Haematology Update for General Practice Dr Naim Akhtar Consultant Haematologist

Haematology Update for
General Practice
Dr Naim Akhtar
Consultant Haematologist
Barts Health/
Whipps Cross University Hospital
13th November 2013
Haematology Update for
General Practice
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The use of the laboratory and interpretation
of blood tests in common haematological
conditions
 The Myeloproliferative disorders
 Iron Overload
 Sickle cell disorders
 Thrombophilia & Anticoagulation
 Malignant Haematology
Normal Ranges
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Haemoglobin (Hb)
Red cell count (RBC)
Haematocrit (Hct)
Mean Cell Volume (MCV)
Platelet count (PLT)
Total White Blood Count (WBC)
Neutrophil count
Lymphocyte count
Erythrocyte Sedimentation Rate
(ESR)
115 – 180 g/L
4.7 – 6.1 x 10 /L
0.42 – 0.52
80 – 95 fL
130 – 400 x 10 /L
4 – 11 x 10 /L
2 – 6 x 10 /L
1 – 3 x 10 /L
0 – 20 mm/H
Normal blood film
Anaemia – MCV as a
determinant of cause

Low MCV - iron studies/blood
loss/thalassaemia
 Normal MCV – chronic disease (CRF, RA,
DM, Liver)
 High MCV –
B12/Folate/alcohol/TFTs/MDS/Retics/
Haemolytic screen direct coomb’s test
Initial approach to anaemia
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History & examination
Hb, MCV
Haematinics
- B12 & Folate assays
- serum Fe/TIBC & Ferritin
Reticulocyte count
ESR
Miscellaneous (FOBs, TFTs, Biochem etc)
Macrocytic anaemia
WBC changes
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Blood film essential (machine differential is
unreliable)
 Reactive secondary to
infection/inflammation
 MPD or inderterminant
 Leukaemia – usually obvious, unless
pancytopenic
WBC changes
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Neutropenia (Infections, Drug-induced, Racial,
myelodysplasia) – concern < 1.0 or persistent
Lymphopenia (Infections, HIV)
Neutrophilia (Infections, Inflammation, chronic
myeloproliferative disorders)
Lymphocytosis (Infections, Leukaemia)
Eosinophilia (allergy, drugs, asthma)
Monocytosis (Infections, myelodysplasia)
Reactive lymphs
Platelet changes
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Factitious (clots in tube/ blood film,
difficult venepuncture)
 Thrombocytopenia
 Thrombocytosis (Reactive, Primary)
 Functional platelet disorders (inherited and
acquired)
Platelet changes
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Thrombocytopenia (Immune,
consumption, bone marrow disorders)
concern < 50
 Thrombocytosis (Reactive,
myeloproliferative disorder) concern >600
& persistent
 Platelet function defects (Aspirin,
hereditary, renal, liver disease)
The Myeloproliferative Disorders
(MPDs aka MPNs):
Recent Advances
Essential thrombocythaemia
Overview of the MPDs
BCR-ABL mutation – CML – TKIs
 BCR-ABL negative MPDs (PRV, ET, IMF)
 JAK-2 V617F mutation
- >95% PRV
- 50-60% ET, IMF
- prognostic value
- indication for cytoreductive therapy
- excludes secondary/reactive states
 Other mutations (e.g. MPL)
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Iron Overload
Type 1 haemochromatosis
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Most common genetic condition (AR) in Northern
Europeans
1:8 carriers, 1:200 homozygous C282Y mutation
of HFE gene. >95% C282Y & H63D mutations.
Chronic iron accumulation in homozygotes lead to
tissue damage (cirrhosis, diabetes, hypogonadism,
arthritis)
Ferritin > 1000 associated with hepatic cirrhosis
Age 40-60
Clinical penetrance is low
HFE & iron status
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Clinical suspicion or incidental finding
 Raised transferrin saturation (>50-55%)
 Raised ferritin (>200-300 mcg/l)
 Liver biopsy to assess tissue damage
 Phlebotomy (weekly to normal ferritin)
 Family testing (1st degree)
 Population screening
Type 2 or secondary iron
overload
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Chronic transfusion therapy (e.g.
Thalassaemia major, myelodysplasia)
 Iron overload & organ damage
 Ferritin > 1000
 IV & SC iron chelation (desferrioxamine)
 Deferiprone – second line
 Deferasirox – first & second line
Sickle cell disorders
Sickle cell disease
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Chronic haemolytic anaemia
 At risk population
 Genotypes (SS, SC, S-thal, AS trait)
 Types of anaemia
 Acute painful crises
 Infections & asplenia
 Common complications
Sickle cell disorders:
Recent recommendations
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Universal screening
 Pain relief and symptom control
 Cranial doppler scanning & stroke
prevention
 Hydroxycarbamide for severe/recurrent
sickle cell crises
 Blood transfusion & exchange
 Bone marrow transplantation
Thrombosis & Anticoagulation
Inherited thrombophilia
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Heritable
- ATIII, PC, PS
- FVL, PTG 20210A
 Acquired
- Antiphospholipid syndromes
 Mixed
- High Clotting Factors (VIII, XI, X)
- Hyperhomocyteinaemia
Prevalence of heritable
thrombophilias
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ATIII
PC
PS
FVL
PTG
pop.
0.02%
0.2%
?
2-15%
1-4%
VTE
0.5-1%
3.0%
1.0%
20-50%
6%
NB: Pregnancy 1:1000 risk of VTE
VTE preg.
4-8%
2%
?
8%
9%
Acquired VTE
(venous thrombo-embolism)
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Inevitable
- age, pregnancy, immobility, dehydration
 Iatrogenic
- post-op., indwelling devices, OCP, chemo.
 Disease-related
- APS, Cancer, Inflammatory, IV drug
abuse, Haematological (PNH, TTP, SCD)
APS
(The antiphospholipid
syndromes)
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Clinical
- arterial, venous or microvascular VTE
- pregnancy complications (IUD,
miscarriages, pre/eclampsia & prematurity
 Laboratory
- Lupus AC
- IgG and/or IgM aCL high titres
Anticoagulation
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Low molecular weight heparins (LMWH)
Oral anticoagulation - Warfarin
Thrombo-prophylaxis with LMWH or UH
Traditional Hospital clinics
POCT & self-testing
Reversal & bleeding
Risks & benefits
Direct Anti-IIa & Xa inhibitors
Direct thrombin inhibitor
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Dabigatran etexilate
Oral, renal excretion, limited license
220 or 110 mg once daily
Non-inferior to enoxaparin in prevention of VTE
in knee/hip surgery, Warfarin in non-valvular AF
No excess bleeding or adverse events
No specific antidote
Cost comparable to enoxaparin (LMWH)
Direct anti-Xa inhibitors
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Rivaroxaban in AF (20 mg daily) and DVT/
PE (15 mg BD x 3 weeks, then 20 mg daily)
 Rivaroxaban dual mode of excretion
 Alternative to conventional heparin/
Warfarin for treatment of VTE
 Apixaban licensed for AF, less incidence of
GI bleeding
Malignant Haematology
Urgent referrals
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2 week cancer target referral form
Abnormal blood results (e.g. lymphocytosis,
pancytopenia, neutropenia)
Acute & Chronic Leukaemia
Lymphadenopathy
Splenomegaly
Iron deficiency & weight loss
Miscellaneous (e.g. drenching night sweats,
abnormal CT or MRI scans)
Questions?
Thank you for your attention