Haematology

Question 1

Plummer-Vinson syndrome

Answer 1

Post-cricoid web that is associated with iron deficiency anaemia

Question 2

Iron deficiency anaemia haematinics

Answer 2

↓ferritin, ↑TIBC, ↓ transferrin saturation

Question 3

Sideroblastic anaemia haematinics

Answer 3

↑Ferritin, ↑ se Fe, ↔TIBC

Rx: Can give pyroxidine

Question 4

B Thalassaemia trait

Answer 4

↓ MCV

↑ HbA2 (α2δ 2) and ↑HbF (α2γ2)

Question 5

B Thalassaemia Major

Answer 5

↓Hb, ↓MCV, ↑↑HbF, ↑HbA2 variable

Film: Target cells and nucleated RBCs

Question 6

Folate deficiency

Answer 6

Typically decreased intake or high demand (pregnancy or medication e.g. methotrexate/phenytoin)
Rx = give B12 first unless this is normal as can worsen SCDC; give folate PO 5mg/d

Question 7

Subacute Combined Degeneration of the Cord

Answer 7

Combined symmetrical dorsal column loss and corticospinal tract loss with a mixed UMN and LMN picture.
Pain and temperature intact
Usually only caused by pernicious anaemia

Question 8

G6PD deficiency triggers

Answer 8

 Broad (Fava) beans
 Mothballs (naphthalene)
 Infection
 Drugs: antimalarials, henna, dapsone, sulphonamides

Can see Heinz bodies

Question 9

Warm AIHA

Answer 9

IgG mediated with extravascular haemolysis and spherocytes and is DAT +ve
Linked to SLE, RA and Evan’s
Rx = immunosuppression +/- splenectomy

Question 10

Cold AIHA

Answer 10

IgM mediated with intravascular haemolysis and is DAT +ve
Linked to mycoplasma
Rx = avoid cold and rituximab

Question 11

Paroxysmal cold haemoglobinuria

Answer 11

IgG “Donath-Landsteiner” Abs bind RBCs in the cold → complement-mediated lysis on rewarming
Associated with Measles, mumps, chickenpox

Question 12

Paroxysmal nocturnal haemoglobinuria

Answer 12

Features
 Visceral venous thrombosis (hepatic, mesenteric, CNS)
 IV haemolysis and haemoglobinuria

Ix
 Anaemia ± thrombocytopenia ± neutropenia
 FACS: ↓CD55 and ↓CD59

Rx
 Chronic disorder therefore long-term anticoagulation
 Eculizumab (prevents complement MAC formation)

Question 13

HUS

Answer 13

E. coli O157:H7 from undercooked meat

Bloody diarrhoea and abdominal pain precedes:
 MAHA (schistocytes)
 Thrombocytopenia
 Renal failure

Spontaneously resolves

Question 14

TTP

Answer 14

Pentad = fever, CNS, MAHA, thrombocytopenia, renal failure

Rx = Plasmapheresis, immunosuppression, splenectomy

Question 15

Hereditary spherocytosis Ix + Rx

Answer 15

 ↑ osmotic fragility
 Spherocytes
 DAT-ve

Rx = folate + splenectomy (after childhood)

Question 16

Pyruvate Kinase Deficiency

Answer 16

Features: splenomegaly, anaemia +/- jaundice

Rx = often not required

Question 17

SCD presentation

Answer 17

SICKLED
Splenomegaly
Infarction - stroke, AVN, spleen (hyposplenism)
Crises - pulmonary, mesenteric, sequestration crises (splenic pooling --> shock and severe anaemia)
Kidney disease
Liver disease
Erection
Dactylitis

Question 18

Increased PT

Answer 18

 Warfarin / Vit K deficiency
 Hepatic failure
 DIC

Question 19

Increased APTT

Answer 19

 Lupus anti-coagulant
 Haemophilia A or B
 vWD (carries factor 8)
 Unfractionated heparin
 DIC
 Hepatic failure

Question 20

Increased bleeding time

Answer 20

 ↓ plats number or function
 vWD
 Aspirin
 DIC (increased thrombin time as well)

Question 21

Haemophilia A Ix and Mx

Answer 21

Ix
↑APTT, normal PT, ↓F8 assay

Mx
 Avoid NSAIDs and IM injections
 Minor bleeds: desmopressin + tranexamic acid
 Major bleeds: rhF8

Question 22

vWD Ix and Mx

Answer 22

Ix
↑ APTT, ↑ bleeding time, normal plat, ↓ vWF AG

Rx
Desmopressin + transexamic acid

Question 23

Thrombophilia conditions

Answer 23

Factor V Leiden
Prothrombin gene mutation (elevated prothrombin levels)
Protein C and S deficiency
Antithrombin III deficiency
Antiphospholipid syndrome
OCP (progesterone)

Make sure to anticoagulate these patients

Question 24

Massive transfusion reaction

Answer 24

Whole blood volume in 24 hrs (10 units)

Features:
↑K
↓ Ca (citrate chelation) ↓ F5 and F8
↓ plats
Hypothermia

Rx:
Massive Transfusion Protocol
1:1:1 ratio of PRBC:FFP:PLT + Warm the blood

Question 25

Delayed transfusion reactions

Answer 25

Delayed haemolytic - jaundice, anaemia Fe overload - typically from chronic transfusion in SCA or Thal Major Post-transfustion purpura GvHD - diarrhoea, skin rash, raised LFTs, pancytopenia

Question 26

Aplastic anaemia causes

Answer 26

Inherited  Fanconi’s anaemia: Ashkenazi, short, pigmented  Dyskeratosis congenita: premature ageing  Swachman-Diamond syn.: pancreatic exocrine dysfunction Acquired  Drugs  Viruses: parvovirus, hepatitis  Autoimmune: SLE Rx = transfusions, ATG for immunosuppression Allogenic BMT is curative

Question 27

Myelodysplastic syndrome

Answer 27

 Cytopenias with <20% blasts  Hypercellular BM  Defective cells: e.g. ringed sideroblasts or Pelger-Huet anamoly  30% → AML Rx = transfusions, EPO, G-CSF Allogenic BMT is curative

Question 28

CML disorders

Answer 28

 RBC → Polycythaemia Vera (secondary is physiological, or pseudo if reduced plasma volume) Rx = aspirin 75mg OD, venesection if young / hydroxycarbamide if older  WBC → CML  Platelets → Essential thrombocythaemia Rx = aspirin if 400-1000; >1000=hydroxycarbamide. Can also use anagralide  Megakaryocytes → Myelofibrosis. 5 year median survival; supportive with blood products and can perform splenectomy. BMT can be curative in younger pts

Question 29

ALL

Answer 29

All children get ALL Mainly B lineage RF: radiation during pregnancy and Down's Mx: Supportive - blood products, allopurinol, portacath, Rx for infxns Chemotherapy - remission induction --> consolidation and CNS Rx --> maintenance for 2-3 years BMT best in younger pts

Question 30

AML FAB classification:

Answer 30

 M2: granulocyte maturation  M3: acute promyelocytic leukaemia – t(15;17). Rx = ATRA  M4: acute myelomonocytic leukaemia  M7: megakaryoblastic leukaemia – trisomy 21

Question 31

AML

Answer 31

``` RF:  Chromosomal abnormalities  Radiation  Down’s  Chemotherapy: e.g. for lymphoma  Myelodysplastic and myeloproliferative syndromes ``` Mx: Supportive: as for ALL Chemotherapy  V. intensive → long periods of neutropenia and ↓ plats  ATRA for APML BMT allogenic if poor prognosis and autogenic if intermediate

Question 32

CLL

Answer 32

↑ WCC = lymphocytosis; Smear cells; +ve DAT; immunophenotyping to distinguish from NHL Can have Richter Transformation: CLL → large B cell lymphoma ``` Rx: Indications  Symptomatic  Ig genes un-mutated (bad prognostic indicator)  17p deletions (bad prognostic indicator) Supportive care Chemotherapy  Cylophosphamide  Fludarabine  Rituximab Radiotherapy  Relieve LN or splenomegaly ``` Prognosis:  1/3 never progress  1/3 progress with time  1/3 are actively progressing

Question 33

Evan's syndrome

Answer 33

CLL, AIHA, ITP

Question 34

CML

Answer 34

t(9,22) = Philadelphia chr Natural Hx  Chronic phase: <5% blasts in blood or DM  Accelerated phase: 10-19% blasts  Blast crisis: usually AML, ≥20% blasts ``` Rx: Imatinib: tyrosine kinase inhibitor  → >90% haematological response  80% 5ys Allogeneic SCT  Indicated if blast crisis or TK-refractory ```

Question 35

Non-hodgkin lymphoma classification

Answer 35

B Cell (commonest)  Low Grade: usually indolent but often incurable  Follicular  Small cell lymphocytic (=CLL)  Marginal Zone (inc. MALTomas)  Lymphoplamsacytoid (e.g. Waldenstrom’s)  High Grade: aggressive but may be curable  Diffuse large B cell (commonest NHL)  Burkitt’s T Cell  Adult T cell lymphoma: Caribs and Japs – HTLV-1  Enteropathy-assoc. T cell lymphoma: chronic coeliac  Cutaneous T cell lymphoma: e.g. Sezary syn.  Anaplastic large cell Mx: RCHOP for high grade BMT if relapse

Question 36

Hodgkin's lymphoma

Answer 36

Pel Ebstein fever - cyclical fever Use Ann Arbor system (NHL as well) for staging 1. Single LN region 2. ≥2 nodal area on same side of diaphragm 3. Nodes on both sides of diaphragm 4. Spread byond nodes: e.g. liver, BM  + B if constitutional symptoms Mx:  Chemo, radio or both  ABVD regimen  BMT for relapse

Question 37

MM

Answer 37

``` CRAB  Ca ↑ (>2.6mM)  Renal insufficiency  Anaemia (<10g/dL)  Bone lesions ``` ``` X-ray: Skeletal Survey  Punched-out lytic lesions  Pepper-pot skull  Vertebral collapse  Fractures ``` Mx: Supportive with bisphosphonates and analgesia Fit pts = Induction chemo: lenalidomide + low-dose dex then allogenic BMT  Unfit pts = Chemo only: melphalan + pred + lenalidomide. Bortezomib (also used for mantle cell lymphoma) for relapse Poor prognostic indicators  ↑ β2-microglobulin  ↓ albumin

Question 38

Causes of massive spleen (>20cm)

Answer 38

```  CML  Myelofibrosis  Malaria  LeishManiasis  Gaucher’s (AR, glucocerebrosidase deficiency) ```

Question 39

Splenectomy signs

Answer 39

Film  Howell-Jolly bodies  Pappenheimer bodies  Target cells

Question 40

Smoldering myeloma

Answer 40

 Se monoclonal protein and/or BM plasma cells ≥10% |  No CRAB

Question 41

MGUS

Answer 41

 Se monoclonal protein <30g/L  Clonal BM plasma cells <10%  No CRAB

Question 42

Waldenstrom’s Macroglobulinaemia

Answer 42

 Lymphoplasmacytoid lymphoma→ monoclonal IgM band Features:  Hyperviscosity: CNS and ocular symptoms  Lymphadenopathy + splenomegaly  Ix: ↑ESR, IgM paraprotein

Question 43

AL Amyloidosis

Answer 43

Features  Renal: proteinuria and nephrotic syndrome  Heart: restrictive cardiomyopathy, arrhythmias, echo - “Sparkling” appearance on echo  Nerves: peripheral and autonomic neuropathy, carpal tunnel.  GIT: macroglossia, malabsorption, perforation, haemorrhage, hepatomegaly, obstruction.  Vascular: periorbital purpura (characteristic) AL amyloid may respond to therapy for myeloma

Question 44

AA Amyloidosis

Answer 44

Amyloid derived from serum amyloid A, an acute phase protein therefore chronic inflammation causes e.g.  RA  IBD  Chronic infection: TB, bronchiectasis Features  Renal: proteinuria and nephrotic syndrome  Hepatosplenomegaly AA amyloid may improve with underlying condition

Question 45

Familial Amyloidosis

Answer 45

 Group of AD disorders caused by mutations in transthyretin (produced by liver)  Features: sensory or autonomic neuropathy  Liver Tx may be curative for familial amyloidosis

Question 46

non-Systemic Amyloidosis

Answer 46

 β-amyloid: Alzheimer’s  β2 microglobulin: chronic dialysis  Amylin: T2DM

Question 47

Hyperviscosity Syndrome

Answer 47

Causes  ↑↑RBC / Hct >0.5: e.g. PV  ↑↑WCC > 100: e.g. leukaemia  ↑↑ plasma proteins: Myeloma, Waldenstrom’s Features  CNS: headache, confusion, seizures, faints  Visual: retinopathy → visual disturbance  Bleeding: mucus membranes, GI, GU  Thrombosis Ix  ↑ plasma viscosity (PV)  FBC, film, clotting  Se + urinary protein electrophoresis ``` Rx  Polycythaemia: venesection  Leukopheresis: leukaemia  Avoid transfusing before lowering WCC  Plasmapheresis: myeloma and Waldenstrom’s ```

Question 48

Tumour Lysis Syndrome

Answer 48

Massive cell destruction  High count leukaemia or bulky lymphoma ↑K, ↑urate → renal failure Prevention: ↑ fluid intake + allopurinol

Question 49

Basophilia causes

Answer 49

 Parasitic infection  IgE-mediated hypersensitivity: urticarial, asthma  CML

Question 50

Eosinophilia causes

Answer 50

 Parasitic infection  Drug reactions: e.g. c¯ EM  Allergies: asthma, atopy, Churg-Strauss  Skin disease: eczema, psoriasis, pemphigus

Question 51

ΔΔ of ESR >100

Answer 51

```  Myeloma  SLE  GCA  AAA  Ca prostate ```

Question 52

Myeloblasts cytochemistry

Answer 52

 Sudan black B  MPO So used for CML

Question 53

Hairy cell leukaemia cytochemistry

Answer 53

tartrate resistant acid phosphatase

Question 54

Leukocyte alkaline phosphatase

Answer 54

 ↑: PV, ET, MF |  ↓: CML, PNH