Haematology

Question 1

What is pancytopoenia?

Answer 1

• Anaemia
• Neutropoenia (infections)
• Thrombocytopoenia (clotting)

Question 2

Key features of aplastic anaemia

Answer 2

• = Rare stem cell disorder
• Causes- Idiopathic (60%), inherited, drugs (chemo, gold, penicillamine), viruses (hepatitis, parvovirus), SLE
• Presentation- pancytopoenia
• Ix- BM= hypocellular
• Tx:
  
  • Supportive- transfusion, Tx sepsis
  • Immunosuppression
  • Allogenic BMT

Question 3

Causes of thrombocytopoenia

Answer 3

• Reduced production- liver disease, BM failur e
• Increased destruction- hypersplenism, liver disease, AI, HIV, Hep C, ITP
• Increased consumption- HELLP, DIC, TTP

Question 4

Key features of AML

Answer 4

• Adults
• Genetic- 8,21
• RF: Down’s, male, chemo/radio to BM, myelodypslastic syndrome
• Presentation:
  
  • BM failure, cytopoenias
  • Infiltrates- gum, skin, bones, hepatosplenomegaly
• Ix:
  
  • Bloods- anaemia, thrombocytopeonia, high WCC (blasts)
  • BM aspirate- >20% blasts, Auer Rods
• Tx: supportive, chemo, BMT

Question 5

Key features of ALL

Answer 5

• Childen
• RF: Genetic (12,21 translocation), radiation, Down’s
• Presentation:
  
  • Pancytopoenia
  • Infiltration- lymphadenopathy, orchidomegaly, thymic englargerment, CNS palsies/ meningism, bone pain
• Ix:
  
  • Bloods- ++ WCC (lymphoblasts), low RBC, low platelets
  • Imaging- CXR/ CT- mediastinal + abdo LN
  • BM aspirate >20% blasts
  • LP- CNS involvement
• Tx:
  
  • Supportive- Blood products, allopurinol, Tx infections (gent, taz)
  • Chemo
  • BMT

Question 6

Key features of CML

Answer 6

• Usually 40-60y.
• Philidelphia chromosome- translocation of 9,22 –> BCR-ABL. Tx= Imatinib
• Features:
  
  • Systemic- weight loss, fever, night seats, lethargy
  • Massive HEPATOSPLENOMEGALY
  • Bruising/ bleeding
  • Gout
  • Hyperviscosity
• 3 phases: chronic, accelerated, blast crisis
• Ix:
  
  • Bloods- ++WCC, high urate, +/- low Hb/platelets
  • BM cytogenic analysis

Question 7

Key featuresof CLL

Answer 7

• V insidious. May be incidental finding in elderly.
• B memory cells.
• Presentation:
  
  • Often Asx
  • Symmetrical painless lymphadenopathy
  • Hepatosplenomegaly
  • Anaemia
  • ?B Sx- weight loss, fever, night sweats
• Ix:
  
  • Bloods- ++ WCC, low serum Ig.
  • Smear cells on blood film.
• Complications:
  
  • AI haemolysis
  • Infection
  • BM failure
  • Richter transformation- CLL –> large B cell lymphoma
• Tx- usually supportive –> chemo/ radio. Rituximab, cyclophosphamide

Question 8

Key Features of Hodgkin’s Lymphoma

Answer 8

• M:F 2:1. Bimodal age: 20-29y, >60y
• May be associated with EBV
• Presentation:
  
  • Lymphadenopathy- Painless (painful w/ alcohol), asymmetrical, spread to adjacent nodes, cervical 70%, mediastinal –> masse effect
  • BSx- Fever, weight loss (>10% 6m), night sweats
  • Itch
  • Hepatosplenomegaly
• Ix:
  
  • Bloods- FBC, film, ESR, LFTs, LDH, calcium
  • LN biopsy- Reed-sternberg cells (owl eye)
  • Staging- CT/MRI chest-abdo-pelvis
  • BM biopsy if B Sx or stage 3/4
• Tx- chemo/ radio –> BMT

Question 9

Ann Arbor Staging

Answer 9

1. Single LN region
2. >1 LN region on one side of diaphragm
3. Nodes on both sides of diaphragm
4. Spread beyond nodes eg liver, BM

• A= if no B Sx, B if B Sx

Question 10

Key Features of Non-Hodgkins Lymphoma

Answer 10

• Presentation:
  
  • Lymphadenopathy - symmetrical, painless, spreads discontinually, multiple sites
  • Splenomegaly
  • BSx
  • Oropharynx
  • CNS
  • Skin - T cell lymphoma
• Ix:
  
  • Bloods- pancytopoenia, hyperviscosity, U+Es, LFTs, LDH, film
  • LN + BM biopsy
  • Staging- CT/MRI. Ann Arbor
• Classification:
  
  • B/T Cell
  • Low grade- follicular, small cell lymphocytic, marginal zone
  • High grade- aggressive, diffuse large B cell, Burkitts (jaw/abdo)- stary sky appearance

Question 11

When to refer a LN

Answer 11

• 1 LN >1cm for >6w
• Widespread LN >2 non-contiguous areas
• <6w but with B Sx

Question 12

What is Multiple Myeloma and how might it present?

Answer 12

• Neoplasm of plasma cells- make Abs –> ++ IgG/A
• –> may produce free light chains (renal failure) and IL-6 (activate osteoclasts)
• Features= CRAB
  
  • Calcium - high
  • Renal impairment - light chains/ casts
  • Anaemia - normocytic, normochromic
  • Bony lytic lesions- bone pain, fracture, hypercalcaemia, high alk phos
• Pre-existing MGUS- high total protein, low albumin

Question 13

Ix and Tx of multiple myeloma

Answer 13

• Ix:
  
  • Bed- urine bence jones protein
  • Bloods- FBC, film (rouleaux, ++ Plasma cells), ++ESR, U+Es, calcium, normal ALP, serum electrophoresis
  • Imaging- skeletal survery- ?lytic lesions - punched ou, fractures
• Tx:
  
  • Supportive- bone pain (analgesia, bisphosphonates), anaemia, renal, Infection
  • Complications- Ca2+, cord compression, hyperviscosity (plasmapheresis)
  • Specific- Chemo, BMT

Question 14

What are the myeloproliferative neoplasms and their key features?

Answer 14

• BM produces ++ Hb, WCC and platelets –> THROMBOSIS RISK
• Polycythaemia Vera- all cell lines. 95% JAK2 mut
  
  • Primary or secondary - smoking, alcohol, high altitude, EP secreting tumour
  • Ix- blood film, FBC, USS
  • Tx- aspirin, venesection, hydroxycarbamide
• Essential thrombocytosis- ++ platelets only. Blood film. Tx <60y= aspirin >60y= hydroxycarbamide
• Myelofibrosis= proliferation of whole BM –> fibrotic and ineffective –> splenomegaly. Presentation- sweats, splenomegaly, cytopoenias. Blood film= RBCs tear shaped. Tx- no cure. Supportive
• CML

Question 15

Measurement of intrinsic and extrinsic clotting pathways and their clotting factors?

Vit K dependent clotting factors

Answer 15

• Intrinsic pathway= APTT. Factors 4, 8, 11, (12)
  
  • APTT corrects= intrinsic
  • APTT doesn’t correct= coagulant inhibitor eg lupus anticoagulant
• Extrinsic pathway= PT. Factor 7
• Vit K dependent clotting factors - 2,7,9,10

Question 16

Key features of Haemophilia A

Answer 16

• VIII deficiency. <1%= severe, 1-5%= Mod, >5%= mild
• Presentation:
  
  • Swollen joints –> joint damage
  • Bruise easily
• Tx:
  
  • Cons- education, ice, physio, immobilisation
  • Med- injections of recombinant VIII, DDAVP, analgesia, desmopressin
  • Avoid aspirin, NSAIDs, heparin

Question 17

Key features of haemophilia B

Answer 17

• IX deficiency. ‘Christmas Disease’
• X-linked
• Presentation- less severe and later than Haemophilia A
• Tx= IX concentrate

Question 18

Key features of acquired haemophilia

Answer 18

• AutoAb against factor VIII suddenly appears –> big mucosal bleeds
• Ix: raised APTT and AutoAb against VIII
• Tx: Steroids

Question 19

Key features of Von Willebrand Disease

Answer 19

• VWF carries VIII around –> raised APTT
• Presentation= mild bleeding disorder- bruising, mucocutaneous bleeding, bleeding from mild wounds, menorrhagia, PPH, bleeding after surgery.
• Classification- mild (dominant), qualitative, severe (recessive)
• Tx:
  
  • Desmopressin
  • DDAVP
  • Plasma containing VWF

Question 20

Aquired bleeding disorders

Answer 20

• Liver disease - less production of coag factors
• Renal disease - abnormal platelet function
• Vitamin K def - haemorrhagic disease of newborn
• DIC - sepsis, malig, trauma, obstetric

Question 21

DIC - causes, presentation, Ix and Tx

Answer 21

• = Dissemintate intravascular coagulation.
• Massive coagulation signal –> coagulation and consumption of clotting factors and platelets –> bleeding an thrombosis in differnt parts of circulation
• Causes- sepsis, malignancy, trauam, obstetric
• Dx- low platelets, low fibrinogen, high PT/ APTT and d-dimer
• Tx- underlying cause! resus. Blood replacement. ?heparin

Question 22

Risk factors for thrombosis

Answer 22

• Arterial- smoking, HTN, hyperlipidaemia, DM
• Venous- surgery, trauma, immobility, pregnancy, OCP, HRT, age, obesity, varicose veins, diseases - HF, malignancy, IBD, nephrotic syndrome
• Inherited:
  
  • Factor V leiden (protein C resistance)
  • Prothrombin gene mutation
  • Protein C and S deficiency
  • Antithrombin deficiency

Question 23

Symptoms of anaemia

Answer 23

• Fatigue
• SOB
• Faintness
• Palpitations
• Tinnitus

Question 24

Ix of anaemia

Answer 24

• FBC - Hb, MCV
• Haematinics - B12, folate, ferratin
• Reticulocytes - increased if anaemic + normal BM. Low in cancer/ B12/folate deficiency
• Iron:
  
  • Ferratin- low in iron deficiency. high in acute phase reaction
  • Total iron binding capacity- ability to bind blod with transferrin. Raised in iron deficiency
  • Transferrin sats
  • Serum iron - ?haemachromatosis

Question 25

Causes of microcytic anaemia

Answer 25

• Loss - Menorrhagia, GI bleeding, thallassaemia
• Reduced intake - diet
• Malabsorption - Crohn’s, coeliac
• Ix –> FBC, haematinics, upper and lower endoscopy

Question 26

Key features of thallassaemia

Answer 26

• Haemolysis whilst still in BM –> removed by spleen
• Beta worse than alpha
• Presentation:
  
  • Severe anaemia
  • Jaundice
  • FTT
  • Hepatoslenomegaly
• Tx- transusions, SC desferroxamine, BM transplant

Question 27

Causes of Normocytic anaemia

Answer 27

• Poor diet
• Inflammation/ chronic disease
• Multiple Myeloma
• Renal failure

Question 28

Causes of macrocytic anaemia + Ix

Answer 28

• B12/ folate deficiency
• Alcohol excess
• Pernicious anaemia - AI gastritis. Increased risk of gastric Ca
• Thyroid dysfunction
• Pregnancy
• Cytotoxics eg trimethoprim
• Ix- blood film (alc= target cells, B12/folate= hypersegmented/ oval macrocytes), LFTs, TFTs, serum B12, red cell folate. ?BM biopsy

Question 29

Key features of folate deficiency

Answer 29

• Causes:
  
  • Reduced intake - diet: green veg, nuts, liver
  • Increased demand - Pregnancy, haemolysis, malignancy
  • Malabsorption - coeliac, crohn’s,
  • Drugs- alcohol, phenytoin, methotrexate
• Tx:
  
  • Tx cauase
  • B12 replacement 1st (SACD)
  • Folate replacement

Question 30

Key features of B12 deficiency

Answer 30

• Causes:
  
  • Reduced intake - diet. vegans.
  • Reduced intrinsic factor- pernicious anaemia, post-gastrectomy
  • Terminal ileum- Crohn’s, ileal resection, bacterial overgrowth
• Features:
  
  • General- Anaemia Sx, pallow, glossitis
  • Neuro- paraesthesia, peripheral neuropathy, optic atrophy, severe combined demyelination
• Ix- Bloods- low WCC, intrinsic factor/ parietal cell Ab
• Tx- malabsorption –> IM B12. Dietary- PO B12

Question 31

Key features of severe combined demyelination

Answer 31

• Complication on low B12/ pernicious anaemia
• Combined symmetrical loss of dorsal collumn and corticospinal tract
• Distal sensory loss (proprioception and vibration) ataxia, wide gait, romberg’s +ve

Question 32

Causes of Haemolysis

Answer 32

• Direct Coomb’s test looks for Abs
• Causes:
  
  • AI - idiopathic, RA, SLE. Tx: Immunosuppresion, splenectomy
  • HUS - E.coli 0157 in kids
  • TTP= Thrombotic thrombocytopoenic purpura. Adult females. Fever, CNS, haemolytic anaemia, renal failure, thrombocytopoenia. Tx: plasmapharesis, immunosuppression, splenectomy.

Question 33

Key features of sickle cell anaemia

Answer 33

• African, Caribbean, Middle-East
• Point mutation in beta globin –> sickling, haemolysis, thrombosis
• Ix- Hb, high retics, high bili, film (sickling), Hb electrophoresis
• Triggers- cold, inf, hypoxia, dehydration
• Features= SICKLED
  
  • Splenomegaly
  • Infarction eg stroke
  • Crisis- pulm, mesenteric, pain
  • Kidney disease
  • Liver/ Lung
  • Erection
  • Dactylisis
• Tx:
  
  • Chronic- imms, folate, hydroxycarbamide
  • Acute- analgesia, o2, hydration, warm. Ceftriaxone, exchange transfusion

Question 34

Early and late complications of blood transfusion

Answer 34

• Early:
  
  • Hameolytic reaction (–> renal damage)
  • Allergic reaction
  • Clotting abrnomalities
  • Fever
  • TRALI (tranfusion associated lung injury)- no HTN
  • TACO (transfusion associated circulatory overload)- RF= HF, chronic anaemia, +ve fluid balance –> Acute resp distress, tachycardia, HTN, oedema CXR. Acute HF Tx
• Late:
  
  • BBV
  • GVHD
  • Iron overload