Acute Idiopathic Thrombocytopenic Purpura of Childhood ... - sepeap

Pediatric Emergency Care Volume 21, Number 10, October 2005
Acute Idiopathic Thrombocytopenic Purpura
TABLE 1. Treatment for Acute Idiopathic Thrombocytopenic Purpura
Treatment
Dosing
Time to Increase
in Platelet Count
Observation N/A 3–4 wk N/A
Corticosteroid
Traditional dose
1–2 mg/kg per
d for 7–21 d
Complications
of Treatment
3–10 d Behavioral changes,
glucosuria, hypertension,
osteopenia, increase in
appetite and weight gain
High dose 4 mg/kg per d for 4 d 2–4 d
IVIg 0.8–1 g/kg IV for 1–2 d 24 h Fever, nausea, vomiting,
chills, headache, aseptic
meningitis
Anti-D immunoglobulin 50–75 mg/kg IV for 1–2 d 24–48 h Fever, nausea, vomiting,
chills, myalgias, hemolysis
N/A indicates not applicable.
corticosteroids includes decreased clearance of the antibodyplatelet
complex and impaired phagocytosis of platelets. 27–31
Early studies of corticosteroids used to treat acute ITP
showed that there was some benefit when given in low doses
over longer periods compared with placebo. This traditional
dosing was 1 to 2 mg/kg of oral prednisone per day for 1 to 3
weeks. 32,33 Time to an increase in platelet count varied from
3 to 10 days. This dose is well tolerated and not usually
associated with significant side effects if it is tapered or
discontinued within a month. However, this is not commonly
used at presentation of acute ITP because of the longer time
it takes to see platelet recovery. Higher dose steroids given
for a short period have recently been shown to be effective at
raising the platelet count within 2 to 4 days. 34–36 The dose of
corticosteroids given varied across the studies and ranged
between 4 mg/kg per day to 30 mg/kg per day of prednisone
or methylprednisolone for up to 4 days. There were no undue
side effects noted when a dose of 4 mg/kg per day for 4 days
orally was used. 34
The benefits of using corticosteroids are the relative
ease of administration in an outpatient or inpatient setting,
the low cost compared with other treatments, and the absence
of exposure to human plasma. The longer time to platelet
increase, however, precludes the use of steroids alone to treat
patients who may have moderate or more severe bleeding
symptoms at presentation. High-dose corticosteroids are
effective initial therapy for acute ITP and are used with some
frequency. The Intercontinental Childhood ITP Study Group
reported recently that approximately 25% to 40% of children
in their registry received corticosteroids as initial therapy
when they presented with acute ITP. 1 The relationship of
bleeding symptoms or dose of corticosteroids used was not
presented in this observational study.
Intravenous Ig
The third treatment option is intravenous (IV)Ig. IVIg
is thought to work, in part, by causing a temporary but
prolonged blockade of the Fc receptor of the phagocyte that
mediates immune clearance. 31,37,38 This blockade leads to a
compensatory increase in the platelet count. Recently, IVIg
has been shown in a mouse model to more specifically act by
causing up-regulation of the inhibitory receptor FcgRIIb to
cause blockade of Fc receptors on splenic macrophages. 39,40
There are a variety of doses of IVIg that may be used, but,
most commonly, the dose given is 0 .8 to 1.0 g/kg daily for 1 to
2 days. 41–45 Given at this dose, IVIg leads to a rapid increase in
platelet count as early as 24 hours after infusion and has been
effective when used for moderate or severe bleeding in acute
ITP. The side effects associated with IVIg are fever, chills,
headache, nausea, vomiting, and aseptic meningitis. There is
also the small risk of an infectious complication as IVIg is an
albumin-containing product. Most often, IVIg, which is
usually administered over 4 to 6 hours or more, is given in a
hospital setting and requires more resources and cost to
administer than corticosteroids. However, it is commonly
used at first presentation of acute ITP.
Anti-D Ig
Anti-D Ig, which is purified human IgG directed at the
erythrocyte D antigen, has more recently been used to treat
acute ITP in children who are nonsplenectomized and who
have rhesus-positive (Rh + ) red blood cells. 43,46,47 The
mechanism of action of anti-D is similar to IVIg in that it
decreases the clearance of platelets. More specifically, anti-D
binds to the Rh + red blood cell and sensitizes it to bind to the
macrophage Fc receptor and thereby promotes its clearance by
the spleen. 31,48 This frees platelet-antibody complexes from
being trapped. 48 Higher doses of anti-D (50–75 mg/kg) have
been shown to be the most effective at increasing the platelet
count within 24 to 48 hours similar to IVIg. 46,47,49,50 Anti-D is
given IV over 15 to 30 minutes and thus can be easily administered
in an outpatient or emergency department setting. It
has also been shown to be less costly than an equivalent dose
of IVIg. 51 The side effects of anti-D include headache, fever,
chills, nausea, and vomiting and myalgias. 52 In addition, anti-
D causes hemolysis and a transient decrease in the hemoglobin
n 2005 Lippincott Williams & Wilkins 693
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