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Common Haematological Problems in Childhood
Philip ConnorPaediatric Haematology
Children’s Hospital for Wales, Cardiff
Sickle Cell
Common Haematological Problems in Childhood
Objectives Of Paediatric Team
• (Diagnosis)• Management– Keep well, educate, prevent complications– Look for complications– Treat complications– (Cure disease)– Reach adult age in as good a state of health as possible
• Growth, development & organ function
– Transition into adult care
Common Haematological Problems in Childhood
Diagnosis
• Early diagnosis reduces morbidity/mortality• Allows parent/family education before “crisis
point” reached • Allows medical team to plan treatment
strategy• Different screening strategies possible
Common Haematological Problems in Childhood
Mind Set
• Haemoglobinopathies are chronic disorders, like diabetes & obesity
• Multidisciplinary team approach addresses largest number of patient issues
Common Haematological Problems in Childhood
Normal Blood
Common Haematological Problems in Childhood
Sickle
Common Haematological Problems in Childhood
History
• Why?– Heterozygote 80-90% less likely to die of cerebral malaria
than non-carrier• Life expectancy for sicklers (time for 50% of newborns
to die) is 20’s in under developed countries, 25% dead by 2nd year
• Natural history is for high mortality in childhood unless managed appropriately
• Life expectancy for in USA is 42 – 48 years– European Haemoglobinopathy registry will give estimate
for UK
Common Haematological Problems in Childhood
Diagnosis
• The earlier the better• Education to keep in good health• Teach parents how to feel for a spleen• Vaccination – Prevenar now universal• Start penicillin (Buchanan et al, 1982)
• Start folate
Common Haematological Problems in Childhood
Screening/Health: Primary School age
• Middle cerebral artery velocity– >200cm/s associated with stroke– Transfusion programme (Adams et al, 1998)
• Consider MRI – SITT study
• 5 yearly pneumoccocal booster• Yearly flu vaccination• Asthma• Enuresis• Growth• Look for iron overload in transfused patients
Common Haematological Problems in Childhood
Screening/Health: Teenage
• Ophthalmology review for retinopathy (earlier in HbSC)
• Cardiology review for pulmonary hypertension
• Monitor creatinine/proteinuria for sickle nephropathy
• Transition into adult care
Common Haematological Problems in Childhood
Crisis Management
• Team to recognise that life threatening episodes can develop rapidly
• Specific protocols for the typical crises of sickle cell– Painful – now NICE guidance on this (Guideline 143)– Chest– Sequestration
• Splenic, hepatic, (mesenteric)– Stroke– Priapism
• How to treat infection– Massive overwhelming sepsis
Common Haematological Problems in Childhood
Crisis Prevention
• Hydroxycarbamide (hydroxyurea)– Decrease mortality from chest crisis– Reduces the incidence of chest crisis– Prolongs life– Reduces painful crises – Charache et al, 1992, 1995, 1996
• Transfusion for stroke prevention (primary and secondary)
• ?Transfusion for cognitive decline
Common Haematological Problems in Childhood
Future Progress
• Historically sepsis, chest crisis and stroke were the biggest killers– As survival prolongs, new problems occurring– Pulmonary hypertension • 40% mortality at 40 months• Present in 1:3 adults
– Sickle nephropathy
• Could it be prevented? • HU or transfusion
Common Haematological Problems in Childhood
Standards and Guidelines
• NHS standards published 2006 for sickle cell
Common Haematological Problems in Childhood
Questions?
Common Haematological Problems in Childhood
Causes of Anaemia
• Destruction– Red cell – Hb, Membrane, Enzyme– Circulation – DAT + (Evans), Bacteria, MAHA (HUS/TTP)– Bleeding
• Production– Haematinics (= B12/folate/iron)– Immune – AIHA, idiopathic aplasia, drug, marrow failure syns, TEC– Infiltration– Infection – B19 in haemolytic anaemia – HbSS & HS– Alcohol/drugs/Lead (basophilic stippling and CDA see picture)– (osteopet/fibrotic)
Common Haematological Problems in Childhood
Iron Deficiency
• RBC • MCV • MCH • RDW • Check ferritin and CRP (acute phase response)• Film may show hyper-segmented neutrophils
Common Haematological Problems in Childhood
B12/Folate
• RBC • MCV • MCH • RDW • (Beware of B12 in thals)• Film – hyper-segmented neutrophils• B12/folate assay– Diet, malabsorbtion, specific antibodies
Common Haematological Problems in Childhood
Thal Indices
• RBC • MCV (<72)• MCH (<25)• RDW Normal (unless Fe defn)• Check HPLC for Hb A2 – increased unless
Fe defn in Beta thal• Check ferritin and CRP
normal trait
Common Haematological Problems in Childhood
Hb SA (trait)
Hb SS
Sickle Solubility test
Common Haematological Problems in Childhood
HPLC (Biorad Variant)
A + S A + C
S + CA + O-Arab
Common Haematological Problems in Childhood
Hb S/beta 0
• Sickling phenotype• Raised Hb A2– NB glycosylated HbS has same retention time as A2
on HPLC, so have to use column
• Targets +++ on film
Common Haematological Problems in Childhood
Other Hb’opathy
• Hb CC (not sickling)– Hb C trait usually normal– Anaemia, microcytic, MCHC
• Hb C/beta thal– Thal intermedia picture (thal indices, moderate anaemia –
may need Tx/splenectomy)• Hb EE– Trait usually normal– Thal indices
• Hb E/beta thal– Hb 2.5 – 13g/dl ie mod/severe thal
EE
C/beta0CC
Common Haematological Problems in Childhood
Other Hb’opathy
• Hb D – punjab– Trait normal– Homozygote – Hb 9-10 with thal indices
• Hb O-arab– Homozygote – mild anaemia with thal indices
• Lots more – look on OMIM• Above are all common and interact badly with
Hb S
Common Haematological Problems in Childhood
Thal Major
• 6/12 with severe anaemia, splenomegally• Film shows nucleated red cells BUT retics are
low• MCV 50-60, MCHC 12-18• Hb F and A2 usually the only haemoglobins
(Hb A can be present in beta0/beta+ cases)• Parents beta thal trait• Mutation analysis/BM (perhaps)
Common Haematological Problems in Childhood
Common Haematological Problems in Childhood
Membrane
• HS (white+spleen+J) and HE (black)• More severe in neonate• HExHS = HPP (HSxHS=RIP, HExHE=RIP)– Splenectomy
• Stomatocytosis/xerosytosis – rare– VTE if splenectomis
Common Haematological Problems in Childhood
Enzyme
• Beware “Favism”– Mediterranean child very anaemic and haemoglobinuria
• Morphology of blood film a “classic”– Blister cells, Heinz bodies, spherocytes
• Transfuse and check G6PD later• Northern Europeans – 5’pyrimidine nucleotidase def (basophilic stippling)– PK (sputnik cells)
Common Haematological Problems in Childhood
G6PD defn
5’pyrimidine etc
PK
Triose phosphate isomerase
G6PD defn
Common Haematological Problems in Childhood
Diagnostic Pathway - Child
• Hx and exam• Screen– FBC for indices with retics and Film
• Confirmatory– DAT, G6PD, Hb HPLC, Haematinics– Bilirubin (direct/indirect), LDH, – BM, (lead)
• Additional– RBC enzyme studies, membrane protein studies (m-eosin
dye binding flow), Hb variant sequencing