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Haematology in Primary Care:Haematology in Primary Care:The Full Blood CountThe Full Blood Count

Charles CrawleyCharles Crawley

George FollowsGeorge Follows

CCambridge ambridge HHaematology aematology PPartnersartners


The FBCThe FBC


HaemoglobinHaemoglobin Low haemoglobin defines anaemiaLow haemoglobin defines anaemia

– Males 13-18g/lMales 13-18g/l– Females 11.5-16g/lFemales 11.5-16g/l– Variations:Variations:

ChildrenChildren– Neonates – 14-24g/lNeonates – 14-24g/l– 2 months – 8.9-13.2g/l2 months – 8.9-13.2g/l– 9-12ys9-12ys - 11.5-15.4g/l - 11.5-15.4g/l

PregnancyPregnancy– 33rdrd Trimester – 9.8-13.7g/l Trimester – 9.8-13.7g/l

AgeAge– 5-75-7thth decade – falls in men rises in women decade – falls in men rises in women

ExerciseExercise– Increases HbIncreases Hb

AltitudeAltitude SmokingSmoking


MCVMCV Mean Cell VolumeMean Cell Volume: average size of RBC : average size of RBC

– Normal adult : 76 (80) - 100 fLNormal adult : 76 (80) - 100 fL MCV < 76 fLMCV < 76 fL (microcytic) (microcytic)

MCV > 100 fLMCV > 100 fL (macrocytic) (macrocytic)

MCV 80 - 100fLMCV 80 - 100fL (normocytic) (normocytic)


Practical Classification of AnaemiaPractical Classification of Anaemia

Microcytic Microcytic (<76fL)(<76fL) NormocyticNormocytic Macrocytic Macrocytic (>100)(>100)

Iron deficiencyIron deficiency

ThalassaemiaThalassaemia

HaemoglobinopathiesHaemoglobinopathies

Anaemia of chronic Anaemia of chronic diseasedisease

LeadLead

HyperthyroidismHyperthyroidism

Blood lossBlood loss

Haemolytic Haemolytic

- RBC membrane- RBC membrane

- Enzyme defects- Enzyme defects

- Extrinsic- Extrinsic

Stem cell defectsStem cell defects

MegaloblasticMegaloblastic

Excess alcoholExcess alcohol

HypothyroidHypothyroid

Liver diseaseLiver disease

ReticulocytosisReticulocytosis

Drug therapyDrug therapy

Marrow failureMarrow failure

Reticulocyte count: In the investigation of anaemia• Reduced: Failure of erythropoiesis

• Increased: Appropriate BM erythroid response


35 year Male35 year Male Hx:Hx: Lethargy, SOBLethargy, SOB Sx:Sx: PalePale FBC:FBC: HbHb 6.4 g/dL6.4 g/dL

MCV MCV 71 fL71 fL

RDWRDW 0.190.19

WCCWCC 5.25.2

PlateletsPlatelets 375375 Film: Severe hypochromasia and Film: Severe hypochromasia and

microcytosismicrocytosis


Commonest Causes Iron Commonest Causes Iron DeficiencyDeficiency

FemaleFemale MaleMale1 – 5 yr1 – 5 yr NutritionNutrition NutritionNutrition

5 – 15 yr5 – 15 yr Increased Increased utilisation/ utilisation/ growthgrowth

Increased Increased utilisation/ utilisation/ growthgrowth

15 – 40 yr15 – 40 yr MenstruationMenstruation

PregnancyPregnancyCoeliac disease Coeliac disease (Malabsorption)(Malabsorption)

> 40 yr> 40 yr Gastrointestinal Gastrointestinal Blood lossBlood loss

Gastrointestinal Gastrointestinal Blood lossBlood loss


Blood FilmBlood Film


Differential DiagnosisDifferential Diagnosis

Causes of microcytic hypochromic Causes of microcytic hypochromic anaemiaanaemia– Iron deficiencyIron deficiency

Blood lossBlood lossMalabsorption - Coeliac disease; gastrectomyMalabsorption - Coeliac disease; gastrectomy Increased utilisation - parasitesIncreased utilisation - parasitesDietary deficiency - rareDietary deficiency - rare

– HaemoglobinopathyHaemoglobinopathy– Anaemia of chronic diseaseAnaemia of chronic disease


Fe Deficiency vs Anaemia of Fe Deficiency vs Anaemia of Chronic DiseaseChronic Disease

VariableVariable Fe Fe deficiencydeficiency

Chronic Chronic diseasedisease

Serum IronSerum Iron

TransferrinTransferrin or Normalor Normal

Transferrin SaturationTransferrin Saturation

FerritinFerritin or Normalor Normal or normalor normal

CRPCRP NormalNormal

GIT studies: endoscopy etcGIT studies: endoscopy etc


26 year Female26 year Female Hx:Hx: Antenatal visit; Antenatal visit; First First

trimestertrimester FBC:FBC: HbHb 11.0 g/dL11.0 g/dL

MCVMCV 73 fL73 fL

MCHMCH 27 pg27 pg

RDWRDW 0.140.14

WCCWCC 8.5 x 108.5 x 1099/L/L

Platelets Platelets 164 x 10164 x 1099/L/L Film:Film: Microcytic RBCMicrocytic RBC


Fe Deficiency vs HbinopathyFe Deficiency vs Hbinopathy Check iron status: FerritinCheck iron status: Ferritin Family history / ethnicity:Family history / ethnicity:

– Thalassaemia / haemoglobinopathyThalassaemia / haemoglobinopathy– Need to determine risk to fetus of severe Need to determine risk to fetus of severe

thalassaemic syndrome (in 1thalassaemic syndrome (in 1stst rimester): rimester):Homozygous thalassaemia (Homozygous thalassaemia (αα or or ββ))Homozygous Hb S (sickle cell disease)Homozygous Hb S (sickle cell disease)Severe compound heterozygous states Severe compound heterozygous states

– E.g.: HbS/E.g.: HbS/ββ; HbE/; HbE/ββ; HbSC; HbSC

– Determine need to check partnerDetermine need to check partner


Red Cell Distribution Width Red Cell Distribution Width (RDW)(RDW)

The degree of variation in size of RBC: N <14The degree of variation in size of RBC: N <14 Increased RDW corresponds with Increased RDW corresponds with anisocytosisanisocytosis::

– Iron deficiency (increased RDW is the earliest lab feature: Iron deficiency (increased RDW is the earliest lab feature: anisocytosis precedes the anaemia)anisocytosis precedes the anaemia)

– Megaloblastic anaemia (can be very high >20)Megaloblastic anaemia (can be very high >20)– Anaemia with bone marrow erythroid response (i.e. Anaemia with bone marrow erythroid response (i.e.

reticulocytosis)reticulocytosis) RDW useful in DDx of microcytic anaemias. RDW useful in DDx of microcytic anaemias.

– Most cases of iron deficiency: raised RDW Most cases of iron deficiency: raised RDW – Most cases thalassaemia trait: normal RDWMost cases thalassaemia trait: normal RDW


MCHMCH Mean Cell HaemoglobinMean Cell Haemoglobin (27-32 pg) (27-32 pg)

– The mean haemoglobin per red blood cell The mean haemoglobin per red blood cell

MCH usually rises or falls as the MCV is MCH usually rises or falls as the MCV is increased or decreased.increased or decreased.

MCH < 25 pg used as a guide to the MCH < 25 pg used as a guide to the presence of thalassaemia or presence of thalassaemia or haemoglobinopathy.haemoglobinopathy.– MCH usually markedly reduced in MCH usually markedly reduced in

thalassaemia (e.g. beta thalassaemia trait thalassaemia (e.g. beta thalassaemia trait MCH 19 pg)MCH 19 pg)


Haemoglobin StudiesHaemoglobin Studies1. Normal adult 2. HPFH (heterozygote)3. Hb S--HPFH 4. Hb C--HPFH 5. Normal newborn A/F/S/C control


73 year male73 year male

Hx:Hx: TirednessTiredness

FBC:FBC: HbHb 4.0 g/dL4.0 g/dLMCVMCV 102 fL102 fLRDWRDW 0.240.24WCC / PltWCC / Plt NormalNormal

Film:Film: Macrocytes, fragmented red Macrocytes, fragmented red cells, occasional NRBCcells, occasional NRBC


Blood FilmBlood Film73 yr old male73 yr old male


Severe Macrocytic AnaemiaSevere Macrocytic Anaemia

Megaloblastic anaemiaMegaloblastic anaemia Liver disease: end-stage failureLiver disease: end-stage failure Red cell aplasia:Red cell aplasia:

– Parvovirus; thymoma, other malignancyParvovirus; thymoma, other malignancy Bone marrow failure or infiltration:Bone marrow failure or infiltration:

– MyelodysplasiMyelodysplasi– Multiple myelomaMultiple myeloma


InvestigationsInvestigations

1.1. Serum vitamin B12Serum vitamin B12

Red cell folate (serum folate)Red cell folate (serum folate)2.2. Reticulocyte count Reticulocyte count (BM (BM

erythroid function)erythroid function)

3.3. Liver functionLiver function

4.4. Parvovirus serologyParvovirus serology

5.5. Bone marrow examinationBone marrow examination


Don’t Forget the AlcoholDon’t Forget the Alcohol


Other Causes of Macrocytic Other Causes of Macrocytic AnaemiaAnaemia

Severe liver diseaseSevere liver disease Excess alcoholExcess alcohol Haemorrhage / haemolysis: Haemorrhage / haemolysis:

reticulocytosisreticulocytosis Drug therapy: esp. cytotoxicsDrug therapy: esp. cytotoxics HypothyroidismHypothyroidism MyelodysplasiaMyelodysplasia Marrow infiltrationMarrow infiltration

– Bone marrow examination may be indicatedBone marrow examination may be indicated


Myelodysplasia (MDS)Myelodysplasia (MDS)

Clonal disorderClonal disorder Ineffective haematopoiesisIneffective haematopoiesis Incidence increases with ageIncidence increases with age

– Age 50yrs - 1 per 100,000Age 50yrs - 1 per 100,000– Age 70yrs – 25 per 100,000Age 70yrs – 25 per 100,000

RBC, WCC, and platelets affectedRBC, WCC, and platelets affected


MyelodysplasiaMyelodysplasia

Bone MarrowPeripheral Blood

http://ashimagebank.hematologylibrary.org/content/vol2004/issue0620/images/large/9B52E1B4_34D6_4F97_82A6_CDAB436E966E.jpeg


MyelodysplasiaMyelodysplasia PrognosisPrognosis

– Number of cytopeniasNumber of cytopenias– BM Blast percentageBM Blast percentage– CytogeneticsCytogenetics– AgeAge

SurvivalSurvival– Varies 11.7 yrs – 0.4yrsVaries 11.7 yrs – 0.4yrs

ManagementManagement– SupportiveSupportive– Stem cell transplantationStem cell transplantation– New drugsNew drugs


Normocytic AnaemiaNormocytic Anaemia Multiple aetiologiesMultiple aetiologies Primary marrow production defectPrimary marrow production defect

– MyelodysplasiaMyelodysplasia– Marrow infiltrationMarrow infiltration– Haematinic deficienciesHaematinic deficiencies

Reduced red cell survivalReduced red cell survival– Blood lossBlood loss– Intrinsic defects (eg. Enzyme; membrane)Intrinsic defects (eg. Enzyme; membrane)– Extrinsic defects (eg. Plasma problems)Extrinsic defects (eg. Plasma problems)


Approach to Normocytic AnaemiaApproach to Normocytic Anaemia

History:History:– Acute blood loss ; jaundice; dark urineAcute blood loss ; jaundice; dark urine

Exclude treatable causes:Exclude treatable causes:– Check ferritin, folate, vitamin B12Check ferritin, folate, vitamin B12– Renal and hepatic functionRenal and hepatic function– Acute phase reactantsAcute phase reactants

Consider haemolysisConsider haemolysis

The blood film may have the answer !The blood film may have the answer !


78 year male78 year male Hx:Hx: Chest painChest pain PMHx:PMHx: Myocardial infarctMyocardial infarct FBC:FBC: HbHb 7.2 g/dL7.2 g/dL

MCVMCV 97 fL97 fL

WCCWCC 4.5 x 104.5 x 1099/L/L

PlateletsPlatelets 320 x 10320 x 1099/L/L

Reticulocytes: 320 (10-100)Reticulocytes: 320 (10-100)



RBC:RBC: SpherocytesSpherocytes

PolychromasiaPolychromasia

Nucleated red cellsNucleated red cells

Spherocytic haemolytic anaemia:Spherocytic haemolytic anaemia:

Auto-immune haemolytic anaemiaAuto-immune haemolytic anaemia

Hereditary spherocytosisHereditary spherocytosis


Other InvestigationsOther Investigations Biochemistry:Biochemistry:

– BilirubinBilirubin 100 100 μμmol/L (<20)mol/L (<20)– Other LFTOther LFT NormalNormal– LDHLDH 1,500 U/L1,500 U/L (120-240) (120-240)– HaptoglobinHaptoglobin <0.1<0.1

HaematologyHaematology::– Reticulocyte countReticulocyte count– Direct anti-globulin (Coombs) test: PositiveDirect anti-globulin (Coombs) test: Positive

Enzymes, Enzymes, Hereditary spherocytosis screenHereditary spherocytosis screen


Haemolytic AnaemiaHaemolytic Anaemia Primary Red Cell Problem:Primary Red Cell Problem:

– Red cell membrane: Hereditary Red cell membrane: Hereditary spherocytosisspherocytosis

– Enzyme defect: G6PD deficiencyEnzyme defect: G6PD deficiency– Haemoglobin defect: thalassaemiaHaemoglobin defect: thalassaemia– Abnormal red cells: dyserythropoiesis (MDS)Abnormal red cells: dyserythropoiesis (MDS)

Secondary Red Cell DestructionSecondary Red Cell Destruction– AutoimmuneAutoimmune– Severe hepatic dysfunctionSevere hepatic dysfunction– Red cell fragmentation: DIC; HUS; TTPRed cell fragmentation: DIC; HUS; TTP– Infections: malaria; clostridiumInfections: malaria; clostridium



Glucose-6-phosphate dehydrogenase deficiency

blister or helmet cells


Normocytic AnaemiaNormocytic Anaemia Blood film may have the answer:Blood film may have the answer:

– Normal red cell morphologyNormal red cell morphology– Dimorphic (high RDW): 2x RBC populationsDimorphic (high RDW): 2x RBC populations– Marked anisocytosis: marrow dysfunction/MDSMarked anisocytosis: marrow dysfunction/MDS– Is there polychromasia?Is there polychromasia?

Yes: Anaemia with marrow responseYes: Anaemia with marrow responseNo:No: Impaired marrow response Impaired marrow response

– Anaemia of Chronic Disease Anaemia of Chronic Disease – BM failureBM failure– Red cell aplasia: Parvovirus; aplastic anaemiaRed cell aplasia: Parvovirus; aplastic anaemia


PolycythaemiaPolycythaemia PseudopolycythaemiaPseudopolycythaemia PrimaryPrimary

– Polycythemia veraPolycythemia vera SecondarySecondary

– HypoxiaHypoxia AltitudeAltitude Cardiac/Pulmonary diseaseCardiac/Pulmonary disease CirrhosisCirrhosis Abnormal HaemoglobinsAbnormal Haemoglobins Chronic CO exposureChronic CO exposure

– Inappropriate erythropoietinInappropriate erythropoietin Renal lesionsRenal lesions TumoursTumours DrugDrug


Clinical FeaturesClinical Features HyperviscosityHyperviscosity

– HeadachesHeadaches– Blurred visionBlurred vision– BreathlessnessBreathlessness– ConfusionConfusion– (Plethora)(Plethora)

ThrombosisThrombosis– Venous + arterialVenous + arterial– BleedingBleeding

OtherOther– PruritisPruritis– GoutGout


Polycythaemia investigationsPolycythaemia investigations

FBC + FilmFBC + Film CXRCXR Cardiac assessmentCardiac assessment Red Cell massRed Cell mass Blood gassesBlood gasses

Major advance – JAK 2 mutation Major advance – JAK 2 mutation screensscreens


JAK2JAK2 Presence of the V617F mutationPresence of the V617F mutation indicates indicates

that the patient has an acquired, clonal that the patient has an acquired, clonal hematological disorder and not a reactive hematological disorder and not a reactive or secondary process. or secondary process.

Absence of the Absence of the JAK2JAK2 V617F mutation V617F mutation does does not exclude a MPD as up to 50% of not exclude a MPD as up to 50% of patients with ET and IMF will have wildtype patients with ET and IMF will have wildtype JAK2JAK2. .

The V617F mutation does The V617F mutation does notnot help in sub- help in sub-classifying the type of MPD of a given classifying the type of MPD of a given patient patient


Pathogenesis: Pathogenesis: Deregulated Tyrosine Kinases in MPDDeregulated Tyrosine Kinases in MPD

CML BCR-ABL

CMML TEL-PDGFRB

CEL FIP1L1-PDGFRA

SM KIT D816V

PV JAK2 V617F

ET JAK2 V617F

IMF JAK2 V617F


Questions so far?


PlateletsPlatelets

Too many (thrombocytosis)Too many (thrombocytosis) Too few (thrombocytopenia)Too few (thrombocytopenia) DysfunctionalDysfunctional

– When should we worry?When should we worry?

http://images.google.co.uk/imgres?imgurl=http://faculty.ccri.edu/kamontgomery/blood%2520cells,%2520RBC,%2520WBC,%2520platelet,%2520SEM.jpg&imgrefurl=http://faculty.ccri.edu/kamontgomery/physiology%2520blood.htm&usg=__6oMOQ7xdZoq5sJ4Mo5GrpRRcr7o=&h=326&w=500&sz=36&hl=en&start=102&sig2=Kw_NwMARU_kUiPXPRyt-Lw&tbnid=he08k-BhLrB2rM:&tbnh=85&tbnw=130&ei=q7JzSYn7MJrCjAfZk7DUBQ&prev=/images%3Fq%3Dplatelets%26start%3D100%26gbv%3D2%26ndsp%3D20%26hl%3Den%26rls%3Dig%26sa%3DN


ThrombocytosisThrombocytosis

> 450 x 10> 450 x 1099/l/l

CausesCauses– Reactive (almost anything!)Reactive (almost anything!)

Common – bleeding, infection, malignancyCommon – bleeding, infection, malignancyTend to be less than 1000 x 10Tend to be less than 1000 x 1099/l/l

– Primary bone marrow disorderPrimary bone marrow disorderMyeloproliferative disorders (up to 3000+)Myeloproliferative disorders (up to 3000+)

(essential thrombocythaemia, myelofibrosis, (essential thrombocythaemia, myelofibrosis, polycythaemia, chronic myeloid leukaemia)polycythaemia, chronic myeloid leukaemia)


History, examination should guide History, examination should guide investigations and referralsinvestigations and referrals

Should the patient be on aspirin?Should the patient be on aspirin?– Only firm evidence is MPDsOnly firm evidence is MPDs– Reactive often given if > 1000, but little Reactive often given if > 1000, but little

evidence for thisevidence for this



Essential Thrombocythaemia (ET)Essential Thrombocythaemia (ET)– Long term management balancing Long term management balancing

thrombotic vs bleeding riskthrombotic vs bleeding risk– Aspirin for intermediate riskAspirin for intermediate risk– Cytoreduction + aspirin for higher riskCytoreduction + aspirin for higher risk

(beware the pseudohyperkalaemia!!)(beware the pseudohyperkalaemia!!)



ThrombocytopeniaThrombocytopenia

Is it real???Is it real???– Poor samplePoor sample– Clumped in EDTA – blood filmClumped in EDTA – blood film

**If at all possible confirm with a repeat **If at all possible confirm with a repeat samplesample


PancytopeniaPancytopenia

vsvs

Isolated low plateletsIsolated low platelets

Pancytopenia – Pancytopenia – – always serious (marrow failure)always serious (marrow failure)

Isolated Isolated – may be relatively unimportantmay be relatively unimportant



Decreased productionDecreased production– Rare in isolationRare in isolation– Viral infectionsViral infections

Increased consumptionIncreased consumption– Autoimmune – ITPAutoimmune – ITP– DrugsDrugs– PregnancyPregnancy– Large spleen / portal hypertensionLarge spleen / portal hypertension– Infections (HIV)Infections (HIV)– RARE but serious TTP – HUS - DICRARE but serious TTP – HUS - DIC



Investigations depend on clinical Investigations depend on clinical suspicionsuspicion– Platelet volume may be helpful Platelet volume may be helpful

(small - think marrow)(small - think marrow)<8.0 and >10.5<8.0 and >10.5

– BM often not requiredBM often not required




(not joint bleeds!)


How real is the bleeding risk?How real is the bleeding risk?– Cause of low plateletsCause of low platelets– Wet vs dry purpuraWet vs dry purpura– Platelet transfusions often not usefulPlatelet transfusions often not useful



ITP – a few useful remindersITP – a few useful reminders

ChildrenChildren– Acute, post viral, Acute, post viral, – spontaneous resolution (often no therapy)spontaneous resolution (often no therapy)

AdultAdult– More insidious onsetMore insidious onset– Chronic = commonChronic = common– Many (not all!) cases do require treatmentMany (not all!) cases do require treatment– Steroids – splenectomySteroids – splenectomy– Novel therapiesNovel therapies


Platelet DysfunctionPlatelet Dysfunction

Range of rare inherited causesRange of rare inherited causes– Family historyFamily history– Refer the child that bleeds abnormally!Refer the child that bleeds abnormally!

Don’t forget the acquired dysfunctionDon’t forget the acquired dysfunction– Renal failureRenal failure– Liver diseaseLiver disease– ASPIRINASPIRIN


Questions and break!


White CellsWhite Cells


White CellsWhite Cells

Important (and commonly problematic!)Important (and commonly problematic!)– NeutrophilsNeutrophils– LymphocytesLymphocytes

Important (less commonly problematic)Important (less commonly problematic)– MonocytesMonocytes– eosinophilseosinophils

Less importantLess important– basophilsbasophils


NeutrophilsNeutrophils


NeutrophiliaNeutrophilia

Often result ‘expected’Often result ‘expected’– HistoryHistory– ExaminationExamination– primary haematological cause NOT primary haematological cause NOT

commoncommon


NeutrophiliaNeutrophilia

InfectionInfection Inflammation / necrosisInflammation / necrosis Cancer – any sort reportedCancer – any sort reported Bone marrow disease (MPDs, CML)Bone marrow disease (MPDs, CML) Drugs (steroids!!, growth factors)Drugs (steroids!!, growth factors)

Not always pathologicalNot always pathologicalPregnancy, smoking, normal variant!Pregnancy, smoking, normal variant!


NeutropeniaNeutropenia (<1.5 x 10 (<1.5 x 1099/l)/l)

Isolated neutropeniaIsolated neutropenia

vsvs



How worried should I be?How worried should I be?

Pancytopenia is ALWAYS worryingPancytopenia is ALWAYS worrying Many cases of isolated neutropenia Many cases of isolated neutropenia

are less seriousare less serious

What should I do with a neutropenic What should I do with a neutropenic patient?patient?

How common is neutropenic sepsis?How common is neutropenic sepsis?



Marrow FailureMarrow Failure– Drugs (chemotherapy)Drugs (chemotherapy)– Infiltration (cancer, MF,lymphoma etc.)Infiltration (cancer, MF,lymphoma etc.)– Myelodysplasia / leukaemia / myelomaMyelodysplasia / leukaemia / myeloma– Aplastic anaemia / PNHAplastic anaemia / PNH– Don’t forget B12 / folate (anorexia)Don’t forget B12 / folate (anorexia)

Peripheral consumptionPeripheral consumption– hypersplenismhypersplenism



Referral usually requiredReferral usually required Bone marrow biopsy usually requiredBone marrow biopsy usually required


Isolated NeutropeniaIsolated Neutropenia Not always easy to identify a cause!Not always easy to identify a cause! Always think drugs (idiopathic vs dose)Always think drugs (idiopathic vs dose) Viral infectionViral infection Auto-immune diseaseAuto-immune disease Marrow causesMarrow causes

(sepsis / very ill elderly)(sepsis / very ill elderly)

Don’t forget Don’t forget – Racial variationRacial variation– cyclical neutropenia (clinical and lab details)cyclical neutropenia (clinical and lab details)– If child, think congenitalIf child, think congenital


Investigations will depend on clinical Investigations will depend on clinical presentationpresentation– Chance finding vs ill patientChance finding vs ill patient– Viral serology may be indicated Viral serology may be indicated

(hepatitis, EBV etc – Think HIV!)(hepatitis, EBV etc – Think HIV!)– Autoimmune (SLE, sjorgrens, RA – Autoimmune (SLE, sjorgrens, RA –

Felty’s)Felty’s)– Serial blood countsSerial blood counts– Referral may be requiredReferral may be required

Isolated NeutropeniaIsolated Neutropenia


When to refer urgentlyWhen to refer urgently– Cause of neutropeniaCause of neutropenia

– Is the patient acutely ill?Is the patient acutely ill?

Neutropenic fever vs sepsisNeutropenic fever vs sepsis– Incidence etcIncidence etc– Antibiotic policies etc.Antibiotic policies etc.– Prophylactic antibiotics - controversialProphylactic antibiotics - controversial

Isolated NeutropeniaIsolated Neutropenia


LymphocytesLymphocytes

Lineage B vs T vs NKLineage B vs T vs NKOriginOriginRoleRole


CausesCauses– ReactiveReactive

(CMV, EBV, hepatitis, toxo, adenov)(CMV, EBV, hepatitis, toxo, adenov)

PertussissPertussiss

Inflammatory reaction (not common)Inflammatory reaction (not common)– Lymphoproliferative disorderLymphoproliferative disorder

Acute and chronic leukaemiasAcute and chronic leukaemias

lymphomaslymphomas

LymphocytosisLymphocytosis


Priorities for investigationPriorities for investigation– Clinical pictureClinical picture– If other FBC abnormalities, speak to a If other FBC abnormalities, speak to a

haematologisthaematologist– If in doubt, ask for an opinion on a blood If in doubt, ask for an opinion on a blood

filmfilm– Monospot test vs viral serologyMonospot test vs viral serology– Flow cytometryFlow cytometry– Molecular testsMolecular tests



Lymphocytosis (>4 x 10Lymphocytosis (>4 x 1099/l)/l)

Blasts vs more mature cellsBlasts vs more mature cells

Clinical picture very importantClinical picture very important– Young sick child vs older well patientYoung sick child vs older well patient

vs vs


Young patient with clinical picture of Young patient with clinical picture of infectious mononucleosisinfectious mononucleosis– Monospot usefulMonospot useful– Film useful (rule out ALL) Film useful (rule out ALL) – Flow cytometry less helpfulFlow cytometry less helpful– Serology as second line investigationSerology as second line investigation– ID referral occasionally requiredID referral occasionally required– (worth thinking about acute HIV)(worth thinking about acute HIV)



Acute lymphoblastic leukaemiaAcute lymphoblastic leukaemia– Children >> adultsChildren >> adults– Often presents very acutelyOften presents very acutely– Range of clinical featuresRange of clinical features– Laboratory features typicalLaboratory features typical– Referral mandatoryReferral mandatory



Older patient with lymphocytosisOlder patient with lymphocytosis– Blood film required (CLL vs LGL)Blood film required (CLL vs LGL)– Flow cytometry usually requiredFlow cytometry usually required– ? Refer? Refer

Clinical picture Clinical picture Underlying diagnosisUnderlying diagnosis



CLLCLL– Relatively common (300 + / year)Relatively common (300 + / year)– New entity of Monoclonal B New entity of Monoclonal B

Lymphocytosis (MBL)Lymphocytosis (MBL)– AgeAge– Clinical presentationClinical presentation

Asymptomatic stage AAsymptomatic stage A

VSVS

Symptomatic stage CSymptomatic stage C



CLLCLL– HistoryHistory

Night sweats, weight loss, INFECTIONSNight sweats, weight loss, INFECTIONS

– ExaminationExaminationLymphadenopathy, hepato-splenomegalyLymphadenopathy, hepato-splenomegaly

– InvestigationInvestigationFlow cytometryFlow cytometry



Flow cytometryFlow cytometry


T cells

LeukaemicB cells



Should I refer CLL?Should I refer CLL?– Long stage A phase in many patientsLong stage A phase in many patients– Patients and the ‘leukaemia’ word!Patients and the ‘leukaemia’ word!– Rough guideRough guide

SymptomaticSymptomatic Unusual / lymphoma phenotypeUnusual / lymphoma phenotype Lymphadenopathy / splenomegalyLymphadenopathy / splenomegaly Lymphocyte doubling time < 12 monthsLymphocyte doubling time < 12 months

with lymphocytes > 30 x 10with lymphocytes > 30 x 1099/l/l Hb < 10 g/dl (or haemolysing)Hb < 10 g/dl (or haemolysing) Platelets < 100x 10Platelets < 100x 1099/l/l


CLL – bewareCLL – beware– Not always benignNot always benign– Infections (hypogamma)Infections (hypogamma)– HaemolysisHaemolysis– ITPITP



Rarer lymphoproliferative disordersRarer lymphoproliferative disorders– LGLLGL– PLLPLL– Leukaemic phase of most lymphomasLeukaemic phase of most lymphomas– Hairy cell leukaemiaHairy cell leukaemia



Lymphopenia (<1.0 x 10Lymphopenia (<1.0 x 1099/l)/l)

Many cases reflect normal variantsMany cases reflect normal variants

How hard should you chase a cause?How hard should you chase a cause?

More common causesMore common causes– HIV / hepatitis / Hodgkin’s (steroids)HIV / hepatitis / Hodgkin’s (steroids)

Rarer causesRarer causes– Autoimmune disease / sarcoidosisAutoimmune disease / sarcoidosis


InvestigationsInvestigations– Clinical pictureClinical picture– Lymphocyte subset analysisLymphocyte subset analysis– RARE – bone marrowRARE – bone marrow

LymphopeniaLymphopenia


Enlarged LN ? causeEnlarged LN ? cause Clinical context is critical Clinical context is critical

– ? Symptom profile? Symptom profile– (?spleen)(?spleen)

Please do first line investigationsPlease do first line investigations– FBC may save a LN biopsyFBC may save a LN biopsy

Neck nodes – ENT fast track referralNeck nodes – ENT fast track referral Axillary and groin nodesAxillary and groin nodes

– Much depends on the clinical contextMuch depends on the clinical context– Haematology review first?Haematology review first?– Biopsy first?Biopsy first?– CT first?CT first?


EosinophilsEosinophils

HighHigh– Allergic disordersAllergic disorders– Drug HypersensitivityDrug Hypersensitivity– Skin DiseasesSkin Diseases– Parasitic infectionsParasitic infections– Myeloproliferative disordersMyeloproliferative disorders– Connective tissue disordersConnective tissue disorders

Churg StraussChurg Strauss


MonocytesMonocytes

HighHigh– Range of infectious and inflammatory stimuliRange of infectious and inflammatory stimuli– Primary BM conditionsPrimary BM conditions

CMML (overlap between myelodysplasia and CMML (overlap between myelodysplasia and myeloproliferative disorder)myeloproliferative disorder)

CMLCML

Clinical picture and blood film importantClinical picture and blood film important

If no clear cause consider haematology referralIf no clear cause consider haematology referral

Questions?

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fbc slide

normal rdw slide

microcytic rbc slide

microcytosis slide

partner slide

blood film slide

fl normocytic slide

fl mcv