cu common haematological problems in childhood

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