Paediatric haematology

Published on 03/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

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Paediatric haematology

Many of the blood disorders encountered in children have been discussed in the preceding pages. For instance, acute lymphoblastic leukaemia is the most common leukaemia of childhood, haemophilia is usually diagnosed in infancy and the haemoglobinopathies are a significant cause of ill health in children worldwide. Chronic and severe diseases of the blood pose particular problems in childhood and usually are best managed by a paediatrician with a special interest in haematology or in a combined paediatric/haematology clinic. The child’s growth and development, and educational needs often require special attention. In this section we discuss some haematological disorders encountered in paediatric practice which are not addressed elsewhere.

Normal values

It is important to appreciate that the normal ranges for many haematological tests vary with age. Table 45.1 illustrates reference values for the total white cell count (WCC) and the differential count in children. More detailed listings of normal ranges of laboratory tests in childhood can be found in specialised paediatric haematology texts.

Table 45.1

Normal white cell counts in children (× 10⁹/L)

Note: Normal haemoglobin values in childhood are shown on page 22, Table 1. The normal platelet count is the same in children and adults (150–400 × 10⁹/L).

Neonatal disorders

Haemolytic disease of the newborn

Haemolytic disease of the newborn (HDN) is a disease of the fetus and newborn child. The haemolysis is caused by maternal IgG antibodies traversing the placenta and attaching to fetal red cells which are destroyed in the child’s reticuloendothelial system. The antibodies are directed against a fetal red cell antigen not shared by the mother. Incompatibility for one of a large number of different red cell blood group systems can cause HDN but most cases of clinically significant disease affect a Rhesus (Rh)D-positive child where the mother is RhD negative. Sensitisation of the mother (i.e. the formation of anti-D) occurs following the haemorrhage of fetal red cells into the maternal circulation. This usually occurs at parturition following a normal pregnancy but may also arise earlier in pregnancy or following abortion. ABO incompatibility between mother and fetus gives some protection against sensitisation to RhD as fetal red cells are quickly destroyed by the mother’s naturally occurring anti-A or anti-B antibodies. Unfortunately, in most cases baby and mother are ABO compatible. With the considerable success of prophylaxis against HDN due to RhD incompatibility (see below), the most common cause of the disorder is the formation of immune antibodies against ABO; most cases are associated with only mild haemolysis.

Diagnosis

Severe HDN can result in intrauterine death. In the newborn child the presentation is entirely dependent on the degree of haemolysis but common features include anaemia, jaundice, oedema and hepatosplenomegaly. High levels of circulating unconjugated bilirubin may lead to high frequency deafness or deposition in the basal ganglia with spasticity and other neurological symptoms and signs (‘kernicterus’). Further investigation of the anaemia reveals features typical of haemolysis (Fig 45.1) with a positive direct antiglobulin test (DAT). In HDN due to RhD incompatibility the baby is RhD positive and the mother RhD negative with a high level of anti-D.

Fig 45.1 Peripheral blood film in a newborn child with severe HDN.
Note the numerous nucleated red cells and polychromasia.

Management

Management of HDN is complex, requiring close liaison between the haematology laboratory and obstetrician. In RhD alloimmunisation, if maternal anti-D levels are high and paternal testing indicates RhD heterozygosity, the fetal Rh genotype can be determined non-invasively by applying PCR technology to a maternal blood sample. Another advance is velocimetry of the fetal middle cerebral artery during an affected pregnancy. High peak systolic velocities predict severe fetal anaemia and allow the selective use of more invasive techniques such as fetal blood sampling and intrauterine transfusion. Newborns may experience ongoing anaemia and require exchange transfusion. Later anaemia may respond to erythropoietin therapy. With optimal management, a healthy child is the outcome in more than 90% of cases.

RhD prophylaxis in RhD-negative mothers

The breakthrough in the prevention of HDN has been the introduction of prophylaxis (Fig 45.2). A dose of Rh anti-D immunoglobulin (Ig) is given to all RhD-negative mothers who deliver a RhD-positive infant. A larger than average feto-maternal haemorrhage necessitates a greater dose of anti-D Ig. It is most likely that anti-D administration prevents HDN by a negative modulation of the primary immune response rather than by simple removal of fetal RhD-positive cells. General recommendations for Rh prophylaxis are shown in Table 45.2. As some women undoubtedly become sensitised earlier in a normal pregnancy, routine antenatal prophylaxis is widely recommended.

Table 45.2

Recommendations for Rh prophylaxis ¹

Rh prophylaxis after delivery

Anti-D (usually 500 IU) is given within 72 hours in RhD-negative mothers where the infant is RhD positive (or group undetermined). If there is a large feto-maternal haemorrhage (assessed in a Kleihauer test) additional anti-D is given

Rh prophylaxis and abortions

In RhD-negative mothers anti-D is given after all therapeutic abortions and after spontaneous or threatened abortions later than 12–13 weeks’ gestation and in selected cases of threatened abortion before 12 weeks (usual dose 250 IU before 20 weeks and 500 IU after 20 weeks)

Rh prophylaxis during pregnancy

Anti-D is given after possible sensitising events in RhD-negative women. These include: amniocentesis, chorionic villus sampling, abdominal trauma, external cephalic version, antepartum haemorrhage, ectopic pregnancy (usual dose of anti-D is 250 IU before 20 weeks and 500 IU after 20 weeks). Anti-D (500 IU) should be given to non-sensitised RhD-negative mothers at 28 and 34 weeks

¹ United Kingdom guidelines.

Fig 45.2 Perinatal deaths/1000 births caused by HDN. (From Derrick Tovey, LA 1992 Haemolytic disease of the newborn and its prevention. In: Contreras, M (ed) ABC of Transfusion. BMJ Publishing.)

Anaemia of prematurity

The haemoglobin concentration falls after birth in all babies but in premature infants it falls faster and to a lower level. At 1–3 months of age haemoglobin concentrations of less than 70 g/L are common and in babies born at less than 32 weeks gestation this anaemia is often associated with inadequate adaptive responses including tachycardia, tachypnoea and apnoeic attacks. The anaemia is due in part to shortened red cell lifespan and the effects of rapid growth but the fundamental problem appears to be a poor erythropoietin response. Erythropoietin levels are highest in premature infants with the most severe anaemia and hypoxia but even in these cases levels are inadequate compared to those achieved in anaemic adults. Recombinant erythropoietin is of benefit in some infants.

Polycythaemia in the neonate

Polycythaemia in the neonate is most simply defined as a packed cell volume (PCV) exceeding 0.65. Causes include placental transfusion (e.g. delayed clamping of the cord), intrauterine hypoxia, endocrine disorders (e.g. maternal diabetes) and genetic disorders (e.g. trisomy 21). Polycythaemia is often well tolerated but if severe it may cause hyperviscosity with congestive heart failure, respiratory distress, neurological disturbances and even gangrene. Partial exchange transfusion using a crystalloid solution to reduce the haematocrit is indicated where a high PCV is associated with symptoms and signs of hyperviscosity.

Thrombocytopenia in the neonate

Some causes of thrombocytopenia in neonates are listed in Table 45.3. In practice the major divide is between seriously ill infants where the low platelet count is caused by disseminated intravascular coagulation (DIC), and relatively well infants where thrombocytopenia is most often of immune aetiology or occurs secondary to a specific inherited syndrome. Immune thrombocytopenia (ITP) may be seen in infants born to mothers with ITP where there is passive transfer of IgG across the placenta. Alloimmune thrombocytopenia arises where the healthy mother becomes sensitised against a fetal platelet antigen in a manner analogous to HDN; the platelet antigen HPA-1a is most commonly implicated.