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
§ 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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