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Phase 3 > Haematology > Flashcards

Haematology Flashcards

1
Q

Describe the sites of haemopoiesis in the foetus, infant and adult

A

Foetus
0-2 months: yolk sac
2-7 months: liver, spleen
5-9 months: bone marrow

Infant
Bone marrow - all bones

Adult
Bone marrow - vertebrae, ribs, sternum; skull; sacrum, pelvis; ends of femurs

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2
Q

Describe the characteristics and location of haemopoietic stem cells

A
  • Self-renewal capacity
  • Unspecialised
  • Ability to differentiate
  • Rare
  • Quiescent (G0)

Location: bone marrow, umbilical cord blood, peripheral blood after treatment with G-CSF

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3
Q

List the components of the bone marrow microenvironment - stromal cells & ECM components

A

Stromal cells
- Fibroblasts
- Macrophages
- Endothelial cells
- Fat cells
- Reticulum cells

ECM
- Fibronectin
- Haemonectin
- Laminin
- Proteoglycans
- Collagen

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4
Q

Give 2 examples of conditions impairing bone marrow function which are 1) hereditary 2) acquired

A

1) Thalassaemia, sickle cell anaemia
2) Aplastic anaemia, leukaemia

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5
Q

Describe the principle of leukemogenesis

A

The neoplastic cell is a haemopoietic stem cell or early myeloid/lymphoid cell

  • Mutation-associated dysregulation of cell growth and differentiation
  • Proliferation of leukaemic clone with differentiation blocked at an early stage
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6
Q

What is meant by a “clonal” disorder?

A

Haematological malignancies and pre-malignant conditions are termed clonal if they arise from a single ancestral cell

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7
Q

Describe clonal disorders of overproduction (Myeloproliferative disorders)

A

Classical
- Polycythaemia rubra vera
- Essential thrombocytosis (Jak2 positive ET)
- Myelofibrosis
- They are variably associated with the JAK2V617F and calreticulin mutation
> Have the potential to transform into acute myeloid leukaemia (AML)

Other
- Mastocytosis
- Clonal hypereosinophilic syndrome
- Chronic neutrophilic leukaemia

Jak2 positive ET

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8
Q

Describe clonal disorders of underproduction

A

Aplastic anaemia
- Fanconi anaemia
> Bone marrow failure may present from birth into adulthood
> Autosomal recessive inheritance

> Characteristics
- Somatic abnormalities
> Short stature, microphthalmia, GU & GI malformations, mental retardation, hearing loss, CNS e.g. hydrocephalus, abnormalities of digits
> Bone marrow failure
> Short telomeres
> Malignancy (especially skin)
> Chromosomal instability (can progress to acute leukaemia)

  • 7 genetic subtypes (FANC A-G)
  • Molecular biology
    > Altered DNA damage response
    > Abnormal oxidative stress response
    > Upregulation of pathways e.g. MAPKs, leading to increase in TNF-alpha
    > Telomere dysfunction
    > Environmental factors
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9
Q

Describe clonal disorders in which abnormal cells are produced

A
  • Myelodysplastic syndromes
    > Characterised by dysplasia and ineffective haemopoiesis in >=1 myeloid series
    > May be secondary to previous chemotherapy or radiotherapy
    > May have increased myeloblasts
    > Multiple subtypes based on morphology & % blasts
    > Often associated with acquired cytogenetic abnormalities
  • Refractory anaemia with excess blasts and monosomy 7
    > Majority are characterised by progressive bone marrow failure; some progress to AML
  • Leukaemia
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10
Q

Describe autologous stem cell transplants, including the main indications & the process

A

Autologous SCTs use the patient’s own blood stem cells

Main indications
- Relapsed Hodgkin’s disease
- Non-Hodgkin’s lymphoma
- Myeloma

Process - mobilised peripheral blood stem cells harvested by apheresis
> Patients receive growth factor (G-CSF) +/- chemotherapy so stem cells leave bone marrow & are collected from blood
> CXCR4 antagonist - Mozobil - can be used to collect stem cells that have failed to mobilise

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11
Q

Describe allogeneic stem cell transplants including the main indications

A

Allogeneic SCTs are transplants in which stem cells come from a donor

Types of donor
> Syngeneic - identical twins
> Allogeneic - HLA identical
- Can use peripheral blood stem cells, bone marrow or umbilical cord blood
- May be full intensity “myeloablative” or reduced intensity “mini” transplant

  • Main indications
    > Acute and chronic leukaemias
    > Relapsed lymphoma
    > Aplastic anaemia
    > Hereditary disorders e.g. thalassaemia

In malignant disease, allograft has the benefit of graft v leukaemia effect but the disadvantage is graft v host disease

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12
Q

Describe a myeloablative regimen

A

Combination of high dose chemotherapy and total body irradiation

Afterwards, stem cells are given (may involve a change in blood group if allogeneic)

> Anti-rejection medication may be required

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13
Q

Explain what a reduced intensity SCT or “mini-transplant” refers to

A

Low dose chemo is given as conditioning treatment for the transplant

> Patient is given donor cells, so they become a mixed chimera (host cells + donor cells)

  • Donor lymphocyte infusion is given so patient’s cells are fully donor
    > If patient relapse and becomes a mixed chimera again, high concentration donor lymphocyte infusion is given to return to donor cells
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14
Q

List problems with stem cell transplants

A
  • limited donor availability, upper age limit (<=65)
  • Mortality 10-50% depending on risk factors
  • Graft v host disease
  • Immunosuppression
  • Infertility in both sexes
  • Risk of cataract formation
  • Hypothyroidism - dry eyes and mouth
  • Risk of secondary malignancy
  • Risk of osteoporosis / avascular necrosis
  • Relapse
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15
Q

Describe the shape of RBCs and its function

A

Biconcave disc shape allows maximal deformability to move through blood vessels & increased surface area for maximum gas transfer across membrane

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16
Q

Describe the production of RBCs

A

Erythropoietin (EPO) produced in the kidney drives erythropoiesis in the red bone marrow

Requirements for normal RBC production
> Correct genes encoding erythropoiesis
> Iron, vitamin B12, folate & minerals
> Functioning bone marrow
> Balance between RBC production & loss

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17
Q

Describe the protein structure of the haemoglobin molecule

A
  • 4 globin chains
    > 2 alpha
    > 2 beta
  • 4 haem groups (one per chain)
  • Structure of haem: protoporphyrin ring
    > Ferrous iron in the centre
    > Allows Hb to reversibly bind oxygen without undergoing oxidation/reduction
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18
Q

Describe the function of RBCs

A

Gas exchange

  • O2 delivery from lungs to tissues
  • CO2 removal: CO2 + H2O (in the presence of carbonic anhydrase) react to form carbonic acid, which dissociates into bicarbonate and a hydrogen ion

The hydrogen ion is buffered by haemoglobin

Bicarbonate passes out in exchange for chloride moving in (chloride shift)

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19
Q

State the total body content of iron, the average daily iron need & the locations where iron is found in the body

A

Total body content: 4mg

Daily iron need: 1-2 mg

Location:
- Bone marrow & RBCs
- Macrophages of reticuloendothelial system (RES)
- Myoglobin
- Enzymes
> Cytochromes
> Peroxidases
> Xanthine oxidase
> Catalase
> RNA reductase

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20
Q

Describe the transport of plasma iron

A
  • Transferrin (Tf)
    > Glycoprotein synthesised in hepatocytes with 2 iron binding sites (usually 30% saturated with Fe)+
    > Delivers iron to all tissues

> Transferrin synthesis is controlled by the amount of iron in the body
- decreased Fe means increased Tf
- increased Fe means decreased Tf

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21
Q

Describe how erythroblasts use iron

A

Tranferrin iron is taken up by the transferrin receptor (TfR)

Iron is taken to the mitochondrion, where it is converted to haem via ALA-S2 enzyme

> Excess iron not required for haem is stored as erythroblast ferritin

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22
Q

Describe how macrophages break down RBCs

A

RES macrophages phagocytose effete RBCs at the end of their lifespan (120d)

> Globin broken down into amino acids
Haem broken down into biliverdin and after some steps, unconjugated bilirubin (goes to liver for conjugation)

> Iron can be stored in the macrophage of the RES as ferritin (soluble) or haemosiderin (insoluble)

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23
Q

Describe the clinical use of serum ferritin

A

Serum ferritin is directly proportional to RES iron, so can be used to estimate the levels of iron storage in the body

However, ferritin is also an acute phase protein - in the presence of inflammation/tissue damage, serum ferritin may rise inappropriately in relation to iron storage

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24
Q

Describe the role of the hormone hepcidin in iron homeostasis & give an example of a disease caused by a mutation in this gene

A

Hepcidin is controlled by the HFE gene, produced in the liver

Function:
- Restricts the absorption of iron from the GI tract
- Regulates the amount of iron released from RES macrophages

Hereditary haemochromatosis is caused by a loss of hepcidin; the patient absorbs excess iron from the GI tract and releases too much iron from RES: iron overload.

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25
Q

Describe the process of iron absorption

A
  • Takes place primarily in duodenum
    > Haem iron (red meats, easier to absorb, ferrous state)

> Non-haem iron (white meats, cereal, harder to absorb, ferric (Fe3+) requires conversion to ferrous (Fe2+) state by duodenal cytochrome b1 - influenced by vitamin C (vitamin C ferrireductase)

  • Ferrous iron enters the enterocyte via DMT1 (divalent metal transporter 1); enters the bloodstream via ferroportin
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26
Q

Describe the causes and laboratory features of iron deficiency anaemia (IDA)

A
  • Commonest anaemia, gradual onset
  • Lack of iron means RBCs cannot produce haem

Causes: dietary, malabsorption, blood loss (males & post-menopausal females: GI blood loss; young females: menstrual blood loss unless GI symptoms)

Laboratory features
- Hypochromic microcytic RBCs
- Decreased transferrin saturation (<15%)
- Low serum ferritin

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27
Q

Describe clinical features of iron deficiency anaemia, as well as its treatment

A

Clinical features

  • Koilonychia: spooning of nails
  • Atrophic glossitis: painless loss of papillae in tongue
  • Angular stomatitis
  • Oesophageal web (Plummer Vinson syndrome), can cause dysphagia

Treatment
- Iron replacement with ferrous sulphate (higher iron content) or ferrous gluconate

  • IV iron if intolerant of oral iron, issues with compliance or renal anaemia & EPO replacement
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28
Q

Describe the causes of anaemia of chronic disease (ACD), as well as the lab values which may be seen

A
  • Caused by a failure of iron utilisation

> iron trapped in RES macrophages, raised hepcidin, reduced EPO response (erythroblasts in bone marrow are insensitive due to cytokines from inflammatory state)

> caused by infection, inflammation, neoplasia

Lab values
- MCV/MCH is normal or low
- ESR is elevated
- RBC rouleaux present
- Ferritin is normal or increased
- Iron is decreased
- Total iron binding capacity is reduced

Treat by treating underlying disorder

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29
Q

Define haemolytic anaemia and describe its general features

A

Anaemia related to reduced RBC lifespan
> No blood loss and no haematinic deficiency

Features
- 20-100d: compensated haemolytic state
> Haemoglobin is normal
> Increased reticulocytes
> Increased unconjugated bilirubin

  • <20d: haemolytic anaemia
    > Decreased haemoglobin
    > Increased reticulocytes
    > Increased unconjugated bilirubin
    > Increased spleen function
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30
Q

List the different types of haemolytic anaemia

A
  • Congenital: abnormalities of RBC membrane (hereditary spherocytosis), haemoglobinopathies (thalassaemia, sickle cell), abnormalities of RBC enzymes (pyruvate kinase deficiency, G6P dehydrogenase deficiency)
  • Acquired

> Autoimmune (AIHA) - warm & cold

> Isoimmune - haemolytic disease of the newborn (HDN)

> Non-immune: fragmentation haemolysis
- Malfunctioning prosthetic valve, haemolytic uraemic syndrome (HUS), thrombotic thrombocytopaenia

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31
Q

Describe the features and treatment of hereditary spherocytosis

A

Autosomal dominant condition characterised by RBCs being spherocytic and polychromatic (reticulocytes have more RNA)

> Also jaundice (increased bilirubin due to haem break down)
Splenomegaly: site of abnormal RBC breakdown

Treatment includes splenectomy & hyposplenic prophylaxis

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32
Q

Describe the risks of a hyposplenic state

A

Risk of overwhelming post splenectomy infections (OPSI) from encapsulated organisms

> Streptococcus pneumoniae, haemophilus influenzae, neisseria meningitidis

> Prophylaxis includes immunisations & long-term penicillin V; carry a splenectomy card at all times

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33
Q

Describe the pathophysiology and features of pyruvate kinase deficiency anaemia

A

Glycolysis is the process of conversion of glucose to pyruvate
> produces 23DPG which influences oxygen dissociation curve

> Final step - conversion of phosphoenolpyruvate to pyruvate - catalysed by pyruvate kinase

> Leads to conversion of ADP to ATP - energy source for RBC

> If patient is deficient in pyruvate kinase, they become deficient in ATP & RBCs haemolyse

> Pyruvate kinase deficiency anaemia is an AR condition in which ATP depletion cayses chronic extravascular haemolytic anaemia

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34
Q

Describe the features and pathophysiology of glucose 6 phosphate dehydrogenase deficiency anaemia

A

The pentose phosphate pathway is involved in the conversion of NADP to NADPH via glucose-6-phosphate dehydrogenase
> gives RBC reducing power to protect it from oxidative damage

  • G6P dehydrogenase deficiency is an X-linked recessive condition characterised by acute episodic intravascular haemolysis from oxidative stress e.g. favism (fava beans), drugs: antimalarials, sulphonamides…
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35
Q

Describe the causes of warm type autoimmune haemolytic anaemia

A

Warm type involves IgG autoantibodies (work better at 37ºC) +/- complement

Causes:
- Idiopathic
- Other autoimmune disease (LSE or RA)
- Lymphoproliferative disorder (NHL/CLL)
- Drug-induced (3 ways)
> Drug acts as hapten, attaches to RBC and the complex raises autoantibodies (mild haemolysis)

> Drug itself leads to antibody generation (e.g. cephalosporins) - antibody + drug create an immune complex which adheres to RBC surface; complement is activated and RBCs are haemolysed (severe)

> Drug itself directs antibodies to RBCs (rare)

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36
Q

Describe the blood film features, tests and treatment for warm type AIHA

A

Features: RBCs are spherocytic (due to IgG attachment to red cell antigen and damage to membrane) and polychromatic
> Splenomegaly as RBCs are phagocytosed here

Tests
- Direct Coombs (antiglobulin) test: detects antibody (+/- complement) on RBC surface
> Positive indicates warm AIHA or HDN

  • Indirect Coombs test: detects RBC antibodies in plasma, used for crossmatching

Treatment
> Stop drugs, give steroids, immunosuppression, splenectomy, folic acid, blood transfusion

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37
Q

Descirbe the causes, features and treatment of cold AIHA

A

> IgM autoantibodies +/- complement

Causes
- Mycoplasma infection
- Idiopathic
- Lymphoproliferative disorders

Features: cold agglutinins on blood film

Treatment
> Mycoplasms infection is self-limiting; resolves same time as pneumonia
> Otherwise, keep patient warm + treat underlying cause

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38
Q

Describe the pathophysiology of haemolytic disease of the newborn (HDN)

A

Rhesus negative mother (RhD-) and rhesus positive foetus (RhD+)

During pregnancy, foetal RBCs leak into maternal circulation
> mother raises antibodies against foetal RBCs
> IgG antibodies cross placenta & attack RBCs in foetal circulation

> Usually after a previous RhD+ pregnancy, so mother has pre-formed antibodies which stimulate a strong immune response due to repeated exposure

> Baby will have a positive DCT as antibodies from mother have crossed placenta

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39
Q

Describe the function of B12 in the body, including dietary sources + absorption

A

B12 is necessary for the methylation of homocysteine to methionine (involved in DNA production) & also methylmalonyl-CoA isomerisation (involved in the breakdown of fatty acids/proteins)

  • Dietary sources of B12 include meat (esp liver & kidney) and dairy products
  • Absorption of B12
    > gastric parietal cells produce intrinsic factor, which binds to B12
    > IF-B12 complex binds to cubulin, a specifi creceptor in the ileum; B12 is absorbed and binds to transcobalamin

(stores 3-4 years)

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40
Q

Describe the function of folate in the body, including dietary sources + absorption

A

Folate is found in green vegetables, is absorbed mainly in the small bowel and stores are a few days only, so it is quickly used up if there is increased demand

Folate is also needed for DNA synthesis and nuclear maturation

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41
Q

Describe the pathophysiology of megaloblastic anaemia

A

B12 / folate deficiency results in a disparity in the rate of synthesis of DNA precursors
> Abnormality of cell division, leucopenia, thrombocytopaenia

> Large immature abnormally made red cells (macrocytic)

Neutrophils also have excess lobes due to failure of division - there is a dissociation between nuclear & cytoplasmic development

Ineffective erythropoiesis results in the death of mature cells whilst still in marrow

Characterised by raised bilirubin (mild jaundice due to haemolysis) and raised LDH

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42
Q

What are the neurological manifestations of B12 deficiency?

A

Bilateral peripheral neuropathy or demyelination of the posterior & pyramidal tracts of the spinal cord

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43
Q

Describe the pathogenesis of pernicious anaemia

A

Autoimmune condition where antibodies are produced against gastric parietal cells and intrinsic factor

> Blocks absorption of vitamin B12

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44
Q

List the causes of macrocytosis

A
  • Megaloblastic anaemia (B12/folate deficiency)
  • Reticulocytosis (20% bigger than average mature red cell)
  • Cell wall abnormality (lipids) due to alcohol, liver disease or hypothyroidism
  • Bone marrow failure syndromes
    > Congenital
    > Myelodysplasia
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45
Q

Define thalassaemias and explain the pathophysiology of alpha thalassaemia

A

Thalassaemias are a group of inherited conditions characterised by a relative lack of globin genes

Alpha thalassaemia is charcterised by alpha gene permutations

> Alpha + positive thalassaemia trait (1 gene missing, mild microcytosis)

> Homozygous alpha + positive thalassaemia trait (1 missing from each parent or 2 from one parent and 0 from another, microcytosis, increased red cell count & asymptomatic anaemia

> HbH disease (3 missing genes, lack of alpha chains, excess beta chains end up joining together (HbH) - significant anaemia, blood transfusions may be required bizarre shaped small red cells)

> Alpha thalassaemia major (4 missing genes, incompatible with life)

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46
Q

Describe the pathophysiology, features and management of beta thalassaemia major

A
  • Transfusion dependent thalassaemia (iron overload affects life expectancy, iron chelation is necessary)
  • AR; missing both beta genes, unable to make adult haemoglobin (HbA) - significant dyserythropoiesis
  • Thalassaemic faces: prominent maxilla & frontal bossing, “Hair on end” appearance as bone becomes thickened
  • Management
    > Safe blood transfusion & iron chelation
  • Venous access
  • Monitoring of organs affected by iron overload: liver, heart, endocrine
  • Consider bone marrow transplantation in childhood, gene therapy in the future
47
Q

Describe the cause of sickle cell disease

A

Sickle cell disease is caused by a single amino acid substitution on the beta gene on chromosome 11.

Glutamine > Valine = Hb S

Continuous polymerisation / depolymerisation

48
Q

Describe the pathophysiology and clinical features of sickle cell disease

A

Reduced red cell survival (anaemia) - due to haemolysis and chronic endothelial dysfunction

Vaso-occlusion - red cells obstruct small capillaries; tissue hypoxia/infarction leads to pain and tissue damage

Multi-system disease
> Brain - stroke / Moya Moya (new vessel growth)

49
Q

Describe the pathophysiology and clinical features of sickle cell disease

A

Reduced red cell survival (anaemia) - due to haemolysis and chronic endothelial dysfunction

Vaso-occlusion - red cells obstruct small capillaries; tissue hypoxia/infarction leads to pain and tissue damage

Multi-system disease
> Brain - stroke / Moya Moya (new vessel growth)

> Lungs - acute chest syndrome / pulmonary hypertension; hypoventilation due to pain leads to V/Q mismatch - continuous cycle of sickling, pain & hypoxia

> Bones - dactilytis or osteonecrosis

> Spleen - hyposplenic

> Kidneys - loss of concentration in urine / infarction

> Urogenital - priapism

> Eyes - vascular retinopathy

> Placenta - intrauterine growth retardation / foetal loss

50
Q

Describe the treatment of sickle cell disease

A

Prevent crises
> Hydration, analgesia & early intervention

> Prophylactic vaccination & antibiotics

> Folic acid

> Hydroxycarbamide therapy: increases HbF & reduces sickling

> If high risk, regular red cell transfusions

Prompt management of crises: oxygen, fluid, analgesia, antibiotics, specialist care, transfusion

Bone marrow transplantation

Gene therapy

51
Q

Explain the process of primary haemostasis

A
  • Damage to the endothelium exposes subendothelial tissue and releases von Willebrand factor
  • Platelets are attracted to von Willebrand factor via glycoprotein receptor (GpIb-V-IX) allowing adhesion
  • Adhesion to vWf activates platelets leading to exposure of phospholipids and release of granular content
  • This causes more platelets to be attracted resulting in platelet aggregation, creating the “platelet plug”
52
Q

Describe the extrinsic pathway of coagulation (initiation)

A
  • Every step requires phospholipid (from platelet surface) and calcium (from blood)
  • Tissue factor (from exposed subendothelial tissue) activates factor VII
  • The reaction of activated factor VII (VIIa) and factor X leads to the activation of factor X (Xa)
  • Factor Xa activates factor II (prothrombin) and factor V creating the prothrombinase complex (Xa + Va + II)

> This complex allows the activation of factor II (IIa - thrombin)

> Thrombin converts fibrinogen to fibrin

> Thrombin activates factor XIII (XIIIa ) - this cross-links fibrin

53
Q

Describe the intrinsic pathway of coagulation (propagation)

A
  • Thrombin activates factor XI (XIa, which then activates factor IX - IXa)

Thrombin also activates factor VIII (VIIIa)

VIIIa + IXa come together and stimulate the prothrombinase complex
> More thrombin is produced, more fibrinogen is converted to fibrin, more cross-link formation

54
Q

Describe the process of fibrinolysis

A

Fibrin stimulates the production of 2 plasminogen activators: tPA (tissue plasminogen activator) and uPA (urokinase plasminogen activator)

> Plasminogen is converted to plasmin
Plasmin breaks down fibrin into fibrin degradation products (FDPs) including D-dimers

55
Q

Describe the regulation of fibrinolysis

A
  • Alpha 2 antiplasmin prevents excess amounts of plasmin
  • Downregulators of plasminogen activators
    > Plasminogen activator inhibitors: PAI-1, PAI-2
    > Thrombin activatable fibrinolysis inhibitor (TAFI)
56
Q

Describe the laboratory assessment of primary and secondary haemostasis

A
  • Primary haemostasis: bleeding time, FBC (platelet count), platelet function (light transmission aggregometry)
  • Secondary haemostasis:

> Prothrombin time (PT):
INR (international normalised ratio) is a standardised form of PT, calculated using patient’s PT & average of normal PTs
- PT depends on factors in extrinsic & common pathways: factors II, V, VII, X and fibrinogen

> Activated partial thromboplastin time (APTT):
- APTT depends on factors in intrinsic & common pathways
Factors VIII, IX, XI & XII
Factors X, V, II & fibrinogen

> Thrombin clotting time (TCT)
- Measurement of conversion of fibrinogen into fibrin clot; depends on quantity & function of fibrinogen in plasma
- TCT will be prolonged by thrombin inhibitors (heparin, dabigatran), fibrin degradation products and inhibitors of fibrin polymerisation (paraproteins)

57
Q

Describe the patterns of coagulation screen abnormality

A

PT only: low factor VII

APTT only: low factor VIII, IX, XI & XII OR lupus anti-coagulant

PT & APTT: common pathway factor low OR multiple factors low due to liver disease or DIC

58
Q

Describe the structure, function and indications of heparins

A

Heparins consist of a mixture of glycosaminoglycans of differing polysaccharide chain length

Augment activity of endogenous antithrombin: anti-IIa & anti-Xa activity

Immediate effect but short half life; administered parenterally & safe in pregnancy

Indications
- Acute DVT or PE (sub cut LMWH)
- Cardiac bypass surgery (IV UFH)
- Acute coronary syndromes (heparin + anti-platelet agents)
- Medium term after venous thromboembolism (VTE( in cancer patients
- Prophylaxis against VTE (medical & post-op, obstetric patients)

59
Q

Describe the advantages of low molecular weight heparin compared to unfractionated heparin

A

LMWH has

  • Superior pharmacokinetic profile allowing a predictable dose response
  • Safer side effect profile
    > Lower rate of heparin induced thrombocytopaenia (HIT)
    > Lower rate of osteoporosis
  • Clinical efficacy at least equal to UFH
  • higher drug costs BUT lower consumable costs & does not require monitoring
  • Can be used in outpatients
60
Q

Describe the structure, function and indications of warfarin

A

Vitamin K antagonist - inhibits vitamin K oxide reductase, resulting in failure of gamma-carboxylation of glutamic acid residues
> Dysfunction of factors II, VII, IX & X

> Delayed onset/offset, higher inter-individual variability and narrow therapeutic window so requires regular INR monitoring (also many food + drug interactions)

  • Indications
    > Atrial fibrillation
    > Acute DVT or PE (reduces risk of recurrence)
    > Prosthetic heart valve
    > NOT for immediate anticoagulation/short-term prophylaxis
61
Q

Describe the function of newer direct oral anticoagulants (DOACs) and compare them to warfarin

A
  • Immediate effect, compliance is important so doses are not missed
  • Thrombin (IIa) antagonist: dabigatran etexilate (Pradaxa)
  • Factor Xa antagonist: apixaban, rivaroxaban, edoxaban
  • Indications: DVT, PE, AF to reduce stroke risk

DOACs v warfarin
- DOACs have a rapid onset/offset, reviewed annually, few drug/food interactions, more minor side effects but no rapid reversing agent (idarucizumab in trials)

  • Warfarin has a slow onset/offset, regular INR monitoring, many interactions, rare side effects aside from bleeding, rapid reversal with PCC & vitamin K
62
Q

List the kinase fibrinolytic agents, their function, indications and risks

A
  • Streptokinase (derived from streptococci bacteria)
    > Antigenic (recent strep infection/previous use of streptokinase makes it ineffective)
  • Urokinase: grown from renal cells in culture (cell derivative - not antigenic)

Both bind to plasminogen, releasing plasmin & leading to enhanced fibrin breakdown

However, act on both clot-bound and free plasminogen - causing fibrinolysis and systemic fibrinogenolysis
> Significant bleeding risk

63
Q

Describe the function and indications for tissue plasminogen activators (tPA)

A

Stimulate conversion of plasminogen to plasmin, which breaks down fibrin; relatively selective for clot-bound plasminogen

> Minimal unwanted fibrinogenolysis

Alteplase, tenecteplase, reteplase

Indications:
> acute MI (within 12h of onset of symptoms) for patients not suitable for PCI
> Ischaemic stroke (within 4.5h of onset of symptoms)
> Massive pulmonary embolism w/ haemodynamic instability (hypotensive and tachycardic)

Side effects: risk of haemorrhage, particularly intracerebral

64
Q

Describe how fibrinolytic agents are administered in a clinical setting

A

Administered systemically or locally (catheter directed)

Catheter-directed thrombolysis can be performed with any fibrinolytic drug, smaller doses injected directly into the vessel containing thrombosis to reduce sytemic effecrs

Used in acute limb ischaemia, massive DVT or blocked CVC (central venous catheter)

65
Q

Describe the anti-platelet agents which work via platelet receptor inhibition

A
  • Irreversible blockage of ADP receptor (P2Y12) - clopidogrel, ticlodipine
    > Decrease expression of GPIIb/IIIa
    > Reduce binding of fibrinogen
    > Inhibit ADP-mediated platelet aggregation
  • GPIIb/IIIa antagonists - abciximab, tirofiban
    > Monoclonal antibodies antagonise IIb/IIIa receptor
    > Reduced platelet aggregation & binding of fibrinogen
66
Q

Describe the anti-platelet agents which work via platelet signaling pathway inhibition

A
  • Irreversible inhibition of cyclooxygenase: aspirin
    > Blocks conversion of arachidonic acid into thromboxane A2; decreased platelet activation
  • Phosphodiesterase III inhibitor: dypiridamole
    > Increased platelet concentration of cAMP leads to reduced platelet responsiveness to ADP
    > Reduced platelet aggregation
67
Q

List the indications for the use of anti-platelet agents

A
  • Acute MI (aspirin indefinitely, ticagrelor/clopidogrel for up to 12 months with tirofiban acutely)
  • Secondary prevention CVD: aspirin
  • Peripheral vascular: clopidogrel/aspirin or dipyridamole
68
Q

Discuss the causes, pathophysiology, investigations & treatment for disseminated intravascular coagulation (DIC)

A
  • Acquired, consumptive process
    > Activation of coagulation cascade leads to microthrombi formation
    > Intravascular deposition of fibrin leads to thrombosis of small or midsize vessels and organ failure
    > Red cell fragments in bloodstream
    > Exhaustion of coagulation cascade (depletion of platelets/coagulation factors) leads to bleeding

Causes; sepsis, malignancy, massive haemorrhage, severe trauma, pregnancy complications (pre-eclampsia, placental abruption, amniotic fluid embolism)

Investigations: find underlying cause
> assess coagulation
» PT, APTT prolonged
» Fibrinogen and platelets reduced
» D-dimers high
» FBC + film to assess platelet & RBC fragments

Treatment: treat underlying cause, if bleeding/high risk give fresh frozen plasma, cryoprecipitate (if low fibrinogen) and platelet transfusion (if low platelets)

69
Q

Describe the management of bleeding complications with warfarin treatment (especially with high INR)

A
  • Stop warfarin/reduce dose
  • Give vitamin K (oral or IV)
  • Give coagulation factors (II, VII, IX, X)
    > prothrombin complex concentrates (beriplex, octaplex)
70
Q

Describe the coagulopathy seen in liver disease

A

Poor coagulation factor synthesis in liver

Vitamin K deficient (poor diet, obstructive jaundice)

Hypersplenism - low platelets

Reduced thrombopoietin (TPO) synthesis - low platelets

71
Q

List acquired thrombophilias

A
  • Antiphospholipid syndrome
  • Anti-cardiolipin antibodies
  • Beta-2 glycoprotein-1 antibodies
72
Q

Describe the effects of the presence of Lupus anticoagulant and how it is tested for

A

Lupus anticoagulant is a lipid-dependent antibody which interferes with phospholipid-dependent tests such as the APTT, which will be prolonged

If it is persistent, may lead to a pro-thrombotic state
> Persistent Lupus anticoagulant + thrombosis (or recurrent foetal loss) = antiphospholipid syndrome

  • Testing: prolonged APTT & only partial correction of APTT 50:50 dilution; also Dilute Russell Viper Venom Test (DRVVT) as the Lupus anticoagulant interferes with this assay, but this ration is corrected with excess phospholipid
73
Q

Why is a 50:50 dilution performed when there is a prolonged APTT?

A

50:50 normal & patient plasma

If the patient has a factor deficiency, there will be a full correction of APTT as it is compensated for by factors in normal plasma

If there is an inhibitor in the patient (such as Lupus anticoagulant), there will only be a partial correction as the inhibitor will affect patient & normal plasma

74
Q

Describe the pathophysiology and treatment of haemophilia A

A
  • X-linked inheritance of factor VIII deficiency leading to a prolonged APTT
    > Severe: spontaneous bleeds, moderate: minor trauma bleeds, mild: surgical bleeding

Treatment:
- Education

  • Desmopressin (ddAVP) - increases release of endogenous factor VIII adhered to the endothelium
  • Replacement therapy: FFP/cryoprecipitate, plasma-derived facgor concentrate, recombinant-produced factor concentrate, gene therapy
75
Q

Describe the pathophysiology and classification of Von Willebrand disease

A
  • Most common mild bleeding disorder; mostly AD with variable penetrance

> Mucosal type bleeding pattern with heavy menstrual periods, epistaxis…

> Reduced von Willebrand factor +/- reduced platelet aggregation +/- reduced factor VIII

Classification
- Type 1: partial quantitative deficiency of VWF

  • Type 2: qualitative deficiency of VWF
    > 2A: absence of high molecular weight VWF multimers
    > 2B: increased affinity for glycoprotein 1b
    > 2M: presence of HMW VWF multimers
    > 2N: decreased affinity for factor VIII
  • Type 3: virtually complete deficiency of VWF
76
Q

Describe the inheritance pattern and cause of 1) Glansmanns thrombasthenia 2) Bernard Soulier syndrome; also treatment of bleeding

A

Both rare AR disorders with mucosal type bleeding pattern

1) Glansmanns thrombasthenia is caused by absent/defective GP IIb/IIIa, but normal platelet count

2) Bernard Soulier syndrome is caused by absent/defective GP Ib/V/IX, presents with macrothrombocytopenia

Bleeding is treated by: pressure, tranexamic acid, desmopressin, HLA-matched platelet transfusion, recombinant FVIIa

77
Q

List inherited thrombophilias

A

Deficiencies of natural anticoagulants, such as antithrombin, protein C or protein S

Specific gene mutations such as factor V Leiden (resistance to activated protein C) or the prothrombin gene mutation G20210A (increased prothrombin)

78
Q

Define lymphoma and describe its presentation

A
  • Lymphoma is a cancer that develops from lymphocytes, is carried around in the lymphatic system and collects in lymph nodes
  • Presentation
    > Painless, rubbery lymphadenopathy
    > Splenomegaly
    > Extranodal disease e.g. breast, brain, lung
    > B symptoms e.g. night sweats, weight loss, unexplained fever
    > Anaemia: due to bone marrow infiltration, splenomegaly, anaemia of chronic disease
79
Q

Describe the investigations used for lymphoma

A
  • History: symptoms, duration, B symptoms
  • Clinical examination: lymphadenopathy, splenomegaly, hepatomegaly
  • Blood tests (help determine fitness for treatment):
    > FBC: anaemia, pancytopaenia
    > LFTs: liver function
    > U&Es: renal function
    > Ca: may be elevated in aggressive lymphomas
    > LDH: lactate dehydrogenase, marker of tumour turnover, likely to be elevated in aggressive tumours
    > Urate: breakdown of blood cells can precipitate gout
  • Imaging
    > CT: neck, chest, abdomen & pelvis for staging
    > PET/CT: diffuse large B cell lymphoma DLBCL - upstages, good for extranodal disease; follicular lymphoma (FL) - to confirm early stage
  • Bone marrow biopsy: aspirate & trephine (from PSIS)
  • Echocardiogram (before prescribing drugs which can affect heart function)
80
Q

Explain the staging method used in lymphoma

A

Ann-Arbor Classification System

Stage I: single lymph node group
Stage II: 1+ lymph nodes same side of diaphragm
Stage III: lymph node groups both sides of diaphragm including spleen
Stage IV: extranodal involvement e.g. liver, bone marrow

A or B added after to signify absence/presence of B symptoms

81
Q

List the classification of the different types of Lymphoma

A
  • Non-Hodgkin’s Lymphoma (85%)
    > B cell (>90%)
    » Indolent: follicular lymphoma
    » Aggressive: diffuse large B cell lymphoma, Burkitt’s lymphoma

> T cell
> Indolent
> Aggressive

  • Hodgkin’s Lymphoma (15%)
    > Classical (>90%)
    > Nodular lymphocyte predominant (behaves like low grade lymphoma)
82
Q

Describe the pathophysiology and treatment of follicular lymphoma

A

t(14;18) involving BCL2 (anti-apoptotic gene)
> Slow growth but reduced apoptosis
> Incidence increases with age, often presents as stage 4, B symptoms uncommon, usually incurable

Treatment
> Early stage: radiotherapy may be curative
> Advanced stages:
- asymptomatic, no bulk, no end organ compromise: watch and wait
- symptomatic, buly disease or end organ compromise: immunochemotherapy (anti CD20 monoclonal antibody - rituximab), chemo (CVP or CHOP or bendamustine), maintenance rituximab

83
Q

Describe the pathophysiology and treament of diffuse large B cell lymphoma

A
  • Resemblance to activated B cells (immunoblasts, centroblasts)
  • Heterogeneous entity, variable phenotype, complex karyotype, may express CD10 & BCL2

Presentation
> Rapidly enlarging lymph node mas
> Extra-nodal presentation: Waldeyer’s ring, GI tract, skin, bone, CNS
> B symptoms

Treatment
> Aggressive chemotherapy with intention to cure
> Early stage (1A) - R-CHOP x 3 + RT
R: rituximab
C: cyclophosphamide
H: adriamcyin (doxorubicin)
O: vincristine (never intrathecal)
P: prednisolone (oral)

84
Q

Describe the pathophysiology, clinical features and treatment of Burkitt’s lymphoma

A
  • Commonest high grade lymphoma in children;
  • t(8;14) involving MYC gene, very high proliferation in germinal centre cells
  • High rate of apoptosis - Tumour Lysis Syndrome is an issue
  • Clinical features
    > Short history with marked B symptoms
    > Rapidly growing tumours with massive tumour bulk
    > Extranodal disease
  • Jaws & facial bone (endemic BL)
  • Ileocaecal region, ovaries, kidneys, breast, CNS…

Treatment: responds well to intensive chemotherapy, aim of treatment is to cure

85
Q

What is Tumour Lysis Syndrome?

A

When cells break down and release metabolites like potassium

Causes problems with hyperkalaemia - leads to cardiac arrest, kidney failure, low calcium, high phosphate

Requires high fluid replacement treatment with rasburicase, may need renal dialysis

86
Q

What is a Reed Sternberg cell?

A

Neoplastic cell characteristic of classical Hodgkin’s lymphoma

It is a large binucleate cell with abundant cytoplasm and a prominent nucleolus (Owl’s eye appearance)
> Resemble atypical activated B cells seen in viral infections like EBV

> Strong expression of CD30+ and loss of B cell antigens (CD20-)

87
Q

Describe the clinical presentation of Hodgkin’s lymphoma, including prognosis and treatment

A
  • Presentation
    > Painless rubbery lymphadenopathy
    > Neck lump
    > Cough, shortness of breath (due to enlarged mediastinal nodes causing irritation)
    > Nodes can also appear in groin/axilla
    > B symptoms
    > Itch
    > Alcohol-related pain (rare)

Treatment: chemotherapy (ABVD) & radiotherapy
> Adriamycin (doxorubicin)
> Blemocyin
> Vinblastine
> Dacarbazine

High cure rates, especially in early stage, but late effects are important e.g. malignancy, cardiac, pulmonary, fertility, endocrine…

88
Q

Describe the neoplastic cell seen in multiple myeloma

A

Resemble normal plasma cells which are functionally active and produce an abnormal monoclonal protein called a paraprotein or “M” protein
> 5 different types: IgG, IgD, IgA; IgM & IgE very rare
> IgM more commonly associated with lymphoma (Waldenstrom’s macroglobulinaemia)

> Express normal plasma cell markers e.g. CD139 but have an aberrant phenotype

> Light chain on antibodies can be kappa or lambda, used to differentiate clonality
> sometimes only the light chain component of the Ig molecule is produced: light chain myeloma
Rarely, no Ig is produced: non-secretory myeloma

89
Q

Describe the pathophysiology and clinical presentation of multiple myeloma

A
  • Neoplastic plasma cells interact with bone marrow stroma & osteoclasts & osteoblasts, leading to an imbalance between bone resorption & formation

> Results in demineralisation and fractures, causing pain

> The release of calcium in the blood also leads to hypercalcaemia

> Non-specific symptoms
- Backache/rib pain
- Fatigue
- Recurrent infections (due to hypogammaglobulinaemia)
- Renal impairment:
Light chain cast nephropathy: acute renal failure caused by free immunoglobulin light chains forming plugs in glomeruli
Hypercalcaemia: causes dehydration which can lead to renal failure
UTIs
Gout (high uric acid levels)

Classical triad:
- Increased plasma cells in bone marrow
- Clonal immunoglobulin or paraprotein
- Lytic bone lesions

90
Q

Describe the diagnosis of multiple myeloma

A

Blood tests: FBC, ESR, U&Es, Ca, serum free light chain (SFLC) quantity via light chain assay

Urine tests: light chains in urine (Bence Jones protein) via protein electorphoresis

Bone marrow aspirate
> Rouleaux seen in peripheral blood
> Bone marrow shows monoclonal neoplastic plasma cells

Imaging:
- X-rays
- MRI/CT: identify lytic lesions, indicate risk of fracture/cord compression

91
Q

Describe the treatment of multiple myeloma

A

Asymptomatic myeloma: watch and wait

Symptomatic myeloma: supportive
- Bisphosphonates: reduce pain, fractures, hypercalcaemia
- Blood transfusion/EPO
- Maintaining good fluid intake
- Prophylactic antibiotics
- Vaccinations
- Radiotherapy
- Surgery
- Interventional radiology

Definitive: incurable but improves survival
- Chemotherapy
- Steroids
- Thalidomide & analogues (lenalidomide)
- Alkylating chemotherapy agents e.g. melphalan, cyclophosphamide
- Proteosome inhibitors e.g. velcaes
- Monoclonal antibodies targeted to the plasma cell e.g. daratumumab
- Autologous haematopoietic stem cell transplantation
- Novel therapies: conjugated antibodies, targeted drugs, CAR T cells

92
Q

Compare myeloma and monoclonal gammopathy of undetermined significance (MGUS)

A

Myeloma has a higher % of marrow plasma cells, most cases present with Bence Jones protein, immune paresis, lytic bone lesions and symptoms such as anaemia, raised calcium, bone pain and renal dysfunction.

MGUS has a lower % of marrow plasma cells, rarely presents with Bence Jones protein, immune paresis, lytic bone lesions or any of the other symptoms. MGUS has a risk of progression.

93
Q

Define leukaemia and list the classification of the different leukaemias

A

Leukaemia is a bone marrow cancer caused by the accumulation of acquired genetic abnormalities
> Leads to the accumulation of abnormal leucocytes in marrow, blood & other tissues

Pre-leukaemic
- Myelodysplastic syndrome
- Myeloproliferative disorder

Acute Leukaemia
- Acute Myeloid Leukaemia (AML)
- Acute Lymphoblastic Leukaemia (ALL)

Chronic Leukaemia
- Chronic Lymphocytic Leukaemia (CLL)
- Chronic Myeloid Leukaemia (CML)

94
Q

Describe the characteristics, risk profile & treatment of myelodysplastic syndrome

A

MDS is a clonal blood disorder characterised by the failure of effective haemopoiesis (common in elderly)

Characterised by dysplastic blood + bone marrow appearances, can transform to AML

Risk profile: dependent on proportion of blast cells in marrow, cytopaenias & cytogenetic profile

Treatment: incurable other than with donor SCT; otherwise, supportive care and consider drug therapy with azacitidine

95
Q

Describe the different types of myeloproliferative disorders and their characteristics

A

Clonal blood disorders in which the JAK2 mutation is prevalent, characterised by effective haemopoiesis

  • Essential thrombocythaemia: too many platelets
  • Polycythaemia vera (PRV): too many red cells, platelets, white cells
    > ET & PRV have a risk of vascular events, so aspirin is given; cytoreduction is required, so hydroxycarbamide, venesection or interferon are provided. Risk of transformation to myelofibrosis or AML.

Myelofibrosis: too much fibrous tissue, platelets, white cells
> Characterised by high or low blood counts, splenomegaly & systemic symptoms. Incurable other than with SCT; JAK2 inhibitors given as treatment.

96
Q

Describe the general characteristics of acute leukaemias, including aetiology, diagnosis and pathophysiology.

A

Acute leukemias are clonal disorders arising due to mutations in precursor cells in the marrow leading to the proliferation of blast cells (maturation arrest)

> Rapid onset, death within days/weeks if untreated due to serious compromise of normal marrow elements

Aetiology: unknown, chemicals, chemotherapy, radiotherapy, genetic e.g. Down’s or Fanconi syndrome, antecedent blood disorders (MDS, MPD) or lack of exposure to infection in childhood

Symptoms: lethargy, infection, bleeding/Bruising, bone pain, gum swelling, lymphadenopathy, skin rash

97
Q

Describe the diagnosis and management of AML

A

Peripheral blood is analysed using flow cytometry, detects:
- Anaemia, neutropenia, thrombocytopenia, blasts >20%

Morphology of blasts is important.
> M3 AML (acute pro-myelocytic leukaemia) is caused by t(15;17) - the marrow fills up with pro-monocytes which have bundles of rods in their cytoplasm.
> M3 AML can present with significant bleeding and coagulation issues (DIC); treat with all-trans retinoic acid

Standard cytogenetics (karyotyping, RT-PCR): determine prognosis
> t(15;17): M3 AML. t(8;21): M2 AML.

Manage with intensive chemotherapy +/- SCT
> High morbidity: bleeding, infection, hair loss, sterility, mucositis
> Young patients entered into trials

98
Q

Describe the presentation, investigations and management of ALL

A

ALL presents as: limping child, purpuric rash, bone pain
> Can spread to cause meningeal leukaemia

Morphology to determine if L1, L2 or L3
Standard cytogenetics have prognostic significance
Hyperploidy in ALL: good prognostic outlook
Unfavourable cytogenetics include t(9;22) and t(4;11)

Management includes initial aggressive therapy, then maintenance

  • Prednisolone
  • Cyclophosphamide, anthracycline, vincristine, etoposide, cytarabine
  • Asparaginase
  • Novel therapies
    > Bilatumomab: bi-specific T cell engager which targets CD19 on B cells, stimulating patient’s own T cells to kill leukaemia
    > CAR T cells: patient’s own T cells target CD19 and kill leukaemia cells via cytotoxicity; memory T cells prevent relapse
  • SCT for relapsed/refractory younger patients
  • Supportive: bood transfusion, FFP, platelet transfusion, antibiotics, G-CSF, granulocytes
99
Q

Describe the presenting features and diagnosis of CLL

A

Often asymptomatic (incidental diagnosis)
Or presents with lethargy, night sweats, weight loss
Symptoms of anemia
Lymphadenopathy
Infection

Can transform to high grade NHL

Diagnosis
FBC shows lymphocytosis
Bone marrow shows nodular or diffuse infiltrate
Flow cytometry shows a clonal population of B lymphocytes (CD 5, 19, 20, 23+, weak surface Ig)
> Unique immunophenotype
Cytogenetics (interphase FISH) to identify aggressive disease such as 17p deletions, which leads to loss of p53 - refractory to chemo but may respond to steroids + antibodies

100
Q

List the immune complications of CLL & explain what a “treatment trigger” is

A
  • Autoimmune haemolytic anaemia
  • Autoimmune thrombocytopaenia
  • Infection (often pulmonary infection e.g. bacterial, viral, pneumocystis (PCP), fungal)
    > Hypogammaglobulinaemia, cell-mediated immunity impaired due to T lymphopenia, neutropenia, defects affecting complement activation

Treatment triggers would prompt clinicians to initiate treatment in patients presenting with symptoms such as sweats, weight loss, symptomatic nodes OR bone marrow failure e.g. anaemia, thrombocytopaenia

101
Q

Describe the clinical presentation, pathophysiology and treatment of CML

A

CML can transform to AML or ALL

Morphology shows different stages of maturation of myeloid cells, with a higher nuclear:cytoplasmic ratio

Clinical presentation: asymptomatic or fatigue, weight loss, night sweats, abdominal discomfort, splenomegaly

Natural history: 3 phases
> Chronic phase: variety of myeloid precursors ; number of blasts is low
> Accelerated phase: increasing blasts
> Blast phase: 20% blasts, looks like acute leukaemia

Caused by Philadelphia chromosome t(9;22) - BCR-ABL fusion gene encodes an oncoprotein which drives proliferation of myeloid cells in the marrow via activation of pathways such as Ras, JAK/STAT, PI3K…

Treat with tyrosine kinase inhibitors e.g. imatinib, which block BCR-ABL kinase, switching off downstream signalling pathways

SCT if in blast crisis

102
Q

Define major haemorrhage, state an average circulatory volume, the death zone and the volume which would cause cardiac arrest

A

Major haemorrhage is defined as the loss of more than one blood volume within 24h (70mL/kg, >5L in a 70kg adult), or 50% of total blood volume lost in <3h or bleeding in excess of 150mL/min

Average circulatory volume is 5000mL
Death zone: 2000-3500 mL
Cardiac arrest >3500mL

103
Q

If there is an issue with circulation (assumed haemorrhage) which steps would be taken during pre-hospital resuscitation?

A

Access with wide bore cannulas in a large, reliable vein e.g. antecubital fossa

Give tranexamic acid (anti-fibrinolytic agent)

Give blood products: O neg RBCs

104
Q

What is a major haemorrhage protocol?

A
  • 6 units O negative blood (cross match ASAP)
  • 4 units FFP (contains coagulation factors)
  • Cryoprecipitate (rich in fibrinogen)
  • Platelets
  • Set up level 1 transfusion with warmed blood products
105
Q

What are the complications associated with major haemorrhage?

A
  • Coagulopathy (give FFP, platelets, cryoprecipitate)
  • Hypothermia (blood warmer, patient warmer, foil hat)
  • Hypocalcaemia (check ionised calcium on blood gas & replace)
  • Acidosis
  • Hyperkalaemia
  • Volume overload (can lead to pulmonary oedema)
  • TRALI (transfusion related acute lung injury)
106
Q

Discuss the causes, types and treatments for impetigo

A

Impetigo is a bacterial skin infection caused by Staphylococcus aureus, Streptococcus pyogenes or MRSA

  • 2 types
    > Bullous: form fluid-filled blisters that can rupture
    > Non-bullous: skin lesions consist of thin-walled vesicles that can exude pus & form a yellow crust

Treatment: antibiotics, oral or topical, not both
Oral; flucloxicillin, or if penicillin allergic, clarithromycin
Topical: hydrogen peroxide, fusidic acid

107
Q

Describe red flags associated with impetigo, risk factors associated with the development of impetigo and differential diagnosis for impetigo

A

Red flags: lymphadenopathy and fever, as these hint at complications such as glomerulonephritis, cellulitis, sepsis.

Risk factors: children, pre-existing skin conditions (eczema); elderly, immunocompromised patients

DDX:
- Other skin infections
> Bacterial (necrotizing fasciitis)
> Fungal (candidiasis)
> Parasitic (scabies)
> Viral (varicella zoster or herpes simplex)

Non-infective skin conditions
> Dermatitis
> Insect bites
> Drug reactions
> Burns & scalds
> Other skin disorders e.g. lupus erythematosus

108
Q

What is the differential diagnosis for fatigue?

A
  • Anaemia
  • Disturbed sleeping pattern
  • Chronic disease e.g. MS
  • Mental illness e.g. depression
  • Social e.g. family problems, school, work
  • Stress
  • Chronic fatigue syndrome aka myalgic encephalomyelitis (ME)
  • Malignancy
109
Q

List the conditions which cause intravascular haemolysis

A
  • RBC fragmentation syndromes e.g. defective mechanical heart valve, haemolytic uraemic syndrome, , microangiopathic haemolytic anaemia
  • ABO incompatible blood transfusion
  • Malaria
  • Cold AIHA (primary is idiopathic, secondary is caused by infections e.g. mycoplasma pneumoniae, infectious mononucleosis or lymphoproliferative disorders)
110
Q

What are the main laboratory findings in intravascular haemolytic anaemia?

A
  • Free haemoglobin saturates the binding protein plasma haptoglobin, which disappears
  • Excess free haemoglobin (haemoglobinaemia) is filtered at the glomerulus leading to haemoglobinuria
    > some haemoglobin is reabsorbed by kidney tubules and broken down into haemosiderin which can appear in the urine (haemosiderinuria)
  • Anaemia, reticulocytosis & raised unconjugated bilirubin
111
Q

Describe the following causes of purpura 1) immune thrombocytopaenic purpura (ITP) 2) Henoch Schonlein purpura

A

1) ITP is caused by the increased destruction of platelets after an infection (thrombocytopaenia), spleen is not enlarged in this condition. It is managed with steroids and possible splenectomy.

  1. Henoch Schonlein purpura presents with normal platelets, it is caused by vasculitis and is seen in children, associated with a viral or streptococcal infection.
112
Q

Describe the cause and diagnosis of infectious mononucleosis or glandular fever

A

Caused by Epstein-Barr virus (EBV) and presents with cervical lymphadenopathy, fever and tonsillar exudate

it is diagnosed via an EBV titre; also, on blood film atypical mononuclear cells ( T cells can be seen)

Monospot will show heterophile antibodies

> Do not give amoxicillin or ampicillin, give pencillin V to cover potential strep throat

113
Q

Describe adverse factors which contribute towards the risk of progression from MGUS to multiple myeloma

A
  • Type of paraprotein
  • Level of paraprotein
  • Abnormal free light chain ratio

Phase 3 (14 decks)

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