1. Haematology in Primary Care
Dr Josh Wright
Consultant Haematologist
Sheffield Teaching Hospitals

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
Adult female
Range Hb
Hct
RBC count
MCV
80-98
MCH
WBC x109/l
Neutrophils
Lymphocytes
Platelets
Range Hb
Hct
WBC
Neutrophils
Lymphocytes
Platelets

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
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 Reactive Chronic 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

9. Malignant Lymphocytosis ?
FBC
Lymphocyte count
more than 10x109/L
Lymphocyte count
less than 10x109/L
anaemia or thrombocytopenia
recurrent infection?
adenopathy, spleen, liver?
Abnormal blood film?
Yes No
Refer to haematologist
Repeat FBC, review 1yrly

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 2009
December 2010
May 2011 Hb
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
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 ( ), functionally normal
Moderate ( )
Severe (<0.5)-RISK OF INFECTION

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

17. Neutropenia pathway Neutropenia <1.0
Consider repeat particularly if recent infection
Patient on chemotherapy No
Moderate or Severe <0.5
Unwell ?
Yes No
Discuss with haematologist and refer
B12, Folate, LFT, GGT, autoAb
Haematology advice/referral

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
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
if other cytopenia or planned surgery/dental work
Investigations
Blood film- platelet clumping
Repeat sample
Renal & liver function
Clotting screen
Autoantibodies

22. ?Myeloma Hb 110 WCC & plts normal U&E normal
Total Protein 66 (60-74)
IgG *
IgA 0.7 ( )
IgM 0.5 ( )
MIg 7.0
IgG Kappa monoclone
History 68yr female, Back pain 4 months ESR 70 X Ray normal
Should I refer to haematology?
Reminder…….Monoclonal or polyclonal?

23. Paraproteins Refer if IgM usually assoc with lymphoma
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
Haemoglobinopathies 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. Isolated macrocytosis
Raised MCV >100
Monitor if screening normal
Check B12, Folate,, LFT, GGT, TFT, Igs, No
Are there cytopenias?
Isolated macrocytosis
Yes
Refer to Haematology

28. Erythrocytosis??

29. Erythrocytosis Apparent True Physiological True none physiological
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 females

30. Erythrocytosis Incidence of polycythaemia rubra vera ~5/100 000
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/
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
B 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/treatable 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
Anemia of chronic disease
30 to 45
Iron deficiency
15 to 30
Posthemorrhagic
5 to 10
Vitamin B12 and folate deficiency
Chronic leukemia or lymphoma 5
Myelodysplastic syndrome
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 myelodysplastic syndrome
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
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 b thal

43. b thalassaemia

44. a thalassaemia

46. thalassaemia heterozygotes a0 a+
UK Africans 25%
India 5-58%
PNG %
Thailand 3-17%
Maori 5-10%
Cypriot 2%
India rare
African rare
Hong Kong 5%
China 3-9%
Phillipines 10%

47. 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