Recommendation:
If a child has mucous membrane bleeding and more extensive cutaneous symptoms, high dose prednisolone 4 mg / kg / d is effective (Grade A recommendation, Level Ib evidence). It can be given as a very short course (maximum 4 d). There are no direct comparisons of low dose (1–2 mg / kg / d) with high dose therapy. If lower doses of 1–2 mg / kg / d are used the treatment should be given for no longer than 14 days, irrespective of response.
Intravenous immunoglobulin
Intravenous immunoglobulin is effective in raising the platelet count in more than 80% of children, and does so more rapidly than steroids or no therapy (Blanchette et al, 1994) (Level 1b evidence). It is expensive and invasive, and should be reserved for emergency treatment of patients who do not remit or respond to steroids and who have active bleeding. It is an appropriate treatment to enable essential surgery or dental extractions. It should not be used to raise the platelet count in children with cutaneous symptoms alone. IVIg is a pooled blood product, the risks of which must be explained to patients. It has signi?cant side effects, noted in 75% of children treated in a recent trial (Blanchette et al, 1993). Severe headache can be troublesome (Kattamis et al, 1997). In addition, IVIg has transmitted hepatitis C, a life-threatening infection (Duhem et al, 1994). Its use in children with trivial symptoms is not justified.
Dose regimen. The traditional dose is 0.4 g/ kg daily for 5 d. This has now been superseded by short course high dose treatment either with a single dose of 0.8 g / kg or 1 g / kg given on 1 or 2 d (Blanchette et al, 1994; Tarantino et al, 1999). These larger doses may be associated with a higher risk of side effects. Another small, randomized multicentre study demonstrated lower doses of 250, 400 or 500 mg / kg / d for 2 d to be effective (count increasing by more than 30×109/ l) in 16 / 17 (94%) children aged 5–12 years (Warrier et al, 1997). The product chosen should be one with at least two viral inactivation steps included in the manufacturing process.
Recommendation:
IVIg can raise the platelet count rapidly, but should be reserved for emergency treatment of serious bleeding symptoms or in children undergoing procedures likely to induce blood loss. It is effective given as a single dose of 0.8 g /kg (Evidence level Ib, Grade A recommendation). Lower doses are also effective, and fewer side effects are seen, in younger children.
Other therapies
Anti-D immunoglobulin. This is less expensive than IVIg and can be given to Rh (D) positive individuals as a short infusion, and is therefore amenable to outpatient therapy. It is effective in children (Scaradavou et al, 1997), but the mechanism of action is not fully understood. Like IVIg, anti-D has the disadvantage of being a pooled blood product, but produces a rise in platelet count as rapidly as IVIg when given at suf?cient dosage (45–50 lg / kg) (Tarantino et al, 1999). Some degree of haemolysis is quite commonly seen, which can occasionally be severe and is associated with renal failure (Gaines, 2000). Lower dose treatment is less effective at raising the platelet count than IVIg (Blanchette et al, 1994).
Other treatments
As with adult ITP, a variety of other drugs have been tried in patients with persistent thrombocytopenia and bleeding. There is insuf?cient information concerning their use in children to make specific recommendations concerning what should be used or in which order. Cytotoxic drugs should be used with extreme caution in children, with appropriate consideration given to infertility and carcinogenesis.
Use of blood products – platelet transfusions
Life-threatening haemorrhage is the only indication for platelet transfusion in ITP, a destructive platelet disorder where transfusions of normal doses are unlikely to be effective. National surveys have demonstrated that platelet transfusions are sometimes given for simple thrombocytopenia. This is never justified. In a life-threatening situation (such as the rare ICH) larger than normal doses are required with monitoring of the increment as a guide, and other modalities such as high dose IV steroids and IVIg should be given at the same time to maximise the chances of raising the count and stopping the haemorrhage.
Recommendation:
Platelet transfusions should only be given for ICH or other life-threatening bleeding, and then in much larger doses than for marrow failure. At the same time, immunomodulatory treatment should be given with high dose intravenous steroids or IVIg (Grade C recommendation).
Chronic ITP in childhood
Most children with ITP will remit within 6 months. The management of children with continuing thrombocytopenia is essentially the same as for acute ITP. Many children settle with an adequate platelet count (i.e. more than 20×109/ l) and have no symptoms unless injured. In children under 10 years of age at diagnosis spontaneous remission is likely to occur eventually; expectant management can continue. Children more than 10 years of age at diagnosis, and in particular adolescent females, are more likely to sustain a chronic course and management considerations are much as for adults. Most children need no specific therapy to raise the count unless injured or requiring surgery or dental extraction. Particular problems may arise for girls at the onset of menstruation. Children and parents should not forget the vulnerability to excessive bleeding following serious accidents and it is advisable for the family to carry a card or letter with details of the disorder in case of emergency. A medical bracelet or pendant may be helpful.
Children with counts persistently below 10×109/ l are likely to have some symptoms, e.g. easy bruising or odd petechiae. Such children have been described as having chronic severe ITP (CSITP), are very rare (estimated annual incidence of perhaps 1 in 2 500 000; Lilleyman, 1999) and are the most difficult to manage (Lilleyman, 2000). There is a strong case for these children to be referred to paediatric haematologists with a special interest. Occasionally, girls carry ITP into adulthood, but it tends to attenuate over time (anecdotal reports). There are no data on boys with persistent ITP beyond their teens.
The risk of serious bleeding is a function of the duration of time with a low count and has been estimated at 0.5% at 12 months in those with a count less than 20×109/ l (Lilleyman, 1999). There is insufficient evidence in the literature to determine the best course of management for these patients (George et al, 1996; Lilleyman, 2000). Treatment must be tailored to the child and situation, based on three criteria: the therapy should be effective, it should not carry more risk than the untreated condition, and it should make the child feel better (George et al, 1996; Lilleyman, 2000).
A significant group of children with ITP have counts of 10–30×109/ l, and although they have no serious bleeding, are nevertheless troubled by purpura. Children, particularly once at secondary school, become very conscious of their appearance and need sympathetic support. Lifestyle issues and restrictions on sporting activities become more important and should be taken into account in considering therapy. Intermittent treatment with IVIg can be given to cover activity holidays after appropriate discussion of the risks. However, it should be noted that this might cause additional problems with insurance cover when a child has been in hospital within 6 months of going on holiday. There is no evidence that air travel predisposes to bleeding in patients with ITP; there is no indication to treat the count prior to holidays other than to cover activities. Parents should always declare the illness to their insurance company before travelling in case treatment is required while on holiday.
Bleeding complications must be managed according to severity and circumstances; there is no straightforward strategy for these young people. Splenectomy is often considered, but it is ineffective in around 25% of cases, and with longer follow-up it is clear that the relapse rate is high, although often the platelet count runs at a more acceptable level with fewer symptoms.
Recommendations:
1. Children with chronic ITP usually do not need active therapy but should be followed up regularly and reminded to report to hospital after injuries. They should have a designated contact person and number.
2. Children with chronic severe ITP should be referred to a paediatric haematologist for management and long term follow-up.
Splenectomy
Splenectomy is rarely indicated in children with ITP. Longterm follow-up demonstrates that spontaneous remissions continue to occur at least up to 15 years from diagnosis (Reid, 1995), so the persistence of a low count beyond 6 or 12 months is therefore not on its own an indication for surgery. Given that the risk of dying from ITP in childhood is extremely low (less than 1 in 500), that the mortality associated with splenectomy is 1.4 (Najean et al, 1997) to 2.7% (Eraklis & Filler, 1972) and that the risk of overwhelming sepsis probably persists for life, splenectomy is only justi?ed in exceptional circumstances (Eden & Lilleyman, 1992). Severe lifestyle restrictions, crippling menorrhagia or life threatening haemorrhage may give good reason for the procedure, but only 70–75% will respond (George et al, 1996), and full precautions against sepsis should be undertaken (BCSH, 1996).
Recommendation:
Splenectomy is rarely indicated in childhood ITP. It is occasionally justi?ed for life-threatening bleeding and for children with chronic unremitting and severe ITP whose disease has been present for more than 12–24 months with demonstrable impairment of their quality of life, but these children are rare, and should be referred to a specialist paediatric haematologist for individual consideration (Grade C recommendation).
