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Year 6 ICSM > Haematology > Flashcards

Haematology Flashcards

1
Q

Learning objectives

A

Answer

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2
Q

Define anti-phospholipid syndrome

A

• Characterised by the presence of antiphospholipid antibodies (APL) in the plasma, venous and arterial thrombosis, recurrent foetal loss and thrombocytopaenia

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3
Q

Explain the aetiology/risk factors of anti-phospholipid syndrome

A
  • Antiphospholipid antibodies (APL) are directed against plasma proteins bound to phospholipids
  • APL may develop in susceptible individuals following exposure to infectious agents
  • Once APL are present, a second event is needed for the syndrome to develop
  • APL has effects on a number of coagulation factors (e.g. protein C, annexin V, platelets, fibrinolysis)
  • Complement activation by APL is critical for the complications
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4
Q

Summarise the epidemiology of anti-phospholipid syndrome

A
  • More common in YOUNG WOMEN
  • Accounts for 20% of strokes in < 45 yrs
  • Accounts for 27% of women with > 2 miscarriages
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5
Q

Recognise the presenting symptoms of anti-phospholipid syndrome

A 
•	RECURRENT MISCARRIAGES 
•	History of:
o	Arterial thromboses (stroke)
o	Venous thromboses (DVT, PE) 
•	Headaches (migraine)
•	Chorea 
•	Epilepsy
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6
Q

Recognise the signs of anti-phospholipid syndrome on physical examination

A

• Livedo reticularis
o A skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discolouration of the skin
• Signs of SLE (e.g. malar rash, discoid lesions)
• Signs of valvular heart disease

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7
Q

Identify appropriate investigations for anti-phospholipid syndrome

A

• FBC - low platelets
• ESR - usually normal
• U&Es - can get APL nephropathy
• Clotting screen - high APTT
• Presence of antiphospholipid antibodies may be demonstrated by:
o ELISA testing for anticardiolipin antibodies
o Lupus anticoagulant assays

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8
Q

Define aplastic anaemia

A

• Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia)

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9
Q

Explain the aetiology/risk factors of aplastic anaemia

A

• Idiopathic (> 40%)
o May be due to destruction or suppression of stem cells via autoimmune mechanisms
• Acquired
o Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)
o Chemicals (e.g. benzene, DDT)
o Radiation
o Viral infection (e.g. parvovirus B19)
o Paroxysmal nocturnal haemoglobinuria
• Inherited
o Fanconi’s anaemia
o Dyskeratosis congenita (a rare, progressive bone marrow failure syndrome)

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10
Q

Summarise the epidemiology of aplastic anaemia

A
  • Annual incidence: 2-4/1,000,000

* Slightly more common in males

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11
Q

Recognise the presenting symptoms of aplastic anaemia

A 
•	Can be both slow-onset (months) or rapid-onset (days)
•	Anaemia Symptoms:
o	Tiredness 
o	Lethargy 
o	Dyspnoea
•	Thrombocytopaenia Symptoms:
o	Easy bruising
o	Bleeding gums 
o	Epistaxis
•	Leukopaenia Symptoms:
o	Increased frequency and severity of infections
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12
Q

Recognise the signs of aplastic anaemia on physical examination

A 
•	Anaemia Signs:
o	Pallor
•	Thrombocytopaenia Signs:
o	Petechiae
o	Bruises
•	Leukopaenia Signs:
o	Multiple bacterial and fungal infections 
o	No hepatomegaly, splenomegaly or lymphadenopathy
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13
Q

Identify appropriate investigations for aplastic anaemia

A 
•	Bloods
o	FBC
•	Low Hb
•	Low platelets 
•	Low WCC
•	Normal MCV 
•	Low or absent reticulocytes 
•	Blood Film
o	Exclude leukaemia (check for abnormal circulating white blood cells)
•	Bone Marrow Trephine Biopsy
•	Fanconi's Anaemia
o	Check for presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents
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14
Q

Define DIC

A

• A disorder of the clotting cascade that can complicate a serious illness.
o DIC can occur in TWO forms:
• Acute overt form where there is bleeding and depletion of platelets and clotting factors
• Chronic non-overt form where thromboembolism is accompanied by generalised activation of the coagulation system

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15
Q

Explain the aetiology/risk factors for DIC

A

• Infection - particularly GRAM-NEGATIVE sepsis
• Obstetric Complications
o Missed miscarriage (when the foetus dies but the body doesn’t realise it and the placenta continues to release hormones)
o Severe pre-eclampsia
o Placental abruption (separation of the placenta from the wall of the uterus during pregnancy)
o Amniotic emboli
• Malignancy
o Acute promyelocytic leukaemia - ACUTE DIC
o Lung, breast and GI malignancy - CHRONIC DIC
• Severe trauma or surgery
• Others: haemolytic transfusion reaction, burns, severe liver disease, aortic aneurysms, haemangiomas
• Pathophysiology

o Acute DIC
• Endothelial damage and the release of granulocyte/macrophage procoagulant substances (e.g. tissue factor) lead to activation of coagulation
• This leads to explosive thrombin generation, which depletes clotting factors and platelets, whilst also activating the fibrinolytic system
• This leads to bleeding in the subcutaneous tissues, skin and mucous membranes
• Occlusion of blood vessels by fibrin in the microcirculation leads to microangiopathic haemolytic anaemia and ischaemic organ damage
o Chronic DIC
• IDENTICAL process to acute DI
• Happens at a slower rate with time for compensatory responses
• The compensatory responses diminish the likelihood of bleeding but give rise to hypercoagulable states and thrombosis can occur

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16
Q

Summarise the epidemiology of DIC

A

• Seen in any severely ill patient

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17
Q

Recognise the presenting symptoms of DIC

A
  • The patients will tend to be severely unwell with symptoms of the underlying disease
  • Confusion
  • Dyspnoea
  • Evidence of bleeding
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18
Q

Recognise the signs of DIC on physical examination

A 
•	Signs of underlying disease 
•	Fever 
•	Evidence of shock (hypotension, tachycardia)
•	Acute DIC
o	Petechiae, purpura, ecchymoses 
o	Epistaxis 
o	Mucosal bleeding 
o	Overt haemorrhage 
o	Signs of end organ damage 
o	Respiratory distress 
o	Oliguria due to renal failure
•	Chronic DIC
o	Signs of deep vein and arterial thrombosis or embolism
o	Superficial venous thrombosis
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19
Q

Identify appropriate investigations for DIC

A 
•	Bloods
o	FBC
•	Low platelets 
•	Low Hb 
•	High APTT/PT
•	Low fibrinogen
•	High fibrin degradation products 
•	High D-dimers
•	Peripheral Blood Film
o	Schistocytes
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20
Q

Define haemolytic anaemia

A

• Premature erythrocyte breakdown causing shortened erythrocyte life span (< 120 days) with anaemia

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21
Q

Explain the aetiology/risk factors of haemolytic anaemia

A 
•	Hereditary
o	Membrane Defects 
•	Hereditary spherocytosis 
•	Elliptocytosis 
o	Metabolic Defects
•	G6PD deficiency 
•	Pyruvate kinase deficiency
o	Haemoglobinopathies
•	Sickle cell disease 
•	Thalassemia
•	Acquired
o	Autoimmune 
•	Antibodies attach to erythrocytes causing intravascular and extravascular haemolysis
o	Isoimmune
•	Transfusion reaction
•	Haemolytic disease of the newborn 
o	Drugs
•	Penicillin
•	Quinine 
•	NOTE: this is caused by the formation of a drug-antibody-erythrocyte complex
o	Trauma
•	Microangiopathic haemolytic anaemia (caused by RBC fragmentation in abnormal microcirculation)
	E.g. haemolytic uraemic syndrome, DIC, malignant hypertension
o	Infection
•	Malaria
•	Sepsis 
o	Paroxysmal nocturnal haemoglobinuria
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22
Q

Summarise the epidemiology of haemolytic anaemia

A
  • COMMON
  • Genetic causes are prevalent if African, Mediterranean and Middle Eastern populations
  • Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europe
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23
Q

Recognise the presenting symptoms of haemolytic anaemia

A
  • Jaundice
  • Haematuria
  • Anaemia
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24
Q

Recognise the signs of haemolytic anaemia on physical examination

A
  • Pallor
  • Jaundice
  • Hepatosplenomegaly
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25
Q

Identify appropriate investigations for haemolytic anaemia

A 
•	Bloods
o	FBC: 
•	Low Hb 
•	High reticulocytes 
•	High MCV 
•	High unconjugated bilirubin 
•	Low haptoglobin (a protein that binds to free Hb released by red blood cells) 
o	U&Es
o	Folate
•	Blood Film
o	Leucoerythroblastic picture 
o	Macrocytosis 
o	Nucleated erythrocytes or reticulocytes 
o	Polychromasia 
o	May identify specific abnormal cells such as:
•	Spherocytes 
•	Elliptocytes 
•	Sickle cells 
•	Schistocytes 
•	Malarial parasites 
•	Urine
o	High urobilinogen
o	Haemoglobinuria
o	Haemosiderinuria
•	Direct Coombs' Test
o	Tests for autoimmune haemolytic anaemia 
o	Identifies erythrocytes coated with antibodies 
•	Osmotic fragility test or Spectrin mutation analysis 
o	Identifies membrane abnormalities 
•	Ham's Test
o	Lysis of erythrocytes in acidified serum in paroxysmal nocturnal haemoglobinuria
•	Hb Electrophoresis or Enzyme Assays
o	To exclude other causes 
•	Bone Marrow Biopsy (rarely performed)
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26
Q

Define HUS and TTP

A 
•	DEFINITION: triad of:
o	Microangiopathic haemolytic anaemia (MAHA)
o	Acute renal failure 
o	Thrombocytopaenia
•	There are TWO forms of HUS:
o	D+ = diarrhoea-associated form 
o	D- = no prodromal illness identified 
•	HUS overlaps with TTP, which has additional features of:
o	Fever 
o	Fluctuating CNS signs
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27
Q

Explain the aetiology/risk factors for HUS and TTP

A 
•	Endothelial injury results in platelet aggregation and the release of unusually large vWF multimers and activation of platelets and the clotting cascade 
•	This leads to small vessel thrombosis
•	The glomerular-afferent arteriole and capillaries are particularly vulnerable - they undergo fibrinoid necrosis
•	This leads to renal ischaemia and acute renal failure
•	The thrombi also promote intravascular haemolysis 
•	CAUSES:
o	Infection 
•	Escherichia coli O157
•	Shigella
•	Neuraminidase-producing infections 
•	HIV 
o	Drugs
•	COCP
•	Ciclosporin 
•	Mitomicin
•	5-fluorouracil
o	Others:
•	Malignant hypertension 
•	Malignancy
•	Pregnancy 
•	SLE 
•	Scleroderma
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28
Q

Summarise the epidemiology of HUS and TTP

A
  • UNCOMMON
  • D+ HUS often affects YOUNG CHILDREN
  • It is the most common cause of acute renal failure in children
  • TTP mainly affects ADULT FEMALES
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29
Q

Recognise the presenting symptoms of HUS and TTP

A 
•	GI
o	Severe abdominal colic 
o	Watery diarrhoea that becomes bloodstained 
•	General
o	Malaise 
o	Fatigue 
o	Nausea 
o	Fever < 38 degrees (D+)
•	Renal
o	Oliguria or anuria
o	Haematuria
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30
Q

Recognise the signs of HUS and TTP on physical examination

A 
•	General
o	Pallor 
o	Slight jaundice (due to haemolysis) 
o	Bruising 
o	Generalise oedema 
o	Hypertension 
o	Retinopathy
•	GI
o	Abdominal tenderness 
•	CNS Signs
o	Occurs in TTP
o	Weakness 
o	Reduced vision 
o	Fits 
o	Reduced consciousness
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31
Q

Identify appropriate investigations for HUS and TTP

A 
•	FBC
o	Normocytic anaemia 
o	High neutrophils 
o	Very low platelets 
•	U&Es
o	High urea 
o	High creatinine
o	High K+ 
o	Low Na+ 
•	Clotting
o	Normal APTT and fibrinogen levels (abnormality may indicate DIC)
•	LFTs
o	High unconjugated bilirubin 
o	High LDH from haemolysis 
•	Blood cultures
•	ABG
o	Low pH 
o	Low bicarbonate 
o	Low PaCO2
o	Normal anion gap 
•	Blood Film
o	Schistocytes 
o	High reticulocytes and spherocytes 
•	Urine
o	1+ g protein/24 hrs
o	Haematuria
•	Stool Samples
o	MC&S
•	Renal Biopsy
o	Can distinguish between D+ and D- HUS
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32
Q

Define haemophilia

A

• Bleeding diatheses resulting from an inherited deficiency of a clotting factor
o THREE subtypes:
• Haemophilia A: MOST COMMON - deficiency in factor 8
• Haemophilia B: deficiency in factor 9
• Haemophilia C: RARE - deficiency in factor 11

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33
Q

Explain the aetiology/risk factors of haemophilia

A
  • Haemophilia A and B have X-linked recessive inheritance
  • 30% of cases are new mutations
  • Due to its inheritance pattern, Haemophilia is mainly seen in MALES
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34
Q

Summarise the epidemiology of haemophilia

A
  • Haemophilia A incidence: 1/10,000 males
  • Haemophilia B incidence: 1/25,000 males
  • Haemophilia C is more common in Ashkenazi Jews
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35
Q

Recognise the presenting symptoms of haemophilia

A
  • Symptoms usually begin in early childhood
  • Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
  • Painful bleeding into muscles
  • Haematuria
  • Excessive bruising or bleeding after surgery or trauma
  • FEMALE carriers are usually asymptomatic, but may experience excessive bleeding after trauma
  • Generally speaking, bleeding in haemophilia is DEEP (into muscles and joints)
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36
Q

Recognise the signs of haemophilia on physical examination

A
  • Multiple bruises
  • Muscle haematomas
  • Haemarthroses
  • Joint deformity
  • Nerve palsies (due to nerve compression by haematomas)
  • Signs of iron deficiency anaemia
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37
Q

Identify appropriate investigations for haemophilia

A
  • Clotting screen (high APTT)
  • Coagulation factor assays (low factor 8, 9 or 11 (depending on type of haemophilia))
  • Other investigations may be performed if there are complications (e.g. arthroscopy)
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38
Q

Define ITP

A

• Syndrome characterised by immune destruction of platelets resulting in bruising or a bleeding tendency

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39
Q

Explain the aetiology/risk factors of ITP

A

• Often IDIOPATHIC
• Acute ITP is often seen after viral infection in children
• Chronic ITP is more common in adults
• ITP may be associated with:
o Infections (e.g. malaria, EBV, HIV)
o Autoimmune diseases (e.g. SLE, thyroid disease)
o Malignancies
o Drugs (e.g. quinine)
• Autoantibodies are generated, which bind to platelet membrane proteins (e.g. GlpIIb/IIIa) resulting in thrombocytopaenia

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40
Q

Summarise the epidemiology of ITP

A

• Acute ITP presenting CHILDREN aged 2-7 yrs
• Chronic ITP is seen in ADULTS
o 4 x more common in WOMEN

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41
Q

Recognise the presenting symptoms of ITP

A
  • Easy bruising
  • Mucosal bleeding
  • Menorrhagia
  • Epistaxis
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42
Q

Recognise the signs of ITP on physical examination

A
  • Visible petechiae and bruises

* Signs of other illness (e.g. infections, wasting, splenomegaly) would suggest that other causes

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43
Q

Identify appropriate investigations for ITP

A 
•	Diagnosis of exclusion - exclude:
o	Myelodysplasia
o	Acute leukaemia
o	Marrow infiltration 
•	Bloods
o	FBC - low platelets 
o	Clotting screen - normal PT, APTT and fibrinogen
o	Autoantibodies (e.g. antiplatelet antibody)
•	Blood Film
o	To rule out pseudothrombocytopaenia (which is caused by platelets clumping together and giving falsely low counts)
•	Bone Marrow
o	To exclude other pathology
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44
Q

Define ALL

A

• Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts (primitive lymphoid cells)

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45
Q

Explain the aetiology / risk factors of ALL

A
  • Lymphoblasts undergo malignancy transformation and proliferation
  • This leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues
Risk Factors:
o	Environmental (radiation, viruses) 
o	Genetic (Down's syndrome, Neurofibromatosis type 1, Fanconi's anaemia, xeroderma pigmentosum)
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46
Q

Summarise the epidemiology of ALL

A
  • MOST COMMON malignancy of CHILDHOOD
  • Peak incidence: 2-5 yrs old
  • There is a second peak in incidence in the elderly
  • Annual UK incidence: 1/70,000
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47
Q

Recognise the presenting symptoms of ALL

A

Symptoms of Bone Marrow Failure:
o Anaemia (fatigue, dyspnoea)
o Bleeding (spontaneous bruising, bleeding gums, menorrhagia)
o Opportunistic infections

Symptoms of Organ Infiltration:
o	Tender bones 
o	Enlarged lymph nodes 
o	Mediastinal compression 
o	Meningeal involvement (headache, visual disturbances, nausea)
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48
Q

Recognise the signs of ALL on physical examination

A 
Signs of Bone Marrow Failure:
o	Pallor 
o	Bruising 
o	Bleeding 
o	Infection
Signs of Organ Infiltration:
o	Lymphadenopathy
o	Hepatosplenomegaly
o	Cranial nerve palsies 
o	Retinal haemorrhage 
o	Papilloedema on fundoscopy 
o	Leukaemic infiltration of the anterior chamber of the eye 
o	Testicular swelling
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49
Q

Identify appropriate investigations for ALL and interpret the results

A 
Bloods
o	FBC - normochromic normocytic anaemia, low platelets, variable WCC
o	High uric acid 
o	High LDH
o	Clotting screen

Blood Film
o Abundant lymphoblasts

Bone Marrow Aspirate or Trephine Biopsy
o Hypercellular with > 20% lymphoblasts

Immunophenotyping - using antibodies to recognise cell surface antigens

Cytogenetic - karyotyping to look for chromosomal abnormalities or translocations

Cytochemistry

Lumbar Puncture - check for CNS involvement

CXR - may show mediastinal lymphadenopathy, lytic bone lesions

Bone Radiographs - mottled appearance with punched out lesions due to leukaemic infiltration

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50
Q

Define AML

A

• Malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood
o Classified using the FAB (French-American-British) System into EIGHT morphological variants

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51
Q

Explain the aetiology / risk factors of AML

A
  • Myeloblasts undergo malignant transformation and proliferation
  • This leads to replacement of normal marrow and bone marrow failure
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52
Q

Summarise the epidemiology of AML

A
  • MOST COMMON acute leukaemia in ADULTS

* Incidence INCREASES with age

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53
Q

Recognise the presenting symptoms of AML

A

Symptoms of Bone Marrow Failure:
o Anaemia (lethargy, dyspnoea)
o Bleeding (due to thrombocytopaenia or DIC)
o Opportunistic or recurrent infections

Symptoms of Tissue Infiltration:
o Gum swelling or bleeding
o CNS involvement (headaches, nausea, diplopia)

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54
Q

Recognise the signs of AML on physical examination

A 
Signs of Bone Marrow Failure:
o	Pallor 
o	Cardiac flow murmur 
o	Ecchymosis 
o	Bleeding 
o	Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections)

Signs of Tissue Infiltration:
o Skin rashes
o Gum hypertrophy
o Deposit of leukaemic blasts in the eye, tongue and bone (RARE)

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55
Q

Identify appropriate investigations for AML and interpret the results

A

Bloods
o FBC - low Hb, low platelets, variable WCC
o High uric acid
o High LDH
o Clotting studies, fibrinogen and D-dimers (to check for DIC)

Blood Film
o Myeloblasts

Bone Marrow Aspirate or Biopsy
o Hypercellular with > 20% blasts

Immunophenotyping
o Antibodies against surface antigens used to classify the lineage of the abnormal clones

Cytogenetics

Immunocytochemistry

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56
Q

Define CLL

A

• Characterised by progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. There is an overlap between CLL and non-Hodgkin’s lymphoma

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57
Q

Explain the aetiology / risk factors of CLL

A

• Malignant cells may accumulate as a result of their inability to undergo apoptosis

The most common chromosomal changes include:
o Trisomy 12
o 11q and 13q deletions

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58
Q

Summarise the epidemiology of CLL

A
  • 90% are > 50 yrs
  • More common in MALES
  • Rare in Asians
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59
Q

Recognise the presenting symptoms of CLL

A

Asymptomatic - 40-50% of cases are diagnosed following routine blood tests

Systemic Symptoms:
o Lethargy
o Malaise
o Night sweats

Symptoms of Bone Marrow Failure:
o Recurrent infections
o Herpes zoster infection
o Easy bruising or bleeding

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60
Q

Recognise the signs of CLL on physical examination

A
  • Non-tender lymphadenopathy
  • Hepatomegaly
  • Splenomegaly

LATE STAGE signs of bone marrow failure:
o Pallor
o Cardiac flow murmur
o Purpura/ecchymosis

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61
Q

Identify appropriate investigations for CLL and interpret the results

A

• NOTE: CLL may be associated with autoimmune phenomena such as haemolytic anaemia (warm agglutinins) or thrombocytopaenia

Bloods
o	FBC
•	Lymphocytosis 
•	Low Hb - Could be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis 
•	Low platelets 
•	Low serum Ig

Blood Film
o Small lymphocytes with thin rims of cytoplasm
o Smudge cells

Bone Marrow Aspirate or Biopsy
o Lymphocytic replacement of normal marrow

Cytogenetics

62
Q

Define CML

A

• Chronic myeloblastic leukaemia is a malignant clonal disease characterised by proliferation of granulocyte precursors in the bone marrow and blood, distinguished from AML by its slower progression

63
Q

Explain the aetiology / risk factors of CML

A

Malignant proliferation of stem cells

95% of cases have a chromosomal translocation between chromosomes 9 and 22 to form the Philadelphia chromosome

Variants of CML include:
o Ph-negative CML
o Chronic neutrophilic leukaemia
o Eosinophilic leukaemia

Pathogenesis
o The Philadelphia chromosome results in the formation of the BCR-ABL fusion gene
o The product of this gene enhances tyrosine kinase activity and drives cell replication

THREE phases of CML
o Relatively stable chronic phase (4-6 yr duration)
o Accelerated phase (3-9 months)
o Acute leukaemia phase - blast transformation

64
Q

Summarise the epidemiology of CML

A
  • Incidence increases with age
  • Mean age of diagnosis: 40-60 yrs
  • 4 x more common in MALES
65
Q

Recognise the presenting symptoms of CML

A

ASYMPTOMATIC in 40-50% of cases - diagnosed on routine blood count

Hypermetabolic Symptoms:
o Weight loss
o Malaise
o Sweating

Bone Marrow Failure Symptoms:
o	Lethargy 
o	Dyspnoea
o	Easy bruising 
o	Epistaxis 
o	Abdominal discomfort and early satiety
o	Rare symptoms:
•	Gout 
•	Hyperviscosity symptoms (visual disturbance, headaches, priapism)
o	May present during a blast crisis with symptoms of AML and ALL
66
Q

Recognise the signs of CML on physical examination

A 
•	SPLENOMEGALY - most common physical finding (90% of cases)
•	Signs of bone marrow failure:
o	Pallor
o	Bleeding 
o	Ecchymosis
67
Q

Identify appropriate investigations for CML and interpret the results

A 
Bloods
o	FBC 
•	High WCC 
•	Low Hb 
•	High basophils/neutrophils/eosinophils
•	High/normal/low platelets 
•	High uric acid 
•	High B12 and transcobalamin I

Blood Film
o Immature granulocytes

Bone Marrow Aspirate or Biopsy
o Hypercellular with raised myeloid-erythroid ratio

Cytogenetics
o Show the Philadelphia chromosome

68
Q

Define lymphoma (Hodgkin’s)

A

• Lymphomas are neoplasms of lymphoid cells, originating in the lymph nodes or other lymphoid tissues. Hodgkin’s lymphoma (15% of all lymphomas) is diagnosed histopathologically by the presence of Reed-Sternberg Cells (binucleate lymphocytes)

69
Q

Explain the aetiology / risk factors of lymphoma (Hodgkin’s)

A
  • UNKNOWN
  • Likely to be an environmental trigger in a genetically susceptible individual
  • EBV genome has been detected in 50% of Hodgkin’s lymphomas
70
Q

Summarise the epidemiology of lymphoma (Hodgkin’s)

A
  • Bimodal age distribution with peaks at 20-30 yrs and > 50 yrs
  • More common in MALES
71
Q

Recognise the presenting symptoms of lymphoma (Hodgkin’s)

A

Painless enlarging mass
o Most commonly in the neck
o Can also be in the axilla or groin

The mass may become painful after alcohol ingestion

B symptoms of Lymphoma
o Fever > 38 degrees
• If this is cyclical it is referred to as Pel-Ebstein fever
o Night sweats
o Weight loss > 10% body weight in the past 6 months

Other symptoms
o Pruritis
o Cough
o Dyspnoea

72
Q

Recognise the signs of lymphoma (Hodgkin’s) on physical examination

A
  • Non-tender firm rubbery lymphadenopathy (may be cervical, axillary or inguinal)
  • Splenomegaly (or sometimes, hepatosplenomegaly)
  • Skin excoriations
  • Signs of intrathoracic disease (e.g. pleural effusion, superior vena cava obstruction)
73
Q

Identify appropriate investigations for lymphoma (Hodgkin’s) and interpret the results

A 
Bloods
o	FBC
•	Anaemia of chronic disease 
•	Leucocytosis 
•	High neutrophils 
•	High eosinophils 
•	Lymphopaenia in advanced disease
o	High ESR and CRP

Lymph Node Biopsy

Bone Marrow Aspirate and Trephine Biopsy

Imaging - CXR, CT, PET

Ann Arbor Staging
o	I = single lymph node region 
o	II = 2+ lymph node regions on one side of the diaphragm
o	III = lymph node regions on both sides of the diaphragm
o	IV = extranodal involvement 
o	A = absence of B symptoms 
o	B = presence of B symptoms 
o	E = localised extranodal extension 
o	S = involvement of spleen
74
Q

Define lymphoma (non-Hodgkin’s)

A

• Lymphomas are malignancies of lymphoid cells originating in lymph nodes or other lymphoid tissues. Non-Hodgkin’s lymphomas are a diverse group consisting of:
o 85% B cell
o 15% T cell and NK cell forms
• It can range from stable, indolent disease to aggressive disease

75
Q

Explain the aetiology / risk factors of lymphoma (non-Hodgkin’s)

A 
•	Complex process involving the accumulation of multiple genetic lesions 
•	The changes in the genome in certain lymphoma subtypes have been associated with the introduction of foreign genes via oncogenic viruses (e.g. EBV and Burkitt's lymphoma) 
•	Other risk factors:
o	Radiotherapy 
o	Immunosuppressive agents 
o	Chemotherapy 
o	HIV, HBV, HCV
o	Connective tissue disease (e.g. SLE)
76
Q

Summarise the epidemiology of lymphoma (non-Hodgkin’s)

A
  • Incidence increases with age
  • More common in MALES
  • More common in the WESTERN WORLD
77
Q

Recognise the presenting symptoms of lymphoma (non-Hodgkin’s)

A

Painless enlarging mass (in neck, axilla or groin)

Systemic Symptoms (occurs less frequently than in Hodkin's):
o	Fever 
o	Night sweats 
o	Weight loss > 10% body weight 
o	Symptoms of hypercalcaemia 
Symptoms related to organ involvement
o	Extranodal disease is MORE COMMON in NHL than in Hodgkin's lymphoma
o	Skin rashes 
o	Headache 
o	Sore throat 
o	Abdominal discomfort 
o	Testicular swelling
78
Q

Recognise the signs of lymphoma (non-Hodgkin’s) on physical examination

A 
•	Painless firm rubbery lymphadenopathy 
Skin rashes 
o	Mycosis fungoides - looks like a fungal infection but is in fact a cutaneous T-cell lymphoma) 
•	Abdominal mass 
•	Hepatosplenomegaly

Signs of bone marrow involvement:
o Anaemia
o Infections
o Purpura

79
Q

Identify appropriate investigations for lymphoma (non-Hodgkin’s) and interpret the results

A 
Bloods
o	FBC
•	Anaemia 
•	Neutropaenia
•	Thrombocytopaenia 
o	High ESR and CRP 
o	Calcium may be raised 
o	HIV, HBV and HCV serology
Blood Film
o	Lymphoma cells may be visible in some patients
Bone Marrow Aspiration and Biopsy
Imaging - CXR, CT, PET
Lymph Node Biopsy - allows histopathological evaluation, immunophenotyping and cytogenetics 
Staging - Ann-Arbor
80
Q

Define macrocytic anaemia

A

• Anaemia associated with a high MCV of erythrocytes (> 100 fl in adults)

81
Q

Explain the aetiology/risk factors of macrocytic anaemia

A

• Megaloblastic - when the bone marrow produces unusually large, structurally abnormal, immature red cells

o Caused by deficiency of B12 or folate required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation
o Causes of Vitamin B12 Deficiency:
• Reduced absorption (e.g. post-gastrectomy, pernicious anaemia, terminal ileal resection or disease)
• Reduced intake (vegans)
• Abnormal metabolism (congenital transcobalamin II deficiency)
o Causes of Folate Deficiency:
• Reduced intake (alcoholics, elderly, anorexia)
• Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
• Reduced absorption
• Jejunal disease (e.g. coeliac disease)
• Drugs (e.g. phenytoin)
o Drugs
• Methotrexate (dihydrofolate reductase inhibitor)
• Hydroxyurea
• Azathioprine
• Zidovudine
• Non-Megaloblastic
o Alcohol excess
o Liver disease
o Myelodysplasia
o Multiple myeloma
o Hypothyroidism
o Haemolysis (shift to immature red cell form - reticulocytosis)
o Drugs (e.g. tyrosine kinase inhibitor)

82
Q

Summarise the epidemiology of macrocytic anaemia

A
  • More common in ELDERLY FEMALES

* Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West

83
Q

Recognise the presenting symptoms of macrocytic anaemia

A 
•	Non-specific symptoms of anaemia:
o	Tiredness 
o	Lethargy 
o	Dyspnoea
•	Family history of autoimmune disease 
•	Previous GI surgery
•	Symptoms of the CAUSE (e.g. weight loss, diarrhoea)
84
Q

Recognise the signs of macrocytic anaemia on physical examination

A 
•	Signs of Anaemia
o	Pallor 
o	Tachycardia 
o	Breathlessness 
•	Signs of Pernicious Anaemia
o	Mild jaundice 
o	Glossitis 
o	Angular stomatitis 
o	Weight loss 
•	Signs of B12 Deficiency
o	Peripheral neuropathy 
o	Ataxia 
o	Subacute combined degeneration of the spinal cord 
o	Optic atrophy 
o	Dementia
85
Q

Identify appropriate investigations for macrocytic anaemia

A

• Bloods
o FBC
• High MCV
• Pancytopaenia in megaloblastic anaemia
• Different degrees of cytopaenia in myelodysplasia
• Exclude reticulocytosis
o LFT
• High bilirubin (due to ineffective erythropoiesis or haemolysis)
o ESR
o TFT
o Serum vitamin B12
o Red cell folate
o Anti-parietal cell and anti-intrinsic factor antibodies
o Serum protein electrophoresis - looking for a dense band in myeloma
• Blood Film
o Large erythrocytes

o In megaloblastic anaemia:
• Megaloblasts
• Hypersegmented neutrophil nuclei

• Schilling Test
o Method of testing for pernicious anaemia
o B12 will only be absorbed when given with intrinsic factor
• Bone Marrow Biopsy (rarely needed)
• Investigations for the cause

86
Q

Generate a management plan for macrocytic anaemia

A 
•	Pernicious Anaemia
o	IM hydroxycobalamin for life 
•	Folate Deficiency
o	Oral folic acid 
o	If B12 deficiency is present, it must be treated before the folic acid deficiency
87
Q

Identify possible complications of macrocytic anaemia

A
  • Pernicious anaemia –> increased risk of gastric cancer

* Pregnancy - folate deficiency increases the risk of neural tube defects

88
Q

Summarise the prognosis for patients with macrocytic anaemia

A

• Majority are treatable if there are no complications

89
Q

Define microcytic anaemia

A

• Anaemia associated with a low MCV (< 80 fl)

90
Q

Explain the aetiology/risk factors of microcytic anaemia

A

• Iron Deficiency - MOST COMMON
o Iron deficiency can be caused by:
• Blood loss (e.g. GI)
• Reduced absorption (e.g. small bowel disease)
• Increased demands (e.g. growth, pregnancy)
• Reduced intake (e.g. vegans)
• Anaemia of Chronic Disease
o Microcytic anaemia in a patient with chronic disease
• Thalassemia
• Sideroblastic Anaemia
o Abnormality of haem synthesis
o It can be inherited or it can be secondary (e.g. to alcohol, drugs)

91
Q

Summarise the epidemiology of microcytic anaemia

A

• Iron deficiency anaemia is the MOST COMMON form of anaemia worldwide

92
Q

Recognise the presenting symptoms of microcytic anaemia

A 
•	Non-Specific
o	Tiredness
o	Lethargy 
o	Malaise 
o	Dyspnoea
o	Pallor
o	Exacerbation of ischaemic conditions (e.g. angina, intermittent claudication)
•	Lead Poisoning - can cause microcytic anaemia
Symptoms of lead poisoning
o	Anorexia
o	Nausea/Vomiting 
o	Abdominal pain 
o	Constipation 
o	Peripheral nerve lesions
93
Q

Recognise the signs of microcytic anaemia on physical examination

A 
•	Signs of anaemia
o	Pallor 
o	Brittle nails and hair 
o	Koilonychia (if severe)
•	Glossitis

• Angular stomatitis

• Signs of thalassemia
• Lead poisoning signs:
o Blue gumline

o Peripheral nerve lesions (causing wrist or foot drop)
o Encephalopathy
o Convulsions
o Reduced consciousness

94
Q

Identify appropriate investigations for microcytic anaemia

A 
•	Bloods
o	FBC
•	Low Hb 
•	Low MCV 
•	Reticulocytes 
o	Serum iron (low in iron deficiency)
o	Total iron binding capacity (high in iron deficiency)
o	Serum ferritin (low in iron deficiency)
o	Serum lead 
•	Blood Film
o	Iron deficiency anaemia:
•	Microcytic 
•	Hypochromic
•	Anisocytosis 
•	Poikilocytosis 
o	Sideroblastic anaemia:
•	Dimorphic blood film 
•	Hypochromic microcytic cells 
o	Lead poisoning:
•	Basophilic stippling

• Hb Electrophoresis
o Checking for haemoglobin variants and thalassemia
• Sideroblastic Anaemia
o Ring sideroblasts in the bone marrow
• Special investigations for iron deficiency anaemia if > 40 yrs and post-menopausal women
These are considered if no obvious cause of blood loss is identified
o Upper GI endoscopy
o Colonoscopy
o Haematuria

95
Q

Generate a management plan for microcytic anaemia

A 
•	Iron Deficiency - oral iron supplements 
•	Sideroblastic Anaemia
o	Treat the cause 
o	Pyridoxine used in inherited forms 
o	Blood transfusion and iron chelation can be considered if there is no response to other treatments 
•	Lead Poisoning
o	Remove the source 
o	Dimercaprol 
o	D-penicillinamine
96
Q

Identify possible complications of microcytic anaemia

A
  • High-output cardiac failure

* Complications related to the CAUSE

97
Q

Summarise the prognosis for patients with microcytic anaemia

A

• Depends on the CAUSE

98
Q

Define multiple myeloma

A

• Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of a monoclonal immunoglobulin (paraprotein, usually IgG or IgA)

99
Q

Explain the aetiology / risk factors of multiple myeloma

A
  • UNKNOWN
  • Possible viral trigger
  • Chromosomal aberrations are frequent
  • Associated with ionising radiation, agricultural work or occupational chemical exposures
100
Q

Summarise the epidemiology of multiple myeloma

A
  • Annual incidence: 4/100,000
  • Peak incidence: 70 yrs
  • Afro-Caribbean > White People > Asians
101
Q

Recognise the presenting symptoms of multiple myeloma

A

• May be an INCIDENTAL finding on routine blood tests

Bone Pain
o Usually in the back and ribs
o Sudden and severe bone pain may be caused by a pathological fracture

Infections - often recurrent

General
o	Tiredness 
o	Thirst 
o	Polyuria
o	Nausea 
o	Constipation
o	Mental change (due to hypercalcaemia)

Hyperviscosity
o Bleeding
o Headaches
o Visual disturbance

102
Q

Recognise the signs of multiple myeloma on physical examination

A
  • Pallor
  • Tachycardia
  • Flow murmur
  • Signs of heart failure
  • Dehydration
  • Purpura
  • Hepatosplenomegaly
  • Macroglossia
  • Carpal tunnel syndrome
  • Peripheral neuropathies
103
Q

Identify appropriate investigations for multiple myeloma and interpret the results

A 
Bloods
o	FBC - low Hb, normochromic normocytic
o	High ESR (and possible high CRP)
o	U&Es - high creatinine, high Ca2+
o	Normal ALP

Blood Film
o Rouleaux formation with bluish background (suggests high protein)

Serum or Urine Electrophoresis
o Serum paraprotein
o Bence-Jones protein (monoclonal immunoglobulin light chain that’s found in the urine and suggests multiple myeloma)

Bone Marrow Aspirate and Trephine
o High plasma cells (usually > 20%)

Chest, Pelvic or Vertebral X-Ray
o Osteolytic lesions without surrounding sclerosis
o Pathological fractures

104
Q

Define myelodysplasia

A

• A series of haematological conditions characterised by chronic cytopaenia (anaemia, neutropaenia, thrombocytopaenia) and abnormal cellular maturation
• There are FIVE subgroups:
o Refractory anaemia (RA)
o RA with ringed sideroblasts (RARS)
o RA with excess blasts (RAEB)
o Chronic myelomonocytic leukaemia (CMML)
o RAEB in transformation (RAEB-t)

105
Q

Explain the aetiology of myelodysplasia

A
  • It may be PRIMARY (intrinsic bone marrow problem)
  • It may arise in patients who have received chemotherapy or radiotherapy for previous malignancies
  • Patients may have chromosomal abnormalities
106
Q

Summarise the epidemiology of myelodysplasia

A
  • Mean age of diagnosis: 65-75 yrs
  • More common in MALES
  • 2 x as common as AML
107
Q

Recognise the presenting symptoms of myelodysplasia

A

• May be ASYMPTOMATIC and diagnosed on routine blood counts
• Symptoms of Bone Marrow Failure
o Anaemia (fatigue, dizziness)
o Neutropaenia (recurrent infections)
o Thrombocytopaenia (easy bruising, epistaxis)
• Check risk factors:
o Occupational exposure to toxic chemicals
o Prior chemotherapy or radiotherapy

108
Q

Recognise the signs of myelodysplasia on physical examination

A 
•	Signs of bone marrow failure
o	Anaemia (pallor, cardiac flow murmur)
o	Neutropaenia (infections)
o	Thrombocytopaenia (purpura or ecchymoses) 
o	Gum hypertrophy 
o	Lymphadenopathy
o	Spleen NOT enlarged (except in CMML)
109
Q

Identify appropriate investigations for myelodysplasia

A 
•	Bloods
o	FBC - pancytopaenia
•	Blood Film
o	Normocytic or macrocytic red cells 
o	Variable microcytic red cells in RARS
o	Low granulocytes 
o	Granulocytes are not granulated 
o	High monocytes in CMML 
•	Bone marrow aspire or biopsy
o	Hypercellularity 
o	Ringed sideroblasts (haemosiderin deposits in the mitochondria of erythroid precursors forming an apparent ring around the nucleus)

o Abnormal granulocyte precursors
o 10% show marrow fibrosis

110
Q

Define myelofibrosis

A

• Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis in associated with extramedullary haematopoiesis and splenomegaly
• Pathogenesis:
o Abnormal megakaryocytes release cytokines that stimulate fibroblast proliferation and collagen deposition in bone marrow
o This results in extramedullary haematopoiesis in the spleen and liver

111
Q

Explain the aetiology/risk factors of myelofibrosis

A
  • Primary stem cell defect is UNKNOWN
  • It results in increased numbers of abnormal megakaryocytes with stromal proliferation secondary to growth factors released by megakaryocytes
  • 30% of patients have a previous history of polycythaemia rubra vera or essential thrombocythaemia (overproduction of platelets by the bone marrow)
112
Q

Summarise the epidemiology of myelofibrosis

A
  • RARE

* Peak onset: 50-70 yrs

113
Q

Recognise the presenting symptoms of myelofibrosis

A 
•	ASYMPTOMATIC - diagnosed after routine blood count 
•	Systemic Symptoms
o	COMMON:
•	Weight loss 
•	Anorexia
•	Fever 
•	Night sweats 
•	Pruritis 
o	UNCOMMON:
•	LUQ pain 
•	Indigestion (due to massive splenomegaly) 
•	Bleeding 
•	Bone pain 
•	Gout
114
Q

Recognise the signs of myelofibrosis on physical examination

A
  • SPLENOMEGALY

* Hepatomegaly (present in 50-60%)

115
Q

Identify appropriate investigations for myelofibrosis

A

• Bloods
o FBC
• Initially variable Hb, WCC and platelets
• Later stages –> anaemia, leukopaenia, thrombocytopaenia
o LFTs - abnormal
• Blood Film
o Leucoerythroblastic changes (red and white cell precursors in the peripheral blood)
o ‘Tear drop’ poikilocyte red cells

• Bone Marrow Aspirate or Biopsy
o Aspiration usually unsuccessful - ‘dry tap’ (due to fibrosis)
o Trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining

116
Q

Define normocytic anaemia

A

• Anaemia with a normal MCV (80-100).

117
Q

Explain the aetiology/risk factors of normocytic anaemia

A

• Causes:
o Decreased production of normal-sized blood cells (e.g. anaemic of chronic disease, aplastic anaemia)
o Increased production of HbS (sickle cell disease)
o Increased destruction of red blood cells (e.g. haemolysis, post-haemorrhagic anaemia)
o Uncompensated increase in plasma volume (e.g. pregnancy, fluid overload)
o Vitamin B2 deficiency
o Vitamin B6 deficiency

118
Q

Summarise the epidemiology of normocytic anaemia

A

• COMMON

119
Q

Recognise the presenting symptoms and signs of normocytic anaemia

A

• Typical symptoms and signs of anaemia (depends on severity)
o E.g. breathlessness, fatigue, conjunctival pallor

120
Q

Identify appropriate investigations for normocytic anaemia

A
  • FBC - check Hb and MCV

* Check history for haemorrhage

121
Q

Define polycythaemia

A 
•	An increase in haemoglobin concentration above the upper limit of normal for a person's age and sex. Classified into:
o	Relative Polycythaemia = normal red cell mass but low plasma volume
o	Absolute (True) Polycythaemia = increased red cell mass
122
Q

Explain the aetiology/risk factors of polycythaemia

A

• Polycythaemia Rubra Vera
o Characterised by clonal proliferation of myeloid cells
o They have varied morphologic maturity and haematopoietic efficiency
o Mutations in JAK2 tyrosine kinase are involved
• Secondary Polycythaemia
o Appropriate increase in erythropoietin
• Due to chronic hypoxia (e.g. chronic lung disease, living at high altitude)
• This leads to upregulation of erythropoiesis
o Inappropriate increase in erythropoietin
• Renal (carcinoma, cysts, hydronephrosis)
• Hepatocellular carcinoma
• Fibroids
• Cerebellar haemangioblastoma
• Secondary polycythaemia may be due to erythropoietin abuse by athletes
• Relative Polycythaemia
o Dehydration (e.g. diuretics, burns, enteropathy)
o Gaisbock’s syndrome
• Occurs in young male smokers with hypertension, which results in a decrease in plasma volume and an apparent increase in red cell count

123
Q

Summarise the epidemiology of polycythaemia

A
  • Annual UK incidence: 1.5/100,000

* Peak age: 45-60 yrs

124
Q

Recognise the presenting symptoms of polycythaemia

A
  • Headaches
  • Dyspnoea
  • Tinnitus
  • Blurred vision
  • Pruritis after hot bath
  • Night sweats
  • Thrombosis (DVT, stroke)
  • Pain from peptic ulcer disease
  • Angina
  • Gout
  • Choreiform movements
125
Q

Recognise the signs of polycythaemia on physical examination

A

• Plethoric complexion (red, ruddy)

  • Scratch marks from itching
  • Conjunctival suffusion (redness of the conjunctiva)
  • Retinal venous engorgement
  • Hypertension
  • Splenomegaly (in 75% of cases)
  • Signs of underlying aetiology in secondary polycythaemia
126
Q

Identify appropriate investigations for polycythaemia

A 
•	Required for Diagnosis
o	FBC 
•	High Hb
•	High haematocrit 
•	Low MCV
•	Isotope Dilution Techniques
o	Allows confirmation of plasma volume and red cell mass 
o	Distinguishes between relative and absolute polycythaemia 
•	Polycythaemia Rubra Vera
o	High WCC 
o	High platelets 
o	Low serum EPO
o	JAK2 mutation 
o	Bone marrow trephine and biopsy shows erythroid hyperplasia and raised megakaryocytes 
•	Secondary Polycythaemia
o	High serum EPO 
o	Exclude chronic lung disease/hypoxia 
o	Check for EPO-secreting tumours
127
Q

Define sickle cell disease

A

• A chronic condition with sickling of red blood cells caused by inheritance of haemoglobin S (HbS)
o Sickle Cell Anaemia = Homozygous HbS
o Sickle Cell Trait = Carrier of one copy of HbS
o Sickle Cell Disease = includes compound heterozygosity for HbS and:
• HbC (abnormal haemoglobin in which glutamic acid is replaced by lysine at the 6th position in the beta-globin chain)
• Beta-thalassemia

128
Q

Explain the aetiology/risk factors of sickle cell disease

A

• Autosomal recessive
• Caused by a point mutation in the beta-globin gene resulting in the substitution of glutamic acid in position 6 by valine
• This results in the formation of abnormal haemoglobin S
• Deoxygenation of HbS alters the conformation resulting in sickling of red cells
• Sickling makes the red cells more fragile and inflexible
• These sickled red cells are prone to:
o Sequestration and destruction (reduced red cell survival ~ 20 days)
o Occlusion of small blood vessels causing hypoxia, which leads to further sickling and occlusion
• Factors that precipitate sickling:
o Infection
o Dehydration
o Hypoxia
o Acidosis

129
Q

Summarise the epidemiology of sickle cell disease

A
  • Rarely presents before 4-6 months (because HbF can compensate for the defect in adult haemoglobin)
  • Common in Africa, Caribbean, Middle-East and other areas with a high prevalence of malaria
130
Q

Recognise the presenting symptoms of sickle cell disease

A

• Symptoms secondary to VASO-OCCLUSION or INFARCTION:
o Autosplenectomy (splenic atrophy or infarction)
• Leads to increased risk of infections with encapsulated organisms (e.g. pneumococcus, meningococcus)
o Abdominal Pain
o Bones
• Painful crises affect small bones of the hands and feet causing dactylitis in CHILDREN

•	Painful crises mainly affect the ribs, spine, pelvis and long bones in ADULTS
o	Myalgia and Arthralgia 
o	CNS 
•	Fits and strokes 
o	Retina 
•	Visual loss (proliferative retinopathy)
•	Symptoms of SEQUESTRATION CRISIS
o	NOTE: sequestration crises occur due to pooling of red cells in various organs (mainly the spleen)
o	Liver --> exacerbation of anaemia 
o	Lungs --> acute chest syndrome
•	Breathlessness 
•	Cough 
•	Pain 
•	Fever 
o	Corpora cavernosa
•	Persistent painful erection (priapism)
•	Impotence
131
Q

Recognise the signs of sickle cell disease on physical examination

A

• Signs secondary to VASO-OCCLUSION, ISCHAEMIA or INFARCTION
o Bone - joint or muscle tenderness or swelling (due to avascular necrosis)
o Short digits - due to infarction in small bones of the hands

• Retina - cotton wool spots due to retinal ischaemia
• Signs secondary to SEQUESTRATION CRISES
o Organomegaly
• The spleen is ENLARGED in early disease
• Later on, the spleen will reduce in size due to splenic atrophy
o Priapism
• Signs of anaemia

132
Q

Identify appropriate investigations for sickle cell disease

A 
•	Bloods
o	FBC
•	Low Hb 
•	Reticulocytes:
	HIGH - in haemolytic crises 
	LOW - in aplastic crises 
o	U&Es
•	Blood Film
o	Sickle cells

o Anisocytosis (variation in size of red cells)
o Features of Hyposplenism:
• Target cells
• Howell-Jolly bodies
• Sickle Solubility Test
o Dithionate is added to the blood
o In sickle cell disease you get increased turbidity
• Haemoglobin Electrophoresis
o Shows HbS
o Absence of HbA (if homozygous HbS)
o High HbF
• Hip X-Ray
o Femoral head is a common site of avascular necrosis
• MRI or CT Head
o If there are neurological complications

133
Q

Generate a management plan for sickle cell disease

A 
•	ACUTE (PAINFUL CRISES)
o	Oxygen
o	IV Fluids 
o	Strong analgesia (IV opiates)
o	Antibiotics
•	Infection Prophylaxis
o	Penicillin V 
o	Regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)
•	Folic Acid
o	If severe haemolysis or in pregnancy 
•	Hydroxyurea/Hydroxycarbamide
o	Increases HbF levels 
o	Reduces the frequency and duration of sickle cell crisis 
•	Red Cell Transfusion
o	For SEVERE anaemia 
o	Repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises 
•	Advice
o	Avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening 
•	Surgical
o	Bone marrow transplantation 
o	Joint replacement in cases with avascular necrosis
134
Q

Identify the possible complications of sickle cell disease

A 
•	Aplastic crises 
o	Infection with Parvovirus B19 can lead to a temporary cessation of erythropoiesis (which can cause red cell count to plummet in sickle cell patients because their red cells have a shortened life span and can't tolerate a cessation of erythropoiesis)
•	Haemolytic crises 
•	Pigment gallstones 
•	Cholecystitis 
•	Renal papillary necrosis 
•	Leg ulcers 
•	Cardiomyopathy
135
Q

Summarise the prognosis for patients with sickle cell disease

A

• Most patients with sickle cell disease who manage their disease well will survive until around the age of 50 yrs
• Mortality is usually the result of:
o Pulmonary or neurological complications in ADULTS
o Infection in CHILDREN

136
Q

Define thalassemia

A

• A group of genetic disorders characterised by reduced globin chain synthesis

137
Q

Explain the aetiology/risk factors of thalassemia

A

• Autosomal recessive
• Result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes
• This leads to:
o Ineffective erythropoiesis
o Haemolysis
o Anaemia
o Extramedullary haematopoiesis
• TYPES:
o ALPHA THALASSEMIA - reduction in alpha-globin chain synthesis. There are FOUR alpha-globin genes on the chromosome.
• 4 gene deletion = Haemoglobin Barts Hydrops Fetalis (intrauterine death)
• 3 gene deletion = Haemoglobin H –> microcytic hypochromic anaemia and splenomegaly
• 2 gene deletion = Alpha 0 thalassemia –> microcytic hypochromic red cells, NO ANAEMIA
• 1 gene deletion = Alpha+ thalassemia –> microcytic hypochromic red cells, NO ANAEMIA
o BETA THALASSEMIA
• Beta Thalassemia Major (homozygous beta thalassemia) –> little or no beta-chain synthesis
• Beta Thalassemia Intermedia - mild defect in beta-chain synthesis leads to:
 Microcytic anaemia
 Reduced alpha-chain synthesis
 Increased gamma-chain synthesis
• Beta Thalassemia Trait (heterozygous carrier state)
 ASYMPTOMATIC
 Mild microcytic anaemia
 Increased red cell count

138
Q

Summarise the epidemiology of thalassemia

A
  • WORLDWIDE

* Most common in the MEDITERRANEAN and areas of the Middle-East

139
Q

Recognise the presenting symptoms of thalassemia

A 
•	Beta Thalassemia Major
o	Anaemia 
o	Presenting at 3-6 months
•	This is when the change from HbF to HbA takes place 
•	Failure to thrive 
•	Prone to infection
•	Alpha or Beta Thalassemia Trait
o	May be ASYMPTOMATIC
o	Detected during routine blood tests or due to family history
140
Q

Recognise the signs of thalassemia on physical examination

A 
•	Beta Thalassemia Major
o	Pallor
o	Malaise 
o	Dyspnoea
o	Mild jaundice 
o	Frontal bossing 
o	Thalassaemia facies (facial features caused by marrow hyperplasia)
o	Hepatosplenomegaly (due to erythrocyte pooling and extramedullary haematopoiesis)
o	Patients with beta-thalassemia intermedia may also have these signs
141
Q

Identify appropriate investigations for thalasemia

A 
•	Bloods
o	FBC
•	Low Hb 
•	Low MCV (microcytic anaemia)
•	Low MCH
•	Blood Film
o	Hypochromic microcytic anaemia 
o	Target cells 
o	Nucleated red cells 
o	High reticulocyte count
•	Hb Electrophoresis
o	Absent or reduced HbA 
o	High HbF 
•	Bone Marrow
o	Hypercellular 
o	Erythroid hyperplasia
•	Genetic Testing (rarely used)
•	Skull X-Ray
o	'Hair on end' appearance in beta thalassemia major 
•	This is caused by expansion of marrow into the cortex
142
Q

Define vitamin B12 deficiency

A

• Having insufficient vitamin B12 to meet demands.

143
Q

Explain the aetiology/risk factors of vitamin B12 deficiency

A
  • B12 is found in meat and animal protein foods
  • Absorption occurs in the terminal ileum and requires intrinsic factor (produced by gastric parietal cells)
  • Pernicious anaemia is an autoimmune condition involving gastritis, atrophy of all layers of the body and fundus of the stomach and loss of normal gastric glands, parietal and chief cells

• Pernicious anaemia leads to a lack of intrinsic factor
• Pernicious anaemia accounts for 80% of megaloblastic anaemia due to impaired vitamin B12 absorption
• Other causes of B12 deficiency:
o Gastric - gastrectomy, atrophic gastritis
o Inadequate intake (e.g. vegan)
o Intestinal - malabsorption, ileal resection, Crohn’s affecting the terminal ileum, tropical sprue
o Drugs - colchicine, metformin

144
Q

Summarise the epidemiology of vitamin B12 deficiency

A
  • Peak age = 60 yrs

* Vegans have a higher risk of dietary vitamin B12 deficiency

145
Q

Recognise the presenting symptoms of vitamin B12 deficiency

A 
•	Typical anaemia symptoms 
•	Fatigue 
•	Lethargy
•	Dyspnoea 
•	Faintness 
•	Palpitations 
•	Headache 
•	Neurological Symptoms
o	Paraesthesia 
o	Numbness 
o	Cognitive changes 
o	Visual disturbances
146
Q

Recognise the signs of vitamin B12 deficiency on physical examination

A

• Pallor
• Heart failure (can occur with severe anaemia)
• Glossitis
• Angular stomatitis
• Neuropsychiatric: irritability, dementia, depression
• Neurological
o Subacute combined degeneration of the spinal cord
o Peripheral neuropathy

147
Q

Identify appropriate investigations for vitamin B12 deficiency

A

• There is NO gold standard for diagnosing vitamin B12 deficiency
• Measurement of serum B12 is not very accurate or reliable
• Other new tests: plasma total homocysteine, plasma methylmalonic acid, holotranscobalamin
• FBC and blood film
o Hypersegmented neutrophils
o Oval macrocytes
o Circulating megaloblasts
• Pernicious Anaemia Tests
o Anti-intrinsic factor antibodies
o Anti-parietal cell antibodies
o Schilling test

148
Q

Define von Willebrand disease

A

• Bleeding disorder which may present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after trauma and easy bruising
• There are THREE types of von Willebrand disease:
o Type 1 - the von Willebrand factor works well but there isn’t enough of it
o Type 2 - there are normal levels of von Willebrand factor but it is abnormal and doesn’t function correctly
o Type 3 - there is NO von Willebrand factor

149
Q

Explain the aetiology/risk factors of von Willebrand disease

A
  • Caused by abnormality in the expression/function of vWF
  • Usually autosomal dominant
  • vWF is an adhesive bridge between platelets and the damaged subendothelial collagen
  • vWF also binds to factor VIII and prevents its degradation
150
Q

Recognise the signs and presenting symptoms of von Willbrand disease

A
  • Easy bruising
  • Epistaxis - hard to stop
  • Prolonged bleeding from gums after dental procedures
  • Heavy or prolonged menstrual bleeding
  • Blood in stools
  • Blood in urine
  • Heavy bleeding from a cut or other accident
151
Q

Identify appropriate investigations for von Willebrand disease

A
  • Bleeding time - HIGH
  • APTT - HIGH
  • Factor VIII - LOW
  • vWF - LOW
  • Ristocetin cofactor - reduced platelet aggregation by vWF in the presence of ristocetin

Year 6 ICSM (18 decks)

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