PAEDIATRIC HAEMATOLOGY

Transcription

1 PAEDIATRIC HAEMATOLOGY AIMS National Scientific Meeting Sydney 2014 GILLIAN ROZENBERG

2 Lymphocytes in a 1 day old neonate

3 Lymphocyte in a 1 day old neonate

4 DEVELOPMENT OF HAEMOPOIESIS

5 RED CELL VALUES DURING GESTATION

6 RED CELL LIFESPAN IN DAYS TERM INFANT 90 PREMATURE INFANT ADULT 120

7 THE NEONATAL CELL MEMBRANE Premature Term Adult Infant Infant Discocyte 40% 43% 78% Bowl form 30% 40% 18% Poikilocyte 30% 17% 4%

8 UNDER 12 MONTHS OF AGE OVER 12 MONTHS OF AGE

9

10

11 FACTORS INFLUENCING HAEMATOLOGICAL VALUES AT BIRTH Gestational age of the infant Conduct of labour Treatment of the umbilical vessels Site of sampling

12 RED CELL REFERENCE RANGES IN INFANCY AND CHILDHOOD Age Hb (g/l) RCC (x /L) Hct (L/L) MCV (fl) MCH (pg) MCHC(g/L) RDW-SD (fl) RDW-CV (%) 0-1 d 1-7 d 1-2 w 2w - 3m 3-6 m 6m 2y 2-4 y 4-8 y 8-12 y

13 RED CELL REFERENCE RANGES IN INFANCY AND CHILDHOOD Age MCV (fl) MCH (pg) 0-1 d d w w - 3m m m 2y y y y

14 WHY THESE CHANGES IN THE MCV AND MCH? Rapid accumulation of iron by the foetus during gestation despite possible iron deficiency in the mother Changes in iron balance and rate of erythropoiesis occur in the first few days after birth. These changes coincide with oxygen supply to the lungs Hb, MCV and reticulocytes fall Released iron salvaged by reticuloendothelial system, increasing neonatal iron stores

15 WHY THESE CHANGES IN THE MCV AND MCH? Reduction in erythropoiesis continues for 6-8 weeks This period is followed by a reticulocyte response The Hb gradually increases to a value of 125 g/l Iron stored during this period provides for the first 6 months of life After this period, dietary iron is necessary to maintain a normal iron balance

16 SUMMARY OF THE RED CELL REFERENCE RANGES 0-3 months macrocytic / normochromic 3-6 months normocytic / normochromic - microcytic / hypochromic 6 months-5 years > 5 years microcytic / hypochromic normocytic / normochromic

17 Iron deficiency anaemia

18 RETICULOCYTE COUNTS GESTATIONAL AGE IN WEEKS RETICULOCYTES % / / / /-2.0 RETICULOCYTES % TERM 5.0+/ / / /-1.4

19 RETICULOCYTE COUNTS DURING THE FIRST 2 WEEKS OF LIFE RETICULO- CYTES % CORD BLOOD DAY 1 DAY DAY DAY

20 ANAEMIA IN THE NEONATE Haemorrhage Haemolysis Impaired red cell production

21 ANAEMIA IN THE NEONATE Haemorrhage Obstetric accident Occult haemorrhage prior to birth (a) Foeto maternal (b) Twin to twin

22 ANAEMIA IN THE NEONATE HAEMOLYSIS Immune Rh incompatibility ABO incompatibility Oxidant-induced haemolytic anaemia Infection Bacterial / Viral Microangiopathic Haemolytic Anaemia Secondary to: renal artery stenosis severe coarctation of the aorta

23 ANAEMIA IN THE NEONATE HAEMOLYSIS Hereditary Disorders of the Red Cell Membrane Hereditary spherocytosis Hereditary elliptocytosis Hereditary pyropoikilocytosis Hereditary stomatocytosis/se Asian ovalocytosis Red Cell Enzyme Deficiencies Glucose-6-phosphate dehydrogenase deficiency Pyruvate kinase deficiency

24 ANAEMIA IN THE NEONATE Impaired Red Cell Production Diamond Blackfan syndrome (pure red cell aplasia) Congenital sideroblastic anaemia Bone marrow replacement (e.g. neuroblastoma)

25 HAEMORRHAGE Occult haemorrhage prior to birth Twin to twin Twin to twin haemorrhage occurs in monozygotic multiple pregnancies where there is a single placenta. The anaemic twin may have a Hb level as low as 35 g/l. It is pale, weak and has cardiac failure The polycythaemic twin has a Hb level as high as 300 g/l. It develops the hyperviscosity syndrome

26 HAEMORRHAGE Occult haemorrhage prior to birth Twin to twin Should the twin to twin haemorrhage be a gradual one there will be a significant difference in the birth weight of the twins

27 Twin to twin transfusion - Hb 29 g/l

28 Twin to twin transfusion - Hb 260 g/l

29 CORD BLOOD During the third trimester of pregnancy red cell production progresses at a rate 3 to 5 times that of an adult This rapid turnover in red cell production results in fewer cell divisions hence the red cells are macrocytic with an MCV ranging in size from fl.

30 CORD BLOOD The number of nucleated red cells at term ranges from 1 to 24 per 100 white blood cells The reticulocyte count ranges from 3-7% The blood film is characteristically macrocytic with polychromasia and in some cases an occasional target cell, spherocyte, nucleated red cell and Howell Jolly body may be present

31 Cord blood

32 HAEMOLYSIS (IMMUNE) ABO haemolytic disease of the newborn ABO haemolytic disease of the newborn occurs most commonly in blood group O mothers and affects group A and B babies The chief clinical manifestation is jaundice within the first 24 hours of life The haemoglobin concentration is usually normal

33 HAEMOLYSIS (IMMUNE) ABO haemolytic disease of the newborn The blood film shows increased numbers of spherocytes which stand out against a background of normochromic round macrocytes. The degree of polychromasia may be increased The direct antiglobulin test (DAT) may be either negative or weakly positive

34 ABO haemolytic disease of the newborn

35 Hereditary spherocytosis (HS) - cord blood

36 HAEMOLYSIS (IMMUNE) Rh haemolytic disease of the newborn When anti-d antibody present in a sensitised Rh negative mother enters the foetal circulation, Rh positive foetal cells are destroyed giving rise to a haemolytic process known as Rh haemolytic disease of the newborn This haemolytic process is characterised by jaundice, a low Hb level (usually below 140 g/l) and a raised reticulocyte count (>7% and as high as 30 to 40%)

37 HAEMOLYSIS (IMMUNE) Rh haemolytic disease of the newborn There is an increase in the number of nucleated red blood cells (NRBC s). This increase may be several 100 NRBC s per 100 WBC s The direct antiglobulin test (DAT) is strongly positive Spherocytes are not usually a feature of this disease

38 Rh haemolytic disease of the newborn

39 ERYTHROBLASTOSIS FETALIS The following conditions can lead to erythroblastosis fetalis birth asphyxia respiratory distress syndrome pulmonary hypertension meconium aspiration The peripheral blood shows increased NRBC s and thrombocytopenia ( NRBC s /100 WBC s)

40 ERYTHROBLASTOSIS FETALIS The Hb and RCC are usually normal The reticulocyte count mildly elevated DAT negative A similar picture, together with thrombocytopenia, may be secondary to an intrauterine infection TORCH screen on infant and mother

41 ERYTHROBLASTOSIS FETALIS TORCH Toxoplasma, others, rubella, cytomegalovirus, herpes simplex This group of congenital infections, together with syphilis, can cause neonatal thrombocytopenia

42 Erythroblastosis fetalis

43 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary spherocytosis Spherocytes result from an intracorpuscular red cell membrane defect Deficiency of spectrin, ankyrin or band 3 protein leads to the uncoupling of the skeletal lipid bilayer resulting in membrane loss in the form of microvesicles This loss of surface area leads to the formation of spherocytes

44 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary spherocytosis Hereditary spherocytosis (HS) is characterised by red cells which lack an area of central pallor, have a smaller diameter than normal and are intensely haemoglobinised The MCV and MCH are within normal range The presence of spherocytes results in a raised MCHC (380 g/l)

45 Hereditary spherocytosis (HS) - cord blood

46 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary elliptocytosis Elliptocytes are oval biconcave discs that vary in shape from slightly oval to cylindrical. They have both a quantitative and qualitative abnormality in spectrin and protein 4.1, two major proteins comprising the membrane skeleton. Approximately 5% od red cells seen in normal blood films are elliptocytes but, in HE between 30% and 100% of red cells are elliptocytes. Elliptocytes are also a feature of iron deficiency but without the spectrin or protein 4.1 abnormality.

47 Hereditary elliptocytosis

48 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary pyropoikilocytosis (HPP) Very rare disorder presenting in the newborn characterised by the presence of extreme poikilocytosis with red cell budding, triangular fragments, spherocytes and elliptocytes. The MCV is significantly reduced at birth. Whereas normal red cells fragment at 49ᴼC the red cells in HPP fragment at 45-46ᴼC. Prolonged heating at 37ᴼC will also induce fragmentation.

49 Hereditary pyropoikilocytosis (newborn)

50 Hereditary pyropoikilocytosis (12 months old)

51 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary stomatocytosis There is a defect in the Na+ / K+ exchange pump in hereditary stomatocytosis There is an imbalance between the amount of Na+ entering the red cell and the amount of K+ exiting the red cell This leads to an increase in monovalent cation content causing the movement of water into the red cells. The red cells swell and are transformed from discocytes to bowl forms

52 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Hereditary stomatocytosis These bowl forms are known as stomatocytes and have an increased mean cell volume (MCV) Patients with hereditary stomatocytosis have haemolytic anaemia. They are jaundiced with a splenomegaly and often develop pigment gallstones later in life Splenectomy may diminish the rate of haemolysis in these patients

53 Hereditary stomatocytosis

54 HEREDITARY DISORDERS OF THE RED CELL MEMBRANE Southeast Asian stomato-ovalocytosis In Southeast Asian stomato-ovalocytosis there is increased ankyrin and decreased protein 3 mobility leading to the production of rigid red cells, oval in shape, often with double transverse slits. They have a normal MCV.

55 Southeast Asian stomato-ovalocytosis

56 HAEMOLYSIS (NON-IMMUNE) RED CELL ENZYME DEFICIENCIES Oxidant drug induced haemolytic anaemia The use of oxidant drugs can be easily recognized from the blood film, provided the patient has not had a splenectomy Oxidant drugs denature haemoglobin to produce Heinz bodies. These are rapidly removed or pitted out by the spleen, together with some red cell content, giving rise to bite cells Should the red cell membrane of the bite cell rejoin, a blister cell will result

57 HAEMOLYSIS (NON-IMMUNE) Oxidant drug induced haemolytic anaemia The red cells of premature and term neonates are susceptible to oxidants Prolonged exposure to naphthalene will induce a haemolytic anaemia in infants despite normal levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD)

58 Oxidant drug haemolysis - bite cells

59 Heinz bodies (post splenectomy)

60 RED CELL ENZYME DEFICIENCIES Glucose-6-phosphate dehydrogenase (G6PD) deficiency G6PD is the enzyme controlling the first step in a chain of reactions that constitute the pentose phosphate pathway Patients with G6PD deficiency are clinically and haematologically normal until subjected to an oxidative challenge either in the form of an oxidant drug or after ingestion of fava beans

61 RED CELL ENZYME DEFICIENCIES Glucose-6-phosphate dehydrogenase (G6PD) deficiency Either of these challenges induce an acute haemolytic anaemia. Within 6-24 hours the patient passes dark urine and the Hb level drops significantly The blood film shows marked numbers of bite and blister cells

62 Oxidant haemolysis - bite/blister cells post fava beans

63 RED CELL ENZYME DEFICIENCIES Pyruvate kinase (Pk) deficiency PK is an erythrocyte glycolytic enzyme involved in the Embden-Meyerhof pathway of metabolism Deficiency of this enzyme is associated with chronic haemolysis and thus anaemia, jaundice and splenomegaly In some cases the anaemia may be profound, presenting in early infancy and requiring frequent blood transfusions

64 RED CELL ENZYME DEFICIENCIES Pyruvate kinase (PK) deficiency In other cases, the anaemia may be so mild that the deficiency may not be discovered until late childhood or even adulthood The blood film shows a red cell picture consistent with that of a haemolytic anaemia with an occasional prickle cell. The number of prickle cells is strikingly increased following splenectomy

65 Pyruvate kinase deficiency - prickle cell

66 Pyruvate kinase deficiency (post splenectomy)

67 MICROANGIOPATHIC HAEMOLYTIC ANAEMIA In the neonate one should consider: Renal artery stenosis Severe coarctation of the aorta However these conditions are rare

68 MICROANGIOPATHIC HAEMOLYTIC ANAEMIA Haemolytic uraemic syndrome (HUS) HUS occurs most commonly in infancy and early childhood and is initiated by infection with the Escherichia coli bacterium, strain 0157 This bacterium produces a Shiga toxin which is a verocytotoxin. This toxin enters the circulation via the gastric mucosa; localises in the kidney, especially the endothelium lining the glomeruli of the kidney, inducing endothelial cell injury. The coagulation cascade is activated and microthrombi are formed.

69 MICROANGIOPATHIC HAEMOLYTIC ANAEMIA Haemolytic uraemic syndrome This process leads to sclerosed, narrow vessels resulting in severe glomerulonephritis and acute renal failure. The blood film in HUS shows the presence of schistocytes, in some cases spherocytes, a reticulocytosis and a marked thrombocytopenia

70 Haemolytic uraemic syndrome - schistocytes

71 Heart valve haemolysis - schistocytes

72 IMPAIRED RED CELL PRODUCTION Diamond Blackfan anaemia (DBA) DBA is a congenital pure red cell aplasia diagnosed in children usually less than one year old Craniofacial abnormalities are associated with DBA. These include a flat nasal bridge, wide set eyes and a thick upper lip as well as deafness and short statue

73 IMPAIRED RED CELL PRODUCTION Diamond Blackfan anaemia The Hb levels at birth have a mean value of 70 g/l and can be as low as 26 g/l The red cells are invariably macrocytic A reticulocytopenia is present The bone marrow shows erythroid hypoplasia The myeloid cells and megakaryocytes are normal in number while the lymphocytes are increased

74 Diamond Blackfan anaemia

75 IMPAIRED RED CELL PRODUCTION Congenital sideroblastic anaemia Presents in early childhood mostly in males Characterised by a dimorphic blood picture The bone marrow is hypercellular with erythroid hyperplasia Some of the erythroblasts show microerythroblastic maturation as well as defective haemoglobinisation with ragged and vacuolated cytoplasm

76 IMPAIRED RED CELL PRODUCTION Congenital sideroblastic anaemia The Perl s Prussian blue stain shows the presence of ringed sideroblasts These ringed sideroblasts represent the presence of perinuclear mitochondria containing large deposits of inorganic iron Haem production is impaired and there is ineffective erythropoiesis Iron stores are increased

77 Congenital sideroblastic anaemia

78 Perl s Prussian blue stain

79 IMPAIRED RED CELL PRODUCTION Bone marrow replacement (neuroblastoma) A tumour of developing sympathetic nervous tissue; an embryonic tumour found mainly in the adrenal medulla and the paraspinal sympathetic ganglia In 50% of cases infiltrates the bone marrow Can occur in utero

80 NEUROBLASTOMA IN THE BONE MARROW

81 NEUROBLASTOMA IN THE BONE MARROW TREPHINE

82 LEUCOCYTE COUNTS AND DIFFERENTIAL IN INFANCY AND CHILDHOOD AGE WCC(x10 9 /L) N(%) L(%) M(%) E(%) B(%) 0-1 d d w w 3m m m 2y y y y AGE N(A) x10 9 /L L(A) x10 9 /L M(A) x10 9 /L E(A) x10 9 /L B(A) x10 9 /L NRBC 0-1 d d w w 3m m m 2y y y y

83 LEUCOCYTE COUNTS AND DIFFERENTIAL IN INFANCY AND CHILDHOOD AGE N(A) x10 9 /L L(A) x10 9 /L 0-1 d d w w 3m m m 2y y y y

84 LEUCOCYTE DISORDERS IN THE NEONATE Congenital Leukaemia Down syndrome Neutropenia Neonatal neutropenia associated with maternal neutropenia Infantile agranulocytosis Chronic benign granulocytopenia Cyclic neutropenia Lymphopenia

85 LEUCOCYTE DISORDERS IN THE NEONATE Infection Bacterial - NEC Viral Leukaemoid reaction G-CSF GM-CSF

86 LEUCOCYTE DISORDERS IN THE NEONATE Congenital Anomalies of the Leucocytes Pelger-Huët anomaly May-Hegglin anomaly Chédiak-Higashi syndrome Mucosaccharidosis Hurler syndrome (Gasser cells)

87 SEPSIS IN THE NEONATE Diagnosis of neonatal sepsis is one of the most difficult tasks in clinical medicine Septicaemia in the neonate has a high mortality rate despite the use of antibiotics Importance of counting every myeloid precursor, including band forms A ratio of band forms to total neutrophils of 0.2 or higher is suggestive of sepsis

88 SEPSIS IN THE NEONATE BAND FORM A band form has no nuclear segmentation The width of the nucleus at any constriction point is not less than one-third of the width at its widest point

89 SEPSIS IN THE NEONATE HYPER GRANULATED NEUTROPHILS (TOXIC GRANULATION) Neutrophil granulation in isolation is not specific for sepsis and may be seen in other conditions: Alder granulation Chédiak-Higashi anomaly Cytokine therapy (G-CSF) Kawasaki disease

90 Sepsis hyper granulated neutrophils (toxic granulation) / vacuolation

91 KAWASAKI DISEASE Kawasaki disease, first described by Kawasaki in 1974, is an acute febrile vasculitis affecting children from 2 months to 5 or more years of age Characterised by a no exudative conjunctivitis, erythematous lips and a strawberry tongue, erythematous and oedematous hands and feet, an erythematous truncal rash and a desquamating perineal rash

92 KAWASAKI DISEASE Blood film: Hypochromic microcytic / normochromic microcytic anaemia Elevated ESR Absolute neutrophilia Neutrophil granulation and vacuolation Neutrophil cytoplasmic swelling Thrombocytosis

93 KAWASAKI DISEASE Treatment: Intravenous immunoglobulin or intragam 2g/Kg body weight If not recognised and treated immediately, Kawasaki disease may lead to coronary aneurysms in early adulthood

94 Non-exudative conjunctivitis

95 Swollen red lips and tongue

96 Oedematous red hands

97 Oedematous red toes

98 Red truncal rash

99 Desquamating red rash

100 Kawasaki disease

101 Kawasaki Disease

102 LEUKAEMOID REACTION Cytokine (G-CSF) induced leukaemoid reaction A leukaemoid reaction is one in which there is an increase in the myeloid line resulting in a blood picture resembling leukaemia There is an increase in immature granulocytes: myeloblasts, promyelocytes, myelocytes, metamyelocytes, band forms and mature neutrophils

103 LEUKAEMOID REACTION Cytokine (G-CSF) induced leukaemoid reaction G-CSF is one such cytokine which produces a leukaemoid reaction Its use is associated with increased primary granulation in the myeloid line It is important to recognise that the changes associated with cytokine therapy are also associated with septicaemia

104 Leukaemoid reaction - G-CSF therapy

105 BACTERIAL INFECTION Bordetella pertussis The persistent lymphocytosis present in the blood of a patient with Bordetella pertussis, is due to a lymphocyte promoting factor produced by the Bordetella pertussis This factor inhibits lymphocyte migration from the blood to the lymphoid tissues

106 BACTERIAL INFECTION Bordetella pertussis Bordetella pertussis (whooping cough) is a highly infectious disease occurring primarily in infants younger than 2 years of age Infection results from inhaling droplets contaminated with Bordetella pertussis The blood film shows a marked increase in the number of T lymphocytes The total leucocyte count ranges from 15 to 50 x 10 9 /L with 70 to 90% lymphocytes

107 Bordetella pertussis

108 JMML - MYELODYSPLASTIC MYELOPROLIFERATIVE NEOPLASM LABORATORY FEATURES JMML is a clonal disease characterised by a WBC count < 100 x 10 9 /L with a left shift in the myeloid line Monocytosis of >1 x 10 9 /L in the PB and < 20% blasts in the PB and BM Hb F is raised for the age of the patient Philadelphia chromosome negative

109 MYELODYSPLASTIC MYELOPROLIFERATIVE NEOPLASM Juvenile myelomonocytic leukaemia (JMML) CLINICAL FEATURES JMML occurs mainly in children less than 3 years of age but can occur in children as old as 14 years Most common in males Often preceded by an eczematous rash which when biopsied, shows a leukaemic infiltrate

110 Juvenile myelomonocytic leukaemia (JMML) PB

111 Juvenile myelomonocytic leukaemia (JMML) BM

112 MYELOID PROLIFERATIONS RELATED TO DOWN SYNDROME Transient abnormal myelopoiesis (TAM) Transient abnormal myelopoiesis (TAM) may occur in the neonatal period It is often associated with Down syndrome or trisomy 21 It is characterised by an uncontrolled proliferation of blasts that spontaneously regress within weeks or months It is associated with a hepatosplenomegaly The Hb is usually normal while the platelets are low

113 MYELOID PROLIFERATIONS RELATED TO DOWN SYNDROME Transient abnormal myelopoiesis (TAM) TAM may be confused with congenital leukaemia in the initial stages until spontaneous remission occurs within the first 3 months of life 25% of cases of TAM will go on to develop acute megakaryoblastic leukaemia by the age of 3 years In about 20% of cases the blasts will persist and a true congenital leukaemia develops

114 Transient Abnormal Myelopoiesis (TAM) PB

115 Transient Abnormal Myelopoiesis-TAM (PB)

116 VIRAL INFECTION Infectious mononucleosis Infectious mononucleosis (IM) is an infection caused by the Epstein-Barr virus (EBV) occurring in teenagers and young adults The blood film shows a proliferation of viral infected B lymphocytes with a population of reactive T lymphocytes The reactive T lymphocytes have round or irregularly shaped nuclei with abundant flowing basophilic cytoplasm

117 VIRAL INFECTION Infectious mononucleosis Thrombocytopenia is a common feature in IM IM is heterophile antibody positive Other viral induced lymphoproliferative disorders are heterophile antibody negative Difficulty may be experienced in diagnosing IM in children under 2 years of age as their immune system is still not developed A definitive diagnosis using viral serology must be made in such cases

118 Infectious mononucleosis

119 B LYMPHOBLASTIC LEUKAEMIA / LYMPHOMA, not otherwise specified B lymphoblastic leukaemia is the most common leukaemia occurring in children under 6 years of age The lymphoblasts range from those with a high N/C ratio, fine to clumped chromatin pattern and inconspicuous nucleoli to those that are heterogeneous in size and have chromatin pattern varying from finely dispersed to coarsely condensed with prominent nucleoli

120 B lymphoblastic leukaemia (PB)

121 CONGENITAL ANOMALIES OF WHITE CELLS STORAGE DISORDERS IN THE NEONATE Sialic acid storage disease A rare autosomal recessive neurodegenerative disorder resulting from a block in sialic acid release from cell lysosomes The accumulation of sialic acid in many cells, including lymphocytes, leads to cytoplasmic vacuolation

122 CONGENITAL ANOMALIES OF WHITE CELLS STORAGE DISORDERS IN THE NEONATE Sialic acid storage disease Diagnosed by the presence of increased amounts of sialic acid in blood, urine and lymphocytes There are two forms of the disease: The aggressive form, infantile sialic acid storage disease (ISSD) and the less aggressive form known as SALLA

123 CONGENITAL ANOMALIES OF WHITE CELLS STORAGE DISORDERS IN THE NEONATE Sialic acid storage disease ISSD is characterised by coarse facial features, lack of skin pigmentation, hepatosplenomegaly and anaemia, progressing to fluid retention, ascites, heart failure and early death SALLA disease has 2 additional features, mental retardation and cerebella ataxia Features of SALLA stop progressing after early childhood

124 Sialic acid storage disease

125 CONGENITAL ANOMALIES OF WHITE CELLS STORAGE DISORDERS IN THE NEONATE Hurler syndrome Hurler syndrome, a mucopolysaccharide storage disorder, is characterised by the presence of lymphocytes whose cytoplasm contains clear vacuoles filled with coarse metachromatic granules of mucopolysaccharide These lymphocytes have been described by Gasser and are known as Gasser lymphocytes

126 Hurler syndrome (Gasser cell)

127 CONGENITAL ANOMALIES OF WHITE CELLS May Hegglin anomaly May Hegglin is a congenital anomaly characterised by the presence of basophilic inclusions or ribonucleic acid (RNA) within the cytoplasm of neutrophils These inclusions resemble Döhle bodies Thrombocytopenia with giant platelets occurs in approximately one third of patients with May Hegglin anomaly

128 May Hegglin anomaly

129 CONGENITAL ANOMALIES OF WHITE CELLS Chédiak-Higashi anomaly Chédiak-Higashi anomaly is a congenital anomaly characterised by the presence of giant granules in the cytoplasm of neutrophils and lymphocytes These granules result from the fusion of primary and secondary granules Chédiak-Higashi granules are not attracted to the phagocytic vacuole during infection, hence bactericidal activity is impaired

130 Chédiak-Higashi anomaly

131 PLATELET REFERENCE RANGES IN INFANCY AND CHILDHOOD AGE PLT(x 10 9 /L) PDW(fL) MPV(fL) 0-1 d d w w 3m m m 2y y y y

132 THROMBOCYTOPENIA IN THE NEONATE Destructive Thrombocytopenia Impaired or Ineffective Platelet Production

133 THROMBOCYTOPENIA IN THE NEONATE Destructive Thrombocytopenia Immune Idiopathic thrombocytopenic purpura Drug-induced thrombocytopenia Infection-induced thrombocytopenia Post-transfusion purpura Auto-immune or lymphoproliferative disorders Neonatal immune thrombocytopenia Allergy and anaphylaxis Post-transplant thrombocytopenia

134 THROMBOCYTOPENIA IN THE NEONATE Destructive Thrombocytopenia Non-Immune Chronic microangiopathic haemolytic anaemia and thrombocytopenia Haemolytic uraemic syndrome Thrombotic thrombocytopenic purpura Congenital or acquired heart disease

135 THROMBOCYTOPENIA IN THE NEONATE Destructive Thrombocytopenia Specific to the Neonate Phototherapy Persistent aspiration syndromes Persistent pulmonary hypertension Rhesus allo-immunisation Post-exchange transfusion

136 THROMBOCYTOPENIA IN THE NEONATE Impaired or Ineffective Platelet Production Primary Haematological Processes TAR syndrome Other congenital thrombocytopenias with megakaryocytic hypoplasia Fanconi anaemia Bernard-Soulier syndrome May-Hegglin anomaly Wiskott-Aldrich syndrome Mediterranean thrombocytopenia

137 THROMBOCYTOPENIA IN THE NEONATE Impaired or Ineffective Thrombocytopenia Acquired Disorders Aplastic anaemia Bone marrow infiltration Drug or radiation-induced

138 THROMBOCYTOPENIA IN THE NEONATE Impaired or Ineffective Platelet Production Sequestration Hypersplenism

139 DESTRUCTIVE THROMBOCYTOPENIA Idiopathic thrombocytopenic purpura (ITP) One of the most frequently seen examples of destructive thrombocytopenia is ITP A typical history is bruising and petechiae appearing suddenly in a child who is otherwise in excellent health The peak age for the presentation of ITP is 2 to 4 years

140 DESTRUCTIVE THROMBOCYTOPENIA Idiopathic thrombocytopenic purpura (ITP) In childhood ITP, males and females are affected with equal frequency, in contrast to adult ITP, in which females predominate by a 3:1 ratio Often there is a history of a viral illness prior to presentation In the majority of children, ITP is an acute self limiting disease, resolving within 6 months whether or not therapy is given

141 DESTRUCTIVE THROMBOCYTOPENIA Idiopathic thrombocytopenic purpura (ITP) One of two medical therapeutic options are chosen - corticosteroids or intravenous immunoglobulin (IgG) Either will increase the platelet count in the majority of patients and presumably decrease the risk of serious haemorrhage

142 Idiopathic thrombocytopenic purpura (ITP)

143 THROMBOCYTOPENIA IN THE NEONATE BERNARD-SOULIER SYNDROME (BSS) BSS is inherited as an autosomal dominant disorder Characterised by thrombocytopenia (usually x 10 9 /L platelets) with giant forms, some the size of small lymphocytes

144 THROMBOCYTOPENIA IN THE NEONATE BERNARD-SOULIER SYNDROME (BSS) The platelets demonstrate both qualitative and quantitative defects in the glycoprotein 1b-V-1X complex within the platelet membrane BSS platelets demonstrate normal aggregation in the presence of adenosine diphosphate (ADP), epinephrine (adrenalin), collagen and arachidonic acid, but do not aggregate in the presence of ristocetin

145 Bernard Soulier syndrome

146 THROMBOCYTOPENIA IN THE NEONATE WISKOTT-ALDRICH SYNDROME (WAS) WAS is an x-linked recessive disorder characterised by thrombocytopenia with small platelets that have a slightly reduced survival time Thrombopoiesis is ineffective while megakaryocyte numbers range from normal to high

147 THROMBOCYTOPENIA IN THE NEONATE WISKOTT-ALDRICH SYNDROME (WAS) Immunodeficiency is a feature of WAS An inability to produce antibodies makes children with WAS susceptible to both bacterial and viral infections (eg. herpes and warts) Eczema is also commonly seen DAT positive haemolytic anaemia may also occur

148 Wiskott-Aldrich syndrome

149 THROMBOCYTOSIS IN THE NEONATE Primary Thrombocytosis Myeloproliferative syndromes Secondary polycythaemia Idiopathic sideroblastic anaemia

150 THROMBOCYTOSIS IN THE NEONATE Secondary or Reactive Thrombocytosis Inflammatory diseases Acute infections Acute rheumatic fever Juvenile rheumatoid arthritis Ulcerative colitis Regional enteritis

151 THROMBOCYTOSIS IN THE NEONATE Haematological Disorders Iron Deficiency Vitamin E deficiency Chronic haemolytic anaemia Haemoglobinopathies

152 THROMBOCYTOSIS IN THE NEONATE Neoplasms Lymphomas Neuroblastoma Other childhood solid tumours

153 THROMBOCYTOSIS Secondary or reactive thrombocytosis By far the most common cause of a high platelet count in children is a reactive thrombocytosis. This may be due to inflammatory disease, infection, a rheumatoid condition or Kawasaki disease In these situations, the thrombocytosis usually parallels the degree of activity of the underlying condition

154 Reactive thrombocytosis