This document discusses common hematological problems in childhood, focusing on sickle cell disease. The objectives of treatment are to diagnose early, manage complications, prevent issues, and help patients transition successfully into adulthood. Screening and monitoring strategies are outlined for different age groups. Crisis management protocols address typical sickle cell crises. Hydroxyurea and transfusions can help prevent complications. Future areas of focus include preventing pulmonary hypertension and sickle nephropathy. Standards of care have been published to guide treatment of sickle cell disease. Common causes of anemia and approaches to diagnosis are also summarized.

1. Common Haematological Problems in Childhood
Philip Connor
Paediatric Haematology
Children’s Hospital for Wales, Cardiff
Sickle Cell

2. 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

3. 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

4. Common Haematological Problems in Childhood
Mind Set
• Haemoglobinopathies are chronic disorders,
like diabetes & obesity
• Multidisciplinary team approach addresses
largest number of patient issues

5. Common Haematological Problems in Childhood
Normal Blood

6. Common Haematological Problems in Childhood
Sickle

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Common Haematological Problems in Childhood
Standards and Guidelines
• NHS standards published 2006 for sickle cell

15. Common Haematological Problems in Childhood
Questions?

16. 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)

17. Common Haematological Problems in Childhood
Iron Deficiency
• RBC ↓
• MCV ↓
• MCH ↓
• RDW ↑ ↑
• Check ferritin and CRP (acute phase response)
• Film may show hyper-segmented neutrophils

18. 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

19. 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

20. Common Haematological Problems in Childhood
Hb SA (trait)
Hb SS
Sickle
Solubility
test

21. Common Haematological Problems in Childhood
HPLC (Biorad Variant)
A + S A + C
S + C
A + O-Arab

22. 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

23. 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/beta0
CC

24. 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

25. 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)

26. Common Haematological Problems in Childhood

27. 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

28. 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)

29. Common Haematological Problems in Childhood
G6PD defn
5’pyrimidine etc
PK
Triose phosphate
isomerase
G6PD defn

30. 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