cu common haematological problems in childhood

Common Haematological Problems in Childhood

Philip ConnorPaediatric Haematology

Children’s Hospital for Wales, Cardiff

Sickle Cell


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


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


Mind Set

• Haemoglobinopathies are chronic disorders, like diabetes & obesity

• Multidisciplinary team approach addresses largest number of patient issues


Normal Blood


Sickle


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


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


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


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


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


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


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


Standards and Guidelines

• NHS standards published 2006 for sickle cell


Questions?


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)


Iron Deficiency

• RBC • MCV • MCH • RDW • Check ferritin and CRP (acute phase response)• Film may show hyper-segmented neutrophils


B12/Folate

• RBC • MCV • MCH • RDW • (Beware of B12 in thals)• Film – hyper-segmented neutrophils• B12/folate assay– Diet, malabsorbtion, specific antibodies


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


Hb SA (trait)

Hb SS

Sickle Solubility test


HPLC (Biorad Variant)

A + S A + C

S + CA + O-Arab


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


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


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


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)


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


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)


G6PD defn

5’pyrimidine etc

PK

Triose phosphate isomerase

G6PD defn


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

cu common haematological problems in childhood

Health & Medicine

common haematological

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incidence of chest crisis

medical team

adult care

cardiffsickle cell

chest sequestration

possible growth