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Year 3 ICSM Sofia > Haematology > Flashcards

Haematology Flashcards

1
Q

What is aplastic anaemia?

A

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

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2
Q

What is the aetiology of idiopathic aplastic anaemia?

A

May be due to destruction or suppression of the stem cell by autoimmune mechanisms

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3
Q

What is the aetiology of acquired anaplastic anaemia?

A
  • Drugs (chloramphenicol, gold, alkylating agents, antiepileptics, sulphonamids, methotrexate, nifedipine)
  • Chemicals (DDT, benzene)
  • Radiation
  • Viral infection (B19 parvovirus, HIV, EBV)
  • Paroxysmal nocturnal haemoglobinuria
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4
Q

What is the aetiology of inherited aplastic anaemia?

A
  • Fanconi’s anaemia

- Dyskeratosis congenita (associated with reitculated hyperpigmented rash, nail dystrophy and mucosa leukoplakia)

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5
Q

What is the epdemiology of aplastic anaemia?

A
  • Can occur at any age

- Slightly more common in males

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6
Q

What are the presenting symptoms of aplastic anaemia?

A

Slow (months) or rapid (days) onset

  • Anaemia: Tiredness, lethargy, dyspnoea
  • Thrombocytopaenia: Easy bruising, bleeding gums, epistaxis
  • Leukopenia: Increased frequency and severity of infections
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7
Q

What are the signs of aplastic anaemia on examination?

A
  • Anaemia: Pale
  • Thrombocytopaenia: Petechiae, bruises
  • Leukopenia: Multiple bacterial or fungal infections. No hepatomegaly, splenomegaly or lymphadenopathy
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8
Q

What are the investigations for aplastic anaemia?

A
  • Blood: FBC (reduced Hb, platelets, WCC, normal MCV, low or absent reticulocytes)
  • Blood film: Exclude leukaemia
  • Bone marrow trephine biopsy:
  • Criteria for severe aplastic anaemia (AA)
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9
Q

What is a blood transfusion?

A

Process of receiving blood or blood products into one’s circulation intravenously

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10
Q

What are the indications for a blood transfusion?

A
  • Anaemia
  • Major surgical operation
  • Accidents resulting in considerable blood loss
  • Cancer pts requiring therapy
  • Severe burn victims
  • Pts of hereditary disorders like Haemophilia and Thalassaemia
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11
Q

What are the possible complications of blood transfusions?

A
  • Acute haemolytic reactions
  • Delayed haemolytic reactions
  • Febrile nonhaemolytic reactions
  • Allergic
  • Tranfusion-associated acute lung injury
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12
Q

What is disseminated intravascular coagulation (DIC)?

A

Disorder of the clotting cascade that can complicate a serious illness. May occur in 2 forms:

1) Acute overt form where there is bleeding and depletion of platelets and clotting factors
2) Chronic non-overt form where thromboembolism is accompanies by generalised activation of the coagulation system

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13
Q

What is the aetiology of DIC?

A
  • Infection: Particularly Gram-negative sepsis
  • Obstetric complications: Missed miscarriage, severe pre-eclampsia, placental abruption, amniotic emboli
  • Malignancy: Acute promyelocytic leukaemia (acute DIC), lung, breast, GI, malignancy (chronic DIC
  • Also haemolytic transfusion reaction, burns, severe liver disease , aortic aneurysms, haemangiomas
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14
Q

What is the aetiology of acute DIC?

A
  • Activation of coagulation is a consequence of endothelial damage and increased release of granulocyte/macrophage procoagulant substances e.g. tissue factor
  • Explosive thrombin generation depletes clotting factors and platelets while simultaneously activating the fibrinolytic system
  • Leads to bleeding in subcutaneous tissues, skin and mucous membranes
  • Occlusion of blood vessels by fibrin results in microangiopathic haemolytic anaemia and ischaemic organ dammage
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15
Q

What is the epidemiology of DIC?

A

Seen in any severely ill patient

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16
Q

What are the presenting symptoms of DIC?

A

If pt is severely unwell with symptoms of the underlying disease, confusion, dyspnoea and evidence of bleeding

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17
Q

What are the signs of DIC on examination?

A

Signs of underlying aetiology, fever, evidence of shock (hypotension, tachycardia)

  • Acute DIC: Petechiae, purpura, echhymoses, epistaxis, mucosal bleeding, over haemorrhage. Signs of end organ damage (e.g. local infarction or gangrene), respiratory distress, oliguria caused by renal failure
  • Chronic DIC: Signs of deep venous or arterial thrombosis or embolism, superficial venous thrombosis, especially without varicose veins
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18
Q

What are the investigations for DIC?

A
  • Blood: FBC (reduced platelets, Hb. Clotting: Increased APTT/PT/TT, fibrin degradation products and d-dimers, reduced fibrinogen)
  • Peripheral blood film: Red blood cell fragments (schistocytes). Other investigations according to aetiology
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19
Q

What is haemochromatosis?

A

Body iron overload resulting from excessive intestinal iron absorption which may lead to organ damage (particular liver, joints, pancreas, pituitary and heart)

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20
Q

What is the aetiology of haemochromatosis?

A
  • Mutation in the HFE gene on chromsome 6p

- Most common mutation is C282Y, less common is H63D

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21
Q

What is the epidemiology of haemochromatosis?

A
  • Carrier frequency is up to 1/10, not all express disease
  • Age of presentation = 40-60 yrs typically
  • Females have later onset and less severe presentation as a result of iron loss through menstruation
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22
Q

What are the presenting symptoms of haemochromatosis?

A
  • May be asymptomatic
  • Non specific symptoms: weakness, fatigue, lethargy and abdo pain
  • Later features: small/large joint pains (most commonly 2nd/3rd MCP joints), symptoms of liver disease, DM, hypogonadism, cardiac failure
  • Exclude causes of secondary iron overload (e.g. multiple transfusions)
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23
Q

What are the signs of haemochromatosis on examination?

A

May be normal, but with severe iron overload:

  • Skin: Pigmentation (‘slate-grey) resulting from increased melanin deposits
  • Liver: Hepatosplenomegaly
  • Heart: Signs of heart failure, arrhythmias
  • Hypogonadism: Testicular atrophy, loss of hair, gynaecomastia
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24
Q

What are the investigations for haemochromatosis?

A
  • Blood: Increased iron, ferritin and transferrin sats, reduced TIBC
  • Gene typing of HFE
  • Test for complications in various organs, LFTs, fasting or random blood glucose, pituitary function test, ECG, Joint X-ray
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25
Q

What is haemolytic anaemia?

A

Premature erythrocyte breakdown causing shortened erythrocyte life span (less than 120 days) and anaemia

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26
Q

What is the aetiology of hereditary haemolytic anaemia?

A
  • Membrane defects: Hereditary spherocytosis, elliptocytosis
  • Metabolic defects: G6PD deficiency. Pyruvate kinase deficiencies (autosomal recessive)
  • Haemoglobinopathies: Sickle cell disease, thalassaemia
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27
Q

What is the aetiology of acquired haemolytic anaemia?

A
  • Autoimmune: Warm or cold antibodies attach to erythrocytes causing intravascular haemolysis and extravascular haemolysis
  • Isoimmune: Transfusion reaction, haemolytic disease of the newborn
  • Drugs: Penicillin, quinine
  • Trauma: Microangiopathic haemolytic anaemia caused by red cell fragmentation in abnormal microcirculation (haemolytic uraemic syndrome, DIC, pre-eclampsia), artificial heart valves
  • Infection: Malaria, sepsis
  • Paroxysmal nocturnal haemoglobinuria
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28
Q

What is the epidemiology of haemolytic anaemia?

A
  • Common
  • Genetic causes prevalent in African, Mediterranean, Middle Eastern populations
  • Hereditary spherocytosis is most common inherited haemolytic anaemia in Northern Europe
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29
Q

What are the presenting symptoms of haemolytic anaemia?

A
  • Jaundice
  • Haematuria
  • Anaemia
  • Ask about systemic illness, family, drug and travel history
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30
Q

What are the signs of haemolytic anaemia on examination?

A
  • Pallor (anaemia)
  • Jaundice
  • Hepatosplenomegaly
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31
Q

What are the investigations for haemolytic anaemia?

A
  • Blood: FBC (reduced Hb, raised reticulocytes, MC, unconjugated bilirubin), U&E, folate
  • Blood film: Leucoerythroblastic picture, macrocytosis, nucleates erythrocytes , polychromasia
  • Urine: Raised urobilirubinogen
  • Direct Coombs’ test: Identifies erythrocytes coated with antibodies
  • Osmotic fragility test
  • Ham’s test
  • Hb electrophoresis
  • Bone marrow biopsy
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32
Q

What is haemolytic uraemic syndrome?

A

Triad of microagniopathic haemolytic anaemia, acute renal failure and thrombocytopaenia. 2 forms

1) D+ (diarrhoea-associated form)
2) D- (no prodromal illness identified

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33
Q

What is the aetiology of haemolytic uraemic syndrome?

A
  • Aetiological factor causing endothelial injury result in platelet aggrregation, release of unusually large wVF multimers and activation of platelets and the clotting cascade
  • Results in small vessel thrombosis, particularly the glomerular afferent arteriole and capillaries which undergo fibrinoid necrosis
  • Followed by renal ischaemic and acute renal failure
  • Thrombi promote intravascular haemolysis
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34
Q

What are the risk factors for haemolytic uraemic syndrome?

A
  • Infection: Verotoxin-producing E.coli, Shigella neuraminidase-producing infections, HIV
  • Drugs: Oral contraceptive pill, ciclosporin, mitomycin, 5-fluorouracil
  • Others: Malignant hypertension, malignany, pregnancy, SLE, scleroderma
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35
Q

What is the epidemiology of haemolytic uraemic syndrome?

A
  • Uncommon
  • D+ often affects young children, occurs more often in summer in endemics and is most common cause of acute renal failure in children
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36
Q

What are the presenting symptoms of haemolytic uraemic syndrome?

A
  • GI: Severe abdominal colic, water diarrhoea that becomes bloodstained
  • General: Malaise, fatigue, nausea, fever, less than 38 (D+)
  • Renal: Oliguria or anuria, haematuria
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37
Q

What are the signs of haemolytic uraemic syndrome on examination?

A
  • General: Pallor (from anaemia), slight jaundice (from haemolysis), bruising (severe thrombocytopaenia), generalised oedema, hypertension and retinopathy
  • GI: Abdominal tenderness
  • CNS signs: Weakness, reduced vision, fits, reduced consciousness
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38
Q

What would be the blood results after investigating haemolytic uraemic syndrome?

A
  • FBC: Normocytic anaemia, raised neutrophils, reduced platelets
  • U&E: Raised urea, creatinine, urate, K+, reduced Na+
  • Clotting: Normal Pit, APTT and fibrinogen levels, abnormality may indicate DIC
  • LFT: Raised unconjugated bilirubin, raised LDH from haemolysis
  • Blood cultures
  • ABG: Reduced pH, bicarbonate, pac02, normal anion group
  • Blood film: Fragmented red blood cells, raised reticulocytes, spherocytes
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39
Q

What are the investigations for haemolytic uraemic syndrome?

A
  • Urine: more than 1g protein/24h
  • Stool samples
  • Renal biopsy: contraindicated in severe thrombocytopaenia
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40
Q

What is haemophilia?

A

Bleeding diatheses resulting from an inherited deficiency of a clotting factor

1) Haemophilia A (most common): deficiency of factor VIII
2) Haemophilia B: deficiency of factor IX (Christmas disease)
3) Haemophilia C (rare): Deficiency of factor XI

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41
Q

What is the aetiology of haemophilia?

A
  • A & B exhibit X-linked recessive inheritance.
  • Factor VIII is vital co-factor in intrinsic pathway of coagulation cascade. Activated factor IX activates factor X (X -> Xa)
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42
Q

What is the epidemiology of haemophilia?

A
  • A= 1/5-10,000 males
  • B= 1/25-30,000 males
  • C more common in Ashkenazi Jews
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43
Q

What are the presenting symptoms of haemophilia?

A
  • Symptoms usually begin from early childhood
  • Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
  • Painful bleeding into muscles. Haematuria. Excessive bleeding or bleeding after surgery or trauma
  • Female carriers usually asymptomatic, but may have low enough levels to cause excess bleeding after trauma
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44
Q

What are the signs of haemophilia on examination?

A
  • Multiple bruises
  • Muscle haematomas. Haemarthroses. Joint deformity,
  • Nerve palsies (nerve compression by haematoma)
  • Signs of iron deficiency anaemia
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45
Q

What are the investigations of haemophilia?

A
  • Clotting screen (raised APTT, reflects the activity of intrinsic and the common pathway)
  • Coagulation factor assays (reduced factor VIII, IX or CI depending on condition)
  • Other investigations according to complications (e.g. arthroscopy)
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46
Q

What is immune thrombocytopenic purpura (ITP)?

A

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

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47
Q

What is the aetiology of ITP?

A
  • Often idiopathic
  • Acute ITP usually seen after a viral infection in children, while chronic form is more common in adults
  • May be associated with infections (malaria, EBV, HIV), autoimmune disease (SLE, thyroid disease), malignancies and drugs (e.e. quinine)
  • Autoantibodies that bind to platelet membrane proteins results in thrombocytopenia (glycoprotein IIb/IIIa and Ib/IX)
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48
Q

What is the epidemiology of ITP?

A
  • Acute ITP presents in children between 2-7 yrs

- Chronic ITP seen in adults & is 4x more common in women

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49
Q

What are the presenting symptoms of ITP?

A
  • Easy bruising
  • Mucosal bleeding
  • Menorrhagia
  • Epistaxis
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50
Q

What are the signs of ITP on examination?

A
  • Visible petechiae, bruises (purpura or ecchymoses

- Typically, signs of other illness (e.g. infections, wasting, splenomegaly) would suggest other causes

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51
Q

What are the investigations for ITP?

A
  • Diagnosis of exclusion: Excluse myelodysplasia, acute leukaemia, marrow infiltration
  • Blood: FBC (reduced platelets), clotting screen, autoantibodies
  • Blood film: Rule out ‘pseudothrombocytopenia’) caused by platelet clumping given falsely low counts
  • Bone marrow: Exclude other pathology
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52
Q

What is acute lymphoblastic leukaemia (ALL)?

A

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

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53
Q

What is the aetiology of ALL?

A

Lymphoblasts undergo malignant transformation and proliferation, with subsequent replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues

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54
Q

What are the risk factors ALL?

A
  • Environment (radiation, viruses)
  • Genetic (Down’s syndrome
  • Neurofibromatosis type 1
  • Fanconi’s anaemia
  • Achondroplasia
  • Ataxia telangiectasia
  • Xeroderma pigmentosum
  • X-linked agammaglobulinaemia
  • Increased risk in siblings
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55
Q

What is the epidemiology of ALL?

A
  • Most common malignancy of childhood
  • Peak incidence 2-5 yrs
  • Second peak in elderly
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56
Q

What are the presenting symptoms of ALL?

A
  • Symptoms of bone marrow failure: Anaemia (fatigue dyspnoea), bleeding (spontaneous bruising, bleeding gums, menorrhagia), opportunistic infections (bacteria, viral, fungal, protozoal)
  • Symptoms of organ infiltration: Tender bones, enlarged lymph nodes, mediastinal compression (in T-cell ALL), meningeal involvement (headache, visual disturbances, nausea)
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57
Q

What are the signs of ALL on examination?

A

Signs of bone marrow failure: Pallor, bruising, infections (e.g. fever, GI, skin, respiratory systems)
- Signs of organ infiltration: Lymphadenopathy, hepatosplenomegaly, cranial nerve palsies, retinal haemorrhage or papilloedema or fundoscopy, leukaemia infiltration of the anterior chamber of the eye (mimic hypopyon), testicular swelling

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58
Q

What are the investigations for ALL?

A
  • Blood: FBC (normochromic, normocytic anaemia, reduced platelets, variable WCC) raised uric acid & LDH, clotting screen
  • Blood film: Lymphoblasts seen
  • Bone marrow aspirate or trephine biopsy: Hypercellular with more than 30% lymphoblasts
  • Immunophenotypic
  • Cytogenics
  • Cytochemistry
  • Lumbar puncture: for CNS involvement
  • CXR: mediastinal lymphadenopathy, thymic enlargement, lytic bone lesiosn
  • Bone radiographs: Mottled appearance with ‘punched out’ lesions
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59
Q

What is acute myeloblastic leukaemia (AML)?

A

Malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood

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60
Q

What is the aetiology of AML?

A

Myeloblasts, arrested at early stage of development, with varying cytogenetic abnormalities, undergo malignant transformation and proliferation. Subsequence replacement of normal marrow elements, bone marrow failure

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61
Q

What is the epidemiology of AML?

A

Most common acute leukaemia in adults

Incidence increases with age

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62
Q

What are the presenting symptoms of AML?

A
  • Symptoms of bone marrow failure: Anaemia (lethargy, dyspnoea), bleeding (thrombocytopenia of DIC), opportunistic or recurrent infections
  • Signs of tissue infiltration: Gum swelling or bleeding, CNS involvement (headaches, nausea, diplopia), especially with M4 & M5 variants
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63
Q

What are the signs of AML on examination?

A
  • Signs of bone marrow failure: Pallor, cardiac flow murmur, echhymoses, bleeding, opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections, PCP)
  • Signs of tissue infiltration: Skin rashes, gum hypertrophy, deposit of leukaemic blasts may rarely be seen in the eye (chloroma), tongue and bone- in latter may cause fractures
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64
Q

What are the investigations for AML?

A
  • Blood: FBC (reduced Hb, platelets, variable WCC), raised uric acid & LDH, clotting studies
  • Blood film: AML blasts may show cytoplasmic granules or Auer rods
  • Bone marrow aspirate or biopsy: Hypercellular with more than 30% blasts (immature cells)
  • Immunophenotyping:
  • Cytogenetics
  • Immunocytochemistry
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65
Q

What is chronic lymphocytic leukaemia (CLL)?

A
  • Characterised by progressive accumulation of functionally incompetent lymphocytes which are monoclonal in origins
  • Overlap between CLL and non-Hodgkin’s lymphomas
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66
Q

What is the aetiology of CLL?

A
  • Malignant cells may accumulate as result of their inability to undergo apoptosis
  • Most common chromosomal change include trisomy 12, 11q and 13q deletions
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67
Q

What is the epidemiology of CLL?

A
  • 90% are over 50yes
  • Males more than females
  • Rare in Asians
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68
Q

What are the presenting symptoms of CLL?

A
  • Asymptomatic: Almost half diagnosed on routine blood count
  • Systemic symptoms: Lethargy, malaise, night sweats
  • Symptoms of bone marrow failure: Recurrent infections (bacterial, viral, fungal), herpes zoster, easy bruising or bleeding (e.g. epistaxis). Assess pts performance status and comorbidites
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69
Q

What are the sides of CLL on examination?

A

Non-tender lymphadenopathy (often symmetrical), hepatomegaly, splenomegaly
- Later stages, signs of bone marrow failure: Pallor, cardiac flow murmur, purpura/echhymoses

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70
Q

What are the investigations for CLL?

A
  • May be associated with autoimmune phenomena: Haemolytic anaemia, thrombocytopenia or combination of both (Evan’s syndrome)
  • Blood: FBC (gross lymphocytosis, reduced platelets). Anaemia may be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis. Reduced serum immunoglobulins
  • Blood film: Small lymphocytes with thin rims of cytoplasm and smudge/smear cells
  • Bone marrow aspirate or biopsy
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71
Q

What is chronic myeloid leukaemia (CML)?

A

Malignant clonal disease, characterised by proliferation of granulocyte precursors in the bone marrow and blood
- Distinguished from AML by its slower progression

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72
Q

What is the aetiology of CML?

A
  • Malignant proliferation of stem cells with characteristic chromosomal translocation t(9;22) resulting in Philadelphia (Ph) chromosome
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73
Q

What are the 3 phases of CML?

A
  • Relative stable chronic phase of variable duration (4-6 yrs)
  • Transforms in accelerated phase (3-9 months)
  • Then acute leukaemia phase (blast transformation)
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74
Q

What are the presenting symptoms of CML?

A
  • Asymptomatic in up to 4-50% and is diagnosed on routine blood count
  • Hypermetabolic symptoms: Weight loss, malaise, sweating
  • Bone marrow failure symptoms: Lethargy, dyspnoea, easy bruising, epistaxis (infection is rare)
  • Abdominal discomfort and early satiety
  • Occasionally presents with gout or hyperviscosity symptoms (visual disturbances, headaches, priapism)
  • May present during blast crisis with symptoms of AML or ALL
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75
Q

What are the signs of CML on examination?

A
  • Splenomegaly: Common physical finding

- Signs of bone marrow failure: Pallor, cardiac flow murmur, bleeding or ecchymoses

76
Q

What are the investigations for CML?

A
  • Blood: FBC (grossly, raised WCC, reduced HB, Increased basophils/oesinophils/neutrophils, raised platelets may be normal or low), raised uric acid and vit b12, reduced neutrophil alkaline phosphatase
  • Blood film: Immature granulocytes in peripheral blood
  • Bone marrow aspirate or biopsy: hypercellular with raised myeloid-erythroid ratio
77
Q

What is Hodgkin’s lymphoma?

A

Lymphomas are neoplasms of lymphoid cells, originating in lymph nodes or other lymphoid tissues
- Hodgkin’s lymphoma is diagnosed histopathologically by the presence of Reed-Sternerg cells (a cell of B-lymphoid lineage)

78
Q

What is the aetiology of Hodgkin’s lymphoma?

A
  • Unknown
  • Likely to be result of environmental trigger in genetically susceptible individual.
  • EBV genome has been detected in 50% of Hodgkin’s lymphoma
79
Q

What is the epidemiology of Hodgkin’s lymphoma?

A
  • Bimodal age distribution
  • Peaks 20-30yrs and over 50yrs
  • More common in males
80
Q

What are the presenting symptoms of Hodgkin’s lymphoma?

A
  • Painless enlarging mass (most often in neck, occasionally in axilla or groin)
  • May become painful after alcohol ingestion
  • ‘B’ symptoms: Feversover 38 (if cyclical, referred to as Pel-Ebstein fever)
  • Night seats
  • Weight loss, more than 10% of body weight in last 6 months
  • Other: Pruritis, cough dyspnoea with intrathoracic disease
81
Q

What are the signs of Hodgkin’s lymphoma on examination?

A
  • Non tender firm rubbery lymphadenopathy: Cervical, axillary or inguinal
  • Splenomegaly, occasionally hepatomegaly
  • Skin excoriations
  • Signs of intrathoracic disease (e.g. pleural effusion, superior vena cava obstruction)
82
Q

What are the investigations for Hodgkin’s lymphoma?

A
  • Blood: FBC: Anaemia of chronic disease, leucocytosis, raised neutrophils and eosinophils. Lymphopenia with advanced disease. Raised CRP, ESR, LFT
  • Lymph node biopsy
  • Bone marrow aspirate and trephine biopsy
  • Imaging: CXR, CT or thorax, abdomen and pelvis, gallium scan, PET scens
  • Ann Arbor staging
83
Q

What is non-Hodgkin’s lymphoma (NHL)?

A
  • Lymphomas are malignancies of lymphoid cell originating in lymph nodes or lymphoid tissues
  • NHL are diverse group consisting of 85% B cell, 15% T cell and NK cell forms, ranging from indolent to aggressive disease and referred to as low, intermediate and high grades
84
Q

What is the aetiology of NHL?

A
  • Involves accumulation of multiple genetic lesions
  • Genome in certain lymphoma subtypes have been altered by introduction of foreign genes via number of oncogenic viruses: EBV in Burkitt’s lymphoma and AIDS associated lymphomas
  • Other factors indicated in development of NHL: radiotherapy, immunosuppressive agents, chemotherapy, HIV, HBV, HCV, connective tissue disease e.g. SLE and inherited and acquired immunodeficiency syndromes
85
Q

What is the epidemiology of NHL?

A
  • Incidence increases with age
  • More common in males
  • More common in the West
86
Q

Wha are the presenting symptoms of NHL?

A
  • Painless enlarging mass: Often in neck, axilla or groin
  • Systemic symptoms: (less frequent that Hodkin’s): fever, night sweats, weight loss more than 10% of body weight, symptoms of hypercalcaemia
  • Symptoms related to organ involvement (extranodal disease more common in NHL): Skin rashes, headache, sore throat, abdominal discomfort, testicular swelling. Establish performance status of the patient
87
Q

What are the signs of NHL on examination?

A
  • Painless firm rubbery lymphadenopathy: Cervical, axillary or inguinal. Oropharyngeal (Waldeyer’s ring of lymph nodes) involvement
  • Skin rashes: Mycosis fungoides (well-defined indurated scaly plaque like lesions with raised ulcerated nodules caused by cutaneous T-cell lymphoma) and Sezary’s syndrome
  • Abdominal mass
  • Hepatosplenomegaly
  • Signs of bone marrow involvement: Anaemia, infections or purpura
88
Q

What are the investigations for NHL?

A
  • Blood: FBC (anaemia, neutropenia and thrombocytopenia if bone marrow involved), U&Es, uric acid, raised ESR and CRP)
  • Blood film: Lymphoma cells may be visible in some pts
  • Bone marrow aspiration and biopsy
  • Lymph node biopsy
  • Staging
89
Q

What is macrocytic anaemia?

A

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

90
Q

What is the aetiology of megaloblastic macrocytic anaemia?

A

Deficiency of B12 or folate required for conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation

91
Q

What are the causes of vitamin B12 deficiency?

A
  • Decreased absorprtion: Post-gastrectomy, pernicious anaemia, terminal ileal resection or disease e.g. Crohn’s, bacterial overgrowth, pancreatic insufficiency, fish tapeworm, metformin, omeprazole
  • Reduced intake: vegans
  • Abnormal metabolism: Congenital transcobalamin II deficiency, inactivation of B12 by nitrous oxide
92
Q

What are the causes of folate deficiency?

A
  • Reduced intake: Alcoholics, elderly, anorexia
  • Increased demand: Pregnancy, lactation, malignancy, chronic inflammation, chronic haemolysis, exfoliative dermatitis
  • Reduced absorption: Jejunal disease e.g. coeliac disease, tropical sprue
  • Drugs: e.g. phenytoin, trimethrprim, methrotrexate
93
Q

What drugs can cause megaloblastic macrocytic anaemia?

A
  • Methrotrexate: inhibition of dihydrofolate reductase
  • Hydroxyurea: Inhibition of ribonucleotide reductase
  • Azathioprine
  • Zidovudine
94
Q

What are the causes of non-megaloblastic macrocytic anaemia?

A
  • Alcohol excess
  • Liver disease
  • Myelodysplasia
  • Multiple myeloma
  • Hypothyroidism
  • Haemolysis (shift to immature red cells: ‘reticulocytosis’)
  • Drugs: e.g. tyrosine kinase inhibitors: imatinib, sinitinib
95
Q

What is the epidemiology of macrocytic anaemia?

A
  • More common in elderly and females
96
Q

What are the presenting symptoms of macrocytic anaemia?

A
  • Non-specific signs of anaemia: tiredness, lethargy, dyspnoea
  • Family history of autoimmune disease
  • Previous gastrointestinal surgery
  • Symptoms of the cause e.g. weight loss, diarrhoea, steatorrhoea in coeliac disease
97
Q

What are the signs of macrocytic anaemia on examination?

A
  • Signs of anaemia: pallor, tachycardia. May be signs of cause e.g. malnutrition, jaundice, hypothyroid appearance
  • Signs of pernicious anaemia: Lemon-tinted skin (mild jaundice), glossitis (sore red tongue), angular stomatitis (chellitis), weight loss
  • Signs of vit B12 deficiency: Peripheral neuropathy, ataxia, subacute combined degeneration of the spinal cord, optic atrophy, dementia
98
Q

What are the investigations for macrocytic anaemia?

A
  • Blood: FBC (raised MCV, pancytopenia in megaloblastic), LFT (raised bilirubin due to ineffective haemolysis or erythropoiesis), ESR, TFT, serum vit B12, red cell folate, antibodies against parietal cells or intrinsic factor, serum protein electrophoresis
  • Blood film: Large erythrocytes (macrocytes). In megaloblastic: Macroovalocytes, hypersegmental neutrophil nuclei
  • Schilling’s test
  • Bone marrow biopsy: rarely necessary
99
Q

How is macrocytic anaemia managed?

A
  • Pernicious anaemia: IM hydroxycobalamin
  • Folate deficiency: Oral folic acid. Vit B12 deficiency must be treated first if present as folic acid may worsen neurological complications if untreated
100
Q

What are the possible complications of macrocytic anaemia?

A
  • In pernicious anaemia, increased risk of gastric cancer

- In pregnancy, folate deficiency predisposed to spinal cord anomalies

101
Q

What is the prognosis of macrocytic anaemia?

A

Majority are treatable if there are no complications

102
Q

What is microcytic anaemia?

A

Anaemia associated with low MCV (less than 80 fl)

103
Q

What is the aetiology of microcytic anaemia?

A
  • Iron deficiency (commonest cause): Blood loss e.g. GI tract, urogenital tract, hookworm
  • Anaemia of chronic disease: often normocytic but may be microcytic
  • Thalassaemia
  • Sideroblastic anaemia: Abnormality of haem synthesis. Can be inherited or secondary to alcohol, drugs, lead, myelodysplasia
104
Q

What are the causes of iron deficiency?

A
  • Blood loss
  • Reduced absorption: Small bowel disease, post-gastrectomy
  • Increased demands: Growth, pregnancy
  • Reduced intake: Vegans
105
Q

What is the epidemiology of microcytic anaemia?

A

Iron deficiency anaemia is the most common form of anaemia worldwide

106
Q

What are the presenting symptoms of microcytic anaemia?

A
  • Non-specific: Tiredness, lethargy, malaise, dyspnoea, pallor. Exacerbation of pre-existing angina or intermittent claudication. Family history of any causative diseases
  • Lead poisoning: Anorexia, nausea, vomiting, abdominal pain, constipation, peripheral nerve lesions
107
Q

What are the signs of microcytic anaemia on examination?

A
  • Signs of anaemia e.g. pallor of skin and mucous membranes. Brittle nails and hair. If long-standing and severe, spoon shaped nails (koilonychia)
  • Glossitis: Atrophy of tongue papillar
  • Cheilits: Angular stomatitis
  • Signs of thalassaemias
  • Lead poisoning: Blue gumline, peripheral nerve lesions (wrist or foot drop), encephalopathy, convulsions, reduced consciousness
108
Q

What are the investigations for microcytic anaemia?

A
  • Blood: FBC (reduced Hb, MCV, reticulocytes), Serum iron (reduced iron deficiency), iron binding capacity (increased in iron deficiency) serum ferritin (reduced in iron deficiency), serum lead (if poisoning suspected)
  • Blood film
  • Hb electrophoresis: for haemoglobin variants or thalassaemias
  • If iron deficiency anaemia in over 40yrs and post-menopausal women: Upper GI endoscopy, colonoscopy and investigations for haematuria should be considered if no blood loss
109
Q

What is seen on a blood film in microcytic anaemia?

A
  • Iron deficiency anaemia: Microcytic (small), hypochromic (central pallor more than 1/3rd cell size), anisocytosis (variable cell size), poikilocytosis (variable cell shapes)
  • Sideroblastic anaemia: Dimorphic blood film with a population of hypochromic microcytic cells
  • Lead poisoning: Basophilic stippling (coarse dots represent condensed RNA in the cytoplasm
110
Q

What is the management of macrocytic anaemia?

A
  • Iron deficiency: Oral iron supplements. If oral iron intolerance or malabsorption, consider parenteral iron supplements
  • Sideroblastic anaemia: Treat the cause (e.g. stop causative drugs) Pyridoxine can be used in inherited forms. If no response, consider blood transfusion and iron chelation
  • Lead poisoning, remove the source, dimercaprol, D-penicillamine, Ca2+ EDTA
111
Q

What are the possible complications of microcytic anaemia?

A

High output cardiac-failure, complications of the cause

112
Q

What is the prognosis for microcytic anaemia?

A

Depends on the underlying cause

113
Q

What is multiple myeloma?

A

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

114
Q

What is the aetiology of multiple myeloma?

A
  • Unknown
  • Postulated viral trigger
  • Chromosomal aberrations are frequent
115
Q

What is the epidemiology of multiple myeloma?

A
  • Peak incidence in 70 yrs olds

- Afro Caribbeans then white people then Asians

116
Q

What are the presenting symptoms of multiple myeloma?

A

May be diagnosed incidentally on routine blood tests

  • Bone pain: Often in back, ribs. Sudden and severe if caused by pathological fracture of vertebral collapse
  • Infections: Often recurrent
  • General: Tiredness, thirst, polyuria, nausea, constipation, mental change (resulting from hypercalcaemia)
  • Hyperviscocity: Bleeding, headaches, visual disturbancee
117
Q

What are the signs of multiple myeloma on examination?

A
  • Pallor
  • Tachycardia
  • Flow murmur
  • Signs of heart failure
  • Dehydration
  • Purpura
  • Hepatosplenomegaly
  • Macroglossia
  • Carpal tunnel syndrome
  • Peripheral neurophaties
118
Q

What are the investigations for multiple myeloma?

A
  • Blood: FBC (reduced Hb, normochromic normocytic), Raised ESR CRP, U&E (raised creatinine Ca+), typically normal AlkPhos
  • Blood film: Rouleaux formation with bluish background (raised protein)
  • Serum or urine electrophoresis
  • Bone marrow aspirate and trephine: Raised plasma cells
  • Chest, pelvic or vertebral X-ray: Osteolytic lesions without surrounding sclerosis. Pathological fractures
119
Q

What is myelodysplasia?

A

Series of haematological conditions characterised by chronic cytopenia (anaemia, neutropenia, thrombocytopenia) and abnormal cellular maturation

120
Q

What are the subgroups of myelodysplasia?

A
  • Refractory anaemia
  • RA with ringed sideroblasts (RARS)
  • RA with excess blasts (RAEB)
  • Chronic myelomonocytic leukaemia (CMML)
  • RAEB in transformation (RAEB-t)
121
Q

What is the aetiology of myelodysplasia?

A
  • May be primary, or arise in pts who have recieved chemotherapy or radiotherapy for previous malignancies
  • Pts may have chromosomal abnormalities, monosomy 7, trisomy 8 or complex karyotypes with multiple abnormalities
122
Q

What is the epidemiology of myelodysplasia?

A
  • Mean age diagnosis= 65-75 yrs
  • More common in males
  • 2x as common as AML
123
Q

What are the presenting symptoms of myelodysplasia?

A

May be asymptomatic and diagnosed after routine blood count

  • Symptoms of bone marrow failure: Anaemia (fatigue, dizziness), neutropenia (recurrent infections), thrombocytopenia (easy bruising, epistaxis)
  • Ask about risk factors (occupational exposure to toxic chemicals, prior chemotherapy or radiotherapy)
124
Q

What are the signs of myelodysplasia on examination?

A

Signs of bone marrow failure:

  • Anaemia (pallor, cardiac flow murmur)
  • Neutropenia (infections)
  • Thrombocytopenia (purpura or echhymoses)
  • Gum hypertrophy and lymphadenopathy
  • Spleen not enlarged except in CMML
125
Q

What are the investigations for myelodysplasia?

A
  • Blood: FBC (pancytopaenia)
  • Blood film: Normocytic or macrocytic red cells, ovalomacrocytosis, variable microcytic red cells in RARS, reduced granulocytes, granulocytes display reduced or absent granulation and bilobed (Pelgeroid) nucleus, raised monocytes (CMML), myeloblasts
  • Bone marrow aspirate or biopsy: Hypercellularity, ringed sideroblasts with dyserythropoietic features
126
Q

What is myelofibrosis?

A

Disorder of haematopoietic stem cells characterised by progressive marrow fibrosis in associated with extramedullary haematopoiesis and splenomegaly

127
Q

What is the aetiology of myelofibrosis?

A
  • Primary stem cell defect not known, but results in increased numbers of abnormal megakaryocytes (platelet precursor cells) with stromal proliferation as secondary reactive phenomenon to growth factors from the megakaryocytes
128
Q

What are the presenting symptoms of myelofibrosis

A

Asymptomatic: diagnosed after abnormal blood count
Systemic symptoms:
- Common: Weight loss, anorexia, fever and night sweats, pruritis
- Uncommon: Left upper quadrant abdo pain, indigestion (caused by massive splenomegaly)
- Bleeding, bone pain and gout are less common complaints

129
Q

What are the signs of myelofibrosis on examination?

A
  • Splenomegaly (massive in 10%) is main physical finding

- Hepatomegaly present in 50-60%

130
Q

What is the epidemiology of myelofibrosis?

A
  • Rare

- Peak onset 50-70 yrs

131
Q

What are the investigations for myelofibrosis?

A
  • Blood: FBC (variable Hb, WCC and platelets initially, but later anaemia, leukopenia and thrombocytopenia). LFT (abnormal)
  • Blood film: Leucoerythroblastic changes (circulating red and white cell precursors) with characteristic ‘tear drop’ poikilocyte red cells
  • Bone marrow aspirate or biopsy: Aspiration usually unsuccessful (‘dry tap’). Trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining
132
Q

What is normocytic anaemia?

A

Anaemia with a mean corpuscular volume (MCV) of 80-100 which is in the normal range
- Haematocrit and haeomoglobin is decreased

133
Q

What are the causes of normocytic anaemia?

A

AHFP

  • Acute blood loss: Peptic blood loss (peptic ulcer, oesophageal varices, trauma), Anaemia of chronic disease
  • Failure of production of red cells: Renal failure, bone marrow failure, bone marrow infiltration, hypothyroid
  • Pregnancy: Increased plasma volume
  • Endocrine dysfunction
134
Q

What are the presenting symptoms of normocytic anaemia?

A
  • Fatigue
  • SOB
  • Faintness
  • Palpitations
  • Headache
  • Tinnitus
  • Anorexia
  • Angina if CAD
135
Q

What are the signs of normocytic anaemia on examination?

A
  • Asymptomatic
  • Pallor
  • Hyperdynamic circulation
136
Q

What are the investigations for normocytic anaemia?

A
  • Anaemia of chronic disease

- Bloods: Normocytic, normal platelets and serum iron, increased ferritin, Reduced TIBC, High CRP and ESR

137
Q

How is normocytic anaemia managed?

A

Blood transfusion

  • Not essential unless Hb less than 70g/dL
  • If acute cause e.g. perforated peptic ulcer, transfusion up to 80h/dL sometimes needed
  • If severe anaemia with heart failure, transfusion vital to restore Hb to 60-80g/dL (safe)
  • Check for fluid overload
138
Q

What are the possibly complications of normocytic anaemia?

A
  • Hypoxia
  • Cardiorenal anaemia syndrome
  • Cardiovascular disease
139
Q

What is polycythaemia?

A
  • An increase in Hb concentration above the upper limit of normal for a person’s age and sex
  • Classified into relative polycythaemia (normal red cell mass but reduced plasma volume) or absolute (true) polycythaemia) (increased red cell mass)
140
Q

What is the aetiology of polycythaemia?

A
  • Polycythaemia rubra vera
  • Secondary polycythaemia
  • Relative polycythaemia
141
Q

What is polycythaemia rubra vera?

A

Characterised by clonal proliferation of myeloid cells with variable morphological maturity and haematopoietic efficiency
- Mutations in JAK2 tyrosine kinase participates in the pathogenesis

142
Q

What is secondary polycythaemia?

A
  • Appropriate increased erythropoietin: Caused by chronic hypoxia (e.g. chronic lung disease) leading to upregulation of erythrogenesis
  • Inappropriate raised eryhtropoietin: Renal (carcinoma, cysts, hydronephrosis), hepatocellular carcinoma, fibroids, cerebellar haemangioblastoma. Secondary polycythaemia may be feature of erythropoietin abuse amongst athletes
143
Q

What is relative polycythaemia?

A
  • Dehydration: eg. diuretics, burns, enteropathy

- Gaisbock’s syndrome (seen in young male smokers with raised vasomotor tone and hypertension

144
Q

What is the epidemiology of polycythaemia?

A

Peak age is 45-60 yrs

145
Q

What are the presenting symptoms of polycythaemia?

A
  • Headaches, dyspnoea, tinnitus, blurred vision as a result of hyperviscosity
  • Pruritis after hot bath, night sweats
  • Thrombosis (DVT, stroke), pain resulting from peptic ulcer disease, angina, gout, chloreiform movements
146
Q

What are the signs of polycythaemia on examination?

A
  • Plethoric complexion
  • Scratch marks as result of itching, conjunctival suffusion and retinal venous engorgement
  • Hypertension
  • Splenomegaly (present in 75% of polycythaemia rubra vera)
  • Signs of underlying aetiology in secondary causes
147
Q

What are the investigations for polycythaemia?

A
  • Required for diagnosis: FBC: Raised Hb haematocrit, low MCV
  • Isotope dilution techniques: distinguish between relative and absolute
  • Polycythaemia rubra vera: Raised WCC platelets, low serum erythropoietin
  • Secondary polycythaemia: Raised serum erythropoietin, exclude lung disease/hypoxia (pulse oximetry, ABG, CXR), look for erythropoietin secreting tumours (e.g. abdo CT, brain MRI)
148
Q

What is sickle cell anaemia?

A

Chronic condition with sickling of red blood cells caused by inheritance of haemoglobin S (Hb S)

  • Sickle cell anaemia: Homozygosity for Hb S
  • Sickle cell trait: Carries one copy of Hb S
  • Sickle cell disease: Includes compound heterozygosity for Hb S and C and for Hb S and B-thalassaemia
149
Q

What is the aetiology of sickle cell anaemia?

A
  • Autosomally recessive point mutation in the B-globin gene resulting in valine substituting glutamic acid on position 6, producing abnormal protein- Hb S
  • Deoxygenation of Hb S alters the conformation with resulting hydrophobic interactions between adjacent Hb S and formation of insoluble polymers, resulting in sickling of red cells with increased fragility and inflexibility. They are prone to:
    1) Sequestration and destruction, leading to reduced RBC survival
    2) Occlusion of small blood vessels causing hypoxia which, in turn, causes further sickling and occlusion
  • Factors precipitating sickling are infection, dehydration hypoxia and acidosis
150
Q

What is the epidemiology of sickle cell anaemia?

A
  • Rarely presents before 4-6 months: because of continuous production of foetal haemoglobin
  • Common in Africa, Caribbean, Middle East and areas with high prevalence of malaria
151
Q

What are the presenting symptoms of sickle cell anaemia which are secondary to vaso-occlusion or infarction?

A
  • Autosplenectomy (splenic atrophy or infarction): Leading to increased risk of infections with encapsulated organisms (e.g. pneumococcus, H. influenzae, meningococcus, Salmonella)
  • Abdominal pain
  • Bones: Painful crises affecting small bones of hands or feet (dactylitis) in children, and ribs, spine, pelvis and long bones in adults. Chronic hip or shoulder pain (avascular necrosis)
  • Myalgia and athralgia
  • CNS: Can cause fits or strokes (e.g. hemiplegia)
  • Retina: Visual loss (proliferative retinopathy)
152
Q

What are the presenting symptoms of sickle cell anaemia secondary to sequestration crises?

A
  • Red cell pooling in various organs: Spleen
  • Liver: Exacerbation of anaemia
  • Lungs: ‘Acute chest syndrome’: breathlessness, cough, pain, fever
  • Corpora cavernosa: Persistent erection (pripiasm) and impotence
153
Q

What are the signs of sickle cell anaemia secondary to vaso-occlusion or infarction on examination?

A
  • Bone: Joint or muscle tenderness or swelling (caused by avascular necrosis)
  • Short digits: caused by infarction in small bones
154
Q

What are the signs of sickle cell anaemia secondary to sequestration crises?

A
  • Organomegaly: Spleen is enlarged in early disease but later reduces in size because of splenic atrophy
  • Priapism
155
Q

What are the investigations for sickle cell anaemia?

A
  • Blood: FBC (anaemia, reticulocytes rise in haemolytic crises and reduced in aplastic crises), U&E
  • Blood film: Sickle cells, anisocytosis, features of hyposplenism (target cells, Howell-Jolly bodies)
  • Sickle cel solubility test: Dithionate added to blood causes increased turbidity
  • Haemoglobin electrophoresis: Shows HbS
  • Hip X-ray: Common site for avascular necrosis of femoral head
  • MRI or CT head: If neurological complications
156
Q

How is sickle cell anaemia managed?

A
  • Acute (painful crises): Oxygen, IV fluids, strong analgesia (IV opiate), antibiotics
  • Infection prophylaxis: Penicillin V. Regular vaccinations (e.g. against pneumococcus)
  • Folic acid: In severe haemolysis or pregnancy
  • Hydroxyurea: Increases Hb F levels and reduces frequency and duration of sickle cell crisis
  • Red cell transfusion: for severe
  • Exchange transfusion: in severe, before surgery, pregnancy
  • Advice: Avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening
  • Surgical: bone marrow transplantation in selected pts, joint replacement for avascular necrosis
157
Q

What is the prognosis for sickle cell anaemia?

A
  • Most of those with sickle cell disease, with good care, survive approx 50 years
  • Major mortality usually result of pulmonary or neurological complications (adults) or infection (children)
158
Q

What are the possible complications of sickle cell anaemia?

A
  • Complications of vaso-occlusion and sequestration
  • Aplastic crises (infection with B19 parvovirus, temporary cessation of erythropoiesis)
  • Haemolytic crises
  • Pigment gallstones
  • Cholecystitis
  • Renal papillary necrosis
  • Leg ulcers (local ischemia)
  • Cardiomyopathy
159
Q

What are thalassaemias?

A

Group of genetic disorders characterised by reduced globin chain synthesis

160
Q

What is the aetiology of thalassaemias?

A

The autosomal recessive genetic defect results in an imbalance of globin change production and deposition of erythroblasts and erythrocytes causing ineffective erythropoiesis, haemolysis, anaemia and extramedullary haemopoiesis

161
Q

What is the aetiology of alpha-thalassaemia?

A

Reduced alpha-globin chain synthesis. Chromosome has 4 alpha-globin genes

  • 4 gene deletion: Hb Barts (gamma4) and intrauterine death (hydrops fetalis)
  • 3 gene deletion: Microcytic hypochromic anaemia, splenomegaly
  • 1-2 gene deletion: Microcytic hypochromic red cells: no anaemia
162
Q

What is the aetiology of beta-Thalassaemia major (homozygous beta-thalassaemia)?

A

Beta-Globin gene mutations on chromosome 11 causes no or minimal beta-chain synthesis

163
Q

What is the aetiology of Beta-Thalassaemia intermedia?

A

Mild defect in Beta-chain synthesis causing mycocytic anaemia, reduced alpha-chain synthesis or increased gamma-chains

164
Q

What is the aetiology of Beta-Thalassaemia trait (heterozygous carrier)?

A
  • Asymptomatic
  • Mild microcytic anaemia
  • Increased red cell count
165
Q

What is the epidemiology of thalassaemias?

A
  • Worldwide

- More common in the Mediterranean and areas of the Middle East

166
Q

What are the presenting symptoms of Beta-Thalassaemia major?

A
  • Anaemia presenting at 3-6 months (when gamma-chain synthesis switches to beta-chain synthesis)
  • Failure to thrive, prone to infections
167
Q

What are the presenting symptoms of alpha or beta Thalassaemia trait?

A
  • May be asymptomatic

- Detected on routine blood tests or from a family history

168
Q

What are the signs of beta-thalassaemia major or examination?

A
  • Pallor, malaise, dyspnoea, mild jaundice
  • Frontal bossing and thalassaemic facies (marrow hyperplasia)
  • Hepatosplenomegaly (erythrocyte pooling, extramedullar haemopoiesis)
  • Patients with beta-thalassaemia intermedia may also have aforementioned signs
169
Q

What are the investigations for thalassaemias?

A
  • Blood: FBC (Decreased Hb MCV MCH)
  • Blood film: Hypochromic, microcytic anaemia, target cells, nucleated red cells, raised reticulocyte count)
  • Hb electrophoresis: Absent or reduced Hb A and increased levels of Hb F
  • Bone marrow: Hypercellular with erythroid hyperplasia
  • Genetic testing: Rarely necessary. For specific mutations
  • Skull X-ray: ‘Hair on end’ appearance (caused by expansion of marrow into cortex) in B-thalassaemia major
170
Q

What is thrombotic thrombocytopenic purpura?

A

A clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura

171
Q

What is the aetiology of thrombotic thrombocytopenic purpura?

A
  • The underlying cause might involve the production of unusually large von Willebrand factor multimers
  • Congenital TTP (known as Upshaw-Schulman syndrome, is a rare life threatening disease
172
Q

What is the epidemiology of thrombotic thrombocytopenic purpura?

A
  • Incidence is rising
  • Most patients with severe von Willebrand factor cleaving enzyme (ADAMTS-13) deficiency as their cause of TTP are between the ages of 20 and 59 years.
173
Q

What are the presenting symptoms of thrombotic thrombocytopenic purpura?

A
  • Non-specific prodrome
  • Servere neurological symptoms: coma, focal abnormalities, seizures
  • Mild neurological symptoms: headache, confusion
  • Age 30-50
  • Digestive symptoms: nausea, vomiting, diarrhoea, abdominal pain)
174
Q

What are the signs of thrombotic thrombocytopenic purpura on examination?

A
  • Risk factors: Black ethnicity, female, obesity, pregnancy (near term or post-partum period), cancer therapies
  • Fever
175
Q

What are the investigations for thrombotic thrombocytopenic purpura?

A
  • Platelet count: decreased
  • Haemoglobin: less than 8g/L
  • Peripheral smear: microangiopathic blood film
  • Urinalysis: proteinuria
  • Urea and creatinine: increased
  • Direct Coombs’ test: negative
176
Q

What is vitamin B12 deficiency?

A

Common condition that can manifest with neurological, psychiatric and haematological disorders
- Vit B12 is essential vitamin only obtained from diet or supplementation

177
Q

What is the aetiology of vitamin B12 deficiency?

A
  • Decreased dietary intake: Vegans,
  • Diminished gastric breakdown of vit B12 from food
  • Malabsorption
  • History of atrophic gastritis
  • History of gastric or intestinal surgery
  • Pernicious anaemia
178
Q

What is the epidemiology of vitamin B12 deficiency?

A
  • Common during pregnancy- levels of B12 decrease from first to third trimester
179
Q

What are the presenting symptoms of vitamin B12 deficiency?

A
  • Old age
  • History of gastric surgery, gastrectomy or bypass for obesity
  • Risk factors: Age over 65, gastric surgery, terminal ileum disease, vegan diet, metformin use, H2 receptor antagonist or protom pump inhibitor use
180
Q

What are the signs of vitamin B12 deficiency on examination?

A
  • Paraesthesias
181
Q

What are the investigations for vitamin B12 deficiency?

A
  • Serum Vitamin B12
  • FBC: Elevated MCV, low haematocrit
  • Peripheral blood smear: Megalocytes, hypersegmented polymorphonucleated cells
  • Reticulocyte count: low corrected reticulocyte index
182
Q

What is Von Willebrand’s disease?

A

Most common inherited bleeding disorder, is due to either a quantitative or qualitative abnormality of von Willebrand factor (VWF). VWF provides the critical link between platelets and exposed vascular subendothelium, and also binds and stabilises coagulation factor VIII.

183
Q

What is the aetiology of Von Willebrand’s disease?

A
  • Usually due to mutation in VWF gene

- Age, blood type, thyroid status, inflammation, stress and hormone levels may affect

184
Q

What is the epidemiology of Von Willebrand’s disease?

A
  • Most common inherited bleeding disorder
  • Males and females are affected equally, but because of the prominent symptom of menorrhagia, adolescent and adult women are more often diagnosed
  • VWF levels in black people than in white people
185
Q

What are the presenting symptoms of Von Willebrand’s disease?

A
  • Risk factors: Positive family history, consanguineous relationships
  • FHx of bleeding
  • Easy and excessive bleeding
  • Postoperative bleeding
  • Bleeding from minor wounds
  • Menorrhagia
  • Epistaxis
186
Q

What are the signs of Von Willebrand’s disease on examination?

A
  • GI bleeding

- Uncommon: Haemarthrosis, CNS bleeding, Haematuria

187
Q

What are the investigations for Von Willebrand’s disease?

A
  • Prothrombin time: Within reference range in VWD
  • APTT
  • FBC : results usually normal except in type 2B where platelets may be reduced
  • VWF antigen
  • VWF function assay
  • Factor VIII activity: may be decreased but often within normal range

Year 3 ICSM Sofia (16 decks)

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