Final Year MB ChB Revision Lecture Haematology

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Final Year MB ChB Revision LectureHaematology

• Dr M Drummond
• Cons Haem, GGH BOC

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Topics

• Anaemia (most clinically relevant types)
•        Haemolytic disease
•         Coagulation disorders
•        Thrombocytopenia
•        Leukaemia/Lymphomas/Myeloma
• In no particular order

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Malignancy
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Haem Malignancy

• History is crucial
• Wt loss (10 in 6 months)
• Night Sweats
• Fever
• Itch (after shower?)
• Fatigue / lethargy / (symptoms of anaemia)
• Bruising / bleeding
• Bone pain

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Examination

• To include
• Mouth (?ulcers, haemorrhage, thrush, tonsillar
  enlargement)
• Skin (purpura, rash, infiltration)
• Fundi (?haemorrhages, infection)
• LNs, liver spleen

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Haem Malignancy

• Dont get too caught up in terminology!!
• 159 separate entities!
• Concentrate on broad categories clinical
  features
• Lymphoma (lumpy HL, NHL)
• Leukaemia (liquid)
• Acute chronic
• Myeloid lymphoid
• Myeloma (marrow bone disease, paraprotein)
• MPDs
• PRV, ET, MF (CML). (marrow, blood, spleen)

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Lymph Node Groups
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Lymphadenopathy (1)

• Site
• Size
• Consistency (rubbery vs craggy)
• Tenderness
• Fixed

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Lymphadenopathy (2)

• Generalised
• EBV, CMV, HIV
• Brucellosis, syphilis
• Toxoplasma
• Lymphoma or CLL
• (occasionally CT disease)
• Localised
• Acute or chronic infection
• Neoplasia (cancer, lymphoma)

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Splenomegaly (1)

• ULN 13cm in long axis (USS or CT)
• May occasionally be tippable in slim healthy
  individual
• Causes of splenomegaly in UK (exams)
• Myelofibrosis
• Lymphoma
• Gauchers disease
• Causes of massive splenomagaly in UK
• Myelofibrosis
• CML (treatment so effective dont see this in
  exams)
• (rarely) lymphoma

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Splenomagaly (2)

• features
• Enlarges towards right IF
• Cant get above it
• Moves with respiration
• Notch
• Dull to percussion

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Spleen Examination 2 line of resonance
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Lymphoma

• Cancer of lymphatic system
• 2 main sub types
• Hodgkin Lymphoma
• Non Hodgkin lymphoma

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Ann Arbor Staging System

• I single LN region (I) or single extralymphatic
  organ or site (IE)
• II 2 LN areas, same side of diaphragm (II) or
  with ltd localised EN extension (IIE)
• III LN areas on both sides of diaphragm (if
  includes spleen IIIS)
• IV extensive disease of 1 extralymphatic organ
  eg liver, bone marrow
• A/B
• Bulk

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HL - clinical features

• Asymptomatic LN enlargement (70)
• Mass on CXR
• Sites
• Neck 60-80
• Mediastinal 60
• Axillae 10-20
• Inguinal 6-12
• Infradiaphragmatic 10

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Hodgkin Lymphoma

• Bimodal age distribution
• Peak 20-30s
• 2nd peak gt50 yrs
• Usually arises in LN and spreads to adjacent LN
  areas
• Later, haematogenous spread to liver, lungs

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HL - clinical features

• B symptoms
• unexplained fever gt38 degrees
• night sweats
• weight loss gt10 body wt in 6 months
• generalised pruritis
• alcohol induced LN pain
• lt10 but highly specific

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Hodgkin Lymphoma
CT Chest at diagnosis Mediastinal mass
CT post treatment with chemotx. And
radiotherapy Complete remission
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Non Hodgkins Lymphoma
B cell
T cell
Low grade
High grade
High grade
Low grade
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Non Hodgkin Lymphoma

• Wide variation in presentation
• localized or generalised lymphadenopathy
• low grade or high grade
• in extranodal sites may mimic carcinoma
• variable prognosis
• accurate sub-classification is essential for
  planning treatment

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Low grade NHL

• Tends to be widely disseminated at presentation
  often involving bone marrow
• Indolent clinical course
• Incurable

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High grade NHL

• Tends to be more localised
• despite rapid growth, 50 are curable

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Aetiology of lymphoma

• EBV Hodgkin Lymphoma,Post transplant lymphomas,
  AIDs related Lymphomas, NK lymphomas
• HTLV-1. Adult T cell leuk./lymphoma
• Helicobacter Low grade gastric lymphomas
• Autoimmune disease eg Sjogrens and low grade B
  cell lymphomas of Sal. Gland
• Coeliac disease T cell lymphoma of small bowel

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Multiple Myeloma

• Neoplastic proliferation of plasma cells
• Involves bone marrow
• presents with
• lytic lesions in bones
• immunosuppression
• anaemia
• monoclonal gammopathy
• renal failure
• prodrome MGUS (3 of gt70s)

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X Ray in myeloma
Multiple lytic lesions in skull and humerus
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Leukaemia Classification
Myeloid
Acute
lymphoid
Leukaemia
Chronic
Myeloid
Pre-leukaemic conditions eg myelodysplasia,
myeloproliferative disorders
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Chronic Leukaemias

• Myeloid
• CML
• CMML, CEL, CNL
• Lymphoid
• CLL
• Hairy Cell Leukaemia
• Prolymphocytic

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CML

• Excess myeloid cells (neutrophils, eos
  basophils) plts in blood
• WCC generally gt100, plts often gt1000
• Splenomegaly, night sweats
• Late middle age (60 yrs)
• Now very effectively managed with TKIs

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Chronic lymphocytic leukaemia (CLL)

• Most common form of leukaemia in the West, rare
  in Asian populations (incidence 3 cases per
  100,000)
• Majority of cases occur in later life.
• Treatable but in most cases not curable.
• Increasing numbers of cases detected at routine
  screening of older population.
• New drugs are having a significant impact.
• Lymphadenopathy, hepatosplenomegaly, B symptoms,
  marrow failure

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Acute Leukaemia

• Medical emergency
• High, Normal, or low WCC
• Marrow failure
• Blasts (immature cells) Marrow /- blood
• Often vague prodrome
• Potentially curable
• ALL vs AML

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Malignancy

• Neutropaenic Sepsis
• ? Likely most chemotherapy regimens neutrophils
  down by day 8-10
• Rapid assessment necessary
• Culture
• Dont delay for CXR etc
• Prompt administration of IV antibiotics
  (Taz/Gent meropenem)
• Meticulous supportive care

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Anaemia
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Normal Ranges

• Red Cells (MCV 80-100fl)
• Hb 12.0-16.0 g/dl females
• Hb 13.0-18.0 g/dl males
• White Cells
• 4.0-11.0 x 109/l
• Platelets
• 150-400 x 109/l

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History Exam

• Symptoms of anaemia
• Blood Loss
• FH
• PMH (eg gastrectomy)
• DHx (eg aspirin, NSAIDs)
• Diet
• Koilonychia, glossitis
• Jaundice
• Lymphadenopathy / hepatosplenomegaly
• PR FOB testing

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Ferritin

• Serum ferritin correlates well with liver and
  macrophage stores
• N range 15-300 ug/ml
• Mean adult male level 100 mean adult
  premenopausal female level 30.
• lt15, specific for depletion of iron stores
  normal values do not exclude this!! Values gt300
  are not usually indicative of iron overload
  (Acute Phase Reactant)!!
• Use of BM for iron stores
• Ferritin lt50 cw absent stores in RA, IBD

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Assessing iron status

• IDA ferritin Lo (absent on BM) TIBC Hi, Serum
  transferrin satn (STS) Lo (lt15)
• Haemochromatosis ferritin hi TIBC lo STS Hi
  HFE gene mutation.
• Anaemia of chronic disorders ferritin N or Hi
  TIBC lo STS lo STR N.
• NB Haemosiderin. Soluble iron storage protein,
  predominantly in macrophages. Found in urine in
  chronic intravascular haemolysis.

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Case 1 Female 18yrs
Hb 8 MCV 65 WBC 5 Plts 150 ESR 5
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Case 1 Female 18yrs
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Case 1 Female 18yrs

• Serum ferritin 3 NR 15-300
• Menorrhagia
• Iron replacement
• No further investigation

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Case 2

• 27 yr old female
• Hb 4.5, MCV 122
• WCC 4.0, Plts 145

Film oval macrocytes, hypersegmented neutrophils
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Diagnosis severe megaloblastic anaemia
Delayed nuclear maturation in the bone marrow
due to defective synthesis of DNA
In clinical practice almost always caused by B12
or folate deficiency
May see some megaloblastic change in the context
of certain drugs (eg methotrexate, azathioprine)
or alcohol.
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Clinical Features

• Common Pancytopaenia Glossitis
  Diarrhoea PV discomfort
• B12 Deficient SACD
• DO NOT GIVE FOLATE IN ISOLATION UNLESS
  SIGNIFICANT B12 DEFICIENCY HAS BEEN EXCLUDED!

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Vitamin B12 Deficiency Reduced Intrinsic
Factor Pernicious Anaemia Gastrectomy Inte
stinal Malabsorption Crohns Disease
Ileal Resection Stagnant Loop
Syndrome Fish Tapeworm Dietary
Deficiency Vegans
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Folate Deficiency Dietary Deficiency Alcoholics
Malabsorption Coeliac Disease Tropical
Sprue Small Bowel Disease /
Resection Increased Requirements Pregnancy
Haemolysis Malignancy
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Learning Points

• B12 and Folate deficiency commonest cause of
  megaloblastic anaemia
• Chronic. Transfusion rarely required and may be
  dangerous!
• Take haematinic assays before transfusion!
• Majority of diagnoses can be made without
  invasive / extensive investigation

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Anaemia 1

• Pattern
• Isolated IDA, haemolysis, bleeding
• Part of pancytopaenia B12/folate deficiency,
  marrow failure (eg aplastic anaemia) or
  hypersplenism

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Anaemia 2

• Describe as
• Size (80-100fl)
• Haemoglobinisation of cells (MCH, MCHC)
• ie hypochromic microcytic (IDA, thalassaemia,
  ACD)
• Normochromic normocytic (acute blood loss, 2o
  anaemia or ACD)
• Macrocytic (B12/folate, liver dis, alcohol,
  hypothyroid, reticulocytosis)

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• Reticulocyte count
• Normal range, lt2
• Anaemia plus reticulocytosis
• Haemolysis
• Blood loss
• Anaemia, no reticulocytosis
• 2o anaemia
• CRF
• B12/folate
• SAA

Ask for and use the reticulocyte count!!
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Anaemia 3

• Defective production of RBCs
• IDA, B12 folate deficiency
• 20 anaemias
• BM failure (eg SAA, leukaemia, MDS etc)
• Renal Failure
• Thalassaemias
• Pure red cell aplasia
• Congenital dyserythropoiesis

Usually low retic count!!
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Anaemia 4

• Reduced red cell survival
• Haemolysis (intrinsic vs extrinsic)
• Blood loss (acute vs chronic)
• Enzyme deficiency
• Pooling of normal rbcs in large spleen
• Sequestration of abnormal rbcs in spleen

Usually High retic count!!
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Anaemia 5

• Defining the cause
• Clinical background
• 16 yr old female vs. 45 yr old male drugs diet
  previous surgery splenomegaly jaundice
• Automated analyser
• Size, hb, WCC and plt count
• Blood film
• Shape of red cells tear drop cells, nucleated
  red cells, polychromasia, fragments, target
  cells, spherocytes
• Abnormal population eg blast cells
• Leucorythroblastic (stressed BM, infiltration,
  severe B12/folate)

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Case Male 28yrs
Hb 7.6 MCV 128 WBC 14 Plts 326 ESR 5
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Case Male 28yrs
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Case Male 28yrs
Reticulocytes 350 (NR 50-100) Bilirubin 112 LDH
2500 NR lt220 Direct Coombs test positive Auto
immune haemolytic anaemia
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Case Male 28yrs
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Haemolytic anaemia Inherited

• Red Cell Membrane disorders
• HS, HE
• Red Cell enzyme disorders
• G6PD PK deficiency

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Haemolytic anaemia Acquired

• Immune (DATve)
• Autoimmune (warm vs cold)
• Alloimmune (transfusion reactions, HDN)
• Non-immune
• Infection (malaria, clos, perfringens,
  septicaemia etc)
• Chemical / physical agents (burns, lead poisoning
  etc)
• Mechanical injury (heart valves, MAHA etc)
• Acquired membrane disorders (eg liver disease,
  PNH)

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Haemolytic Anaemia

• Laboratory features
• Anaemia polychromasia spherocytes (HS, AIHA)
  fragments (MAHA)
• Reticulocytosis
• Raised bilirubin (generally 30-50)
• Raised LDH
• Absent haptoglobins
• Folic Acid Deficiency (chronic HA, acute
  aggravation)
• Iron Deficiency (Chronic IV haemolysis increased
  urinary haemosiderin but not in EV haemolysis)

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Clotting
Pattern of Clotting Abnormalities Over
anticoagulation
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Clotting Cascade
PT
APTT
Intrinsic system
Extrinsic system
Tissue factor
Contact activation
VII
XII XI IX
Final Common Pathway
VIII
X II (prothrombin) I (fibrinogen)
V
PS/aPC
Clot (fibrin)
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Clotting Disorders
Inherited
Acquired
Factor VIII IX deficiency vWD
DIC
Vit K deficiency or antagonists
Liver disease
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Patterns of results in clotting disorders
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Clinical Bleeding

• Platelet disorders (eg aspirin, thrombocytopaenia
• Mucocutaneous
• Clotting disorders (eg haemophilia)
• Musculoskeletal

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Warfarin
Guidelines on Oral Anticoagulation Brit J Haem
1998, 101, 374-387

• Commencing warfarin
• Proteins C S (natural anticoagulants) are Vit K
  dependent
• Initial fall can promote thrombosis
• Therefore cover with heparin (at least 4 days and
  for 2 days with therapeutic INR)
• Particular caution with protein C deficiency
  cautious introduction with heparin no loading
  dose

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Over Warfarinisation
Warfarin Guidelines Brit J Haem, 1998, 101
374-387

• INRgt8.0, no bleeding or minor bleeding
• If no other risk factors for haemorrhage (agegt70,
  previous bleeding) stop warfarin until lt5
• if risk factors / minor bleeding Vit K (1mg
  oral)
• INRgt8.0, major bleeding
• IV Vit K (5-10mg)
• IV PCC (Octaplex) sliding scale (based on INR
  weight)

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Haematological Rashes
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Describe? Classify?
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This is palpable. ? Further investigations
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Purpura classification
palpable
vasculitis
purpura
Petaechiae (lt3mm)
Non-palpable
thrombocytopaenia
CT disorders
Ecchymotic (gt3mm)
Clotting disorder
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11 year old boy. ? Other symptoms / signs ?
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Purpura in BM failure

• Sites
• local trauma, lower limbs, under dressings,
  clothes (eg bra straps), mouth, but most
  important fundi
• Wet vs Dry purpura
• Avoid aspirin / NSAIDS
• Prophylactic platelet transfusion (threshold 10
  20)

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Thrombocytopaenia
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Thrombocytopaenia

• Plt count lt150
• Few problems gt50
• Most problems lt20
• History drugs, viral illness, malignancy
• Exam spleen, liver, LNs, mouth skin

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Case

• 6 year old. Flu like illness 3 weeks ago.
  Spontaneous bruising and rash.
• Hb11.7, WCC 9.5, Platelets 5.
• What is it likely to be?
• What should you do as 1st basic Ix(s)?

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Causes of low plts

• Decreased Production
• Marrow Failure / infiltration
• Marrow Suppression (eg chemo / radiotherapy/drugs/
  alcohol)
• Viral
• B12/Folate deficiency
• Increased Destruction
• Immune
• ITP, drugs, infection
• Non-Immune
• DIC, TTP, Cardiac Bypass.

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Hyposplenism
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Guidelines for the prevention and treatment of
infection in patients with an absent or
dysfunctional spleen

• BMJ 1996 312 430 - 434http//www.bcshguidelines.
  com/pdf/SPLEEN96.pdf

• Post Splenectomy / partial splenectomy patients
• Functional Hyposplenism
• Sickle cell anaemia / thalassaemia
• Lymphoproliferative disorders (eg NHL, HL CLL)
• Coeliac disease, IBD, dermatitis herpetiformis

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Howell Jolly Bodies
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Infecting micro organisms

• NB effect of age children lt5 have infection risk
  of 10, adults lt1
• Encapsulated bacteria
• Pneumococcus (mortality up to 60 in some cases)
• Haemophilus influenzae type B
• Meningococcus
• Others
• Malaria, E Coli, capnocytophaga canimorsus
• Duration of risk most occur within 2 years, up
  to a third at least 5 years later, and some
  reports of 20 years later!
• The risk of dying of serious infection is
  clinically significant and almost certainly
  lifelong!!

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Antibiotic Prophylaxis

• Lifelong
• Phenoxymethylpenicillin (plus supply of
  amoxycillin to hand)
• Erythromycin in allergic
• Antimalarial prophylaxis
• Prompt treatment (IV penicillin / cephalosporin)
• Infective symptoms
• Animal bites!! (5 days of augmentin)
• Medic alert bracelets

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Good Luck!!
The End!!