Final Year logy Revision Lecture

8/8/2019 Final Year logy Revision Lecture

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Final Year MB ChB RevisionLecture

Haematology

Dr M Drummond

Cons Haem, GGH & BOC


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Anaemia (most clinically relevant types)

Haemolytic disease

Coagulation disorders

Thrombocytopenia

Leukaemia/Lymphomas/Myeloma

In no particular order

Topics


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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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Symptom

Distribution

in haem

malignancy

Sweats /

feverWt loss Itch

Marrow

Failure

Splenom

egaly

Lymphad

enopathy

Bone

Disease

Lymphoma

/ LPDs++++ ++++ ++ ++ ++ ++++ +

Acute

Leukaemia+ + 0/+ ++++ + 0/+ 0

Myeloma

0/+ ++

0++

0 0++++

MPDs

(Myeloproli

ferative

disorders)

+++ +++ +++ + ++++ 0 0


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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 ofsplenomegaly in UK (exams)

Myelofibrosis

Lymphoma

Gauchers disease

Causes ofmassive 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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LymphomaLymphoma

Cancer of lymphatic systemCancer of lymphatic system

2 main sub types2 main sub types Hodgkin LymphomaHodgkin Lymphoma

Non Hodgkin lymphomaNon Hodgkin lymphoma

14


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Ann Arbor Staging SystemAnn Arbor Staging System

I = single LN region (I) or single extralymphaticI = single LN region (I) or single extralymphatic

organ or site (IE)organ or site (IE)

II = 2 LN areas, same side of diaphragm (II) orII = 2 LN areas, same side of diaphragm (II) or

with ltd localised EN extension (IIE)with ltd localised EN extension (IIE)

III = LN areas on both sides of diaphragm (ifIII = LN areas on both sides of diaphragm (if

includes spleen IIIS)includes spleen IIIS)

IV = extensive disease of 1 extralymphaticIV = extensive disease of 1 extralymphaticorgan eg liver, bone marroworgan eg liver, bone marrow

A/BA/B

BulkBulk


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16

HLHL -- clinical featuresclinical features

Asymptomatic LN enlargement (70%)Asymptomatic LN enlargement (70%)

Mass on CXRMass on CXR

SitesSites Neck 60Neck 60--80%80%

Mediastinal ~60%Mediastinal ~60%

Axillae 10Axillae 10--20%20%

Inguinal 6Inguinal 6--12%12%

Infradiaphragmatic ~10%Infradiaphragmatic ~10%


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Hodgkin Lymphoma

Bimodal age distribution

Peak 20-30s

2nd

peak >50 yrs Usually arises in LN and spreads to

adjacent LN areas

Later, haematogenous spread to liver,lungs


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HLHL -- clinical featuresclinical features

B symptomsB symptoms

unexplained fever >38 degreesunexplained fever >38 degrees

night sweatsnight sweats weight loss >10% body wt in 6 monthsweight loss >10% body wt in 6 months

generalised pruritisgeneralised pruritis

alcohol induced LN painalcohol induced LN pain


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CT Chest atdiagnosis

Mediastinal

mass

CT

post treatment

with chemotx. And

radiotherapy

Complete

remission

Hodgkin

Lymphoma


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Non Hodgkins Lymphoma

B cell T cell

Low gradeHigh grade Low

grade

High

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 forplanning 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 >70s)


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X Ray in myeloma

Multiple

lytic

lesions in

skull and

humerus


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Leukaemia Classification

Leukaemia

Acute

Chronic

Myeloid

lymphoid

Myeloid

Pre-leukaemic conditions eg myelodysplasia, myeloproliferative disorders


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Chronic Leukaemias

Myeloid

CML

CMML, CE

L, CNL Lymphoid

CLL

Hairy Cell Leukaemia

Prolymphocytic


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CML

Excess myeloid cells (neutrophils, eos &

basophils) & plts in blood

WCC generally >100, plts often >1000 Splenomegaly, night sweats

Late middle age (60 yrs)

Now very effectively managed with TKIs


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Most common form of leukaemiain the West, rare in Asianpopulations (incidence 3 casesper 100,000)

Majority of cases occur in later

life. Treatable but in most cases not

curable.

Increasing numbers of cases

detected at routine screening ofolder population.

New drugs are having asignificant impact.

Lymphadenopathy,hepatosplenomegaly, B

symptoms, marrow failure

Chronic lymphocytic leukaemia (CLL)

nci ence o CLL

0

5

10

15

20

25

30

35

40

0-4

5-9

10-1

4

15-19

20-2

4

25-29

30-3

4

35-39

40-4

4

45-49

50-5

4

55-59

60-6

4

65-69

70-7

4

75-79

80-8

4

85-89

e

Cae

100,0

00


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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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Symptom

Distribution

in haem

malignancy

Sweats /

feverWt loss Itch

Marrow

Failure

Splenom

egaly

Lymphad

enopathy

Bone

Disease

Lymphoma

/ LPDs++++ ++++ ++ ++ ++ ++++ +

Acute

Leukaemia+ + 0/+ ++++ + 0/+ 0

Myeloma

0/+ ++ 0 ++ 0 0 ++++

MPDs

(Myeloproli

ferative

disorders)

+++ +++ +++ + ++++ 0 0


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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 andmacrophage stores

N range 15-300 ug/ml

Mean adult male level: 100; mean adultpremenopausal female level 30.

300 are not usually indicative of ironoverload (Acute Phase Reactant)!!

Use of BM for iron stores

Ferritin


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Assessing iron status

IDA: ferritin Lo (absent on BM); TIBC Hi,Serum transferrin satn (STS) Lo (


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Case 1 Female 18yrs

Hb: 8

MCV: 65

WBC: 5

Plts: 150ESR: 5


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Case 1 Female 18yrs


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Serum ferritin 3 NR 15-300

Menorrhagia

Iron replacement

No further investigation

Case 1 Female 18yrs


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Case

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

B12orfolate 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

GlossitisDiarrhoeaPV discomfort

B12 Deficient SACD

DO NOT GIVE FOLATE IN ISOLATION UNLESSSIGNIFICANT B12 DEFICIENCY HAS BEEN

EXCLUDED!


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Vitamin B12Deficiency

Reduced Intrinsic Factor Pernicious Anaemia

Gastrectomy

Intestinal 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 requiredand may bedangerous!

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 < %

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 (acutevs chronic)

Enzyme deficiency

Pooling ofnormalrbcs in large

spleen

Sequestration ofabnormalrbcs in

spleen

Usually High retic count!!


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Anaemia 5Defining 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


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Case Male 28yrs


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Red Cell Membrane disorders HS, HE

Red Cell enzyme disorders G6PD & PK deficiency

Haemolytic anaemia: Inherited


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Haemolytic anaemia: Acquired

Immune (DAT+ve): 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)

H l i A i


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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

Intrinsic system Extrinsic systemContact activation Tissue factor

XII

XI

IX

VII

Final Common Pathway

VIII

APTT PT

XII (prothrombin)

I (fibrinogen)

V

Clot (fibrin)

PS/aPC


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Inherited Acquired

DIC Vit K

deficiency orantagonists

Clotting Disorders

Factor VIII & IX

deficiency;vWD

Liver disease

Patterns of results in clotting


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Patterns of results in clotting

disorders

PT APTT TCT BT plts Fib

Haem AN N N N N

Haem B N N N N N

vWDN / N N / N N N

DIC

warfarin N / N N N N


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Clinical Bleeding

Platelet disorders (eg aspirin, thrombocytopaenia

Mucocutaneous

Clotting disorders (eg haemophilia)

Musculoskeletal


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Warfarin

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 loadingdose

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


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Over Warfarinisation

INR>8.0, no bleeding or minor bleeding

If no other risk factors for haemorrhage (age>70,

previous bleeding) stop warfarin until 8.0, major bleeding

IV Vit K (5-10mg) IV PCC (Octaplex) sliding scale (based on INR &

weight)

Warfarin Guidelines: Brit J Haem, 1998, 101 374-387


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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

purpura

palpable

Non palpable

vasculitis

Petaechiae (3mm)

thrombocytopaenia

Clotting disorder

CT disorders


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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 50

Most problems


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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


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Antibiotic Prophylaxis

Lifelong Phenoxymethylpenicillin (plus supply of

amoxycillin to hand)

E

rythromycin 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!!

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Final Year logy Revision Lecture