Haematology in Primary Haematology in Primary CareCare

Dr Josh WrightDr Josh WrightConsultant HaematologistConsultant Haematologist

Sheffield Teaching HospitalsSheffield Teaching Hospitals

Referral Hit ParadeReferral Hit ParadeRaised HbRaised Hb

Leucocytosis- neutrophilia/lymphocytosisLeucocytosis- neutrophilia/lymphocytosis

Thrombocytosis/thrombocytopeniaThrombocytosis/thrombocytopenia

ParaproteinsParaproteins

macrocytosismacrocytosis

Low B12Low B12

Anaemia in the elderlyAnaemia in the elderly

Microcytosis/ iron deficiency/alpha thalMicrocytosis/ iron deficiency/alpha thal

Common haematological Common haematological issues in primary careissues in primary care

LectureLecture► Interpreting the blood Interpreting the blood

countcount► Common referral Common referral

issuesissues White cell problemsWhite cell problems Platelet problemsPlatelet problems ParaproteinsParaproteins

WorkshopWorkshop► Red cell issuesRed cell issues

ErythrocytosisErythrocytosis Haematinics inc low Haematinics inc low

B12B12

► Haemoglobinpathy inc Haemoglobinpathy inc alpha thalalpha thal

► Anaemia in the elderlyAnaemia in the elderly► Any cases brought for Any cases brought for

discussiondiscussion

Full blood countFull blood countNormal rangeNormal range

Adult maleAdult maleRangeRange

Hb Hb 131-166131-166

Hct Hct 0.38-0.480.38-0.48

RBC countRBC count 3.6-4.83.6-4.8

MCVMCV 80-9880-98

MCHMCH 27-34.227-34.2

WBC x10WBC x1099/l/l 3.5-9.53.5-9.5

NeutrophilsNeutrophils 1.7-6.51.7-6.5

LymphocytesLymphocytes 1.0-3.01.0-3.0

PlateletsPlatelets 140-370140-370

Adult femaleAdult femaleRangeRange

HbHb 110-147110-147

HctHct 0.32-0.420.32-0.42

WBCWBC 3.5-9.53.5-9.5

NeutrophilsNeutrophils 1.7-6.51.7-6.5

LymphocytesLymphocytes 1.0-3.01.0-3.0

PlateletsPlatelets 140-370140-370

What is the definition of What is the definition of normal?normal?

White Blood CountWhite Blood CountLymphocytosisLymphocytosis

HistoryHistory

Male age 58 yearsMale age 58 yearsHypertension, Type II DM Hypertension, Type II DM Smokes 10 cigsSmokes 10 cigs

DrugsDrugsSimvastatin, AmlodopineSimvastatin, Amlodopine

ExamExamBMI 38BMI 38Bp 140/85Bp 140/85 FBCFBC SeptembeSeptembe

r 2011r 2011October October 20112011

November November 20112011

HbHb 139139 141141 140140

WBCWBCLymphocytLymphocytesesNeutrophilsNeutrophils

6.76.73.93.92.82.8

6.96.94.14.12.82.8

6.96.94.24.22.52.5

PlateletsPlatelets 249249 310310 270270

LymphocytosisLymphocytosis

►Does the patient have haematological Does the patient have haematological cancer?cancer?

►Should I refer to haematology?Should I refer to haematology?

►Should I continue to monitor the Should I continue to monitor the lymphocyte count?lymphocyte count?

►Are there any other tests I should do?Are there any other tests I should do?

LymphocytosisLymphocytosis

► PrimaryPrimary Lymphoid malignanciesLymphoid malignancies

► Chronic Lymphocytic Chronic Lymphocytic LeukaemiaLeukaemia

► LymphomaLymphoma► Monclonal B Monclonal B

LymphocytosisLymphocytosis

► ReactiveReactive Viral (EBV, CMV, HSV, VZV)Viral (EBV, CMV, HSV, VZV) Stress LymphocytosisStress Lymphocytosis

► Drug inducedDrug induced► Septic shockSeptic shock► Myocardial infarctMyocardial infarct► TraumaTrauma► Other co-morbiditiesOther co-morbidities

► ChronicChronic Cigarette smokingCigarette smoking Autoimmune disorderAutoimmune disorder Chronic inflammationChronic inflammation SarcoidSarcoid Raised BMI/metabolic Raised BMI/metabolic

syndromesyndrome

Malignant Lymphocytosis ?

Lymphocyte count more than 10x109/L

Lymphocyte count less than 10x109/L

Refer to haematologist

anaemia or thrombocytopeniarecurrent infection?adenopathy, spleen, liver?Abnormal blood film?

Yes

No

Repeat FBC, review 1yrly

FBC

The Neutrophil CountThe Neutrophil Count

White Blood CountWhite Blood CountNeutrophil LeucocytosisNeutrophil Leucocytosis

HistoryHistory

Male age 68 yearsMale age 68 yearsOsteoarthritis, Osteoarthritis, CABG 2001CABG 2001Non smoker Non smoker (stopped 2001)(stopped 2001)Type 2 DMType 2 DM

DrugsDrugsSimvastatin, Aspirin, Simvastatin, Aspirin, Gliclazide Gliclazide

ExamExamUnremarkableUnremarkable

FBCFBC July July 20092009

DecembeDecember 2010r 2010

May May 20112011

HbHb 163163 163163 165165

WBCWBCLymphocytLymphocytesesNeutrophilsNeutrophils

15.715.72.42.413.013.0

17.017.02.02.013.513.5

14.014.02.12.111.911.9

PlateletsPlatelets 430430 420420 400400

Neutrophil leucocytosisNeutrophil leucocytosis► Acute neutrophiliaAcute neutrophilia

ReactiveReactive► Infection/Infection/

Inflammation Inflammation ► neoplasianeoplasia► BleedingBleeding► PainPain► SmokingSmoking► Drugs (glucocorticoids)Drugs (glucocorticoids)

► Chronic neutrophiliaChronic neutrophilia ReactiveReactive DrugsDrugs BMI/metabolic synBMI/metabolic syn Haematologic Haematologic Eg CML 1/100000Eg CML 1/100000

(Neutrophil) Leucocytosis(Neutrophil) LeucocytosisImportant pointsImportant points

► Urgent referralUrgent referral► >50>50► Blood film features of Blood film features of

CML or CMML (film CML or CMML (film comment)comment)

► Consider ifConsider if► Chronic Chronic

neutrophilia>20neutrophilia>20► Chronic monocytosis Chronic monocytosis

>1>1► Chronic Chronic

eosinophila>2eosinophila>2

History & ExamHistory & Exam

infection, inflammation, autoimmune, neoplasiarash, arthritis, weight loss

CRP, U&E,LFT,TFTCaAuto AbMicro culture

FBC,ESR

CXRUrine

Reactive screen negative

Haematology referral

NeutropeniaNeutropenia

► Caucasian female Caucasian female aged 36yrs, no aged 36yrs, no significant medical significant medical history, no regular history, no regular medicationmedication

► FH rheumatoid FH rheumatoid arthritisarthritis

► Hb 126 g/lHb 126 g/l► WCC 3.1WCC 3.1► Neutrophils 0.4Neutrophils 0.4► Platelets 180Platelets 180

NeutropeniaNeutropenia(Neutrophils<1.7)(Neutrophils<1.7)

What do I need to know?What do I need to know?► Is the patient unwell? Is the patient unwell?

(Viral assoc transient)(Viral assoc transient)► Any previous counts?Any previous counts?► Any other cytopenia?Any other cytopenia?► Is the patient on Is the patient on

chemotherapy?chemotherapy?► Other drugsOther drugs

► How severe is it? How severe is it? Mild (1.0-1.7), Mild (1.0-1.7),

functionally normalfunctionally normal Moderate (0.5-1.0)Moderate (0.5-1.0) Severe (<0.5)-RISK Severe (<0.5)-RISK

OF INFECTIONOF INFECTION

NeutropeniaNeutropenia

What are the common What are the common causes?causes?

► InfectionInfection►Drugs Drugs (chemotherapy!)(chemotherapy!)►AutoimmuneAutoimmune►HereditaryHereditary

Racial (African origin 1.0-1.3)Racial (African origin 1.0-1.3)

Neutropenia <1.0

Patient on chemotherapy

Discuss with haematologist and refer

Unwell ?

Moderate or Severe <0.5

No

No

B12, Folate, LFT, GGT, autoAb

Haematology advice/referral

Neutropenia pathway

Yes

Consider repeat particularly if recent infection

ThrombocytosisThrombocytosis

►Male 65yrs, mild hypertension on Male 65yrs, mild hypertension on ramipril.ramipril.

►Hb 160, Hct 0.50, WCC 11.0 plts 450Hb 160, Hct 0.50, WCC 11.0 plts 450►Refer or not?Refer or not?

ThrombocytosisThrombocytosis

► Maybe reactive to Maybe reactive to inflammation, inflammation, infection other infection other malignancy, iron malignancy, iron deficiency or deficiency or bleedingbleeding

► In MPD very high In MPD very high counts >1500 assoc counts >1500 assoc with vascular with vascular events and bleedingevents and bleeding

► Urgent referral Urgent referral >1000>1000 600-1000 if assoc 600-1000 if assoc

with CVA, TIA, VTEwith CVA, TIA, VTE

► Consider if Consider if >600 consistently>600 consistently >450 with vascular >450 with vascular

eventevent High wcc or HbHigh wcc or Hb

ThrombocytopeniaThrombocytopenia

► >100 functionally >100 functionally normalnormal

► <20 bleeding risk <20 bleeding risk rises but most rises but most symptom freesymptom free

► CausesCauses► ImmuneImmune► Drugs eg quinineDrugs eg quinine► Bone marrow failure Bone marrow failure

syndromes eg MDSsyndromes eg MDS► ALCOHOLALCOHOL► Liver diseaseLiver disease► PregnancyPregnancy

ThrombocytopeniaThrombocytopenia

► ReferRefer► <50<50► 50-100 if other 50-100 if other

cytopenia or cytopenia or planned planned surgery/dental worksurgery/dental work

► InvestigationsInvestigations► Blood film- platelet Blood film- platelet

clumpingclumping► Repeat sampleRepeat sample► Renal & liver Renal & liver

functionfunction► Clotting screen Clotting screen ► AutoantibodiesAutoantibodies

?Myeloma?Myeloma

HistoryHistory68yr female, 68yr female, Back pain 4 monthsBack pain 4 monthsESR 70ESR 70X Ray normalX Ray normal

► Hb 110► WCC & plts normal► U&E normal► Total Protein 66 (60-74)► IgG *► IgA 0.7 (0.8-4.0)► IgM 0.5 (0.5-2.0)► MIg 7.0► IgG Kappa monoclone

Should I refer to haematology?

Reminder…….Monoclonal or polyclonal?

ParaproteinsParaproteins

► Refer ifRefer if IgG>15g, IgA>10gIgG>15g, IgA>10g IgD or EIgD or E Lower levels if assoc Lower levels if assoc

with CRABwith CRAB

► IgM usually assoc IgM usually assoc with lymphomawith lymphoma Any other features?Any other features? Paraprotein>10gParaprotein>10g ?Hyperviscosity?Hyperviscosity

► C- HypercalacemiaC- Hypercalacemia► R- unexplained R- unexplained

renal failurerenal failure► A-anaemia/A-anaemia/

cytopeniacytopenia► B-bone B-bone

pain/fracturepain/fracture

Paraproteinaemia

►Most will be MGUS►Present 3% over 70 and 5% over 80►1% risk of progression to MM per

annum►A few secondary to auto-immune

disease & rarely other malignancies►If criteria for referral not met then

monitor on a 6-12 monthly basis.

Common Red cell ProblemsCommon Red cell Problems

► MacrocytosisMacrocytosis► ErythrocytosisErythrocytosis► Haematinic Haematinic

assessmentassessment► Anaemia in the Anaemia in the

elderlyelderly► HaemoglobinopathiHaemoglobinopathi

es including alpha es including alpha thal carriagethal carriage

MacrocytosisMacrocytosis

►Approx 8% populationApprox 8% population►Commonest causes alcohol & Commonest causes alcohol &

hypothyroidismhypothyroidism B12/ folate deficiencyB12/ folate deficiency Drugs (including those used for HIV)Drugs (including those used for HIV) ReticulocytosisReticulocytosis ParaproteinParaprotein Myelodysplasia (elderly population & Myelodysplasia (elderly population &

associated with cytopenias)associated with cytopenias)

MacrocytosisMacrocytosis

Raised MCV >100

Are there cytopenias?

Check B12, Folate,, LFT, GGT, TFT, Igs,

Refer to Haematology

Yes

No

Isolated macrocytosis

Isolated macrocytosis

Monitor if screening normal

Erythrocytosis??Erythrocytosis??

ErythrocytosisErythrocytosis

► ApparentApparent DehydrationDehydration DiureticsDiuretics AlcoholAlcohol Raised BMIRaised BMI

► True PhysiologicalTrue Physiological Hypoxia eg COPD, Hypoxia eg COPD,

sleep apnoeasleep apnoea High altitudeHigh altitude SmokingSmoking

► True none True none physiologicalphysiological Primary Primary

polycythaemiapolycythaemia Certain rare tumoursCertain rare tumours Anabolic steroid Anabolic steroid

usageusageURGENT REFERRAL• Hct >60 males or 0.56 females

ErythrocytosisErythrocytosis

Male

Hct >0.52for at least 2 months

Female

Hct >0.48for at least 2 months

Refer to Haematology

Incidence of polycythaemia rubra vera ~5/100 000

Incidence of apparent polycythaemia~ HIGH!

HaematinicsHaematinics

►There is no entirely reliable blood test There is no entirely reliable blood test for iron statusfor iron status

►There is no entirely reliable blood test There is no entirely reliable blood test for folatefor folate

►There is no entirely reliable blood test There is no entirely reliable blood test for B12for B12

►Ferritin is the test of choiceFerritin is the test of choice►Inaccurate in the presence of inflammationInaccurate in the presence of inflammation►A trial of iron remains a valid approachA trial of iron remains a valid approach►ALCOHOL/FATTY LIVER & FERRITINALCOHOL/FATTY LIVER & FERRITIN

►Serum folate is a good reflection of what Serum folate is a good reflection of what you have just eatenyou have just eaten

► I’m not sure what B12 is a good reflection I’m not sure what B12 is a good reflection of!of!

►Interpret borderline values with cautionInterpret borderline values with caution►Schilling test no longer availableSchilling test no longer available

Reduced serum B12Reduced serum B12

► B12< 100 True B12< 100 True deficiency highly deficiency highly likely parenteral likely parenteral replacementreplacement

► B12 100-145 replace B12 100-145 replace especially if raised especially if raised MCV, cytopenia, MCV, cytopenia, neuropathyneuropathy

► B12>140 deficiency B12>140 deficiency unlikelyunlikely

► B12 is an unreliable B12 is an unreliable testtest

► Always reduced in Always reduced in pregnancypregnancy

► Uncomplicated Uncomplicated B12/folate B12/folate deficiency does not deficiency does not require OP referral.require OP referral.

Anaemia in the elderlyAnaemia in the elderly

► Frequency of Frequency of anaemia increases anaemia increases with agewith age

► Incidence 10-40%Incidence 10-40%► Many have Many have

diagnosable/treatabdiagnosable/treatable causele cause

► 25% no identified 25% no identified causecause

► InvestigationsInvestigations► FBC & filmFBC & film► ReticulocytosisReticulocytosis► Renal/ liver functionRenal/ liver function► ImmunoglobulinsImmunoglobulins► HaematinicsHaematinics► Coeliac screenCoeliac screen

► Dietary historyDietary history► GI investigationsGI investigations► Bone marrowBone marrow

Anaemia in the elderlyAnaemia in the elderly

CAUSE OF ANEMIA PERCENTAGE OF CASES

Anemia of chronic disease 30 to 45

Iron deficiency 15 to 30

Posthemorrhagic 5 to 10

Vitamin B12 and folate deficiency

5 to 10

Chronic leukemia or lymphoma

5

Myelodysplastic syndrome 5

No identifiable cause 15 to 25

The lost 25%?The lost 25%?

►MULTIFACTORIALMULTIFACTORIAL►Decline in erythropoetinDecline in erythropoetin►Decline in androgensDecline in androgens► Increased inflammatory cytokines even in Increased inflammatory cytokines even in

absence of a recognised diseaseabsence of a recognised disease►Age associated decline in stem cell Age associated decline in stem cell

functionfunction►Early MDS without other cytopenias or BM Early MDS without other cytopenias or BM

changeschanges

Indications for haematology Indications for haematology referralreferral

Pancytopenia

Monoclonal gammopathy

Suspicion of myelodysplastic syndrome

Blood smear showing immature white cells or nucleated red cells

Indeterminate status of iron stores

Unexplained progressive or unresponsive anemia

What are What are haemoglobinopathies?haemoglobinopathies?

►Commonest single gene disorders Commonest single gene disorders worldwideworldwide

►Autosomal recessiveAutosomal recessive►Disease states homozygous or combined Disease states homozygous or combined

heterozygotesheterozygotes

►Defects of quality or quantity of Defects of quality or quantity of haemoglobinhaemoglobin

►QualityQuality Variant Hbs eg sickleVariant Hbs eg sickle►QuantityQuantity Under production eg thalsUnder production eg thals

National Screening PlanNational Screening Plan

► NHS Plan commits NHS Plan commits to to “a new national “a new national linked antenatal & linked antenatal & neonatal screening neonatal screening programme for programme for haemoglobinopathy & haemoglobinopathy & sickle cell disease by sickle cell disease by 2004”2004”

► Universal neonatalUniversal neonatal► Antenatal ?selective Antenatal ?selective

?universal?universal

The haemoglobinopathy The haemoglobinopathy screenscreen

► HaemoglobinHaemoglobin► MCV, MCHMCV, MCH► Hb A2Hb A2► HPLCHPLC► ZPP/ferritinZPP/ferritin► Sickle solubility Sickle solubility

test, test, electrophoresis, electrophoresis, molecular analysismolecular analysis

Case studyCase study

►32 year old female of Pakistani origin 32 year old female of Pakistani origin attends c/o fatigueattends c/o fatigue

►Hb 11.9, MCV 71, MCH 23Hb 11.9, MCV 71, MCH 23►Ferritin 109Ferritin 109►Hb A2 normal, no evidence of Hb A2 normal, no evidence of thal thal

thalassaemiathalassaemia

/ No Normal

0/ Thal trait Low MCV/MCH

+/ Thal trait Mild anaemia

0/0 Thal major Transfusion dependant

0/+ Thal intermedia Anaemia, splenomegally

0/HbE Thal major

thalassaemiathalassaemia

/ Normal

-/ Heterozygous + Low MCV/ MCH

-/- Homozygous + Low MCV/MCH

--/ Heterozygous 0 Low MCV/MCH

--/- Haemoglobin H disease

Thal Intermedia

--/-- Hb Barts Hydrops Stillbirth

thalassaemia thalassaemia heterozygotesheterozygotes

00 ++

► CypriotCypriot 2%2%► IndiaIndia rarerare► AfricanAfrican rarerare► Hong KongHong Kong 5%5%► China China 3-9%3-9%► PhillipinesPhillipines 10%10%

► UK AfricansUK Africans 25%25%► IndiaIndia 5-58%5-58%► PNGPNG 20-80%20-80%► ThailandThailand 3-3-

17%17%► MaoriMaori 5-5-

10%10%

Summary pointsSummary points

►Other than for individuals of E. Med or Other than for individuals of E. Med or SE Asian origin SE Asian origin thal trait is thal trait is insignificantinsignificant

►Microcytosis is commonly due to thal Microcytosis is commonly due to thal traittrait

►A national antenatal/neonatal A national antenatal/neonatal screening programme is now in placescreening programme is now in place