Abnormal blood counts in children Dr Tina Biss Consultant Paediatric Haematologist Newcastle upon Tyne Hospitals NHS Foundation Trust
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1 Abnormal blood counts in children Dr Tina Biss Consultant Paediatric Haematologist Newcastle upon Tyne Hospitals NHS Foundation Trust Regional Paediatric Specialty Trainees teaching 4 th July 2017
2 Scope of haematology Blood cells Cytopenias Normal and abnormal cell proliferations Haemoglobinopathies Coagulation/haemostasis Marrow pathology Lymphoproliferative disorders
3 Normal Full Blood Count (FBC/CBC) Hb g/l HCT % Neuts x 10 9 /L WBC 4-10 x 10 9 /l MCV fl Lymphs 1-4 x 10 9 /L Platelets x 10 9 /L MCH pg Monos x 10 9 /L RBC x /L MCHC g/l Eos x 10 9 /L
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15 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 days
16 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
17 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
18 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)
19 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
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21 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 10 9 /L (50-100)
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24 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
25 White Blood Cells Neutrophils Lymphocytes Monocytes Eosinophils Basophils
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28 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 x 10 9 /L) Severe neutropenia: neutrophil count <0.5 x 10 9 /L
29 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
30 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 10 9 /L Blood count otherwise normal, film normal No previous blood counts No medications
31 B12/folate normal, Igs normal, lymphocyte subsets normal Neutrophil count 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
32 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
33 Platelets Smallest blood cell Vital role in arresting bleeding Normal count x 10 9 /L
34 Small anucleate cellular fragments μm 100 billion platelets produced every day
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36 Structure of resting platelet
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38 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: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.
39 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: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.
40 Platelets Thrombocytopenia Platelet count <150 x 10 9 /L Decreased platelet production: Bone marrow malignancy/infiltration Congenital thrombocytopenia Drug related Viral infection Increased platelet destruction: ITP DIC Sepsis Hypersplenism
41 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
42 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
43 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
44 Risk of serious bleeding in ITP Serious bleeding in childhood ITP is rare Intracranial haemorrhage occurs in % 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
45 The art of medicine consists of amusing the patient until nature cures the disease
46 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
47 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.
48 Paediatric ITP Management Plan
49 Paediatric ITP Management Plan
50 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
51 ITP- differential diagnosis Congenital thrombocytopenias: Congenital amegakaryocytic thrombocytopenia Wiscott Aldrich syndrome Bernard Soulier syndrome Fanconi s anaemia, aplastic anaemia Leukaemia, marrow infiltration
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