

tumour lysis syndrome?

A 
Life threatening metabolic
derangement that occurs when
malignant cells BREAKDOWN resulting
in neuro, cardio and renal
complications
152
Q

signs of tumour lysis syndrome?

A

High uric acid

  • Hyperkalaemia
  • Hyperphosphatemia
  • Hypocalcaemia
153
Q

treatment of tumour lysis syndrome?

A

Aggressive hydration
- ALLOPURINOL (xanthine oxidase inhibitor) or RASBURICASE (recombinant
urate oxidase) both work to reduce uric acid production
- Monitor electrolytes
- Refer for dialysis if required

Phase 2a (12 decks)

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