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 Are there cytopenias? Check B12, Folate,, LFT, GGT, TFT, Igs, Refer to Haematology Yes No Isolated macrocytosis Monitor if screening normal

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 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/ 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 ► 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.

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 ANEMIAPERCENTAGE OF CASES Anemia of chronic disease30 to 45 Iron deficiency15 to 30 Posthemorrhagic5 to 10 Vitamin B 12 and folate deficiency 5 to 10 Chronic leukemia or lymphoma 5 Myelodysplastic syndrome5 No identifiable cause15 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 ► QualityVariant Hbs eg sickle ► QuantityUnder 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  thal

 thalassaemia

 thalassaemia

 thalassaemia heterozygotes  0  + ► Cypriot2% ► Indiarare ► Africanrare ► Hong Kong5% ► China 3-9% ► Phillipines10% ► UK Africans25% ► India5-58% ► PNG20-80% ► Thailand3-17% ► Maori5-10%

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