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Path Laz (condensed) (COPY) > Haem > Flashcards

Haem Flashcards

1
Q

List some examples of extra-vascular haemolysis.

A

Autoimmune haemolytic anaemia

Hereditary spherocytosis

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2
Q

List some examples of intra-vascular haemolysis.

A

Malaria

G6PD deficiency

Pyruvate kinase deficiency

Mismatched blood transfusion

MAHA

Paroxysmal nocturnal haemoglobinuria

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3
Q

What is the most common cause of intravascular haemolysis worldwide?

A

Malaria

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4
Q

List some consequences of haemolytic anaemia.

A

Anaemia

Erythroid hyperplasia

Increased folate demand

Susceptibility to parvovirus B19 infection

Propensity to gallstones

Increased risk of iron overload

Increased risk of osteoporosis

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5
Q

Why is parvovirus B19 infection dangerous in patients with haemolytic anaemia?

A

It infects erythroid cells in the bone marrow and arrests their maturation

If this happens in someone with shortened red cell survival, it can cause a dramatic drop in Hb (aplastic crisis)

NOTE: this can be identified by observing a low reticulocyte count

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6
Q

Why do people with haemolytic anaemia have an increased risk of developing gallstones?

A

Increased generation of bilirubin

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7
Q

List some laboratory features of haemolytic anaemia.

A

Anaemia

Increased reticulocytes

Polychromasia

Increased LDH

Increased bilirubin

Reduced/absent haptoglobins

Haemoglobinuria

Haemosiderinuria

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8
Q

What is polychromasia?

A

Red cells take up both eosinophilic and basophilic dye giving them a bluish appearance – this is due to the presence of reticulocytes

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9
Q

What is increased LDH a marker of?

A

LDH is an enzyme found in high concentrations within red cells

Increased LDH suggests intravascular haemolysis

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10
Q

What are haptoglobins? What is the significance of reduced haptoglobins?

A

Haptoglobins are proteins in the bloodstream that bind to and remove free haemoglobin from the bloodstream

Low haptoglobins suggests that there is a lot of free haemoglobin in the bloodstream

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11
Q

Which stains are used for haemosiderinaemia?

A

Perl’s stain

Prussian blue stain

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12
Q

What does the presence of haemoglobinuria and haemosiderinaemia imply?

A

Intravascular haemolysis

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13
Q

Describe the inheritance of hereditary spherocytosis.

A

75% family history (autosomal dominant)

25% de novo mutations

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14
Q

What is the hall mark of red cells in hereditary spherocytosis?

A

Osmotic fragility – red cells show increases sensitivity to lysis in hypotonic saline

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15
Q

What is another test for hereditary spherocytosis?

A

Reduced binding to eosin 5-maleimide (dye)

This is shown by flow cytometry

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16
Q

Describe the appearance of the blood film in hereditary spherocytosis.

A

The cells lack a central area of pallor because they have lost the biconcave shape

The cells are small and more densely stained

There may be polychromatic cells (due to the presence of a young red cell population)

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17
Q

Outline the blood film and FBC features of eliptocytosis.

A

The red cells are elliptical but there is no polychromasia and the blood count is likely to be normal because there is little haemolysis

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18
Q

Describe the inheritance pattern of G6PD deficiency.

A

X-linked recessive

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19
Q

List some triggers for haemolysis in G6PD deficiency.

A

Drugs (antimalarials, antibiotics, dapsone, vitamin K)

Infections

Fava beans

Naphthalene mothballs

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20
Q

Describe the appearance of the blood film in G6PD deficiency during acute haemolysis.

A

Contracted cells

Nucleated red cells

Bite cells

Hemighosts (Hb retracted to one side of the cell)

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21
Q

What is a Heinz body? What is it suggestive of?

A

Denatured haemoglobin

Suggestive of oxidative haemolysis

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22
Q

Which stain is used to look for Heinz bodies?

A

Methylviolet

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23
Q

What is a characteristic blood film feature of pyruvate kinase deficiency?

A

Echinocytes – red cells with a lot of short projections

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24
Q

What is a characteristic blood film feature of pyrimidine 5-nucleotidase deficiency?

A

Basophilic stippling

NOTE: this is also seen in lead poisoning because lead inhibits pyrimidine 5-nucleotidase

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25
Q

What are Ham’s test and flow cytometry for GPI-linked proteins used for?

A

Paroxysmal nocturnal haemoglobinuria

NOTE: Ham’s test looks at the sensitivity of red cells to lysis by acidified serum

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26
Q

Outline the principles of management of haemolytic anaemia.

A

Folic acid supplementation

Avoidance of triggers in G6PD deficiency

Blood transfusions/exchange

Immunisations against blood-borne viruses

Monitor for chronic complications (e.g. gallstones)

Splenectomy if needed

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27
Q

List some indications for splenectomy related to haemolytic anaemia.

A

Pyruvate kinase deficiency

Hereditary spherocytosis

Severe eliptocytosis/pyropoikilocytosis

Thalassemia syndromes

Autoimmune haemolytic anaemia

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28
Q

What is the main risk of splenectomy?

A

Overwhelming sepsis due to susceptibility to capsulated bacteria (e.g. pneumococcus)

NOTE: risk can be reduced by using penicillin prophylaxis and immunisations

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29
Q

List some specific criteria for splenectomy.

A

Transfusion dependence

Growth delay

Physical limitation

Hypersplenism (where it causes pooling and physical symptoms)

Age > 3 years and < 10 years

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30
Q

Which cell level does CML tend to occur in?

A

Pluripotent haematopoietic stem cell

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31
Q

Which cell level does AML tend to occur in?

A

Pluripotent haematopoietic stem cell or multipotent myeloid stem cell

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32
Q

Which chromosomal duplications are most commonly associated with AML?

A

8 and 21 (there is a predisposition seen in Down syndrome)

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33
Q

Which chromosomal aberration causes APML?

A

Translocation 15;17

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34
Q

What is a characteristic feature of APML? Why does this occur?

A

Haemorrhage – this is because APML is associated with DIC and hyperactive fibrinolysis

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35
Q

In what way are the promyelocytes in APML considered ‘abnormal’?

A

They contain multiple Auer rods

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36
Q

Describe how the variant version of APML is different from the original version.

A

The variant form has granules that are below the resolution of a light microscope

They also tend to have bilobed nuclei

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37
Q

Which microscopic feature is pathognomonic of myeloid leukaemias?

A

Auer rods

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38
Q

Which stain can be used to distinguish myeloid leukaemias from other leukaemias?

A

Myeloperoxidase, sudan black, non-specific esterase

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39
Q

List the clinical features of AML.

A

Bone marrow failure (anaemia, neutropaenia, thrombocytopaenia)

Local infiltration (splenomegaly, hepatomegaly, gum infiltration, lymphadenopathy, CNS, skin)

Hyperviscosity if WBC is very high (can cause retinal haemorrhages and exudates)

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40
Q

Outline the tests that may be used to diagnose AML.

A

Blood film

Bone marrow aspirate

Cytogenetic studies (done in EVERY patient)

Molecular studies and FISH

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41
Q

Outline the supportive care given for AML.

A

Red cells

Platelets

FFC/cryoprecipitate in DIC

Antibiotics

Allopurinol (prevent gout)

Fluid and electrolyte balance

Chemotherapy

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42
Q

List some determinants of prognosis in AML.

A

List some determinants of prognosis in AML.

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43
Q

What are the four phases of chemotherapy for ALL?

A

Remission induction

Consolidation and CNS therapy

Intensification

Maintenance

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44
Q

List some investigations used in the diagnosis of ALL.

A

FBC and blood film

Bone marrow aspirate

Immunophenotyping

Cytogenetic/molecular analysis

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45
Q

How long does chemotherapy for ALL usually take? Why is it longer in boys?

A

2-3 years

Longer in boys because the testes are a site of accumulation of lymphoblasts

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46
Q

Outline the supportive care for ALL.

A

Blood products

Antibiotics

General medical care (central line, gout management, hyperkalaemia management, sometimes dialysis)

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47
Q

List some pro-coagulant factors in the body.

A

Platelets

Endothelium

vWF

Coagulation cascade

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48
Q

List some anti-coagulant factors in the body.

A

Fibrinolysis

Anti-thrombins

Protein C/S

Tissue factor pathway inhibitor

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49
Q

What is the life span of platelets?

A

10 days

NOTE: this is important because it means that the effect of antiplatelet drugs lasts for 10 days after stopping the drug

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50
Q

What are the two ways in which platelets can adhere to sub-endothelial structures?

A

DIRECTLY – via GlpIa

INDIRECTLY – via binding of GlpIb to vWF (this is MORE IMPORTANT)

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51
Q

Which factors, released by platelets after adhesion, promote platelet aggregation?

A

Thromboxane A2

ADP

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52
Q

Describe the effects of aspirin and other NSAIDs on the arachidonic acid pathway.

A

Aspirin is an irreversible COX inhibitor

Other NSAIDs reversibly inhibit COX

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53
Q

What is the rate-limiting step for fibrin formation?

A

Factor 10a

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54
Q

What are the effects of thrombin?

A

Activates fibrinogen

Activates platelets

Activates profactors (factor 5 and 8)

Activates zymogens (factor 7, 11 and 13)

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55
Q

Name the complex that is responsible for activating prothrombin to thrombin.

A

Prothrombinase complex

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56
Q

What is required for adequate production/absorption of vitamin K?

A

Bacteria in the gut produce vitamin K

It is fat-soluble so bile is needed for vitamin K to be absorbed

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57
Q

What is the most common cause of vitamin K deficiency?

A

Warfarin

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58
Q

Name two factors that convert plasminogen to plasmin.

A

Tissue plasminogen activator

Urokinase

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59
Q

Name two factors that directly inhibit plasmin.

A

Alpha-2 antiplasmin

Alpha-2 macroglobulin

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60
Q

What is the role of thrombin-activatable fibrinolysis inhibitor (TAFI)?

A

Inhibitor of fibrin breakdown

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61
Q

Describe the action of antithrombins.

A

Bind to thrombin in a 1:1 ratio and this complex is excreted in the urine

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62
Q

How many types of antithrombin are there?

A

Five (antithrombin-III is the most active)

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63
Q

What is the most thrombogenic hereditary condition?

A

Antithrombin deficiency

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64
Q

Why does Factor V Leiden cause a prothrombotic state?

A

The factor 5a will be resistant to breakdown by protein C

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65
Q

What is the role of tissue factor pathway inhibitor?

A

TFPI neutralises the tissue factor-factor 7a complex once it has initiated the clotting cascade

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66
Q

List some genetic defects that cause excessive bleeding.

A

Platelet abnormalities

Vessel wall abnormalities

Clotting factor deficiencies

Excess clot breakdown

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67
Q

List some acquired defects that cause excessive bleeding.

A

Liver disease

Vitamin K deficiency

Autoimmune diseases (platelet destruction)

Trauma

Anti-coagulants/anti-platelets

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68
Q

What is the difference between immediate and delayed bleeding with regards to the underlying pathological process?

A

Immediate – issue with the primary haemostatic plug (platelets, endothelium, vWF)

Delayed – issue with the coagulation cascade

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69
Q

Describe the key clinical differences between platelet disorders and coagulation factor disorders.

A

Platelet disord

· Bleeding from skin and mucous membranes

· Petechiae

· Small, superficial ecchymoses

· Bleeding after cuts and scratches

· Bleeding immediately after surgery/trauma

· Usually mild

Coagulation factor disorders

· Bleeding into soft tissues, joints and muscles

· No Petechiae

· Large, deep ecchymoses

· Haemarthroses

· No bleeding from cuts and scratches

· Delayed bleeding from surgery or trauma

· Often SEVERE

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70
Q

What can cause immune-mediated thrombocytopaenia?

A

Idiopathic

Drug-induced (e.g. quinine, rifampicin)

Connective tissue disorder (e.g. SLE)

Lymphoproliferative disease

Sarcoidosis

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71
Q

List two non-immune mediated conditions that cause thrombocytopaenia.

A

DIC

MAHA

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72
Q

What are the main differences between acute and chronic ITP?

A

Acute

· Mainly children

· Usually there is a preceding infection

· Abrupt onset of symptoms

· Lasts 2-6 weeks

· Spontaneously resolves

Chronic

· Mainly occurs in adults

· More common in females

· Can be abrupt or indolent

· Does not resolve spontaneously

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73
Q

How is ITP treated?

A

Mainly with steroids and IVIG based on the platelet count

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74
Q

Give some examples of causes of thrombocytopaenia that can be diagnosed by blood film.

A

Vitamin B12 deficiency

Acute leukaemia

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75
Q

What clotting study abnormality would be seen in Haemophilia?

A

Prolonged APTT

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76
Q

Outline the clinical features of haemophilia.

A

Haemarthroses (MOST COMMON)

Soft tissue haematomas (e.g. shortened tendons, muscle atrophy)

Prolonged bleeding after surgery/dental extractions

NOTE: haemophilia A and B are clinically indistinguishable

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77
Q

What is a typical lesion seen in coagulation factor disorders?

A

Ecchymoses

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78
Q

What is the most common coagulation disorder? What is its inheritance pattern?

A

Von Willebrand disease

Autosomal dominant – type 1 and 2

Autosomal recessive – type 3

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79
Q

What is the main clinical feature in von Willebrand disease?

A

Mucocutaneous bleeding

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80
Q

Outline the classification of von Willebrand disease.

A

Type 1 – partial quantitative deficiency

Type 2 – qualitative deficiency

Type 3 – complete quantitative deficiency

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81
Q

Describe the expected laboratory test results for the three types of von Willebrand disease.

A

Type 1 – low antigen, low activity, normal multimer

Type 2 – normal antigen, low activity, normal multimer

Type 3 – very low antigen, very low activity, absent multimer

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82
Q

Name a source of vitamin K.

A

Green vegetables

Vitamin K is synthesised by intestinal flora

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83
Q

List some causes of DIC.

A

Sepsis (MOST COMMON)

Trauma (e.g. fat embolism)

Obstetric complications (e.g. amniotic fluid embolism)

Malignancy

Vascular disorders

Reaction to toxin

Immunological (e.g. transplant rejection)

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84
Q

Describe the typical clotting study results in DIC.

A

Prolonged APTT and PT

Prolonged TT

Decreased fibrinogen

Increased FDP

Decreased platelets

Schistocytes (due to shearing of red blood cells as it passes through a fibrin mesh)

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85
Q

Outline the treatment of DIC.

A

Treat underlying disorder

Anticoagulation with heparin

Platelet transfusion

FFP

Coagulation inhibitor concentrate

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86
Q

What are Janus Kinases?

A

A family of four tyrosine kinase receptors associated with haemopoietic cell growth factor receptors

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87
Q

What is a chronic myeloproliferative disorder?

A

A group of clonal disorders of haemopoietic stem cells characterised by the overproduction of one or more mature myeloid cellular elements in the blood

There is a trend towards increased fibrosis in the bone marrow

Some cases will develop into acute leukaemia

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88
Q

Outline the usual presentation of myeloproliferative disorders.

A

Preponderance to thrombosis

Splenomegaly

Haemorrhage

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89
Q

List some chronic myeloproliferative disorders.

A

Polycythaemia vera

Essential thrombocythaemia

Idiopathic myelofibrosis

Idiopathic erythrocytosis

Chronic granulocytic leukaemia

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90
Q

Describe the clinical presentation of polycythaemia vera.

A

Incidental finding

Symptoms of hyperviscosity (headaches, visual disturbances, fatigue, dyspnoea)

Increased histamine release (Aquagenic pruritus, peptic ulceration)

Splenomegaly

Plethora

Erythromelalgia (red painful extremities)

Thrombosis

Retinal vein engorgement

Gout

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91
Q

Describe the appearance of a bone marrow biopsy in polycythaemia vera.

A

Increased cellularity (mainly erythroid cells)

Slight reticulin fibrosis and megakaryocyte abnormalities

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92
Q

What investigation finding is considered diagnostic of polycythaemia vera?

A

Presence of JAK 2 V617F mutation

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93
Q

Which other JAK mutation is a significant finding and which condition is it associated with?

A

Exon 12 mutation

It is associated with idiopathic erythrocytosis

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94
Q

What are some causes of JAK 2 V617F negative polycythaemia?

A

Pseudopolycythaemia

True polycythaemia that is secondary to increased EPO (e.g. hypoxia, renal disease, tumours)

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95
Q

What is idiopathic erythrocytosis?

A

Isolated erythrocytosis with low EPO

Treated with venesection only

NO JAK 2 V617F mutation, but some cases will have an exon 12 mutation

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96
Q

Outline the prognosis of idiopathic erythrocytosis and polycythaemia vera.

A

Idiopathic erythrocytosis – no adverse prognosis if Hct is maintained

Polycythaemia vera – most survive 10 years, causes of death include thrombosis, leukaemia and myelofibrosis

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97
Q

What is essential thrombocythaemia?

A

Myeloproliferative disorder mainly involving the megakaryocyte lineage (platelet count > 600 x 109/L)

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98
Q

What proportion of essential thrombocythaemia patients have JAK 2 mutations?

A

50%

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99
Q

Outline the treatment options for essential thrombocythaemia.

A

Aspirin

Anagrelide (specific inhibitor of platelet formation – may accelerate myelofibrosis)

Hydroxycarbamide (MAIN TREATMENT – may be leukaemogenic)

Alpha-interferon (may be used in patients < 40 years)

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100
Q

Describe the prognosis of essential thrombocythaemia.

A

Normal life span

Leukaemic transformation in about 5% of patients after 10 years

Myelofibrosis is uncommon

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101
Q

Define chronic idiopathic myelofibrosis.

A

A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haemopoiesis

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102
Q

Describe the typical clinical presentation of myelofibrosis.

A

Incidental finding

Cytopaenias

Thrombocytosis

Splenomegaly (can be MASSIVE)

Hepatomegaly

FLAWS

Gout

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103
Q

Describe the two stages of myelofibrosis.

A

Pre-fibrotic = blood changes are mild with hypercellular marrow

Fibrotic = splenomegaly, blood changes, dry tap, prominent fibrosis and later osteosclerosis

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104
Q

Describe the appearance of myelofibrosis on a blood film.

A

Leukoerythroblastic picture

Tear drop poikilocytes

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105
Q

What are some features of the bone marrow in myelofibrosis?

A

Dry tap

Trephine biopsy will show increased reticulin or collagen fibrosis, prominent megakaryocyte hyperplasia and new bone formation

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106
Q

Outline the treatment options for myelofibrosis.

A

Symptomatic treatment (e.g. transfusions for anaemia)

Splenectomy

Cytoreductive therapy (hydroxycarbamide and thalidomide)

Bone marrow transplant (in younger patients)

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107
Q

Describe the prognosis of myelofibrosis.

A

Median 3-5 year survival

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108
Q

Which types of cancer are associated with causing secondary polycythaemia?

A

Renal cell carcinoma

Liver cancer

Due to the production of EPO

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109
Q

What are the typical laboratory findings of iron deficiency anaemia?

A

Low ferritin

Low transferrin saturation

High TIBC

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110
Q

What is leucoerythroblastic anaemia?

A

Anaemia characterised by the presence of red and white cell precursors

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111
Q

What are the morphological features of leucoerythroblastic anaemia seen on blood film?

A

Tear drop red blood cells (aniso- and poikilocytosis)

Nucleated RBCs

Immature myeloid cells

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112
Q

What does leucoerythroblastic anaemia tend to be caused by?

A

Bone marrow infiltration (leukaemia, lymphoma, myeloma, solid tumours, myelofibrosis, military TB, severe fungal infection)

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113
Q

Which test distinguishes immune-mediated and non-immune mediated haemolytic anaemia?

A

DAT or Coombs’ test

DAT +ve means that the haemolytic anaemia is mediated through immune destruction of red cells

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114
Q

What morphological change is seen on the blood film of patients with autoimmune haemolytic anaemia?

A

Spherocytes

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115
Q

List some causes of non-immune haemolytic anaemia.

A

Infection (e.g. malaria)

Microangiopathic haemolytic anaemia (MAHA)

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116
Q

List some key features of MAHA.

A

Usually caused by underlying adenocarcinoma

Red cell fragments

Low platelets

DIC/bleeding

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117
Q

Outline the mechanism of MAHA.

A

An underlying adenocarcinoma produces procoagulant cytokines that activate the coagulation cascade

This leads to DIC and the formation of fibrin strands in various parts of the microvasculature

Red cells will be pushed through these fibrin strands and fragment

NOTE: always consider underlying adenocarcinoma in any patient presenting with MAHA

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118
Q

What is the main difference seen in the blood film of patients with acute and chronic leukaemia?

A

Chronic – mature white cells are raised

Acute – immature blast cells are raised

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119
Q

List some causes of neutrophilia.

A

Corticosteroids (due to demargination)

Underlying neoplasia

Tissue inflammation (e.g. colitis, pancreatitis)

Myeloproliferative/leukaemia disorder

Infection

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120
Q

List some infections that characteristically do not cause neutrophilia.

A

Brucella

Typhoid

Many viral diseases

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121
Q

List some key features of a reactive neutrophilia on a blood film.

A

Band cells (presence of immature neutrophils (band cells) show that the bone marrow has been signalled to release more WBCs)

Toxic granulation

Clinical signs of infection/inflammation

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122
Q

What are some key blood film and clinical features suggestive of a myeloproliferative disorder?

A

Neutrophilia

Basophilia

Immature myelocytes

Splenomegaly

NOTE: you may see raised Hb and raised platelets in CML if it affects those lineages

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123
Q

What are some key blood film features suggestive of AML?

A

Neutrophilia

Myeloblasts

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124
Q

List some causes of monocytosis.

A

Bacteria: TB, Brucella, typhoid

Viral: CMV, VZV

Sarcoidosis

Chronic myelomonocytic leukaemia

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125
Q

List some causes of reactive eosinophilia.

A

Parasitic infection

Allergy (e.g. asthma, rheumatoid arthritis)

Underlying neoplasms (e.g. Hodgkin’s lymphoma, T cell lymphoma, NHL)

Drug reaction (e.g. erythema multiforme)

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126
Q

Which gene mutation causes chronic eosinophilic leukaemia?

A

FIP1L1-PDGFRa fusion gene

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127
Q

Which type of virus typically causes basophilia?

A

Pox viruses

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128
Q

List some causes of reactive lymphocytosis.

A

Infection (EBV, CMV, toxoplasmosis, rubella, HSV)

Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia)

Sarcoidosis

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129
Q

How would the lymphocytes seen on a blood film due to a viral infection be different from leukaemia/lymphoma?

A

Viral infection: reactive or atypical lymphocytes (EBV)

CLL or NHL: small lymphocytes and smear cells

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130
Q

What is light chain restriction?

A

An individual B cell will either express kappa or lambda light chains (not both)

In response to an infection, you will get a polyclonal B cell response so there will be a roughly even mixture of kappa and lambda light chains

In lymphoproliferative disorders, monoclonal proliferation of a B cell expressing only one type of light chain (e.g. kappa) will mean that the proportion of kappa relative to lambda will increase (e.g. showing an overwhelming majority of kappa)

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131
Q

What percentage of hospital deaths are caused by PE?

A

5-10%

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132
Q

List some anticoagulant molecules produced by the endothelium.

A

Thrombomodulin

Endothelial protein C receptor

Tissue factor pathway inhibitor

Heparans

NOTE: it does not normally produce tissue factor

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133
Q

Which antiplatelet factors are produced by the endothelium?

A

NO

Prostacyclin

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134
Q

What is the mechanism of action of heparin?

A

Increases anticoagulant activity by potentiating anti-thrombin III

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135
Q

How is unfractionated heparin monitored?

A

It has variable pharmacokinetics and a variable dose-response

Must be monitored with APTT or anti-Xa levels

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136
Q

How can the action of warfarin be reversed?

A

Administering vitamin K – takes 12 hours

Giving factors 2, 7, 9 and 10 – immediate

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137
Q

What is the antidote for heparin?

A

Protamine

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138
Q

Describe the gender difference regarding the risk of recurrent of VTE.

A

Men have a greater risk of recurrence

NOTE: proximal thrombosis has a higher rate of recurrence than distal thrombosis

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139
Q

What should all patients > 60 years old with idiopathic thromboembolic disease be offered?

A

CT scan to check for an underlying cause

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140
Q

Define myelodysplastic syndrome.

A

Biologically heterogenous group of acquired haematological stem cell disorders. elderly pts

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141
Q

What are the key characteristics of myelodysplastic syndromes?

A

Development of a clone of marrow stem cell with abnormal maturation resulting in functionally defective blood cells and a reduction in cell counts

This leads to cytopaenia, functional abnormalities of cell maturation and an increased risk of transformation to leukaemia

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142
Q

How do myelodysplastic syndromes typically present?

A

Symptoms/signs of bone marrow failure developing over weeks/months

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143
Q

List and describe some blood and bone marrow features of myelodysplastic syndromes.

A

Pelger-Huet anomaly (bilobed neutrophils)

Dysgranulopoiesis of neutr7ophils (failure of granulation)

Dyserythropoiesis of red blood cells (lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of precursor red cells)

Dysplastic megakaryocytes (micro-megakaryocytes)

Increased proportion of blast cells in the bone marrow (normally < 5%)

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144
Q

What might you see if you stained for iron in the bone marrow of a patient with a myelodysplastic syndrome?

A

Ringed sideroblasts (accumulation of iron around the nuclei of red blood cell precursors)

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145
Q

What is the presence of myeloblasts with Auer rods suggestive of?

A

Acute myeloid leukaemia

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146
Q

List some factors that are taken into account when classifying types of myelodysplastic syndrome.

A

Cell lineage affected

Blast cell proportions

Cytogenetics

Presence of ringed sideroblasts

Cytopaenias

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147
Q

What are the five prognostic variables that are used to calculate prognostic risk using the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes?

A

Bone marrow blast percentage

Karyotype

Haemoglobin

Platelets

Neutrophils

NOTE: high risk is considered a score > 6, low risk < 1.5

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148
Q

What are the usual causes of death in patients with myelodysplasia?

A

1/3 infection

1/3 bleeding

1/3 leukaemia

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149
Q

What are the two treatments that can prolong life in myelodysplastic syndromes?

A

Allogeneic stem cell transplantation

Intensive chemotherapy

NOTE: as most MDS patients are elderly, they often cannot tolerate treatment

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150
Q

List some other treatments that may be used in myelodysplastic syndromes.

A

Supportive Care (blood products, antimicrobials, growth factors (e.g. EPO, GM-CSF))

Biological modifiers

· Immunosuppression

· Azacytidine (hypomethylating agent)

· Decitabine

· Lenalidomide (used in 5q minus syndrome)

Oral chemotherapy (e.g. hydroxyurea)

Low-dose chemotherapy (SC low-dose cytarabine)

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151
Q

List some causes of primary bone marrow failure.

A

Fanconi anaemia (multipotent stem cell)

Diamond-Blackfan syndrome (red cell progenitor)

Kostmann syndrome (neutrophil progenitor)

Acquired: idiopathic aplastic anaemia (multipotent stem cell)

152
Q

List some secondary causes of bone marrow failure.

A

Marrow infiltration

Haematological malignancies

Solid tumours spreading to bone marrow

Radiation

Drugs

Chemicals (e.g. benzene)

Autoimmune

Infection (e.g. parvovirus B19)

153
Q

List some drugs that can cause bone marrow failure.

A

Cytotoxic drugs (predictable, dose-dependent)

Phenylbutazone, Gold salts (idiosyncratic, rare)

Antibiotics – chloramphenicol, sulphonamides

Diuretics – thiazide

Antithyroid drugs – carbimazole

154
Q

What is the most common cause of aplastic anaemia?

A

Idiopathic (70-80%)

155
Q

List some inherited causes of aplastic anaemia.

A

Fanconi anaemia

Schwachman-Diamond syndrome

Dyskeratosis Congenita

156
Q

What are some investigative features of aplastic anaemia?

A

Peripheral blood – cytopaenia

Bone marrow – hypocellular

157
Q

List some differential diagnosis for pancytopaenia and hypocellular marrow.

A

Hypoplastic MDS/AML

Hypocellular ALL

Hairy cell leukaemia

Atypical mycobacterial infection

Anorexia nervosa

ITP (although Hb and RBC will be normal)

158
Q

What is the Camitta criteria for severe aplastic anaemia?

A

2 out of 3 peripheral blood features:

· Reticulocytes < 1% (< 20 x 109/L)

· Neutrophils < 0.5 x 109/L

· Platelets < 20 x 109/L

Bone marrow cellularity < 25%

159
Q

How might the age of the patient influence decisions regarding their management?

A

Immunosuppressive therapies tend to be used in older patients

SCT tends to be used in younger patients (80% cure rate)

160
Q

What is the most common cause of inherited aplastic anaemia?

A

Fanconi anaemia

161
Q

What is the inheritance pattern of Fanconi anaemia?

A

Autosomal Recessive or X-linked Recessive

162
Q

List some somatic abnormalities that are seen in Fanconi anaemia.

A

Short stature

Hypopigmented spots/café-au-lait spots

Abnormality of thumbs

Microcephaly or hydrocephaly

Hypogonadism

Developmental delay

NOTE: these are only present in 70% of patients

163
Q

List some complications of Fanconi anaemia.

A

Aplastic anaemia (90%)

Myelodysplasia

Leukaemia

Cancer (epithelial)

Liver disease

164
Q

What are the characteristic features of dyskeratosis congenita?

A

Bone marrow failure

Cancer predisposition

Somatic abnormalities

165
Q

What are the three main somatic features of dyskeratosis congenita?

A

Abnormal skin pigmentation

Nail dystrophy

Leukoplakia

166
Q

Which genes are involved in dyskeratosis congenita and what are the inheritance patterns?

A

X-linked recessive (MOST COMMON) – DKC1 gene (defective telomere functioning)

Autosomal dominant – TERC (RNA components of telomerase)

Autosomal recessive – no mutation identified

NOTE: abnormal telomeric structure and function is heavily implicated in dyskeratosis congenita

167
Q

Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.

A

NHL = 80%

Hodgkin = 20

168
Q

List some oncogenes that are implicated in lymphoma/leukaemia.

A

Bcl2

Bcl6

Cyclin D1

c-Myc

169
Q

List some examples of how constant antigenic stimulation can lead to lymphoma.

A

H. pylori à gastric MALT marginal zone NHL of the stomach

Sjogren syndrome à marginal zone NHL of the parotid

Coeliac disease à small bowel T cell lymphoma, enteropathy-associated T cell NHL

170
Q

List two examples of viral infections that can lead to lymphoma.

A

Direct viral integration: HTLV1

· HTLV1 infects T cells by vertical transmission

· May cause adult T cell leukaemia/lymphoma (very aggressive)

· Caused by viral genome integrating into T cell genome and driving proliferation

EBV infection and immunosuppression

· EBV established latent infection in B cells which is kept in check by cytotoxic T cell (kill EBV antigen-expressing B cells)

· Loss of T cell function (e.g. HIV, post-transplant immunosuppression) can lead to EBV-driven lymphoma

171
Q

What are the main markers used for B and T cells?

A

T cell = CD3, CD5

B cell = CD20

172
Q

Outline the WHO classification of lymphoma.

A

Hodgkin lymphoma

· Classical

· Lymphocyte predominant

Non-Hodgkin lymphoma

· B cell (MOST COMMON)

o Precursor B cell neoplasm

o Peripheral B cell neoplasm (low and high grade)

· T cell

o Precursor T cell neoplasm

o Peripheral T cell neoplasm

173
Q

Give an example of a chromosomal translocation that is diagnostic of lymphoma.

A

11;14 = Mantle Cell Lymphoma

174
Q

Give an example of a chromosomal translocation that is prognostic in lymphoma.

A

2;5 = anaplastic large cell lymphoma

175
Q

List some types of low grade lymphoma.

A

Follicular lymphoma

Small lymphocytic lymphoma (CLL)

Marginal zone lymphoma

Mantle cell lymphoma

176
Q

Name a type of intermediate grade lymphoma.

A

Burkitt’s lymphoma

177
Q

Name a type of high grade lymphoma.

A

Diffuse large B cell lymphoma

178
Q

Describe the histological features of follicular lymphoma.

A

Follicular pattern – the follicles are neoplastic and spread from the node into adjacent tissues

Cells have a germinal centre cell origin (positive staining for CD10 and Bcl6)

179
Q

Describe the typical presentation of small lymphocytic lymphoma.

A

Lymphadenopathy or high blood lymphocyte count in middle-aged or elderly patients

180
Q

Outline the histological features of small lymphocytic lymphoma.

A

Small lymphocytes

Arise form naïve B cells or post-germinal centre memory B cells

Cells are CD5 and CD23 positive

They replace the entire lymph node so that you can no longer identify follicles or T cell areas

181
Q

What is marginal zone lymphoma?

A

Arise mainly in extra-nodal sites (e.g. gut, spleen)

Thought to arise due to chronic antigenic stimulation

Arise from post-germinal centre memory B cells

Low-grade disease can be treated by non-chemotherapeutic methods (e.g. H. pylori eradication)

182
Q

Outline the typical presentation of mantle cell lymphoma.

A

Typically affects middle-aged males

Affects lymph nodes and the GI tract

Often present with disseminated disease

NOTE: median survival = 3-5 years

183
Q

Outline the key histological features of mantle cell lymphoma.

A

Located in the mantle zone of the lymph node

Arise from pre-germinal centre cells

Show aberrant expression of cyclin D1 and CD5

184
Q

Outline the typical presentation of Burkitt’s lymphoma.

A

Jaw or abdominal mass in children and young adults

Associated with EBV

NOTE: this is very aggressive

185
Q

Outline the histological features of Burkitt’s lymphoma.

A

Arises from germinal centre cells

Starry sky appearance

186
Q

Outline the typical presentation of diffuse large B cell lymphoma.

A

Middle-aged and elderly patients with lymphadenopathy

187
Q

Outline the histological features of diffuse large B cell lymphoma.

A

Arise from germinal centre or pre-germinal centre B cells

Large lymphoid cells

Lymph node is effaced so follicles and germinal centres cannot be identified

188
Q

List some prognostic association of diffuse large B cell lymphoma.

A

Good prognosis – germinal centre phenotype

Poor prognosis – p53-positive and high proliferation fraction

189
Q

Outline the typical presentation of T cell lymphomas.

A

Middle-aged and elderly patients with lymphadenopathy

NOTE: these are aggressive

190
Q

Outline some key histological features of T cell lymphomas.

A

Large T lymphocytes

Associated reactive cell population (especially eosinophils)

191
Q

List some types of T cell lymphoma and their associations.

A

Adult T cell leukaemia/lymphoma – HTLV1

Enteropathy-associated T cell lymphoma – Coeliac disease

Cutaneous T cell lymphoma (mycosis fungoides)

Anaplastic large cell lymphoma

192
Q

Outline the typical presentation of anaplastic large cell lymphoma.

A

Children and young adults with lymphadenopathy

NOTE: this is aggressive

193
Q

Outline the key histological features of anaplastic large cell lymphoma.

A

Large epithelioid lymphocytes

T cell or null phenotype (anaplastic)

194
Q

List some key differences between Hodgkin and Non-Hodgkin Lymphoma.

A

Hodgkin is more localised (usually one nodal site)

Hodgkin spreads contiguously to adjacent lymph nodes

NOTE: NHL tends to involve multiple lymph node sites and spread discontinuously

195
Q

Outline some histological features of classical Hodgkin lymphoma.

A

Nodular sclerosis

Mixed cell population of Reed-Sternberg cells

Lymphoma cells are few in number and are scattered around

Eosinophils

Arise from germinal centre or post-germinal centre cells

196
Q

What are the diagnostic markers for Hodgkin lymphoma?

197
Q

Describe the typical presentation of nodular lymphocyte predominant Hodgkin lymphoma.

A

Isolated lymphadenopathy

NO association with EBV

198
Q

Outline the key histological features of lymphocyte predominant Hodgkin lymphoma.

A

B cell rich nodules

Scattered around L&H cells

Reactive population in the background consisting of small lymphocytes

NO eosinophils and macrophages

199
Q

Which markers are key in the diagnosis of lymphocyte predominant Hodgkin lymphoma?

A

Positive = CD20

Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)

200
Q

Which chemotherapy regimen is usually used for Hodgkin lymphoma?

A

ABVD: Adriamycin, Bleomycin, Vincristine, Dacarbazine

NOTE: this is usually given at 4-weekly intervals for 2-6 cycles

201
Q

What are some possible long-term consequences of chemotherapy for Hodgkin lymphoma?

A

Pulmonary fibrosis

Cardiomyopathy

202
Q

How might a relapse of Hodgkin lymphoma be treated?

A

High-dose chemotherapy

Autologous stem cell transplant

NOTE: intensifying chemotherapy will lead to an increased cure rate but it will also lead to an increase in secondary cancers

203
Q

What proportion of lymphomas are Non-Hodgkin Lymphoma?

204
Q

What is the fastest growing human cancer?

A

Burkitt’s lymphoma

205
Q

Describe the typical presentation of Non-Hodgkin lymphoma.

A

Painless lymphadenopathy

Compression symptoms

B symptoms

206
Q

What are some important tests to perform in non-Hodgkin lymphoma and why are they important?

A

LDH – marker of cell turnover

HIV serology – HIV can predispose to NHL (HTLV1 serology may also be important)

Hepatitis B serology – NHL treatment may deplete B cells resulting in fulminant liver failure due to reactivation of hepatitis B in chronic carriers

207
Q

What are the two most common types of non-Hodgkin lymphoma?

A

Diffuse large B cell lymphoma (DLBCL) (40%)

Follicular lymphoma (35%)

208
Q

Which factors are taken into account by the international prognostic index (IPI) for lymphoma?

A

Age > 60

High LDH

Performance status 2-4

Stage III or IV

More than one extranodal site

209
Q

What treatment option may be considered for patients with diffuse large B cell lymphoma who relapse?

A

Autologous stem cell transplantation

210
Q

What is the usual first-line treatment approach to follicular lymphoma?

A

Watch and wait

Only treat it clinically indicated (e.g. compression symptoms, massive nodes, recurrent infection)

211
Q

Which genetic abnormality is associated with follicular lymphoma?

A

T(14;18) – resulting in over-expression of Bcl2 (which is an anti-apoptosis gene)

NOTE: follicular lymphoma is incurable but is indolent

212
Q

List some diseases that can lead to marginal zone lymphoma.

A

H. pylori infection – gastric MALToma

Sjogren’s syndrome – parotid lymphoma

Hashimoto’s thyroiditis – thyroid lymphoma

Psittaci infection – lacrimal gland

213
Q

Where is marginal zone lymphoma most commonly seen and how does it tend to present?

A

Usually in the stomach

Presenting with dyspepsia or epigastric pain

Usually Stage 1[E] (E = extranodal)

B symptoms are uncommon

214
Q

What are the main features of enteropathy-associated T cell lymphoma?

A

Mature T cells

Involves small intestines

Aggressive

Caused by chronic antigenic stimulation by gliadin/gluten

215
Q

Describe the typical presenting features of enteropathy-associated T cell lymphoma.

A

Abdominal pain/obstruction/bleeding/perforation

Malabsorption

Systemic symptoms

216
Q

Why is it important to prevent EATL by following a strict gluten-free diet?

A

EATL responds poorly to chemotherapy and is usually fatal

217
Q

What is the most common leukaemia in the Western world?

A

Chronic lymphocytic leukaemia

218
Q

What are the typical laboratory findings in a patient with CLL?

A

Lymphocytosis

Smear cells

Normocytic normochromic anaemia

Thrombocytopaenia

Bone marrow lymphocytic replacement of normal marrow elements

NOTE: it is indolent so is often only picked up on routine blood tests

219
Q

What distinctive antigen phenotype (presence and absence) is suggestive of Mature B cells

A

CD19 positive

CD5 negative

220
Q

What distinctive antigen phenotype (presence and absence) is suggestive of Mature T cells

A

CD19 negative

CD5 positive

CD3 positive

CD4 or CD8 positive

221
Q

Which antigen phenotype is suggestive of CLL?

A

CD5+ B cells (i.e. CD19+ and CD5+)

NOTE: this could potentially also be mantle cell lymphoma

222
Q

Which staging system is used for CLL?

A

Rai and Binet

Binet: stages A-C depending on number of lymphoid areas (< or > 3, Hb and platelets)

223
Q

Which laboratory tests are used in CLL to help gauge prognosis?

A

CD38 expression (associated with poor prognosis)

Cytogenetics (FISH)

Immunoglobulin gene mutation status (IgH mutated or unmutated)

224
Q

How does VH gene mutations affect prognosis?

A

Unmutated = poor prognosis

Mutated = better prognosis

225
Q

What is an important chromosomal abnormality in CLL that is tested for using FISH?

A

Deletion of 17p (Tp53)

This is part of the p53 tumour suppressor gene

This deletion is associated with a poor prognosis

226
Q

Describe the immunoglobulin levels you would expect to see in CLL?

A

Hypogammaglobulinaemia

Because the malignant B cells are suppressing antibody production by other B cells

227
Q

What is the term used to describe CLL changing into a high grade lymphoma?

A

Richter transformation – 1% risk per year

228
Q

What are some supportive measures used in the treatment of CLL?

A

Vaccination (flu, pneumococcus)

Infection prophylaxis and treatment (may include aciclovir, PCP prophylaxis, IVIG)

229
Q

How would autoimmune cytopaenias caused by CLL be treated?

A

Steroids

NOTE: 2nd line is rituximab

230
Q

What is the first line treatment for TP53 intact CLL?

A

FCR – Fludarabine, Cyclophosphamide, Rituximab

NOTE: less intensive options may include, rituximab and bendamustine or obinutuzumab (anti-CD20) and chlorambucil (alkylating agent)

231
Q

Under what conditions might CLL be considered high risk?

A

Patients with TP53/17p deletion

Refractory disease or early relapse (< 24 months)

232
Q

What are some newer treatment options for high risk CLL?

A

Bruton Tyrosine Kinase Inhibitors – ibrutinib, idelalisib

Bcl2 Inhibitors – venetoclax

CAR-T therapy

233
Q

How can myeloproliferative neoplasms be broadly categorised?

A

Philadelphia positive: CML

Philadelphia negative: polycythaemia vera, essential thrombocythaemia, primary myelofibrosis

234
Q

Outline the typical presentation of primary myelofibrosis.

A

Cytopaenias (anaemia, thrombocytopaenia)

Thrombosis

MASSIVE splenomegaly

Hepatomegaly

Hypermetabolic state (FLAWS)

235
Q

What might you expect to see in the blood film of a patient with primary myelofibrosis?

A

Leucoerythroblastic picture

Tear drop poikilocytes

Giant platelets

Circulating megakaryocytes

236
Q

What are some bad prognostic features in primary myelofibrosis?

A

Severe anaemia

Thrombocytopaenia

Massive splenomegaly

NOTE: median survival is 3-5 years

237
Q

What might you expect to see in the FBC of a patient with CML?

A

Leucocytosis (MASSIVE)

Normal or raised Hb and platelets

238
Q

What would you expect to see in abundance in the blood film of a patient with CML?

A

Neutrophils

Basophils

Myelocytes (NOT blasts)

NOTE: myelocytes are immature myeloid cells that are NOT blasts (analogous to reticulocytes for red blood cells)

239
Q

Briefly describe the natural history of CML before targeted treatment because available?

A

5-6 years stable phase

6-12 months accelerated phase

3-6 months blast crisis

240
Q

What is the Philadelphia chromosome?

A

CML is caused by a translocation between 9;22 producing a derivative chromosome, 22q, which is called the Philadelphia chromosome

241
Q

List some normal FBC changes that you would expect to see in pregnancy.

A

Mild anaemia (net dilution due to increased plasma volume)

High MCV (NOTE: could be caused by B12 and folate deficiency)

High neutrophils

Low platelets

242
Q

What is the recommended daily intake of iron in pregnancy?

243
Q

How much does the platelet count tend to drop by in pregnancy?

A

Roughly 10%

NOTE: there is an increase in platelet size

244
Q

Why is epidural anaesthesia a risk in patients with thrombocytopaenia and at what platelet count would this be considered dangerous?

A

Can cause spinal haematoma

A platelet count > 70 x 109/L is required

245
Q

How is ITP in pregnancy treated?

A

IVIG

Steroids

Anti-D (if RhD-negative)

246
Q

How might the baby be affected by ITP?

A

Unpredictable degree of penetration

Check cord blood

Platelet count may fall for 5 days after delivery

Bleeding may occur in 25% of those severely affected

Usually a normal delivery (but avoid forceps, ventouse)

247
Q

How is the relative risk of thromboembolic disease in pregnancy different from the general population?

248
Q

List some other conditions in pregnancy that can increase the risk of thromboembolic disease.

A

Hyperemesis/dehydration

Pre-eclampsia

Obesity

Thrombophilia

Age (> 35 years)

Parity

Multiple pregnancy

Ovarian hyperstimulation (IVF)

249
Q

How long should be left after the last heparin dose before an epidural can be performed?

A

24 hrs = treatment dose heparin

12 hrs = prophylactic dose heparin

NOTE: there is a hypothesis that thrombosis tendency in pregnancy is associated with impaired placental circulation

250
Q

What are the key features of antiphospholipid syndrome?

A

Recurrent miscarriage

DVT/PE

Thrombocytopaenia

251
Q

Which antibodies are present in antiphospholipid syndrome?

A

Lupus anticoagulant

Anticardiolipin antibodies

252
Q

How might miscarriage in women with antiphospholipid syndrome be treated?

A

Aspirin and heparin

253
Q

What can trigger DIC in pregnancy?

A

Amniotic fluid embolism

Placental abruption

Missed miscarriage

Pre-eclampsia

Sepsis

254
Q

What are the possible complications that a mother with sickle cell disease may encounter during pregnancy?

A

More frequent vaso-occlusive crises

Foetal growth restriction

Miscarriage

Preterm labour

Pre-eclampsia

Venous thrombosis

255
Q

How can sickle cell disease in pregnancy be managed?

A

Red cell transfusion

Prophylactic transfusion

Alloimmunisation

256
Q

How does RDW change in iron deficiency anaemia and thalassemia trait?

A

IDA – increased

Thalassemia trait – normal

257
Q

List some key features of multiple myeloma.

A

Cancer of monoclonal plasma cells

Abundance of monoclonal immunoglobulin

Osteolytic bone lesions

Anaemia

Infections (due to deficient polyclonal response)

Kidney failure (due to hypercalcaemia)

258
Q

What is the pre-malignant condition for multiple myeloma?

A

Monoclonal gammopathy of uncertain significance (MGUS)

259
Q

How common is multiple myeloma compared to other haematological malignancies?

A

2nd most common after B cell lymphoma

260
Q

What is another term of activated B cells?

A

Centroblasts

261
Q

What are the main clinical features of multiple myeloma?

A

Calcium (high)

Renal failure

Anaemia

Bone lesions (pain, pathological fractures)

Monoclonal paraprotein

NOTE: patients with MGUS have no clinical features – there are some arbitrary cut-offs for MGUS/multiple myeloma based on monoclonal serum protein, bone marrow plasma cells and annual risk of progression to multiple myeloma

262
Q

What is the median survival for patients with multiple myeloma?

263
Q

Describe the histological appearance of mature plasmacytic cells.

A

Nucleus is pushed to one side of the cell

Clumped chromatin

Large cytoplasm (low nuclear-to-cytoplasmic ratio)

264
Q

Describe the histological appearance of immature plasmablastic cells.

A

Prominent nucleoli

Reticular chromatin

Less abundant cytoplasm

NOTE: the presence of these cells is associated with a poor prognosis

265
Q

Which antigens do myeloma cells test positive for on immunohistochemistry?

A

CD138

CD38

CD56/CD58

Monotypic cytoplasmic immunoglobulin

Light chain restriction

266
Q

Which antigens do myeloma cells test negative for on immunohistochemistry?

A

CD19

CD20 (unlike B cell lymphomas and CLL)

Surface immunoglobulin

267
Q

How does multiple myeloma lead to lytic bone disease?

A

The myeloma cells release osteoclast activating factors and osteoblast inhibiting factors

268
Q

Outline the mechanisms by which multiple myeloma causes kidney injury.

A

Immunoglobulin light chains activate inflammatory mediators in the proximal tubule epithelium

Proximal tubule necrosis

Fanconi syndrome (renal tubule acidosis with failure of reabsorption in the proximal tubule) with light chain crystal deposition

Cast nephropathy

269
Q

What are the four main domains of treatment of multiple myeloma?

A

Classical cytostatic drugs (e.g. melphalan)

Steroids (very cytotoxic to lymphocytes)

Immunomodulators (IMIDs e.g. thalidomide)

Proteasome inhibitors

270
Q

Describe how the consequences of rhesus incompatibility are different from ABO incompatibility in a patient receiving a blood transfusion.

A

ABO – immediate haemolytic transfusion reaction (can be fatal)

Rhesus – delayed haemolytic transfusion reaction

271
Q

List some other red cell antigens that can lead to transfusion reactions.

A

C, c, E, c

Duffy and Kidd (particularly important for delayed transfusion reactions)

272
Q

Which patient group should receive K negative blood?

A

Women of childbearing potential

273
Q

How long do red cells survive in storage?

A

35 days in 4 degrees

274
Q

How soon after leaving storage do red cells need to be transfused?

A

4 hours

NOTE: red cells can be returned to the fridge within 30 mins of leaving storage

275
Q

If a patient develops a reaction to a plasma transfusion, what is the most likely cause?

A

Allergic reaction

NOTE: plasma is frozen so it is unlikely to get contaminated by bacteria

276
Q

List some indications for transfusion.

A

Major blood loss

Peri-operative care

Post-chemotherapy

Symptomatic anaemia

277
Q

By how much would 1 unit of RBC increase the haemoglobin level in a 70 kg patient?

278
Q

Which patient groups would cell salvage be used for?

A

Patients with rare blood groups

Jehovah’s witnesses

279
Q

Which patient groups require CMV-negative blood?

A

For intra-uterine and neonatal transfusions

Elective transfusion in pregnancy

280
Q

Which patients require irradiated blood and why?

A

Highly immunosuppressed patients

These patients cannot destroy donor lymphocytes and the presence of lymphocytes in donated blood can cause graft-versus-host disease

281
Q

Which patients require washed blood?

A

Patients who have severe allergic reactions to donors’ plasma proteins

This takes 4 hours so must be requested in advance

NOTE: IgA deficient patients are more likely to need washed blood

282
Q

List some indications for platelet transfusions.

A

Massive transfusion

Prevent bleeding (post-chemotherapy)

Prevent bleeding (surgery)

Platelet dysfunction

283
Q

List some contraindications for platelet transfusion.

A

Heparin-induced thrombocytopaenia

TTP

284
Q

By what level will 1 unit of platelets increase the platelet count in a 70 kg adult?

A

By what level will 1 unit of platelets increase the platelet count in a 70 kg adult?

30-40 x 109/L

285
Q

List some indications for FFP transfusion.

A

Massive transfusion

DIC

Liver disease

286
Q

What does FFP contain?

A

All the coagulation factors

287
Q

What is the adult dose of FFP?

288
Q

How many mLs is 1 unit of FFP?

289
Q

List some causes of acute transfusion reactions.

A

Acute haemolytic (ABO incompatibility)

Allergic/anaphylaxis

Infection (bacterial)

Febrile non-haemolytic

Respiratory (TACO and TRALI)

290
Q

List some causes of delayed transfusion reactions.

A

Delayed haemolytic transfusion reaction

Infection (viral, malaria, vCJD)

TA-GvHD

Post-transfusion purpura

Iron overload

291
Q

What is the most common transfusion reaction?

A

Transplant-associated circulatory overload (TACO)

292
Q

What are some early features that might be suggestive of acute transfusion reaction?

A

Rise in temperature or pulse

Fall in BP

NOTE: these can occur before the patient experiences any symptoms

293
Q

List some symptoms of an acute transfusion reaction.

A

Fever

Rigors

Flushing

Vomiting

Dyspnoea

Pain at transfusion site

Collapse

294
Q

What are the clinical features of a febrile non-haemolytic transfusion reaction?

A

Occurs during/soon after transfusion (of blood or platelets)

Rise in temperature, chills and rigors

NOTE: this used to be common before blood was leucodepleted

295
Q

What causes febrile non-haemolytic transfusion reactions?

A

Release of cytokines from white cell during storage

296
Q

How is febrile non-haemolytic transfusion reaction treated?

A

Slow/stop the transfusion and treat with paracetamol

297
Q

Describe the clinical features of an allergic transfusion reaction

A

Mild urticarial or itchy rash

Sometimes causes a wheeze

298
Q

How is an allergic transfusion reaction managed?

A

Stop or slow the transfusion

IV antihistamines

299
Q

List some symptoms of an acute haemolytic transfusion reaction.

A

Chest/loin pain

Fever

Vomiting

Flushing

Collapse

Haemoglobinuria

Low BP

High HR

High Temp

300
Q

In an acute haemolytic transfusion reaction, why is it important to take a blood sample?

A

Send for FBC, biochemistry, coagulation, repeat X-match and DAT

301
Q

Describe the storage and shelf-life of platelets.

A

Stored at 22 degrees for 7 days

NOTE: they are screened for bacterial before release

302
Q

Which patient group is more likely to have severe allergic reactions to blood products?

A

IgA deficient patients (anti-IgA antibodies may develop in response to exposure to IgA in donor’s blood)

303
Q

What causes TACO and what are the main clinical features?

A

Usually caused by a lack of attention to fluid balance (especially in cardiac failure, hypoalbuminaemia, extremes of age)

Leads to pulmonary oedema

SOB

Low oxygen saturations

High HR

High BP

NOTE: this is very common

304
Q

What are the main clinical features of TRALI?

A

Looks like ARDS

SOB

Drop in oxygen saturation

Rise in HR

Rise in BP

305
Q

Outline the mechanism of TRALI.

A

Anti-WBC antibodies in donor blood interact with WBC in the patient

Aggregates of WBCs get stuck to pulmonary capillaries resulting in the release of neutrophil proteolytic enzymes and toxic oxygen metabolites

This leads to lung damage

306
Q

What are the main differences between TACO and TRALI?

A

JVP is not raised and the patient will not respond to frusemide in TRALI

307
Q

How can TRALI be avoided?

A

Using male donors (haven’t been pregnant) who haven’t had a transplant so they will not have produced antibodies against HLA

308
Q

What are the consequences of alloimmunisation with regards to blood transfusions?

A

Repeat transfusion with blood containing the antigen will lead to extravascular haemolysis

This is IgG mediated so will take 5-10 days

309
Q

What is the dangerous effect of parvovirus infection?

A

Causes temporary red cell aplasia

310
Q

Which patients are most affected by parvovirus infection?

A

Foetuses

Patients with haemolytic anaemias (e.g. sickle cell disease)

311
Q

What are the clinical manifestations of transfusion-associated Graft-versus-Host Disease?

A

Diarrhoea

Liver failure

Skin desquamation

Bone marrow failure

Death (weeks to months)

312
Q

How can transfusion-associated Graft-versus-Host Disease be prevented?

A

Irradiate blood components for very immunocompromised patients

313
Q

At what point after transfusion does post-transfusion purpura happen?

A

7-10 days after transfusion of platelets or red blood cells

NOTE: it usually resolves in 1-4 weeks but can cause life-threatening bleeding

314
Q

How is post-transfusion purpura treated?

315
Q

How can iron overload be prevented?

A

Iron chelators (e.g. exjade)

316
Q

When should all women have a group and screen during pregnancy?

A

12 weeks

28 weeks

317
Q

If anti-D antibodies are detected in a pregnant women, what further steps should be taken?

A

Check if the father has the antigen

Monitor the level of antibody

Check cffDNA

Monitor foetus for signs of anaemia (MCA Doppler ultrasound)

Deliver the baby early because it gets a lot worse around term

318
Q

What intervention may be performed if the foetus is found to be very anaemic?

A

Intrauterine transfusion into the umbilical vein

NOTE: anti-D is the most important antibody for causing haemolytic disease of the newborn

319
Q

Outline the mechanism of action of anti-D immunoglobulin.

A

RhD-positive cells of the foetus get coated by exogenous anti-D

These will then be removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother’s immune system

320
Q

List some occasions in which anti-D immunoglobulin should be given.

A

At delivery if the baby is found to be RhD-positive

Spontaneous miscarriages if surgical evacuation was needed

Surgical termination of pregnancy

Amniocentesis and chorionic villous sampling

Abdominal trauma

External cephalic version

Stillbirth or intrauterine death

321
Q

Which test is done if a sensitising event occurs > 20 weeks to determine if more anti-D is needed?

A

Kleihauer test

322
Q

What is the main cellular marker of stem cells?

323
Q

What is the risk of dying from bone marrow transplant?

A

More than 50%

It is the most expensive and risky elective procedure

324
Q

What are the most common reasons for autologous stem cell transplantation?

A

Myeloma

Lymphoma

CLL

325
Q

When is allogeneic bone marrow transplantation used?

A

When it is very unlikely that the patient’s disease will be eradicated from the bone marrow by standard chemotherapy

NOTE: suitable for acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune deficiencies

326
Q

List some parameters used to gauge outcome of transplantation techniques.

A

Overall survival

Disease-free survival

Transplant-related mortality

Relapse incidence

327
Q

Outline the process of peripheral blood sampling for stem cells.

A

Hormones (e.g. G-CSF) is given to stimulate granulocyte production

This leads to the bone marrow producing some stem cells along with the granulocytes

G-CSF is given for 5 days and stem cells are harvested on the 5th day

The donor is connected to a centrifuge which spins the blood, removes the white cell component, reassembles the red cells and plasma and reinfuses it into the patient

328
Q

What factor (related to stem cell harvesting) does the success of a bone marrow transplant depend on?

A

Number of CD34 cells per kg of weight of the recipient

329
Q

List some complications of stem cell transplantation.

A

Graft failure

Infections

GvHD

Relapse

330
Q

List some other factors affecting the outcome of a bone marrow transplant.

A

Age

Disease phase (early or late)

Gender of recipient and donor

Time to BMT

Donor (sibling or not)

NOTE: this is used to calculate the EBMT risk score

331
Q

List some risk factors for infection that are related to bone marrow transplantation.

A

Neutropaenia

Breakdown of protective barriers

Decreased antibody levels

Depressed T cell responses

332
Q

Which parts of the body are affected in acute graft-versus-host disease?

A

Skin

GI tract

Live

333
Q

Which parts of the body are affected in chronic graft-versus-host disease?

A

Skin

Mucosal membranes

Lungs

Liver

Eyes

Joints

334
Q

Why must patients receiving chemotherapy or radiotherapy have a treatment-free interval before stem cell transplantation?

A

Chemotherapy and radiotherapy can damage tissues leading to the release of loads of cytokines which activate antigen-presenting cells which present antigens to donor lymphocytes

335
Q

List some risk factors for acute graft-versus-host disease

A

Degree of HLA disparity

Recipient age

Conditioning regimen

Recipient and donor gender combination (male donors with female patients have worse GvHD)

Stem cell source

Disease phase

Viral infections

336
Q

List some treatment options for GvHD.

A

Corticosteroids

Ciclosporin A

FK506

Mycophenolate mofetil

Monoclonal antibodies

Photophoresis

Total lymphoid irradiation

337
Q

List some drugs used to prevent GvHD.

A

Methotrexate

Corticosteroids

Ciclosporin A

FK506

T cell depletion

Post-transplant cyclophosphamide

338
Q

Which component of the transplanted cells is responsible for GvHD?

A

It is the mature lymphocytes within the cell population (i.e. not the stem cells) that are responsible for GvHD

You cannot, however, remove these mature lymphocytes from the sample because they are important in preventing relapse

339
Q

What are the main differences between the blood count of neonate and an adult?

A

Higher WCC (neutrophils, lymphocytes)

Higher Hb

Higher MCV

340
Q

How are the enzyme levels in the red blood cells of neonates different to adults?

A

They have 50% of the concentration of G6PD of adults

341
Q

List some causes of polycythaemia in a foetus.

A

Twin-to-Twin transfusion syndrome

Intrauterine hypoxia

Placental insufficiency

342
Q

List some causes of anaemia in a foetus.

A

Twin-to-twin transfusion syndrome

Foetal-to-maternal transfusion

Parvovirus B19 infection

Haemorrhage from cord or placenta

343
Q

What is another term to describe congenital leukaemia?

A

Transient abnormal myelopoiesis (TAM)

344
Q

Describe the usual course of congenital leukaemia.

A

Remits spontaneously within the first 2 months of life

However, 25% of infants will relapse after 1-2 years

NOTE: the leukaemia is myeloid with major involvement of the megakaryocyte lineage

345
Q

Define thalassemia.

A

A group of conditions resulting from a reduced rate of synthesis of one or more globin chains as a result of a genetic defect

346
Q

What is the normal HbA2 level in a healthy adult?

347
Q

What feature of hyposplenism might you see on a blood film of a patient with sickle cell anaemia?

A

Howell Jolly bodies

348
Q

Why does sickle cell anaemia in a child differ from sickle cell anaemia in an adult?

A

Mainly because the distribution of red bone marrow (contains haematopoietic precursors) differs

Red bone marrow is vascular, metabolically active and susceptible to infarction

Bone pain due to infarction is a prominent clinical feature in sickle cell anaemia

349
Q

How is the pattern of bone pain due to infarction different in adults with sickle cell anaemia compared to children?

A

Adults – only happens in central skeleton

Infants/Children – can happen anywhere (including hands and feet causing hand-foot syndrome)

350
Q

How is splenic function different in children with sickle cell anaemia compared to adults and what risks does this pose?

A

Children still have functioning spleens meaning that a child is much more likely to undergo splenic sequestration

This can lead to severe anaemia, shock and death

Teenagers and adults don’t tend to experience splenic sequestration because recurrent infarction has left their spleen small and fibrotic

However, as the risk of splenic sequestration declines with time, the risks of hyposplenism increase

351
Q

Define splenic sequestration

A

Acute pooling of a large percentage of circulating red cells in the spleen

352
Q

How is splenic sequestration managed?

A

Parents should be taught how to palpate the spleen and to seek help when the child is acutely unwell with a large spleen

Blood transfusion

353
Q

Which complications of sickle cell anaemia occur in younger children (2-10 years old)?

A

Acute chest syndrome (caused by infarction of the ribs and lungs)

Painful crises

Stroke (SCD is the most common cause of stroke in children)

354
Q

Which infectious agents are children with sickle cell anaemia particularly vulnerable to?

A

Pneumococcus

Parvovirus B19 (causes aplastic anaemia)

355
Q

Why do children with sickle cell anaemia have increased folate demands?

A

Hyperplastic erythropoiesis

Growth spurts

Reduced red cell lifespan

356
Q

List some clinical features of poorly controlled beta thalassemia major.

A

Anaemia à heart failure, growth retardation

Erythropoietic drive à bone expansion, hepatomegaly, splenomegaly

Iron overload à heart failure, gonadal failure

357
Q

What are the principles of treatment of beta thalassemia major?

A

Accurate diagnosis and family counselling

Blood transfusion

Iron chelation

358
Q

List some types of inherited haemolytic anaemia.

A

Red cell membrane – hereditary spherocytosis, hereditary eliptocytosis

Haemoglobin molecule – sickle cell anaemia

Glycolytic pathway – pyruvate kinase deficiency

Pentose shunt – G6PD deficiency

359
Q

List some differential diagnoses for haemophilia.

A

Inherited thrombocytopaenia/platelet defect

Acquired defects of coagulation (e.g. ITP, acute leukaemia)

Non-accidental injury

Henoch-Schonlein purpura

360
Q

Describe the typical presentation of ITP.

A

Petechiae

Bruises

Blood blisters in the mouth

361
Q

List some differential diagnoses for ITP.

A

HSP

Non-accidental injury

Coagulation factor defect

Inherited thrombocytopaenia

Acute leukaemia

362
Q

List some treatment approaches for ITP.

A

Observation (most common)

Corticosteroids

High dose IVIG

IV anti-RhD (if RhD positive)

363
Q

How is hyposplenism managed?

A

Vaccination

Prophylactic penicillin

Advice about other risks (e.g. malaria, dog bites)

364
Q

What is a mediastinal mass in a child with a high WBC likely to be?

365
Q

Which type of leukaemia can cause a thymoma?

A

Acute lymphoblastic leukaemia of T cell lineage

366
Q

What is a bad prognostic feature in leukaemia?

A

Very high WCC

367
Q

Which techniques are used to determine whether cells are lymphoid or myeloid?

A

Cytochemistry

Immunophenotyping

368
Q

How is a diagnosis of acute promyelocytic leukaemia confirmed?

A

Cytogenetic/FISH/molecular genetic analysis

15;17 translocation forming the PML: RARA fusion gene

369
Q

How is acute promyelocytic leukaemia treated?

A

Platelets

Chemotherapy

All-trans-retinoic acid (ATRA)

370
Q

Aside from chronic leukaemia, which other condition must you consider in an elderly patient with anaemia?

A

Myelodysplastic syndrome

371
Q

How is polycythaemia vera treated?

A

Venesection + hydroxycarbamide

NOTE: venesection alone is NOT sufficient if the patient also has a high platelet count

372
Q

Outline the mechanisms by which anaemia of chronic disease causes anaemia.

A

Reduced red cell lifespan

Cytokine release (IFN-gamma, IL1, TNF)

Reduced proliferation of erythroid precursors

Suppression of endogenous EPO production

Impaired iron utilisation

373
Q

Describe the typical ferritin and transferrin levels you’d expect to see in anaemia of chronic disease.

A

Ferritin – high or normal (acute phase protein)

Transferrin – reduced

374
Q

Which HLA genotype is associated with Hodgkin lymphoma?

A

HLA-DPB1

NOTE: EBV is found in >79% of people over 50 years

375
Q

List some blood film features of iron deficiency anaemia.

A

Pencil cells

Anisocytosis

Poikilocytosis

Hypochromic

376
Q

Which type of major infection is classically seen in AML?

A

Gram-negative septicaemia

Path Laz (condensed) (COPY) (5 decks)

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