Transcript The FBC - Home Page - Cambridge Haematology Partners

Haematology in Primary Care:
The Full Blood Count
Charles Crawley
George Follows
Cambridge Haematology Partners
www.cambridgehaematology.com
The FBC
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Haemoglobin

Low haemoglobin defines anaemia
– Males 13-18g/l
– Females 11.5-16g/l
– Variations:
 Children
– Neonates – 14-24g/l
– 2 months – 8.9-13.2g/l
– 9-12ys
- 11.5-15.4g/l
 Pregnancy
– 3rd Trimester – 9.8-13.7g/l
 Age
– 5-7th decade – falls in men rises in women
 Exercise
– Increases Hb
 Altitude
 Smoking
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MCV

Mean Cell Volume: average size of RBC
– Normal adult : 76 (80) - 100 fL

MCV < 76 fL (microcytic)

MCV > 100 fL (macrocytic)

MCV 80 - 100fL (normocytic)
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Practical Classification of Anaemia
Microcytic (<76fL)
Iron deficiency
Thalassaemia
Haemoglobinopathies
Anaemia of chronic
disease
Lead
Hyperthyroidism
Normocytic
Blood loss
Haemolytic
- RBC membrane
- Enzyme defects
- Extrinsic
Stem cell defects
Macrocytic (>100)
Megaloblastic
Excess alcohol
Hypothyroid
Liver disease
Reticulocytosis
Drug therapy
Marrow failure
Reticulocyte count: In the investigation of anaemia
•
•
Reduced: Failure of erythropoiesis
Increased: Appropriate BM erythroid response
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35 year Male
 Hx:
Lethargy, SOB
 Sx:
Pale
 FBC:
Hb
6.4 g/dL
MCV
71 fL
RDW
0.19
WCC
5.2
Platelets 375
 Film: Severe hypochromasia and
microcytosis
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Commonest Causes Iron
Deficiency
1 – 5 yr
5 – 15 yr
Female
Male
Nutrition
Nutrition
Increased
utilisation/
growth
15 – 40 yr Menstruation
Pregnancy
> 40 yr
Increased
utilisation/
growth
Coeliac disease
(Malabsorption)
Gastrointestinal Gastrointestinal
Blood loss
Blood loss
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Blood Film
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Differential Diagnosis
 Causes
of microcytic
hypochromic anaemia
– Iron deficiency
 Blood
loss
 Malabsorption - Coeliac disease;
gastrectomy
 Increased utilisation - parasites
 Dietary deficiency - rare
– Haemoglobinopathy
– Anaemia of chronic disease
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Fe Deficiency vs Anaemia of
Chronic Disease
Variable
Serum Iron
Fe
deficiency

Chronic
disease

Transferrin

 or Normal
Transferrin Saturation 

Ferritin
 or
Normal
 or normal
CRP
Normal

GIT studies: endoscopy etc
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26 year Female
 Hx:
 FBC:
 Film:
Antenatal visit; First
trimester
Hb
11.0 g/dL
MCV
73 fL
MCH
27 pg
RDW
0.14
WCC
8.5 x 109/L
Platelets
164 x 109/L
Microcytic RBC
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Fe Deficiency vs Hbinopathy
 Check
iron status: Ferritin
 Family history / ethnicity:
– Thalassaemia / haemoglobinopathy
– Need to determine risk to fetus of severe
thalassaemic syndrome (in 1st rimester):
 Homozygous
thalassaemia (α or β)
 Homozygous Hb S (sickle cell disease)
 Severe compound heterozygous states
– E.g.: HbS/β; HbE/β; HbSC
– Determine need to check partner
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Red Cell Distribution Width
(RDW)


The degree of variation in size of RBC: N <14
Increased RDW corresponds with anisocytosis:
– Iron deficiency (increased RDW is the earliest lab feature:
anisocytosis precedes the anaemia)
– Megaloblastic anaemia (can be very high >20)
– Anaemia with bone marrow erythroid response (i.e.
reticulocytosis)

RDW useful in DDx of microcytic anaemias.
– Most cases of iron deficiency: raised RDW
– Most cases thalassaemia trait: normal RDW
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MCH

Mean Cell Haemoglobin (27-32 pg)
– The mean haemoglobin per red blood cell


MCH usually rises or falls as the MCV is
increased or decreased.
MCH < 25 pg used as a guide to the
presence of thalassaemia or
haemoglobinopathy.
– MCH usually markedly reduced in
thalassaemia (e.g. beta thalassaemia trait
MCH 19 pg)
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Haemoglobin Studies
1. Normal adult
2. HPFH (heterozygote)
3. Hb S--HPFH
4. Hb C--HPFH
5. Normal newborn
A/F/S/C control
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73 year male

Hx:
Tiredness

FBC:

Film:
Hb 4.0 g/dL
MCV 102 fL
RDW 0.24
WCC / Plt Normal
Macrocytes, fragmented red
cells, occasional NRBC
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Blood Film
73 yr old male
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Severe Macrocytic Anaemia
 Megaloblastic
anaemia
 Liver disease: end-stage failure
 Red cell aplasia:
– Parvovirus; thymoma, other
malignancy
 Bone
marrow failure or infiltration:
– Myelodysplasi
– Multiple myeloma
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Investigations
1.
2.
Serum vitamin B12
Red cell folate (serum folate)
Reticulocyte count (BM
3.
4.
5.
Liver function
Parvovirus serology
Bone marrow examination
erythroid function)
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Don’t Forget the Alcohol
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Other Causes of Macrocytic
Anaemia
Severe liver disease
 Excess alcohol
 Haemorrhage / haemolysis:
reticulocytosis
 Drug therapy: esp. cytotoxics
 Hypothyroidism
 Myelodysplasia
 Marrow infiltration

– Bone marrow examination may be indicated
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Myelodysplasia (MDS)
 Clonal
disorder
 Ineffective haematopoiesis
 Incidence increases with age
– Age 50yrs - 1 per 100,000
– Age 70yrs – 25 per 100,000
 RBC,
WCC, and platelets affected
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Myelodysplasia
Bone Marrow
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Peripheral Blood
Myelodysplasia

Prognosis
–
–
–
–

Number of cytopenias
BM Blast percentage
Cytogenetics
Age
Survival
– Varies 11.7 yrs – 0.4yrs

Management
– Supportive
– Stem cell transplantation
– New drugs
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Normocytic Anaemia
Multiple aetiologies
 Primary marrow production defect

– Myelodysplasia
– Marrow infiltration
– Haematinic deficiencies

Reduced red cell survival
– Blood loss
– Intrinsic defects (eg. Enzyme; membrane)
– Extrinsic defects (eg. Plasma problems)
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Approach to Normocytic Anaemia
 History:
– Acute blood loss ; jaundice; dark urine
 Exclude
treatable causes:
– Check ferritin, folate, vitamin B12
– Renal and hepatic function
– Acute phase reactants
 Consider
haemolysis
The blood film may have the answer !
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78 year male
 Hx:
Chest pain
 PMHx: Myocardial infarct
 FBC:
Hb
7.2 g/dL
MCV
97 fL
WCC
4.5 x 109/L
Platelets 320 x 109/L
Reticulocytes: 320 (10-100)
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Blood Film
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Blood Film
 RBC:
Spherocytes
Polychromasia
Nucleated red cells
Spherocytic haemolytic anaemia:
Auto-immune haemolytic
anaemia
Hereditary spherocytosis
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Other Investigations

Biochemistry:
–
–
–
–

Bilirubin
Other LFT
LDH
Haptoglobin
100 μmol/L (<20)
Normal
1,500 U/L
(120-240)
<0.1
Haematology:
– Reticulocyte count
– Direct anti-globulin (Coombs) test: Positive
 Enzymes,
 Hereditary
spherocytosis screen
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Haemolytic Anaemia

Primary Red Cell Problem:
– Red cell membrane: Hereditary
spherocytosis
– Enzyme defect: G6PD deficiency
– Haemoglobin defect: thalassaemia
– Abnormal red cells: dyserythropoiesis (MDS)

Secondary Red Cell Destruction
–
–
–
–
Autoimmune
Severe hepatic dysfunction
Red cell fragmentation: DIC; HUS; TTP
Infections: malaria; clostridium
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Blood Film
blister or helmet cells
Glucose-6-phosphate dehydrogenase deficiency
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Normocytic Anaemia
 Blood
film may have the answer:
– Normal red cell morphology
– Dimorphic (high RDW): 2x RBC
populations
– Marked anisocytosis: marrow
dysfunction/MDS
– Is there polychromasia?
 Yes:
Anaemia with marrow response
 No: Impaired marrow response
– Anaemia of Chronic Disease
– BM failure
– Red cell aplasia:
Parvovirus; aplastic anaemia
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Polycythaemia
Pseudopolycythaemia
 Primary

– Polycythemia vera

Secondary
– Hypoxia
 Altitude
 Cardiac/Pulmonary
 Cirrhosis
disease
 Abnormal
Haemoglobins
 Chronic CO exposure
– Inappropriate erythropoietin
 Renal
lesions
 Tumours
 Drug
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Clinical Features

Hyperviscosity
–
–
–
–
–

Headaches
Blurred vision
Breathlessness
Confusion
(Plethora)
Thrombosis
– Venous + arterial
– Bleeding

Other
– Pruritis
– Gout
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Polycythaemia investigations
 FBC
+ Film
 CXR
 Cardiac
assessment
 Red Cell mass
 Blood gasses
 Major
advance – JAK 2 mutation
screens
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JAK2
Presence of the V617F mutation indicates
that the patient has an acquired, clonal
hematological disorder and not a reactive
or secondary process.
 Absence of the JAK2 V617F mutation does
not exclude a MPD as up to 50% of
patients with ET and IMF will have
wildtype JAK2.
 The V617F mutation does not help in subclassifying the type of MPD of a given
patient

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Pathogenesis:
Deregulated 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
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Questions so far?
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Platelets
 Too
many (thrombocytosis)
 Too few (thrombocytopenia)
 Dysfunctional
– When should we worry?
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Thrombocytosis
>
450 x 109/l
 Causes
– Reactive (almost anything!)
 Common
– bleeding, infection, malignancy
 Tend to be less than 1000 x 109/l
– Primary bone marrow disorder
 Myeloproliferative
disorders (up to 3000+)
(essential thrombocythaemia, myelofibrosis,
polycythaemia, chronic myeloid leukaemia)
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Thrombocytosis
 History,
examination should guide
investigations and referrals
 Should
the patient be on aspirin?
– Only firm evidence is MPDs
– Reactive often given if > 1000, but little
evidence for this
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Thrombocytosis
 Essential
Thrombocythaemia (ET)
– Long term management balancing
thrombotic vs bleeding risk
– Aspirin for intermediate risk
– Cytoreduction + aspirin for higher risk
(beware the pseudohyperkalaemia!!)
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Thrombocytopenia
 Is
it real???
– Poor sample
– Clumped in EDTA – blood film
**If at all possible confirm with a repeat
sample
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Thrombocytopenia
Pancytopenia
vs
Isolated low platelets
 Pancytopenia
–
– always serious (marrow failure)
 Isolated
– may be relatively unimportant
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Thrombocytopenia

Decreased production
– Rare in isolation
– Viral infections

Increased consumption
–
–
–
–
–
–
Autoimmune – ITP
Drugs
Pregnancy
Large spleen / portal hypertension
Infections (HIV)
RARE but serious TTP – HUS - DIC
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Thrombocytopenia
 Investigations
suspicion
depend on clinical
– Platelet volume may be helpful
(small - think marrow)
 <8.0
and >10.5
– BM often not required
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Thrombocytopenia
(not joint bleeds!)
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Thrombocytopenia
 How
real is the bleeding risk?
– Cause of low platelets
– Wet vs dry purpura
– Platelet transfusions often not useful
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ITP – a few useful reminders

Children
– Acute, post viral,
– spontaneous resolution (often no therapy)

Adult
–
–
–
–
–
More insidious onset
Chronic = common
Many (not all!) cases do require treatment
Steroids – splenectomy
Novel therapies
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Platelet Dysfunction
 Range
of rare inherited causes
– Family history
– Refer the child that bleeds abnormally!
 Don’t
forget the acquired dysfunction
– Renal failure
– Liver disease
– ASPIRIN
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Questions and break!
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White Cells
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White Cells
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White Cells
Important (and commonly problematic!)
– Neutrophils
– Lymphocytes
 Important (less commonly problematic)
– Monocytes
– eosinophils
 Less important

– basophils
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Neutrophils
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Neutrophilia
 Often
result ‘expected’
– History
– Examination
– primary haematological cause NOT
common
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Neutrophilia
 Infection
 Inflammation
/ necrosis
 Cancer – any sort reported
 Bone marrow disease (MPDs, CML)
 Drugs (steroids!!, growth factors)
Not always pathological
Pregnancy, smoking, normal variant!
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Neutropenia
(<1.5 x 109/l)
Isolated neutropenia
vs
Pancytopenia
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How worried should I be?
 Pancytopenia
is ALWAYS worrying
 Many cases of isolated neutropenia
are less serious
 What
should I do with a neutropenic
patient?
 How common is neutropenic sepsis?
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Pancytopenia
 Marrow
Failure
– Drugs (chemotherapy)
– Infiltration (cancer, MF,lymphoma etc.)
– Myelodysplasia / leukaemia / myeloma
– Aplastic anaemia / PNH
– Don’t forget B12 / folate (anorexia)
 Peripheral
consumption
– hypersplenism
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Pancytopenia
 Referral
usually required
 Bone marrow biopsy usually required
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Isolated Neutropenia
Not always easy to identify a cause!
 Always think drugs (idiopathic vs dose)
 Viral infection
 Auto-immune disease
 Marrow causes

(sepsis / very ill elderly)

Don’t forget
– Racial variation
– cyclical neutropenia (clinical and lab details)
– If child, think congenital
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Isolated Neutropenia
 Investigations
presentation
will depend on clinical
– Chance finding vs ill patient
– Viral serology may be indicated
(hepatitis, EBV etc – Think HIV!)
– Autoimmune (SLE, sjorgrens, RA –
Felty’s)
– Serial blood counts
– Referral may be required
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Isolated Neutropenia
 When
to refer urgently
– Cause of neutropenia
– Is the patient acutely ill?
 Neutropenic
fever vs sepsis
– Incidence etc
– Antibiotic policies etc.
– Prophylactic antibiotics - controversial
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Lymphocytes
Lineage B vs T vs NK
Origin
Role
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Lymphocytosis
 Causes
– Reactive
(CMV, EBV, hepatitis, toxo, adenov)
Pertussiss
Inflammatory reaction (not common)
– Lymphoproliferative disorder
Acute and chronic leukaemias
lymphomas
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Lymphocytosis
 Priorities
for investigation
– Clinical picture
– If other FBC abnormalities, speak to a
haematologist
– If in doubt, ask for an opinion on a
blood film
– Monospot test vs viral serology
– Flow cytometry
– Molecular tests
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Lymphocytosis (>4 x 109/l)
vs
 Blasts
vs
vs more mature cells
 Clinical
picture very important
– Young sick child vs older well patient
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Lymphocytosis
 Young
patient with clinical picture of
infectious mononucleosis
– Monospot useful
– Film useful (rule out ALL)
– Flow cytometry less helpful
– Serology as second line investigation
– ID referral occasionally required
– (worth thinking about acute HIV)
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Lymphocytosis
 Acute
lymphoblastic leukaemia
– Children >> adults
– Often presents very acutely
– Range of clinical features
– Laboratory features typical
– Referral mandatory
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Lymphocytosis
 Older
patient with lymphocytosis
– Blood film required (CLL vs LGL)
– Flow cytometry usually required
– ? Refer
 Clinical
picture
 Underlying diagnosis
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Lymphocytosis
 CLL
– Relatively common (300 + / year)
– New entity of Monoclonal B
Lymphocytosis (MBL)
– Age
– Clinical presentation
Asymptomatic stage A
VS
Symptomatic stage C
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Lymphocytosis
 CLL
– History
 Night
sweats, weight loss, INFECTIONS
– Examination
 Lymphadenopathy,
hepato-splenomegaly
– Investigation
 Flow
cytometry
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Lymphocytosis
 Flow
cytometry
T cells
Leukaemic
B cells
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Lymphocytosis

Should I refer CLL?
– Long stage A phase in many patients
– Patients and the ‘leukaemia’ word!
– Rough guide
 Symptomatic
 Unusual
/ lymphoma phenotype
 Lymphadenopathy / splenomegaly
 Lymphocyte doubling time < 12 months
with lymphocytes > 30 x 109/l
 Hb < 10 g/dl (or haemolysing)
 Platelets < 100x 109/l
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Lymphocytosis
 CLL
– beware
– Not always benign
– Infections (hypogamma)
– Haemolysis
– ITP
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Lymphocytosis
 Rarer
lymphoproliferative disorders
– LGL
– PLL
– Leukaemic phase of most lymphomas
– Hairy cell leukaemia
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Lymphopenia (<1.0 x 109/l)
 Many
 How
cases reflect normal variants
hard should you chase a cause?
 More
common causes
– HIV / hepatitis / Hodgkin’s (steroids)
 Rarer
causes
– Autoimmune disease / sarcoidosis
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Lymphopenia
 Investigations
– Clinical picture
– Lymphocyte subset analysis
– RARE – bone marrow
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Enlarged LN ? cause

Clinical context is critical
– ? Symptom profile
– (?spleen)

Please do first line investigations
– FBC may save a LN biopsy
Neck nodes – ENT fast track referral
 Axillary and groin nodes

–
–
–
–
Much depends on the clinical context
Haematology review first?
Biopsy first?
CT first?
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Eosinophils
 High
– Allergic disorders
– Drug Hypersensitivity
– Skin Diseases
– Parasitic infections
– Myeloproliferative disorders
– Connective tissue disorders
 Churg
Strauss
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Monocytes

High
– Range of infectious and inflammatory stimuli
– Primary BM conditions
 CMML
(overlap between myelodysplasia and
myeloproliferative disorder)
 CML
Clinical picture and blood film important
If no clear cause consider haematology referral
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Questions?
Cambridge Haematology Partners
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[email protected]
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