Abnormal blood counts in

children

Dr Tina Biss
Consultant Paediatric Haematologist
Newcastle upon Tyne Hospitals NHS Foundation Trust

Regional Paediatric Specialty Trainees teaching

4th July 2017
Scope of haematology
• Blood cells
• Cytopenias
• Normal and abnormal cell proliferations
• Haemoglobinopathies
• Coagulation/haemostasis
• Marrow pathology
• Lymphoproliferative disorders
 Normal Full Blood
Count (FBC/CBC)

Hb WBC Platelets RBC

120-180 4-10 150-400 4.5-6.5
9 9 12
g/L x 10 /l x 10 /L x 10 /L
HCT MCV MCH MCHC
40-52 76-102 27-32 300-350
% fL pg g/L
Neuts Lymphs Monos Eos
2-7.5 1-4 0.2-0.8 0.04-0.4
9 9 9 9
x 10 /L x 10 /L x 10 /L x 10 /L
 Red Cells

• Most common blood cell

• Made in the bone marrow – erythropoiesis
• Red – due to protein Haemoglobin
• Haemoglobin – contains iron
• Transports Oxygen and Carbon dioxide
• Hb in red blood cells – responsible for >98 % of oxygen
• Lifespan – 100 –120 days
 Anaemia

• From Ancient Greek – “without blood”

• Qualitative or quantitative deficiency of haemoglobin
• Hb concentration – defines anaemia
• Anaemia < lower limit of normal adjusted for age and sex
• Values differ between males and females – androgens
drive red blood cell production
• Mean cell volume (MCV) – further help in defining
anaemia
 Anaemia

• MCV - size of the red cell

• Low MCV: microcytic – iron deficiency, thalassaemias

• Normal MCV: normocytic – acute blood loss, chronic

disease, malignancy, bone marrow disorders

• Raised MCV: macrocytic – Vit B12/folate deficiency, drug

therapy
 Anaemia
• Reduced/abnormal red cell production:
• Haematinic deficiency- Iron, B12, folate
• Congenital anaemia (e.g. Diamond Blackfan anaemia, Fanconi anaemia)
• Marrow infiltration (e.g. Leukaemia)
• Aplastic anaemia
• Haemoglobinopathy
• Viral infection (e.g. Parvovirus B19)
• Transient erythroblastopenia of childhood
• Anaemia of chronic disease

• Increased red cell destruction:

• Congenital membrane disorder (e.g. Hereditary spherocytosis)
• Red cell enzyme disorder (e.g. Pyruvate kinase deficiency, G6PD deficiency)
• Autoimmune haemolytic anaemia
• Haemolytic uraemic syndrome (HUS)
Case history

• 6 y o girl
• Anaemia as an infant
• HEREDITARY SPHEROCYTOSIS diagnosed aged 6 months
• No family history
• Baseline Hb 110 g/L, falls to around 80 g/L with viral infection
• One previous blood transfusion
• Not on any treatment
• Admitted Nov 2016:
• Fever, vomiting and diarrhoea for 48 hours
• Pallor and lethargy on day of admission

• Bloods:
• Hb 48 g/L
• MCV 78 fl
• Reticulocyte count 24 x 109/L (50-100)
• Further bloods:
• Parvovirus B19 IgM and IgG present

• APLASTIC CRISIS DUE TO PARVOVIRUS INFECTION

• Treatment:
• Red cell transfusion- 1 unit
• Folic acid
• Observe for reticulocyte recovery

• ?? Splenectomy
White Blood Cells

• Neutrophils
• Lymphocytes
• Monocytes
• Eosinophils
• Basophils
 Neutrophils

• Most common white blood cell

• Migrate towards sites of infection or inflammation
• Once migration – lifespan 1-2 days
• Phagocytosis – ingest and kill microbes
• Low neutrophil count: neutropenia (normal range 1.8-3.0
x 109/L)
• Severe neutropenia: neutrophil count <0.5 x 109/L
Causes of Neutropenia
• Congenital:
• Bone marrow failure, e.g. Shwachman Diamond syndrome,
Kostmanns syndrome
• Cyclical neutropenia
• Storage disorders
• Congenital immunodeficiencies
• Ethnic neutropenia

• Acquired:
• Viral infection
• Severe bacterial infection
• Drug related
• B12/folate deficiency
• Bone marrow infiltration
• Benign autoimmune neutropenia of childhood
• Hypersplenism
Case history
• 12 month old boy
• 2 previous admissions to hospital:
• Bronchiolitis- 3 months old
• Febrile illness- 10 months old
• Bloods had shown neutrophil count 0.2 x 109/L
• Blood count otherwise normal, film normal
• No previous blood counts
• No medications
• B12/folate normal, Igs normal, lymphocyte subsets normal

• Neutrophil count 0.14-0.7

• Frequent viral infections but otherwise well

• Antineutrophil antibodies- negative

• Bone marrow biopsy- plentiful early myeloid cells, evidence of
maturation arrest

• Further report confirmed antineutrophil antibodies present

• BENIGN AUTOIMMUNE NEUTROPENIA OF CHILDHOOD

Benign autoimmune neutropenia of
childhood
• Most frequent cause of chronic neutropenia in childhood
• Onset is usually during infancy
• Neutrophil count often <0.5
• Serious infection rare
• Recovery within 2-3 years, by 5 years of age
• Anti-neutrophil antibodies detected in 75% of cases
• Antibiotic prophylaxis not usually required
 Platelets

• Smallest blood cell

• Vital role in arresting bleeding
• Normal count – 150-450 x 109/L
• Small anucleate cellular
fragments 0.5-3.0μm
• 100 billion platelets
produced every day
Structure of resting platelet
Figure 1. Damage to the vascular endothelium results in recruitment of platelets which
aggregate at the site, forming the primary hemostatic plug

Maslak, P. ASH Image Bank 2008;2008:8-00146

Copyright ©2008 American Society of Hematology. Copyright restrictions may apply.

Figure 2. Through the processes of adhesion, aggregation, and secretion, platelets
successfully coalesce to complete the formation of the primary hemostatic plug

Maslak, P. ASH Image Bank 2008;2008:8-00146

Copyright ©2008 American Society of Hematology. Copyright restrictions may apply.

 Platelets
• Thrombocytopenia
• Platelet count <150 x 109/L

• Decreased platelet production:

• Bone marrow malignancy/infiltration
• Congenital thrombocytopenia
• Drug related
• Viral infection
• Increased platelet destruction:
• ITP
• DIC
• Sepsis
• Hypersplenism
Case history
• 16 month old girl
• Presented at 14 months of age to WGH
• Widespread petechial rash
• No other bleeding symptoms
• Fever and vomiting for 2 days prior
• FBC: Plt 5, normal blood film
• Managed conservatively
• Referred to RVI due to persisting thrombocytopenia
• Intermittent petechial rash
• Occasional epistaxis, usually brief
• Petechiae on and off since birth, no prior blood tests
• Bone marrow biopsy 4 months later
• Normal appearances
• Consistent with diagnosis of ITP
• Progress
• Trauma-related bruising only, despite plt <10
• No treatment with steroids/IVIg required
• Gradual rise in platelet count from 1 year post-diagnosis
• Discharged from clinic at 2 years post-diagnosis with normal
platelet count
Diagnosis of Childhood ITP
• Presentation generally acute, although may give a history of bruising
over several months
• May follow viral infection or vaccination
• Diagnosis of exclusion:
• Blood film
• Previous blood counts
• Family history
• Other abnormalities, e.g. skeletal
• Majority spontaneously remit within 6 months
• Only 3% have clinically significant symptoms
• Only 5% develop chronic ITP
Risk of serious bleeding in ITP
• Serious bleeding in childhood ITP is rare
• Intracranial haemorrhage occurs in 0.1-0.5%
• Cannot reliably predict those who are at risk of serious
bleeding
• ICH has previously been associated with:
• Severe thrombocytopenia
• NSAIDs
• Head trauma
• Vasculitis (SLE, VZV)
• ‘Wet’ purpura
“The art of
medicine consists
of amusing the
patient until
nature cures the
disease”
Challenges in Childhood ITP

• Get the diagnosis right

• always a ‘working diagnosis’/diagnosis of exclusion
• Avoid unnecessary intervention
• diagnostic tests/therapy
• Manage the child, not the platelet count
• intervention when appropriate and justifiable
• Chronic ITP
• rare but problematic if severe
• Practice evidence based medicine
• lack of high level evidence base
Get the diagnosis right
• Presence of typical features
• Acute onset purpura/mucosal bleeding, otherwise well
• (history of recent infection)
• Age 2-10 years
• Numerically severe thrombocytopenia, less severe clinical bleeding
• Otherwise normal blood film appearance
• Absence of atypical features
• Ill child, bone pain, lymphadenopathy, (splenomegaly), drug
therapy
• Other cytopenias, abnormal WBC, abnormal platelet morphology,
microangiopathic/leucoerythroblastic picture, etc.
Paediatric ITP
Management
Plan
Paediatric ITP
Management
Plan
Supportive care in chronic ITP
• Antifibrinolytics (tranexamic acid)- epistaxis, menorrhagia, oral
cavity bleeding

• Suppression of menstruation- COCP

• Avoidance of NSAIDs/aspirin

• Education
• awareness of risk of haemorrhage
• avoidance of contact sports
• medic-alert
• open access for assessment
ITP- differential diagnosis
• Congenital thrombocytopenias:
• Congenital amegakaryocytic thrombocytopenia
• Wiscott Aldrich syndrome
• Bernard Soulier syndrome

• Fanconi’s anaemia, aplastic anaemia

• Leukaemia, marrow infiltration