Paediatric haematology


Paediatric haematology

 

 

Blood Counts

§        Red cells

§        Polycythaemic at birth

§        Self corrects by 3 months and becomes anaemic relative to adults

§        Reticulocyte count low as polycthaemia corrects

§        Macrocytic at birth

§        Corrects by 6 months as HbA replaces HbF

§        HbF 75% at birth, 10% at 5 months, 2% at 1 year

§        Neonatal rbcs marked poikilocytosis esp. if prem

§        Occasional NRBC normal within first 24-48hrs

§        Iron deficiency common by 1 year

§        Increased demand and poor supply

§        Cows milk virtually no iron content

§        In prems all changes exaggerated

§        Children slightly lower Hb than adults until puberty

§        Some red cell enzymes have greater activity in neonates (eg G6PD, PK, hexokinase – 150-200%)

§        B12 and folate levels often higher in children

§        White cells

§        <4 years, lymphocytes >neutrophils

§        Healthy term babies, transient neutrophilia (7-14) 24hrs after birth

§        Returns to normal by 48hrs

§        Immature neutrophils may comprise 5-10% of total wbc in healthy neonates

§        Sick neonates may have neutropenia

§        Very high lymphocytosis in certain infections esp. pertussis

§        Platelets

§        Volatility at upper end of normal (>500) as part of an acute phase response

§        Normalises from 4 years

§        Cord blood platelets less responsive to aggregating agents and have other features of hypofunction

 

Polcythaemia

§        In childhood

§        Usually secondary

§        Congenital cyanotic heart disease

§        High affinity haemoglobin

§        In neonates

§        Pathological rather than physiological, HCT > 65%, Hb >22

§        Relative – dehydration

§        Hypertransfusion – delayed cord clamping, maternofetal or twin-twin haemorrhage

§        Hypoxia – placental insufficiency, IUGR

§        Endocrine – congenital adrenal hyperplasia, thyrotoxicosis

§        Maternal disease – toxaemia, DM, heart disease, drugs (propanolol)

§        Down’s syndrome

§        Symptoms

§        Vomiting

§        Poor feeding, hypoglycaemia

§        Hypotonia, lethargy, irritable, tremulous

§        Signs

§        Plethora, cyanosis, jaundice, hepatomegaly

§        Complications

§        ICH, respiratory distress, cardiac failure

§        NEC, neonatal thrombosis

§        Management

§        Iv fluids

§        Exchange transfusion

§        Partial against FFP/ albumin to reduce HCT <60%

 

Neonatal anaemia

§        Cord blood Hb <14 in term babies

§        Impaired production

§        Anaemia of prematurity

§        Infection

§        Alpha thal (microcytosis)

§        DBA

§        FA

§        CDA

§        Increased destruction

§        Non-immune

§        TORCH infection

§        Toxoplasma, rubella, cytomegalovirus, herpes simplex

§        Congenital rbc abnormality

§        Drugs

§        MAHA

§        Immune

§        Rh/ ABO HDN (reticulocyte count normally low)

§        Maternal AIHA

§        Loss

§        Bleeding (kleihauer)

§        Repeated venepuncture

 

Anaemia of prematurity

§        Almost invariable

§        Pathogenesis

§        Reduced red cell production and survival

§        Epo production very low

§        Repeated blood sampling

§        Clinical features

§        Less able to tolerate anaemia because of increased O2 needs and metabolic demand

§        High HbF with increased oxygen affinity exaggerates hypoxia

§        Treatment

§        Delayed cord clamping

§        Minimise blood sampling

§        Avoid transfusion if retics increasing

§        Transfuse

§        <2 weeks, Hb<14, HCT <40%

§        >2 weeks, Hb <11, HCT <32%

§        Iron supplement after 2 weeks

 

Haemolytic anaemia in the neonate

§        Red cell survival in adults 120 days, infants 80 days, prems 50days

§        Physiological red cell ‘cull’ in first month

§        Clinical features

§        Pathological jaundice at birth or within 24 hours

§        Physiological jaundice occurs after 48 hours

§        In utero infections (TORCH) don’t usually cause severe jaundice cf. post natal bacterial sepsis

§        Splenomegaly

§        Kernicterus

§        Family and drug history

§        Diagnosis

§        Unconjugated bilirubin

§        Increased retics

§        Haptoglobins unreliable in neonates

§        Film

§        DAT

§        May be negative in ABO HDN

§        Heinz body test

§        Drug induced haemolysis, G6PD

§        Haemoglobinuria

 

Congenital red cell defects

§        Neonate less able to cope

§        Hepatic immaturity

§        Altered enzyme activity

§        B-globin chains don’t present in the neonate

§        SCD, beta-thal

§        Membrane defects

§        HS, HE, stomatocytosis, pyropoikilocytosis

§        Blood film, osmotic fragility tests

§        Hb defects

§        Alpha delta beta thal, unstable haemoglobins

§        electrophoresis

§        Enzyme defects

§        Glycolytic pathway

§        PK

§        Hexose monophosphate shunt

§        G6PD

§        Heinz body, specific assay

 

Acquired red cell defects

§        Altered enzyme activity renders them more susceptible to oxidative stress

§        Causes

§        Infection

§        In utero - TORCH + malaria, syphilis

§        Postnatal – normally bacterial

§        Microangiopathy

§        Severe infection +/- DIC

§        Kasabach-Merritt syndrome – giant haemangioma with haemolysis and local DIC

§        Drugs

§        Most often if also G6PD

§        Infantile pyknocytosis

§        Vitamin E deficiency

§        Pyknocytes – irregularly contracted rbcs with multiple projections

§        Self limiting

§        Metabolic diseases

§        Wilsons, galactosaemia

 

Hyperbilirubinaemia

§        Causes

§        Unconjugated

§        Physiological

§        Haemolytic

§        Haematoma

§        Polycythaemia

§        Biochemical defects

§        Conjugated

§        Mechanical obstruction

§        Bile duct abnormalities

§        Hepatocellular disorders

§        Hepatitis

§        Clinical jaundice in 1st 24 hours is always pathological

§        Treatment

§        Phototherapy (400-500mm wavelength)

§        Contraindicated in conjugated

§        Exchange transfusion

§        Bili >340

§        Bili often higher in breast fed infants

 

Congenital dyserythropoietic anaemia

§        Abnormal marrow erythroblasts with ineffective erythropoiesis and excess iron

Type

BM

Blood

Inheritance

I

Megaloblastic

Intranuclear chromatin bridges

Macrocytic

Recessive

II

HEMPAS

Commonest

Bi/ multinuclearity

Normocytic

Pluirpolar mitosis

Recessive

III

Giant erythroblasts

Multinuclearity

Macrocytic

Dominant

§        HEMPAS = hereditary erythroblast multinuclearity with positive acidified serum test (HAMs test)

§        Clinical features

§        Usually present in older children >10 yrs

§        Type II – most severe, may be transfusion dependant

§        Jaundice, splenomegaly, gall stones

§        Diagnosis

§        Anisopoikilocytosis

§        Relatively low retics, but other markers of haemolysis up

§        BM – increased cellularity with excess abnormal erythroblasts

§        Type II – positive acidified serum test

§        Increased ferritin due to increased iron absorption

§        Haemosiderosis without transfusion dependence

§        Occasionally iron deficient due to IVH

§        In PNH, HAMS test positive with normal and own serum, in type II, positive only with normal serum and sucrose lysis test also negative

 

Acquired red cell aplasia

§        Parvovirus B19

§        Transient reticulocytopenia

§        Occasionally neutropenia and thrombocytopenia

§        Subsides following antibody response by 7-10 days

§        In immunocompromised, anaemia can be chronic with persistent viraemia

§        Shows tropism for red cells via P antigen

§        Cytotoxic to erythroid progenitors at colony forming stage in vitro

§        Transient erythroblastopenia of childhood

§        Idiopathic or secondary to viral infections

§        IgG Ab against erythroblasts

§        EBV, mumps

§        Serum and cellular inhibitors to erythropoiesis and defective marrow response to stimulating cytokines

§        Insidious onset

§        Pallor and anemia, no other abnormality

§        Reticulocytopenia unless recovering

§        Spontaneously remits within 4-8 weeks

 

Neutropenia

§        Cyclical neutropenia

§        May improve after puberty

§        Usually positive family history when problems in childhood (AD in1/3rd)

§        Treat with GCSF; no association with MDS/ AML unlike severe congenital neutropenia (SCN)

§        Defect in neutrophil elastase (same as SCN)

§        Chronic benign neutropenia

§        Persistent but mild

§        To be distinguished from Kostmann’s = severe congenital neutropenia

§        Infections

§        Autoimmune neutropenia

§        Infant form within 1 year of life

§        Demonstrable autoantibodies

§        Not familial

§        Self limiting and usually relative benign

§        Treatment supportive, can use IVIG

§        Older children

§        Isolated

§        SLE, Felty’s

§        All potentially more complicated

§        Isoimmune neutropenia of the newborn

§        Maternal antibodies to fetal neutrophil antigens (NA1, NA2)

§        Resolves by 2 months as antibody disappears

 

Disorders of neutrophil function

§        Reduced chemotaxis

§        Lazy leucocyte syndrome

§        Adhesion deficiency secondary to reduced HMW membrane GPs

§        AR

§        Recurrent infections esp. oral, delayed wound healing

§        Abnormal chemotaxis on Rebuck skin window test

§        Hyperimmunoglobulin window syndrome (Jobs)

§        AR

§        Assoc with atopic dermatitis, other AI phenomena

§        Bacterial/ fungal infections, chronic dermatitis

§        Increased IgE and increased eosinophils

§        Chediak-Higashi

§        AR

§        Partial oculocutaneous albinism, recurrent infection, LAP, peripheral neuropathy and cerebellar ataxia

§        Fatal accelerated phase in 2nd decade in 85%

§        Lymphocytic infiltration liver, spleen, BM, nodes

§        Characteristic giant greenish grey refractile granules in neutrophils

§        Reduced opsonisation

§        Complement C3 deficiency

§        AR

§        Esp encapsulated organisms

§        Reduced killing

§        Chronic granulomatous disease

§        Commonest

§        Most are sex linked

§        Carriers are asymptomatic

§        Skin and visceral abscesses

§        Associated with McLeod phenotype

§        Nitro blue tetrazolium test positive

§        Antibiotics and IFN-gamma

§        MPO deficiency

§        AR

§        Often asymptomatic

§        Manifests in diabetics, candida albicans common

§        Good prognosis

§        Automated cell counters sing MPO activity may give spurious neutropenia

§        Reduced neutrophil/ monocyte peroxidase on histochemical analysis

 

Storage disorders

§        Gauchers

§        AR

§        Deficiency of glucocerebrosidase

§        Glycolipid accumulation in macrophages

§        Spleen, liver, bone marrow

§        Type 2 = rarer

§        Severe progressive neurological deterioration, usually fatal within 1 year

§        Diagnose with enzyme assay, characteristic marrow appearance

§        Pseudo-gaucher cells in CML, thalassaemia, atypical MB

§        Nieman-Pick disease

§        Foamy macrophages

§        Inherited deficiency of sphingomyelinase – accumulation of sphingomyelin

§        4 types

§        A – classic,

§        Developmental delay, death within 3 years

§        4 – live to adult hood

 

Histiocytic Syndromes

§        Monocytes move into tissues and become histiocytes

§        Mononuclear phagocytic system

§        Antigen processing

§        Kupfer, pulmonary alveolar macrophages

§        Dendritic cell system

§        Antigen presenting

§        Langerhans cells

§        Class I

§        Disorders of dendritic cells

§        Langerhans cell histiocytosis

§        Cellular destructive tissue infiltration with LCs

§        Not phagocytic

§        Burbeck granules on EM and positivity for CD1a

§        Usually 1-3 years

§        Staged on the basis of number of organ systems involved

§        Most commonly lytic bone lesions

§        Treatment

§        Local curettage +/- intralesional steroids

§        Occas. steroids and chemotherapy

§        Outcome

§        Overall mortality 15-20%

§        Risk of pulmonary/ liver fibrosis

§        Diabetes insipidus +growth failure

§        Increased risk of malignant disease

§        Class II

§        Disorders of macrophages

§        Haemophagocytic syndrome (HLH)

§        Primary (genetic)

§        AR

§        Cytokine dysregulation with high IL-1, IL-2, GM-CSF, TNF

§        PB cytopenias, hypertriglyceridaemia, hypofibrinogenaemia

§        Histopath – lymphocyte, histiocyte infiltration and haemophagocytosis

§        Usually rapidly fatal

§        Secondary

§        Older, immunocompromised patients

§        Commonly associated with underlying infection

·        EBV and malaria

§        Also assoc with malignancy, lipid infusions

§        Outcome depends on available treatment for cause

§        Class III

§        Malignant histiocytosis

§        AKA large cell anaplastic lymphoma



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