Haematology in Primary
Care
Dr Josh Wright
Consultant Haematologist
Sheffield Teaching Hospitals
Referral Hit Parade
Raised Hb
Leucocytosis- neutrophilia/lymphocytosis
Thrombocytosis/thrombocytopenia
Paraproteins
macrocytosis
Low B12
Anaemia in the elderly
Microcytosis/ iron deficiency/alpha thal
Common haematological issues
in primary care
Lecture
► Interpreting the blood
count
► Common referral issues
 White cell problems
 Platelet problems
 Paraproteins
Workshop
► Red cell issues
 Erythrocytosis
 Haematinics inc low B12
►
►
►
Haemoglobinpathy inc
alpha thal
Anaemia in the elderly
Any cases brought for
discussion
Full blood count
Normal range
Adult male
Adult female
Range
Range
Hb
131-166
Hb
110-147
Hct
0.38-0.48
Hct
0.32-0.42
RBC count
3.6-4.8
WBC
3.5-9.5
MCV
80-98
Neutrophils
1.7-6.5
MCH
27-34.2
Lymphocytes
1.0-3.0
WBC x109/l
3.5-9.5
Platelets
140-370
Neutrophils
1.7-6.5
Lymphocytes
1.0-3.0
Platelets
140-370
What is the definition of normal?
White Blood Count
Lymphocytosis
History
Male age 58 years
Hypertension, Type II DM
Smokes 10 cigs
Drugs
Simvastatin, Amlodopine
Exam
BMI 38
Bp 140/85
FBC
September
2011
October
2011
November
2011
Hb
139
141
140
WBC
Lymphocytes
Neutrophils
6.7
3.9
2.8
6.9
4.1
2.8
6.9
4.2
2.5
Platelets
249
310
270
Lymphocytosis
► Does
the patient have haematological
cancer?
► Should
I refer to haematology?
► Should
I continue to monitor the
lymphocyte count?
► Are
there any other tests I should do?
►
Primary
 Lymphoid malignancies
► Chronic Lymphocytic
Leukaemia
► Lymphoma
► Monclonal B Lymphocytosis
►
Reactive
 Viral (EBV, CMV, HSV, VZV)
 Stress Lymphocytosis
► Drug induced
► Septic shock
► Myocardial infarct
► Trauma
► Other co-morbidities
►
Chronic





Cigarette smoking
Autoimmune disorder
Chronic inflammation
Sarcoid
Raised BMI/metabolic
syndrome
Lymphocytosis
Malignant Lymphocytosis ?
FBC
Lymphocyte count
more than 10x109/L
Lymphocyte count
less than 10x109/L
Yes
anaemia or thrombocytopenia
recurrent infection?
adenopathy, spleen, liver?
Abnormal blood film?
No
Refer to haematologist
Repeat FBC, review 1yrly
The Neutrophil Count
White Blood Count
Neutrophil Leucocytosis
History
Male age 68 years
Osteoarthritis, CABG
2001
Non smoker (stopped
2001)
Type 2 DM
Drugs
Simvastatin, Aspirin,
Gliclazide
Exam
Unremarkable
FBC
July 2009 December
2010
May 2011
Hb
163
163
165
WBC
Lymphocytes
Neutrophils
15.7
2.4
13.0
17.0
2.0
13.5
14.0
2.1
11.9
Platelets
430
420
400
Neutrophil leucocytosis
►
Acute neutrophilia
 Reactive
► Infection/Inflammation
► neoplasia
► Bleeding
► Pain
► Smoking
► Drugs
►
(glucocorticoids)
Chronic neutrophilia
 Reactive
 Drugs
 BMI/metabolic syn
 Haematologic
 Eg CML 1/100000
(Neutrophil) Leucocytosis
Important points
► Urgent
referral
History & Exam
► >50
► Blood
film features of
CML or CMML (film
comment)
► Consider
infection, inflammation,
autoimmune, neoplasia
rash, arthritis, weight loss
if
► Chronic
neutrophilia>20
► Chronic monocytosis >1
► Chronic eosinophila>2
CRP,
U&E,
LFT,
TFT
Ca
Auto Ab
Micro
culture
FBC,
ESR
CXR
Urine
Reactive screen
negative
Haematology referral
Neutropenia
► Caucasian
female aged
36yrs, no significant
medical history, no
regular medication
► FH rheumatoid arthritis
► Hb
126 g/l
► WCC 3.1
► Neutrophils 0.4
► Platelets 180
Neutropenia
(Neutrophils<1.7)
What do I need to know?
► Is the patient unwell?
(Viral assoc transient)
► Any previous counts?
► Any other cytopenia?
► Is the patient on
chemotherapy?
► Other drugs
► How
severe is it?
 Mild (1.0-1.7),
functionally normal
 Moderate (0.5-1.0)
 Severe (<0.5)-RISK OF
INFECTION
Neutropenia
What are the common causes?
► Infection
► Drugs (chemotherapy!)
► Autoimmune
► Hereditary
 Racial (African origin 1.0-1.3)
Neutropenia pathway
Neutropenia <1.0
Patient on chemotherapy
Consider repeat
particularly if
recent infection
No
Moderate or Severe
<0.5
Unwell ?
Yes
No
Discuss with
haematologist and
refer
Haematology
advice/referral
B12, Folate,
LFT, GGT,
autoAb
Thrombocytosis
► Male
65yrs, mild hypertension on ramipril.
► Hb 160, Hct 0.50, WCC 11.0 plts 450
► Refer or not?
Thrombocytosis
► Maybe
reactive to
inflammation, infection
other malignancy, iron
deficiency or bleeding
► In MPD very high
counts >1500 assoc
with vascular events
and bleeding
► Urgent
referral
 >1000
 600-1000 if assoc with
CVA, TIA, VTE
► Consider
if
 >600 consistently
 >450 with vascular
event
 High wcc or Hb
Thrombocytopenia
► >100
functionally
normal
► <20 bleeding risk rises
but most symptom
free
► Causes
► Immune
► Drugs
eg quinine
► Bone marrow failure
syndromes eg MDS
► ALCOHOL
► Liver disease
► Pregnancy
Thrombocytopenia
► Refer
► Investigations
► <50
► Blood
► 50-100
if other
cytopenia or planned
surgery/dental work
film- platelet
clumping
► Repeat sample
► Renal & liver function
► Clotting screen
► Autoantibodies
?Myeloma
► Hb
History
68yr female,
Back pain 4 months
ESR 70
X Ray normal
Should I refer to haematology?
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
Reminder…….Monoclonal or polyclonal?
Paraproteins
► Refer
if
 IgG>15g, IgA>10g
 IgD or E
 Lower levels if assoc
with CRAB
► IgM
usually assoc with
lymphoma
 Any other features?
 Paraprotein>10g
 ?Hyperviscosity
► C-
Hypercalacemia
► R- unexplained renal
failure
► A-anaemia/cytopenia
► B-bone pain/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 Problems
► Macrocytosis
► Erythrocytosis
► Haematinic
assessment
► Anaemia in the elderly
► Haemoglobinopathies
including alpha thal
carriage
Macrocytosis
► Approx
8% population
► Commonest causes alcohol &
hypothyroidism





B12/ folate deficiency
Drugs (including those used for HIV)
Reticulocytosis
Paraprotein
Myelodysplasia (elderly population & associated
with cytopenias)
Macrocytosis
Raised MCV >100
Monitor if
screening
normal
Check B12,
Folate,, LFT, GGT,
TFT, Igs,
Are there cytopenias?
Yes
Refer to Haematology
No
Isolated
macrocytosis
Erythrocytosis??
Erythrocytosis
► Apparent




Dehydration
Diuretics
Alcohol
Raised BMI
► True
Physiological
 Hypoxia eg COPD, sleep
apnoea
 High altitude
 Smoking
► True
none
physiological
 Primary polycythaemia
 Certain rare tumours
 Anabolic steroid usage
URGENT REFERRAL
• Hct >60 males or
0.56 females
Erythrocytosis
Male
Female
Hct >0.52
for at least 2 months
Hct >0.48
for at least 2 months
Refer to Haematology
Incidence of polycythaemia rubra vera ~5/100 000
Incidence of apparent polycythaemia~ HIGH!
Haematinics
► There
is no entirely reliable blood test for
iron status
► There is no entirely reliable blood test for
folate
► There is no entirely reliable blood test for
B12
► Ferritin
is the test of choice
►Inaccurate
in the presence of inflammation
►A trial of iron remains a valid approach
►ALCOHOL/FATTY LIVER & FERRITIN
► Serum
folate is a good reflection of what
you have just eaten
► I’m not sure what B12 is a good reflection
of!
►Interpret
borderline values with caution
►Schilling test no longer available
Reduced serum B12
► B12<
100 True
deficiency highly likely
parenteral replacement
► B12 100-145 replace
especially if raised
MCV, cytopenia,
neuropathy
► B12>140 deficiency
unlikely
► B12
is an unreliable
test
► Always reduced in
pregnancy
► Uncomplicated
B12/folate deficiency
does not require OP
referral.
Anaemia in the elderly
► Frequency
of anaemia
increases with age
► Incidence 10-40%
► Many have
diagnosable/treatable
cause
► 25% no identified
cause
► Investigations
► FBC
& film
► Reticulocytosis
► Renal/ liver function
► Immunoglobulins
► Haematinics
► Coeliac screen
► Dietary
history
► GI investigations
► Bone marrow
Anaemia 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%?
► MULTIFACTORIAL
► Decline
in erythropoetin
► Decline in androgens
► Increased inflammatory cytokines even in
absence of a recognised disease
► Age associated decline in stem cell function
► Early MDS without other cytopenias or BM
changes
Indications for haematology
referral
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 haemoglobinopathies?
► Commonest
single gene disorders worldwide
► Autosomal recessive
►Disease
states homozygous or combined
heterozygotes
► Defects
of quality or quantity of
haemoglobin
►Quality
►Quantity
Variant Hbs eg sickle
Under production eg thals
National Screening Plan
► NHS
Plan commits to
“a new national linked
antenatal & neonatal
screening programme for
haemoglobinopathy &
sickle cell disease by 2004”
► Universal
neonatal
► Antenatal ?selective
?universal
The haemoglobinopathy screen
► Haemoglobin
► MCV,
MCH
► Hb A2
► HPLC
► ZPP/ferritin
► Sickle solubility test,
electrophoresis,
molecular analysis
Case study
► 32
year old female of Pakistani origin
attends c/o fatigue
► Hb 11.9, MCV 71, MCH 23
► Ferritin 109
► Hb A2 normal, no evidence of b thal
b thalassaemia
b/b
No Normal
0
b /b
Thal trait
Low MCV/MCH
b /b
Thal trait
Mild anaemia
b0/b0
Thal major
b /b
Thal intermedia
Transfusion
dependant
Anaemia,
splenomegally
+
0
+
b /HbE
0
Thal major
a thalassaemia
aa/aa
Normal
-a/aa
Heterozygous a+
Low MCV/ MCH
-a/-a
Homozygous a+
Low MCV/MCH
--/aa
Heterozygous a0
Low MCV/MCH
--/-a
Haemoglobin H
disease
Hb Barts Hydrops
Thal Intermedia
--/--
Stillbirth
a thalassaemia heterozygotes
a0
a+
► Cypriot
► India
► African
► Hong
Kong
► China
► Phillipines
2%
rare
rare
5%
3-9%
10%
► UK
Africans
► India
► PNG
► Thailand
► Maori
25%
5-58%
20-80%
3-17%
5-10%
Summary points
► Other
than for individuals of E. Med or SE
Asian origin a thal trait is insignificant
► Microcytosis is commonly due to thal trait
► A national antenatal/neonatal screening
programme is now in place