Haem

HAEMATOLOGY IN PRIMARY HEALTH CARE

1. Hematology in Primary
Care
Nathan Kikku Mubiru
Medical Laboratory Scientist(MLSO)

2. Referral Hit Parade
Raised Hb
Leucocytosis-neutrophilia/lymphocytosis
Thrombocytosis/thrombocytopenia
Paraproteins
macrocytosis
Low B12
Anaemia in the elderly
Microcytosis/ iron deficiency/alpha thal

3. Common haematological issues in
primary care
Lecture Workshop
►Interpreting the
blood count
►Common referral
issues
◦White cell problems
◦Platelet problems
◦Paraproteins
►Red cell issues
◦Erythrocytosis
◦Haematinics inc low
B12
►Haemoglobinpathy
inc alpha thal
►Anaemia in the
elderly
►Any cases brought for
discussion

4. Full blood count
Normal range
Adult male
Range
Hb 131-166
Hct 0.38-0.48
RBC count 3.6-4.8
MCV 80-98
MCH 27-34.2
WBC x10
9
/l 3.5-9.5
Neutrophils 1.7-6.5
Lymphocytes 1.0-3.0
Platelets 140-370
Adult female
Range
Hb 110-147
Hct 0.32-0.42
WBC 3.5-9.5
Neutrophils 1.7-6.5
Lymphocytes 1.0-3.0
Platelets 140-370

5. What is the definition of normal?

6. 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

7. 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?

8. Lymphocytosis
►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

9. Malignant Lymphocytosis ?
Lymphocyte count
more than 10x10
9
/L
Lymphocyte count
less than 10x10
9
/L
Refer to haematologist
anaemia or thrombocytopenia
recurrent infection?
adenopathy, spleen, liver?
Abnormal blood film?
Yes
No
Repeat FBC, review 1yrly
FBC

10. The Neutrophil Count

11. 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 2009December
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

12. 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

13. (Neutrophil) Leucocytosis
Important points
►Urgent referral
►>50
►Blood film features of
CML or CMML (film
comment)
►Consider if
►Chronic
neutrophilia>20
►Chronic monocytosis
>1
►Chronic eosinophila>2
History & Exam
infection, inflammation,
autoimmune, neoplasia
rash, arthritis, weight loss
CRP,
U&E,
LFT,
TFT
Ca
Auto Ab
Micro
culture
FBC,
ESR
CXR
Urine
Reactive screen
negative
Haematology referral

14. 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

15. 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

16. Neutropenia
What are the common causes?
►Infection
►Drugs (chemotherapy!)
►Autoimmune
►Hereditary
◦Racial (African origin 1.0-1.3)

17. 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

18. Thrombocytosis
►Male 65yrs, mild hypertension on ramipril.
►Hb 160, Hct 0.50, WCC 11.0 plts 450
►Refer or not?

19. 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

20. 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

21. Thrombocytopenia
►Refer
►<50
►50-100 if other
cytopenia or planned
surgery/dental work
►Investigations
►Blood film-platelet
clumping
►Repeat sample
►Renal & liver
function
►Clotting screen
►Autoantibodies

22. ?Myeloma
History
68yr female,
Back pain 4 months
ESR 70
X 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?

23. 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

24. 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.

25. Common Red cell Problems
►Macrocytosis
►Erythrocytosis
►Haematinic
assessment
►Anaemia in the
elderly
►Haemoglobinopathi
es including alpha
thal carriage

26. 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)

27. Macrocytosis
Raised MCV >100
Are there cytopenias?
Check B12,
Folate,, LFT, GGT,
TFT, Igs,
Refer to Haematology
Yes
No
Isolated
macrocytosis
Monitor if
screening
normal

28. Erythrocytosis??

29. 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

30. Erythrocytosis
Male
Hct >0.52
for at least 2 months
Female
Hct >0.48
for at least 2 months
Refer to Haematology
Incidence of polycythaemia rubra vera ~5/100 000
Incidence of apparent polycythaemia~ HIGH!

31. 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

32. ►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

33. 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.

34. Anaemia in the elderly
►Frequency of
anaemia increases
with age
►Incidence 10-40%
►Many have
diagnosable/treatab
le cause
►25% no identified
cause
►Investigations
►FBC & film
►Reticulocytosis
►Renal/ liver function
►Immunoglobulins
►Haematinics
►Coeliac screen
►Dietary history
►GI investigations
►Bone marrow

35. Anaemia in the elderly
CAUSE OF ANEMIA PERCENTAGE OF CASES
Anemiaof chronic disease30 to 45
Iron deficiency 15 to 30
Posthemorrhagic 5 to 10
Vitamin B12and folate
deficiency
5 to 10
Chronic leukemia or
lymphoma
5
Myelodysplastic syndrome 5
No identifiable cause 15 to 25

36. 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

37. Indications for haematology
referral
Pancytopenia
Monoclonal gammopathy
Suspicion of myelodysplasticsyndrome
Blood smear showing immature white cells
or nucleated red cells
Indeterminate status of iron stores
Unexplained progressive or unresponsive
anemia

38. What are
haemoglobinopathies?
►Commonest single gene disorders
worldwide
►Autosomal recessive
►Disease states homozygous or combined
heterozygotes
►Defects of quality or quantity of
haemoglobin
►Quality Variant Hbs eg sickle
►Quantity Under production eg thals

39. 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

40. The haemoglobinopathy screen
►Haemoglobin
►MCV, MCH
►Hb A2
►HPLC
►ZPP/ferritin
►Sickle solubility
test,
electrophoresis,
molecular analysis

41. 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 bthal

43. bthalassaemiab/b
No Normal
b
0
/b
Thal trait Low MCV/MCH
b
+
/b
Thal trait Mild anaemia
b
0
/b
0

Thal major Transfusion
dependant
b
0
/b
+

Thal intermedia Anaemia,
splenomegally
b
0
/HbE
Thal major

44. athalassaemiaaa/aa
Normal
-a/aa
Heterozygous a
+
Low MCV/ MCH
-a/-a
Homozygous a
+
Low MCV/MCH
--/aa
Heterozygous a
0
Low MCV/MCH
--/-a
Haemoglobin H
disease
Thal Intermedia
--/--
Hb Barts Hydrops Stillbirth

46. athalassaemia heterozygotes
a
0
a
+
►Cypriot 2%
►India rare
►African rare
►Hong Kong 5%
►China 3-9%
►Phillipines10%
►UK Africans25%
►India 5-58%
►PNG 20-
80%
►Thailand 3-17%
►Maori 5-10%

47. Summary points
►Other than for individuals of E. Med or SE
Asian origin athal trait is insignificant
►Microcytosis is commonly due to thal trait
►A national antenatal/neonatal screening
programme is now in place