Dr Mere Kende MBBS, MMED (Path), MACTM, MAACB, MACRRM Lecturer: SMHS

Transcription

1 Dr Mere Kende MBBS, MMED (Path), MACTM, MAACB, MACRRM Lecturer: SMHS

2 Topics Anaemia Iron Deficiency Vitamin B12 deficiency Hemolysis Haemoglobinopathies Petechiae/Bruising Coagulopathies Neonatal Jaundice Leukaemia

3 Clinical Presentation of Hematological Disorders Asymptomatic Non-specific symptoms Poor Growth /Nutritional Issues Anaemia Jaundice Skin bruising Haematuria Lympadenopathy Joint Swelling Organomegaly

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5 Anaemia Definition: Hb <lower Limit of reference range for age Age 24hrs months months months years 115 LL of normal Range (g/l) >12 years girls 120 boys 130

6 Changes in Hb after Birth [Hb] at birth: g/L. Hb g/l It rises transiently in the first 24 hours Slowly falls to as low as 95 g/l by the 9 th week. By 6 months, Hb stabilises at around 125 g/l, the lower end of the adult range, Then increases towards adolescence Birth 24hours 3months 6months adult

7 PREMATURE BABIES Fall in Hb is accelerated may fall to less than 90 g/l by the 4th week. Prone to multiple nutritional deficiencies because of rapid growth. Anaemia is worse if the infant gains insufficient weight or is fatigued while feeding.

8 Clinical Features (NON-SPECIFIC) Poor Feeding/intake Pallor Pale conjunctivae Flow murmur Lethargy Poor growth Signs of cardiac failure Listlessness SOB

9 Anaemia associated with infection HIV Malaria CMV & rubella, Toxoplasmosis, congenital syphilis -rarely Parvovirus B19 (BM aplasia) Cause: haemolysis or BM suppression.

10 HIV infection Causes chronic multisystem Perinatal transmission 20-40% of Pregnancies Thrombocytopenia occurs in up to 15% of children with HIV infection Normocytic, Normochromic Anaemia is common Leucopenia and lymphopenia are also seen, in which the BM shows non-specific features of chronic infection

11 Investigation of Anaemia FBE Blood Film Exam Ferritin/Iron studies Reticulocyte Count

12 Causes: Classification based on MCV

13 Microcytic (Low MCV) Serum Ferritin Normal Hb Electrophoresi s Thalassaemia minor Low Iron Deficiency

14 Normocytic (Normal MCV) Reticulocyte Count Increased Low/Normal Hemolysis/ Blood Loss Marrow hypoplasia/ leukaemia/infiltrate

15 Macrocytic (high MCV) Serum & red cell folate Serum B12 Normal Reduced Myelodysplasia, Fanconi s Anemia, TC II deficiency B12/folate Deficiency

16 Iron Deficiency Anaemia Commonest cause of anaemia throughout the world May be subclinical -role cognitive and psychomotor development Leads to anaemia in those with severe deficiency Present in 10-30% of children in high risk groups Most due to inadequate dietary intake Lost through cow milk provoked GIT loss in infants/worm infestation & menstruation in adolescent girls

17 Children at High Risk for iron Deficiency Anaemia Group/Age mechanism Additional Risk Factors <6months Prematurity Inadequate Stores LBW/Multiple Births Maternal iron deficiency 6-24months Exclusively Breastfed Inadequate Intake Delayed introduction of iron containing food Excessive Cow milks Adolescent Females Menstrual loss Poor Diet Rapid Growth Spurt Socially Disadvantaged Worm Infection Fad diets/ Vegeterians Poor diet Inadequate Intake

18 Diagnosis Hypochromic, microcytic blood film, Low iron and Ferritin and raised TIBC and transferrin Ferritin is acute phase reactant Early sign reduced ferritin & FBE can be normal Remember low iron due to poor diet may be associated with other micronutrient deficiency Empiric iron treatment may be a strategy

19 Treatment Supplement iron Iron as ferrous gluconate mixture 1ml/kg (300mg/5ml prep) Continue 3 months after Hb has normalised to replenish iron stores Transfusion may be indicated if heart failure/severe infection/if urgent surgery is needed

20 Stools may become black/grey Note: iron overload is fatal- advise locked cabinet

21 Prevention of Iron Deficiency Introduce iron containing food at 4-6 months Avoid cows milk in the first 12months(small amounts allowed in custards, cereal, etc) Cows milk should only form small part of diet up to 2 years of age Ensure that formulas (if used) and cereals are iron fortified Consider supplements in high risk groups

22 Good Sources of Iron Infant milk formula Fortified breakfast cereals Meat (red meat/chicken/fish) FGLV Dried beans and fruits Egg york Food rich in Vitamin C increases iron absorption from non-meat sources

23 Vitamin B12 deficiency Presents commonly in 1 st 2 years of life Commonly nutritional due to maternal B12 deficiency Presentation: neurological abnormalities +macrocytosis + pancytopenia + hypersegnmented neuophils Should be urgently diagnosed and treated due to lack of reversibility of neuro symptons/signs BM shows megaloblastic Changes

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25 FBE: Anaemia- mild to severe Elevated MCV Normal MCV can occur with B12 deficiency Caution : co-existing iron defciency /thalassaemia (normal MCV)

26 Blood Film: hypersegmented neutrophils (3-4 lobes) anisocytosis and poikilocytosis macro-ovalocyte, low reticulocytes Pancytopenia (severe cases)

27 Bone Marrow Aspirate- Megaloblast

28 Macroovalocytes Lymphocytes This hypersegmented neutrophil is present along with macro-ovalocytes in a case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at the lower left center. Note that the large RBCs lack a zone of central pallor.

29 Measure serum vitamin B12 Methyl Malonic Acid-measured as indicator of early B12 deficiency (HPLC)

30 Acute Hemolysis May require admission & transfusion May present with non-specific symptoms

31 Haemolytic disease in newborn infants Immune hemolysis by antibodies from the mother that cross the placenta. Rhesus D antibodies to RhD antigen. Prevention: Immunise mother with anti-d immunoglobulin. Anti-D immunoglobulin is administered to non-sensitised RhD negative women, Mortality 40% if baby affected Treatment : exchange transfusion improves survival rate by 85%.

32 Recommendations for prophylactic anti-d immunoglobulin in RhD negative women After delivery if the infant is Rh positive After abortion (therapeutic or spontaneous) To cover antenatal procedures (amniocentesis, chorionic villus sampling) After threatened abortion or miscarriage Antenatally at 28 and 34 weeks (not yet universal)

33 Reasons for failure of prophylaxis Failure of administration (commonest cause) Inadequate dosage (routine Kleihauer tests should be performed) Earlier sensitisation that may not be detectable at birth Poor injection technique (should be deep IM)

34 General Features of Acute Hemolysis Anaemia/Pallor/Jaundice +/-Hepatospenomegaly Reticulocytosis Unconjugated hyperbilirubinaemia Raised AST/LDH Haemoglobinaemia

35 Haemoglobinuria Raised urobilinogen in Urine No bilirubinuria (unconjugated/insoluble) Raised MCV -Early nucleated Red cells Haptoglobin (less useful in children)

36 Acute Hemolysis Anaemia /Reticulo cytosis Extrinsic Intrinsic Microangip athic Infective Antibody Mediated Membrane Disorder Enzyme Disorder Hb Disorder

37 Intrinsic Membrane Enzyme Hemoglobinopathies Hereditary Sperecytosis/Ov alocytosis G6PD Deficiency Pyruvate kinase deficiency Thalassemia Unstable Hb Sickle Cell

38 Hemoglobinopathies β-globin thalassemia α- globin thalassemia Sickle Cell Anemia Others: Hemoglobin C/E

39 Thalassemia

40 Thalassemia Normal Hb ( 2 2) Individuals inherit one gene from each parents compared to two genes Alpha thalassemia- alpha chain defect/gene deletion Silent carrier ( -/ ) Alpha-thalassemia trait ( -/ - ) or (--/ ) Hb H Disease (- -/ -) or lacks 3 alpha genes Hydrops Fetalis /IUD(- -/- -) -Hb Barts ( 4) or lacks all 4 alpha genes - Thalassemia- beta chain defect/reduced beta chain amount/qantitative defect

41 -Thalassemia Major (inadequate -chain) Marked relative excess of α- chain Uncommon in 1 st world due to increased antenatal screen & prenatal termination Symptoms begin second 6 months of life [switch of HbF ( 2 2) - HbA1 ( 2 2) during 1 st 6months] Presentation: severe hemolytic anaemia, slow growth, skeletal deformities, hepatosplenomegaly (always), heart failure hypochromic, microcytic anaemia, PCV <20%: Normal/high Fe++

42 Blood Film in Beta Thalassaemia This peripheral blood smear shows marked poikilocytosis (abnormally shaped RBC's) as well as some anisocytosis (variation in RBC size), though many are small (microcytes). This patient has beta-thalassemia, a hereditary disorder of beta globin chain synthesis that leads to ineffective erythropoiesis and a microcytic anemia. Some of these abnormally shaped RBC's resemble jigsaw puzzle pieces.

43 Excess alpha chains Increased HbF ( 2 2) a & 2-fold increase in HbA2 ( 2 2) Depend on transfusion Reduced life expectancy Iron Overload Genetic Counselling/Antenatal diagnosis Bone Marrow Transplant

44 Beta-Thalassemia Minor (Thalassemia trait) very common Rarely show significant anaemia and symptoms Causes microcytic, hypochromic Anaemia Clues on FBE include elevated RBC count/marked microcytosis Diagnosis: Hb electrophoresis- elevated HBA2 Often treated unnecessarily with iron HbA2 levels may be corrected with iron therapy obscuring the dx

45 Alpha Thalassemia AT /Trait is 1 or 2 gene deletions relatively common in Asian populations Asymptomatic throughout life Microcytosis /target cells may be seen Hb electrophoresis normal except decreased HbA2

46 HbH 3 gene deletions microcytic but asymptomatic when well May develop anaemia when stressed DDx G6PD Blue Inclusions (methylene Blue)

47 Hydrops Fetalis- Hb Barts -4 gene deletion Generalized edema from fluid collection in the soft tissues results in hydrops fetalis. Incompatible with life Other Causes: Infections Cardiac Failure Rh Incompatibility

48 Sickle Cell Anaemia Abnormal Hb SS is prone to form crystals when oxygen tension is low, and the RBC's change shape to long, thin sickle forms that are "sticky" and sludge in capillaries, further decreasing blood flow and oxygen tension. The sickled RBCs tend to adhere to endothelium, and the bioavailability of endothelial nitric oxide is reduced as well, further promoting vaso-occlusion.

49 Sickle Cell Anemia Homozygous (ss) or double heterozygous (HbS/b-thalassemia) Defect in beta chain: substitution of valine for glutamic acid at 6 th residue of beta chain Deoxygenated HbS cell sickles easily from biconcave disk to elongated crescent-shaped or sickled cell Lack flexibility and rigid to transverse capillaries ---hemolysed 8% black Americans Up to 30% Central Africa (associated with malaria endemic areas) Gives slight protection from malaria

50 Clinically Asymptomatic carrier Symptoms onset at 6 months of age (HbF HbA switch) Multiple systems Disease CNS/Resp/skin/eyes/GUT/MSS etc Anaemia (hemolysis/aplasia) Reduced RBC half-life (10-15 days) Rapidly progressive anaemia with splenomegaly Delayed growth & Development

51 Acute Chest syndrome (pneumonia-like) Arterial ischaemia stroke Painless haematuria Painful crisis (joint/abdomen) Sepsis/Sickling crisis in carriers if severely hypoxic

52 Diagnosis Blood Film- demonstrate sickling under reduced oxygen tension Normocytic, normochromic anaemia, Target cells Hb Electrophoresis- Hb S 76-96% HbF 2-20% HbA2 2-4% HbA1-0% HbS Heterozygotes- minimal problems, normal Life expectancy

53 Treatment Supportive Conservative Antenatal Counselling

54 Prenatal Diagnosis (DNA analysis)- CVS/AFS

55 Acute Hemolysis Extrinsic Ab - mediated Microangiopathy Infections Coomb s +ve autoimmune, ABO/Rh-related, Drug Induced, Cold Agglutinins, T-antigen activation HUS TTP DIC Post-heart valve Malaria Severe Sepsis

56 Autoimmune Hemolytic Disease Mechanism of antibody-mediated immune destruction of red cells

57 General Considerations Acquired disorder Production of IgG autoantibody against RBC membrane antigens. IgG most commonly directed against ABO and Rhesus antigen Mechanism Red Cell is first coded by IgG- - recognised by RES/Spleen removal of RBC membrane - formation of spherocytes - removal of RBC by RES --> Hemolysis

58 Coomb s Anti-globulin test Used to diagnose AUTOIMMUNEHEMOLYTIC ANAEMIA. Coomb's reagent Is a rabbit IgM antibody raised against human IgG or human complement. Direct Coomb's test - mix the patient's red blood cells with the Coomb's reagent Positive Agglutination Presence of bound antibody on patient s RBC surface.

59 Indirect Coomb's test Mixing the patient's serum with a panel of type O red blood cells. Incubate test serum and panel O red blood cells, Add Coomb's reagent Positive Agglutination Presence of free antibody in the Patient's serum.

60 Haemolytic Uraemic Syndrome Essentials of Diagnosis Microangiopathic hemolytic anemia. Thrombocytopenia and renal failure. Normal coagulation tests. Follows gastro (E.Coli) Absence of neurologic abnormalities (cf. TTP) Complete recovery /Good prognosis

61 Lab Investigation of Hemolysis Blood Film spherocytes-hereditary Target cells-thalassemia Hypochromia/microcytosis-Thalassemia Fragmented cells-mah Direct Coomb s test-autoimmune HA

62 Hemolysis-Reticulocytosis This peripheral blood smear demonstrates many larger bluish reticulocytes as well as smaller RBC's lacking central pallor-- spherocytes. This patient had an autoimmune hemolytic anemia. Antibody coated the RBC's, and portions of the RBC's were removed, decreasing cell size. Many RBC's were removed entirely, resulting in anemia and a bone marrow response with increased erythropoiesis and elevated reticulocyte count (20%). The patient developed an indirect hyperbilirubinemia as well.

63 Thalassemia This peripheral blood smear shows marked poikilocytosis (abnormally shaped RBC's) as well as some anisocytosis (variation in RBC size), though many are small (microcytes). This patient has beta-thalassemia, a hereditary disorder of beta globin chain synthesis that leads to ineffective erythropoiesis and a microcytic anemia. Some of these abnormally shaped RBC's resemble jigsaw puzzle pieces

64 Spherocytosis -Hereditary The size of many of these RBC's is quite small, with lack of the central zone of pallor. These RBC's are spherocytes. In hereditary spherocytosis, there is an abnormality of RBC cytokeletal membrane proteins such as ankyrin and spectrin. This produces membrane instability that forces the cell to the smallest volume--a sphere. In the laboratory, this is shown by increased osmotic fragility. The spherocytes do not survive as long as normal RBC's

65 Intra-vascular Hemolysis (DIC) There are numerous fragmented RBC's seen here. Some of the irregular shapes appear as "helmet" cells. Such fragmented RBC's are known as "schistocytes" and they are indicative of a microangiopathic hemolytic anemia (MAHA) or other cause for intravascular hemolysis. This finding is typical for disseminated intravascular coagulopathy (DIC).

66 Viral Infection The WBC's seen here are "atypical" lymphocytes. They are atypical because they are larger (more cytoplasm) and have nucleoli in their nuclei. The cytoplasm tends to be indented by surrounding RBC's. Such atypical lymphocytes are often associated with infectious mononucleosis from Epstein-Barr virus (EBV) infection

67 Toxicity Basophilic stippling The nucleated RBC in the center contains basophilic stippling of the cytoplasm. This suggests a toxic injury to the bone marrow, such as with lead poisoning. Such stippling may also appear with severe anemia, such as a megaloblastic anemia.

68 Specific Tests Heinz Body stains-unstable Hb, G6PD Assay- Hb electrophoresis- thalassemia/sickle Cell Further Test in consultation with specialist

69 Coagulopathies Can present anytime Bruising of varying ages, unusual sites Positive Drug hx Positive Family hx Previous bleeding episodes/problems at surgery/tooth extractions Coagulation studies (child) not routine unless clinically indicated

70 Major Coagulopathies Haemorrhagic Disease of Newborn Idiopathic /Immune thrombocytopenic purpura (ITP) Haemophila A & B (Christmas Disease) Von willebrand disease (vwd)

71 Vitamin K deficiency Causes haemorrhagic disease in newborn infants It may present soon after birth with generalised bruising and internal bleeding, or as late as age one month. It may be seen in otherwise healthy term infants, especially if they are being breast fed. Precipitated if the mother is taking anticonvulsant drugs or warfarin. Treatment: Vitamin K prophylaxis at birth

72 Other causes of purpura Septicaemia/meningococcus Enterovirus Henoch-shonlein pupura Leukaemia Child abuse Trauma/vasomotor straining Slapped cheek Parvovirus B19/Fifth Ds/Erythema infectiosum

73 Thrombocytopenia Ref Range: ( /L). most common haemostatic abnormality in newborn infants, occurs in 25% in NICU. Commonest causes: Asphyxia at birth, infection, and DIC. Can occur following exchange transfusion. Platelet transfusions should be given to any infant whose count is /L.

74 Maternal ITP may be associated with neonatal thrombocytopenia because of placental transfer of anti-plt antibodies. Fetal platelet counts rarely drop below 50000/l, and intracranial haemorrhage is rare either prenatally or at birth. There are no reliable predictors of severe thrombocytopenia. Treatment: PLT transfusions & steroids; IV immunoglobulin is safe & effective in over 80% of infants.

75 Common causes of thrombocytopenia Immune mediated Neonatal ITP Maternal ITP Drug-induced Infection Viral eg cytomegalovirus, HIV, rubella Toxoplasmosis Post exchange transfusion Disorders of haemostasis DIC/hypthermia/hypoxia Maternal pre-eclampsia Rhesus isoimmunisation Type IIB von Willebrand s disease Liver disease Marrow infiltration

76 Idiopathic thrombocytopenic purpura (ITP), Synonyms: primary Immune P & autoimmune TP Definition: isolated thrombocytopenia normal bone marrow and no identifiable cause. Two distinct clinical syndromes acute condition in children chronic condition in adults.

77 Cause Immunoglobulin G (IgG) autoantibodies on the platelet surface Increased peripheral platelet destruction Low platelet count + absence of toxic exposure or a disease

78 Precipitating Factors Acute ITP (infection) and has a spontaneous resolution within 2 months. Chronic ITP (adults) persists longer than 6 months without a specific cause.

79 Sex Incidence : Acute ITP (children),m=fm. Age Peak age: 2-4 years. ~ 40% younger than 10 years. Children commonly than adults

80 Common signs, symptoms, and precipitating factors include the following Abrupt onset (childhood ITP) Purpura /Epistaxis Gingival bleeding Recent live virus immunization (childhood ITP) Recent viral illness (childhood ITP) Bruising tendency

81 Physical Skin-bruises/purpura Non-palpable petechiae, which mostly occur in dependent regions No sign of liver Disease No sign of DIC/vasculitis Check for sign neuro sign (IC bleeding) Spontaneous bleeding when platelet count is less than 20,000/mm

82 Differential Diagnoses DIC HIV Infection and AIDS Other Problems Pseudothrombocytopenia (PLT clumping in EDTA tube) Myelodysplasia Lymphoproliferative, autoimmune, or infectious ds Drug-induced Infection/sepsis/Acute leukemia Megaloblastic anemia Isoimmune neonatal purpura Transfusion Factitious Vasculitis (PAN)

83 Laboratory Studies CBC Isolated thrombocytopenia (key finding). Normal appearing platelets No giant platelets on peripheral smear (if present suggest congenital thrombocytopenia.) Normal WBC count and hemoglobin. Coagulation studies are normal Bleeding time is may be prolonged.

84 Haemophilia A & B Deficiencies of clotting factor VIII (haemophilia A) or factor IX (haemophilia B or Christmas disease) First day of life rare Severe bleeding usually occurs at, for example, circumcision or when mobility increases. Both disorders of coagulation affect 1 in of the population. They are X linked and clinically indistinguishable. The diagnosis may be suspected from the family history and can be confirmed antenatally.

85 Hemarthrosis

86 Purpuric Rashes Sepis (very sick) Enteroviral infections (well) Leukaemia Henoch-Scholein Purpura Child Abuse (family hx) Trauma & Vasomotor Straining

87 Investigation of Coagulopathy FBE/platelet count Blood Film aptt PT or INR Fibrinogen Further test requires specialist/haemotologist consult

88 Screening Test & Result Result Low platelet Isolated prolonged aptt Isolated/prolonged PT/INR Prolonged PT, aptt Low fibrinogen Causes -ITP -Congenital thromobocytopenic syndromes -Chemotherapy -Marrow replacement -Factor XI, IX, VIII deficiency Heparin, vwf deficiency Factor VII deficiency, Warfarin Vitamin K deficiency Liver ds, DIC (also low PLT)

89 If above screening tests are normal consider Factor XIII deficiency vwf deficiency Platelet function defect Capillary fragility syndrome If still in doubt trial of FFP+/- platelet

90 General measures Analgesic: avoid spirin Splint joints to relieve pain Avoid IM injections Avoid arterial punctures Consult with haematologist/specialist consultant if Haemophilia A/B

91 Neonatal Jaundice Markedly elevated Unconjugated Bil risk of damage to cells of basal ganglia and brainstem. Excess unconj Bilirubin release and decreased capacity of liver to conjugate Jaundice obvious at 80umol/l White child ---skin is visible to the naked eye Black child- sclerae should be examined as jaundice is more difficult to recognise. Jaundice first appears in the face and spreads to the periphery of the limbs The level is more than 270umol/l if the hands or feet are jaundiced.

92 Spread of jaundice in the skin.

93 Causes of jaundice Cause Onset Red cell incompatibility Within 24 hours of birth Physiological jaundice After 24 hours Septicaemia Usually after fourth day

94 Common causes hepatic immaturity, /physiological is common both in preterm and in full term babies. Temporary deficiency of glucuronyl transferase enzymes Full Term bab y : jaundice always appears after the first 24 hours of life and reaches a peak on the fourth or fifth day. In preterm infants: usually begins 48 hours after birth and may last up to two weeks.

95 Red cell incompatibility, jaundice appears within 24 hours of birth. Causes are; (a) incompatible Rhesus grouping, and (b) incompatible ABO grouping; the mother s blood is usually group O and the infant s group A or, less commonly, group B.

96 infective causes Septicaemia (jaundice after day 4/unwell child) UTI.

97 Breast milk jaundice Breastfed neonate /infant About 2.5% of infants who are breastfed the serum bilirubin rises to levels between 260 and 360umol/l Occurs 2 nd /3 rd week of life. Asymptomatic and appears well level remains constant for 3 or 4 weeks if continued BF & then fall to normal levels at 4 16 weeks. Abnormal progesterone has been shown in the milk of some of the mothers.

98 Rare causes Hypothyroidism (TSH/FT4) Galactosaemia, (+ve reducing substances but ve glucose test) G6PD deficiency (early jaundice or prolonged) Viral hepatitis (IU infection, dark, pale stool, conj hyperbil Atresia of the bile ducts (dark /pale stool, conj hyperbil) Usually last more than 10 days.

99 Indications for phototherapy and exchange transfusion.

100

101 Treatment Symptomatic prevent kernicterus Feeding Hydration Phototherapy (isomerisation) Exchange transfusion Phenobarb (enzyme induction) Identify and treat specific cause

102 Complication of Phototherapy Dermatitis Dehydration Diarrhoea

103 Leukaemia Acute lymphoblastic leukaemia (ALL) most common in the age range 2-10 years, with a peak at 3-4 years. Incidence decreases with increasing age, though there is a secondary rise after 40 years. In children it is the most common malignant disease and accounts for 85% of childhood leukaemia.

104 Cause? ALL: The bcr gene is found on chromosome 22 and abl gene on 9. This is known as the Philadelphia chromosome (named because it was discovered at hospital in Philadelphia). The Philadelphia chromosome is found in 25% of ALL patients (not AML). -poor prognosis

105 Presentation symptoms and signs commonly result from BM failure or, less commonly, organ infiltration. Anaemia (pallor, lethargy, and dyspnoea) Neutropenia (bacterial infections of the mouth, throat, skin, chest or perianal region. Thrombocytopenia (spontaneous bruising, menorrhagia, bleeding from venepuncture sites, gingival bleeding, or prolonged nose bleeds)

106 Bone pain (organ infiltration) Superficial lymphadenopathy, Abdominal distension (abdominal lymphadenopathy and hepatosplenomegaly) Respiratory distress (large mediastinal mass) Testicular enlargement, Meningeal syndrome.

107 Investigations FBE/FBC Anaemia (normochromic, normocytic) WBC count to g/l Neutropenia Presence of blast cells Thrombocytopenia Biochemical screening is particularly important if the leucocyte count is very high, when there may be evidence of renal impairment & hyperuricaemia

108 Chest X-ray: mediastinal mass (+ve 70% of patients) Bone X-rays. -lytic bone lesions BM Aspiration with or without trephination is hypercellular, with a predominance of immature (blast) cells. Immunophenotyping of the antigens present on blasts isolated (myeloid vs lymphoid origin)

109 Cytogenetics and molecular studies often detect abnormalities, prognostic information e.g,. Philadelphia chromosome (translocation 9 & 22) carries very poor prognosis Atraumatic LP with cerebrospinal fluid neurological symptoms - detect leukaemic cells in the cerebrospinal fluid, indicating involvement of the central nervous system.

110 Prognosis. Higher Risk Group Age: <1 year & >10 year old. WBC: High count Boys > girls Organ Spread: CSF/testicles) T-cell or mature B-cell (Burkitt) leukemia

111 Better prognosis with increased number of chromosomes (called hyperdiploidy). Philadelphia chromosome or translocation between 1 and 19, or 4 and 11 have a less favorable prognosis. Response to therapy: Children whose leukemia responds completely to therapy within 7 or 14 days of chemotherapy have a better outlook.

112 Management Specialist/Specialist Centres Supportive Care Transfusion Platelet/FFP/cryoprecipitate Antibiotics Chemotherapy INDUCTION Consolidation/Maintenance 3/more drugs Monitor and manage Complications Immediate/long term problems

113 References Paediatric Handbook, RCH, Melbourne 7 th Ed Emedicine.medscape.com ABC of clinical Haematology BMJ 2 nd Ed, 2003