Treatment and prognosis of immune (idiopathic)

thrombocytopenic purpura in children

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2013. | This topic last updated: Apr 8, 2011.
INTRODUCTION Immune (idiopathic) thrombocytopenic purpura (ITP) of
childhood is characterized by acquired thrombocytopenia and is a generally benign
disorder of unknown cause. ITP is also referred to as autoimmune
thrombocytopenic purpura or isoimmune thrombocytopenic purpura.
Although both acute and chronic forms of ITP exist, they have similar presentation
in a child who presents with ITP. Twenty percent of affected children will go on to
have chronic ITP, generally defined as persistent thrombocytopenia for more than
six months beyond presentation. However, some authors have suggested that 12
months is a more appropriate parameter for defining chronic ITP.
The treatment and prognosis of acute and chronic ITP in children will be reviewed
here. The epidemiology, clinical manifestations, and diagnosis of ITP in children are
discussed separately.
OVERVIEW The management of children with ITP is the subject of much debate
because it is unclear whether "watchful waiting" or pharmacologic intervention
provides the most appropriate care for affected children.
Proponents of "watchful waiting" without pharmacologic intervention base their
decisions upon the following observations:
Seventy to 80 percent of children with ITP will recover within a few months
of presentation with or without treatment.
Most patients do not have serious bleeding including those with platelet
counts <10,000/microL. Intracranial hemorrhage, the most serious
consequence of ITP, is rare with an incidence of 0.1 to 0.5 percent.
In one report from the Intercontinental Childhood ITP Study Group, the risk
of severe bleeding following diagnosis was 0.9 percent in patients with no,
mild, or moderated bleeding and was unrelated to initial management.
Those who favor pharmacologic intervention base their decision upon the evidence
that pharmacologic therapies are available that raise the platelet count more rapidly
than if no treatment was administered. They suggest drug treatment be used in
patients with serious bleeding or who are at risk for serious bleeding. In a
retrospective study from five Nordic countries (Sweden, Finland, Denmark, Norway,
and Iceland), early treatment accelerated platelet recovery in patients with acute
ITP, but did not reduce the risk of developing chronic ITP or morbidity.
There are no randomized trials comparing pharmacologic therapy and observation
upon the outcome of children with ITP. Data based upon retrospective studies
suggest that pharmacologic therapy does not reduce the risk of developing chronic
ITP but it remains unclear whether pharmacologic therapy reduces the risk of life-

threatening complications associated with acute ITP because of their low prevalence
rate.
Both the American Society of Hematology (ASH) and British Society of Haematology
have published guidelines for the management of ITP in children and adults. Both
societies acknowledge that published evidence for recommendations is weak. As a
result, both sets of guidelines are based primarily upon expert opinions and
observational studies.
The ASH guidelines (published in 1996) are based upon the risk of bleeding
associated with a given platelet count. They recognize that no therapeutic
intervention is generally needed for children with platelet counts greater
than 30,000/microL as they are unlikely to have serious bleeding.
Pharmacologic therapy is recommended for the following:
Any child with significant bleeding (eg, mucosal bleeding) regardless of the
platelet count
Children with platelet counts less than 10,000/microL and cutaneous
bleeding (bruising, petechiae, and/or purpura)
The British guidelines (published in 2003), in contrast to the ASH guidelines,
base treatment upon the severity of clinical symptoms without regard for
the platelet count of the patient. They reserve pharmacologic
interventions for children with severe bleeding or in children undergoing
procedures (such as surgery) likely to include blood loss.
In 2010, an international consensus report recommended that treatment be based
upon a composite of factors that includes clinical symptoms, circulating platelet
count, and the impact of ITP upon the patient's quality of life. This approach takes
into consideration the use of pharmacologic therapy in patients who partake in
strenuous activity. However, patients should not participate in competitive contact
activities that have a high risk of head trauma.
In our practice, treatment decisions are based upon the available data that suggest
most patients with platelet counts above 10,000/microL will not have serious
bleeding. Pharmacologic therapy is given to patients with serious bleeding and
those with a platelet count <10,000/microL and cutaneous bleeding (bruising,
petechiae, and/or purpura).
INITIAL MANAGEMENT
Supportive care Regardless of whether pharmacologic therapy is used,
restriction of activity (especially contact sports) should be recommended in all
children with ITP. In addition, medications with antiplatelet activity (including
aspirin-containing preparations, ibuprofen and other non-steroidal antiinflammatory drugs) or those with anticoagulant activity should be avoided.
Pharmacologic intervention As previously noted, there are limited data on the
use of pharmacologic intervention in children with ITP. In our practice, the presence
of one or more of the following factors is used as an indication for pharmacologic
intervention:

 Presence of severe or life-threatening bleeding

Risk of significant bleeding, such as a child undergoing a procedure that is
likely to induce blood loss, or a child with a platelet
count<10,000/microL and signs of cutaneous bleeding (bruising,
petechiae, and/or purpura)
Any concomitant or preexisting condition that increases the risk of
thrombocytopenia or bleeding (eg, hemophilia)
When it is decided to use pharmacologic therapy, treatment options include
corticosteroids, intravenous immunoglobulin (IVIG or IGIV), or intravenous antiRho(D) immune globulin. Several studies have shown that the duration of
symptomatic thrombocytopenia is shortened by any of these three modalities
compared to no treatment (table 1A-C).
A study from the Intercontinental Childhood ITP Study (ICIS) registry, which
included selected patients from 39 countries and 147 institutions voluntarily
reported by physicians, demonstrated the variability of management for childhood
ITP. Review of the treatment data, which were available for 1976 patients, showed
that therapy included corticosteroids alone (33 percent), IVIG alone (29 percent), a
combination of corticosteroids and IVIG (7 percent), and no pharmacologic
intervention (31 percent).
Corticosteroids Corticosteroids have been used for many years for the
management of ITP in all age groups. Steroids are presumed to reduce the risk of
symptoms in ITP patients by:
Reducing antibody production
Reducing reticuloendothelial system phagocytosis of antibody-coated
platelets
Improving vascular integrity
Improving platelet production
In randomized trials of children with ITP, prednisone therapy has been shown to
more rapidly increase platelet counts than placebo. In one study, children treated
with oral prednisone (2 mg/kg per day) for 14 days followed by a taper over a week
had a higher platelet count and lower bleeding scores compared to those who
received placebo. In another study, children treated with oral prednisone
(2 mg/kg per day) for 21 days were more likely to have a platelet count greater
than 30,000/microL with the first 10 days of treatment compared to placebotreated children (90 versus 45 percent).
A variety of dose regimens have been used ranging from prednisone at a dose of
2 mg/kg per day for two to four weeks, to high pulse doses of intravenous or
oral methylprednisolone (50 mg/kg per day) for three to seven days (table 1A-C).
Some evidence suggests that time of response and rate of response are doserelated, but comparative studies among the multiple regimens are few and involve
only small numbers of patients. Thus, there is insufficient evidence to recommend

selecting among low-, moderate-, or high-dose steroid regimens. This is reflected at

our institution, where practice varies among members of our group. The following
three steroid regimens are commonly used:
Prednisone 1 to 2 mg/kg (maximum dose 60 mg) per day in 3 divided
doses for 14 days followed by a week of tapering
Prednisone 4 mg/kg per day divided into 3 doses for four days
Methylprednisolone 30 mg/kg per day intravenously for 3 days
Repeat courses may be given for patients with persistent, recurrent, or chronic
disease.
Although most patients respond to corticosteroids, a drop in platelet count after the
steroids are discontinued is not unusual. Occasionally, repeated courses of
treatment may be necessary if significant hemorrhagic symptoms persist or recur.
Side effects of corticosteroids include behavioral change, sleep disturbance,
increased appetite, and weight gain. Avoidance of chronic administration of steroids
is desirable because of these side effects as well as the long-term consequence of
poor growth. Thus, alternative therapies such as IVIG should be considered for
children who appear to need prolonged or repeated therapy.
IVIG Steroids were the only therapy used for children presenting with acute ITP
until 1981, when the successful use of intravenous immunoglobulin (IVIG) in
children with ITP was first published.
The exact mechanism of action is unknown and is likely multifactorial, and could
involve the following:
Competitive inhibition or steric hindrance of autoantibody adsorption to the
patient's platelets.
Prevention of reticuloendothelial uptake of autoantibody-coated platelets
directly through blockade of macrophage Fc-receptors, or indirectly by
activating Fc-receptors on dendritic cells.
Interaction of the autoantibodies with anti-idiotype antibodies in the IGIV.
Regardless of its mechanism of action, IVIG appears to more reliably improve
platelet numbers in patients with ITP than corticosteroids or no treatment. This was
best illustrated in a meta-analysis that demonstrated that IVIG therapy is superior
to corticosteroids when early recovery of platelet numbers is desired. The following
findings were noted:
In six studies of 401 children with ITP, children receiving corticosteroids
compared to those receiving IVIG were less likely to achieve a platelet
count greater than 20,000/microL, 48 hours after initiation of therapy (RR
0.74, 95% CI 0.65-0.85).
In five studies, corticosteroids were less likely to achieve a platelet count
greater than 20,000/microL versus IVIG when comparisons between the

two treatment modalities were made at 24 hours (RR 0.63, 95% CI 0.480. 83) and at 72 hours after initiation of therapy (RR 0.83, 95% CI 0.760.91).
Chronic ITP, defined as a platelet count <150,000/microL, developed in 25
percent of patients treated with corticosteroids and 18 percent of those
with IVIG.
A retrospective study from the ICIS registry reported that children with acute ITP
who were treated with IVIG were more likely to have a normal platelet count six
months after diagnosis than those who did not receive IVIG (Odds ratio 1.81, 95%
CI 1.25 to 2.64).
Reported dose regimens for children with ITP range from 400 mg/kg per day for
five days to a single dose of 1000 mg/kg. A single dose regimen appears to be
preferable. In one study, a single dose of IVIG of 800 mg/kg was as effective as a
higher dose regimen of 1000 mg/kg per day for two days in raising the platelet
count. The response to therapy is usually within 24 hours of initiation of IVIG
therapy with the single dose of IVIG.
Side effects of IVIG include flu-like symptoms, such as nausea and vomiting (63
percent), headache (56 percent), or fever (19 percent). Adverse effects tend to be
more pronounced in older patients. Neutropenia (absolute neutrophil count
less than1500/microL) develops in about 30 percent of patients.
Cost/benefit ratios must be considered in the selection of therapy for ITP; the cost
of a course of IVIG is greater than that of a conventional oral corticosteroid
regimen. However this cost differential is lower when initial and retreatment costs
are combined.
In our center, we administer IVIG as a single dose of 1000 mg/kg per day for one
or two days in patients with significant bleeding manifestations including "wet
purpura".
Anti-Rho(D) immune globulin Based upon the premise that IVIG acts in part
by producing antibody-coated red cells that block antibody-coated platelets
sequestration by the reticuloendothelial system, trials were conducted to study the
effect of anti-Rho(D) immunoglobulin [anti-Rho(D) Ig] in patients with ITP who
were Rho(D)-positive.
These trials demonstrated that anti-Rho(D) Ig is effective in improving platelet
counts. Limited data comparing the efficacy of anti-Rho(D) Ig versus IVIG and
corticosteroids include the following two studies:
The first study was a randomized controlled trial in which 146 patients were
assigned to receive one of four treatments; IVIG (1000 mg/kg for two
doses on consecutive days), IVIG as a single dose (800 mg/kg), antiRho(D) Ig (25 microgram/kg for two doses on consecutive days), or oral
prednisone (initial dose 4 mg/kg tapered and weaned over 21 days). At 72
hours after the start of treatment, the groups treated with IVIG had the
best response to therapy. Response to treatment, as defined by the
percent of patients with a posttreatment platelet count greater than
20,000, was seen in 97, 94, 82, and 79 percent of patients treated with
one dose of IVIG (800 mg/kg), two doses of IVIG (each 1000 mg/kg), two

doses of Anti-Rho(D) Ig (each 25 micrograms/kg), and oral prednisone,

respectively.
Hemoglobin levels fell below 10 g/dL in 24 percent of patients treated with
anti-Rho(D) Ig. Patients who received IVIG were more likely to have
complaints of fever, nausea, vomiting, and headache.
The second study was a randomized controlled trial in which 105 patients
were assigned to receive IVIG as a single dose of 800 mg/kg, or antiRho(D) Ig as a single dose of either 75 microgram/kg or
50 microgram/kg. At 24 hours after the start of therapy, the response to
therapy with a platelet count greater than 20,000 was 77, 50, and 72
percent in patients treated with IVIG, anti-Rho(D) Ig
(50 microgram/kg), and anti-Rho(D) Ig (75 microgram/kg), respectively.
By day seven, hemoglobin levels had decreased by 0.3, 1.6, and 2 g/dL in
the IVIG, anti-Rho(D) Ig (50 microgram/kg), and anti-Rho(D) Ig
(75microgram/kg) groups, respectively. The side effects of headache,
fever, or chills occurred in all three groups but were less frequent in the
group treated with the lower dose of anti-Rho(D) Ig.
Thus, anti-Rho(D) Ig is effective in the treatment of children with ITP and with
higher doses appears to have comparable results to IVIG. However, anti-Rho(D) Ig
is associated with an increased incidence of significant hemolysis. Similarly, in a
retrospective report, patients treated with anti-Rho(D) Ig experienced an increased
rate of adverse effects as compared with those treated with IVIG.
Based upon these results, in patients with ITP when earlier recovery of platelet
numbers is desirable, we prefer to treat with IVIG rather than anti-Rho(D) Ig. We
administer IVIG as a single dose of 1000 mg/kg.
If anti-Rho(D) is used, it should only be given to children with a hemoglobin level
greater than 10 g/dL. Patients also should be screened with a Coombs antibody to
identify the rare patient with Evans syndrome. In addition, careful monitoring for
acute hemolysis and/or hemoglobinuria, and their possible sequelae should be
performed.
Our approach If pharmacologic therapy is used, we prefer IVIG to
corticosteroids or intravenous anti-Rho(D) Ig because it reliably increases platelet
counts and more quickly than corticosteroids, and is safer than anti-Rho(D) IG. We
administer IVIG as a single 1000 mg/kg dose. Alternate options include intravenous
or oral corticosteroids, different dosing regimens of IVIG, and intravenous antiRho(D) Ig.
Platelet transfusions The only indication for platelet transfusions is lifethreatening hemorrhage, such as intracranial hemorrhage. Larger-than-normal
doses are required because normal doses are ineffective due to platelet destruction.
Monitoring Almost all children with ITP are managed in the ambulatory setting.
Patients who receive pharmacologic intervention are usually hospitalized for an
average length of stay of two days.
In the ambulatory setting, platelet counts are generally monitored once or twice
weekly, depending on the clinical situation and severity of thrombocytopenia. When
recovery of platelet counts is detected, the interval between measuring platelet

counts is lengthened, but monitoring should continue until the platelet count has
returned to normal (>150,000/microL) and is stable. This return occurs within one
month after presentation in one-half of children with ITP, and by three months in
about 70 percent of children.
In our practice, we stop monitoring after the platelet count has returned to normal
and has remained stable for two to three months. Recurrence of acute ITP is rare,
probably occurring in less than 1 percent of cases, although the possibility of wellcompensated chronic ITP cannot be ruled out.
Since all ITP therapies are temporizing interventions intended to reverse
expeditiously a real or perceived risk for hemorrhage, they do not need to be
continued until normal platelet counts are reached. Therapy is targeted to increase
the platelet count above a threshold (usually greater than20,000/microL) that stops
bleeding or eliminates the risk of serious bleeding.
Life-threatening bleeding Life-threatening bleeding is rare. Although
intracranial hemorrhage (ICH) has an incidence of only 0.1 to 0.5 percent, it is the
most serious consequence of ITP. The presence of significant headache should
prompt careful evaluation for any other neurologic signs, and early diagnostic
imaging should be considered to identify ICH.
If ICH or any other life-threatening hemorrhage occurs, immediate intervention
should be given to the affected patient. Our practice is consistent with the
recommendations of the previously mentioned 2010 International consensus report
and includes the following:
Platelet transfusions
IVIG 1000 mg/kg per day for two days
Methylprednisolone 30 mg/kg per day administered intravenously for
three days
For ITP patients with unstable or progressive ICH, emergency craniotomy may be
necessary. Emergency splenectomy may be considered in selected clinical situations
but only as a last resort.
CHRONIC ITP Approximately 20 to 30 percent of children who present with ITP
will have chronic ITP, defined as persistent thrombocytopenia (platelet count less
than 150,000/microL) beyond six months from the time of presentation. Patients
with chronic ITP are usually clinically indistinguishable from those with acute ITP at
presentation.
Individuals with chronic ITP should undergo evaluation to exclude other causes of
thrombocytopenia, such as chronic infections (including HIV), bone marrow failure,
collagen vascular disorders, and other autoimmune or immunodeficiency disorders.
Studies should include viral antibody titers, bone marrow examination, and studies
for collagen vascular disorders (eg, antinuclear antibody test).
Management In up to one-third of children with chronic ITP, spontaneous
remission will occur months or even years later. Children younger than 10 years of
age are more likely to remit than older patients and treatment is usually not

necessary. Children older than 10 years of age, especially adolescent females, have
a disease course more like that seen in adults with ITP and should be treated in a
similar manner.
In chronic ITP, platelet counts tend to range between 20,000
and 75,000/microL; consequently, many patients will require no treatment. It is
very uncommon for an individual with chronic ITP to have a platelet count less
than 10,000/microl.
Management of children with chronic ITP should focus on minimizing the individual's
risk for bleeding. Pharmacologic intervention is used as a temporizing measure. In
some cases, such as patients with chronic severe ITP, splenectomy is performed
because of persistent significant hemorrhagic symptoms that require repeated,
sometimes almost continuous, pharmacologic interventions.
Pharmacologic therapy In children with chronic ITP, pharmacologic therapy
usually is used when patients have significant bleeding, or require surgery or dental
extraction. Adolescent girls may have excessive bleeding during their menses and
may require therapeutic intervention. Therapy generally raises the platelet count
temporarily.
Pharmacologic options are similar to those used in the initial management of
patients with ITP at presentation and include the following:
Corticosteroids Patients may receive periodic short courses or pulses of
corticosteroids. For patients who are steroid dependent in order to remain
symptom free, alternate day dosing may be effective in preventing
bleeding while reducing side effects. Prolonged daily steroid treatment is
to be avoided because of its adverse effects, especially poor growth. In
our practice, we prefer to avoid the prolonged use of glucocorticoid
therapy.
Immunoglobulin therapy Intravenous IgG (IVIG) or anti-Rho(D) also have
been effective in chronic ITP patients, even those who are resistant to
steroids. All of these strategies offer temporary alleviation of symptoms
and improvement in platelet numbers, but no data demonstrate an effect
on resolution of chronic ITP.
In our practice, IVIG is administered at a dose of 500 mg/kg per day for two days
and repeated when symptoms recur.
Splenectomy A small percentage of patients with chronic ITP will have
persistent significant hemorrhagic symptoms and require repeated, sometimes
almost continuous, pharmacologic interventions. For such patients, the risks and
benefits of splenectomy must be considered.
Splenectomy is effective in improving the platelet count and reducing the
associated risk of bleeding in 60 to 90 percent of children with chronic ITP. No
universally accepted standards for the timing of splenectomy in chronic ITP exist,
but the American Society of Hematology guidelines recommend waiting until at
least 12 months after diagnosis, if possible. When possible, surgery should be
performed using laparoscopic techniques.

The anticipated improvement in hemostasis and platelet count must be balanced

with the small risk of overwhelming post-splenectomy infection, which may be lifethreatening. Because of the high infection rates in younger asplenic individuals,
temporizing therapies are especially important for patients younger than 4 to 5
years of age with chronic ITP. Presplenectomy immunizations and subsequent
penicillin prophylaxis are necessary for all age groups.
Platelet counts in splenectomized patients generally are followed for an indefinite
period; any decompensation in platelet counts or increase in symptoms should
prompt assessment for the presence of an accessory spleen.
Treatment of refractory chronic ITP Approximately 25 to 30 percent of
children with chronic ITP have ongoing hemorrhagic problems after splenectomy. In
these cases, evaluation should identify any possible accessory spleen, which should
be removed, if present.
Rituximab is a chimeric murine/human anti-CD20 monoclonal antibody which
targets autoantibody producing lymphocytes. It promises to be useful in treating
both primary and secondary refractory chronic ITP in children with reported
remission rates of about 30 percent.
In an open label study of 36 children (2 to 19 years of age) in the United
States who received a weekly intravenous dose
of rituximab (375mg/m2) for four doses, rituximab improved the platelet
count to greater than 50,000/microL in 11 children (31 percent). However,
six patients had serious side effects including two with serum sickness. In
a one-year follow-up study, eight of the 11 initial responders maintained a
platelet count greater than 150,000/microL without further interventions.
One initially nonresponding patient achieved remission after 16 weeks and
two additional patients maintained platelet counts of 50,000/microL.
In another study of 49 Italian children (2 to 18 years of age) with refractory
ITP treated with rituximab (375 mg/m2 weekly for four weeks), 34
patients responded (69 percent) with a platelet count greater
than 50,000/microL. Thirteen patients of responders relapsed within four
months from the first infusion, the remaining 21 patients maintained a
platelet count greater than 50,000/microL over a median follow-up period
of 20 months. Only mild and transient side effects were reported including
urticarial rash, headache, fever, and chills.
Studies are ongoing to determine the efficacy, safety, and dose of rituximab in the
treatment of chronic refractory ITP in children.
For those refractory patients with significant hemorrhagic problems who fail trials of
steroids, IVIG, anti-Rho(D) Ig, and rituximab , the use of various agents such
as danazol , interferon, cyclosporine , cyclophosphamide , and azathioprine has
been suggested, based primarily upon observational studies and small clinical trials
in adults. The use of thrombopoietin (TPO)-receptor agonists such
as romiplostim and eltrombopag has been reported in adults with refractory ITP, but
data regarding the use of these agents are limited or do not exist in children.
OUTCOME In children with ITP, the risk of serious bleeding is small, regardless
of whether pharmacologic treatment is given. This was illustrated from the two
previously mentioned registry studies.

In the original cohort of 501 patients from the Nordic Society for Pediatric
Haematology and Oncology (NSPHO) study, 285 patients (57 percent) received
pharmacologic treatment within two weeks of diagnosis; in most cases one or two
doses of IVIG were administered. Six-month follow-up data were available for 409
patients. The following findings were noted:
Of the 409 patients, 376 children had a platelet count less
than 20,000/microL during the course of their disease and were classified
as being at risk for serious bleeding.
In the high-risk group of patients, the risk period for serious bleeding lasted
less than one month in 75 percent of patients and persisted for more than
six months in 10 percent.
There were 141 events that required medical attention during the six-month
follow-up period. More than half of the events (74 reports) were
accounted for by the 101 patients with chronic ITP.
Most of the reported events were due to cutaneous bleeding (bruising,
petechiae, and/or purpura). There were 33 episodes of mucosal bleeding,
which included 23 reports of epistaxis, 6 reports of oral bleeding, 1 report
of menorrhagia, and 1 report of rectal bleeding.
None of the events were life-threatening and there were no reports of
intracranial hemorrhage or significant trauma. In 15 cases, blood
transfusions were required.
In the 409 patients with complete follow-up data, there was no difference in
the risk of developing chronic ITP in patients who did not receive
treatment compared to those who did (23 versus 26 percent).
In the Intercontinental Childhood ITP Study (ICIS) study, three of the 1742 patients
with available six-month follow-up data had intracranial hemorrhage. The following
findings were noted:
Initial platelet counts for the three patients were 8000, 11,000,
and 16,000/microL.
Management varied with one patient receiving no pharmacologic therapy,
one treated with corticosteroids, and one received a combination of
corticosteroids and IVIG.
Subsequent follow-up data were only available for two of the three patients.
The patient who received both corticosteroids and IVIG died within the
first week of diagnosis of ITP and the patient who received corticosteroid
alone fully recovered without neurologic sequelae.
A small number of children with acute ITP (<5 percent), who initially remit with
recovery of a normal platelet count, will have an episode of recurrent acute
thrombocytopenia. When it occurs, it usually is a self-limited event and
management principles remain the same as for the initial acute episode. Prolonged
monitoring of such patients is necessary to eliminate the possibility that chronic ITP
is the actual diagnosis.

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SUMMARY AND RECOMMENDATIONS Immune (idiopathic) thrombocytopenic
purpura (ITP) of childhood is characterized by thrombocytopenia (platelet count
usually less than 20,000/microL) that is an acquired and usually benign disorder.
In children with ITP, the risk of serious bleeding is small regardless of whether
pharmacologic treatment is administered.
Initial medical management
The management of childhood ITP is the subject of much debate because it
is unclear whether observation alone or observation with pharmacologic
intervention in defined circumstances provides the most appropriate care
for the child with ITP.
Whether or not pharmacologic therapy is used, physical activity, especially
contact sports, should be restricted, and medications with either
antiplatelet or anticoagulant activity should be avoided.
Options for pharmacologic intervention include corticosteroids, intravenous
immunoglobulin (IVIG), or intravenous anti-Rho(D) immune globulin
[anti-Rho(D) Ig]. These agents raise the platelet count more quickly than
no therapy.
For children with ITP with severe or life-threatening bleeding, we
recommend pharmacologic therapy in ( Grade 1B ). For these patients, we
also recommend platelet transfusion ( Grade 1C ). In our practice, we
administer platelets, high-dose glucocorticoids, and IVIG to children with
life-threatening bleeding.
For children with ITP with a platelet count less
than 10,000/microL with cutaneous bleeding (bruising,
petechiae and/or purpura), or for those with anticipated risk for significant
bleeding (eg, patient scheduled for surgery or dental extraction), we
suggest pharmacologic therapy ( Grade 2C). We also suggest
pharmacologic therapy in patients who have a concomitant or preexisting
condition that increases the risk of thrombocytopenia or bleeding (eg,
hemophilia) ( Grade 2C ).

 If treatment is indicated, we suggest administering IVIG rather than

corticosteroids or intravenous anti-Rho(D) Ig ( Grade 2B ). In our practice,
we administer IVIG as a single 1000 mg/kg dose. Alternate options
include intravenous or oral corticosteroids, different dosing regimens of
IVIG, and intravenous anti-Rho(D) Ig.
Chronic ITP About 20 to 30 percent of children with ITP will have chronic ITP,
defined as persistent thrombocytopenia (platelet count less
than150,000/microL) six months after presentation.
The management for childhood chronic ITP includes the following:
Evaluation to exclude other disorders.
In children younger than 10 years of age, treatment is usually unnecessary
because they are likely to have spontaneous remission. We recommend
that pharmacologic therapy be used as a temporary measure during
episodes of significant bleeding, or for surgery or dental extraction
( Grade 1B).
Children with chronic ITP who are older than 10 years of age, especially
adolescent females, have a disorder that is more like that seen in adults
with ITP and should be treated in a similar manner.
Splenectomy is reserved for patients who continue to have significant and
persistent hemorrhagic symptoms requiring repeated pharmacologic
interventions 12 months after diagnosis.

1. Steroids in childhood ITP I

2. 2013 UpToDate
3. Clinical trial evidence: effectiveness of
glucocorticoids, IVIg, and anti-D in initial treatment
of ITP in children-I
Authors

McWilliams
and Mauner

Stu
dy
N

Pop
.
age

Foll
owup

27

6 yr
mea
n

NR

Randomized
treatment arms
Prednisone (2
mg/kg/d x 21 d)

Outcome measure

Median time to platelet count

of 150K

No treatment

Sartorius

93

60
mo16
yr

>6
mo

Prednisone (60
mg/m2/d x 21 d, then
tapered)

Proportion with platelet count

>30K and >100K, and with (p
<.01) negative Rumpel-Leede
test

Platelet
count

27

<11
yr

28 d

Prednisone (2
mg/kg/d x 14 d, then
taper to d 21)

Platelet count, Bleeding time,

clinical bleeding score at d 028

94

<16
yr

1 yr

Prednisone (60
mg/m2/d x 21 d,
follow-up protocol for
poor response/

Proportion with platelet count

>100K

Deaths

NR

NR

(p .03) 60
d

NR

NR

Prednisone
> Placebo
(p <.01)

Prednisone
< placebo
(by
RumpelLeede test

NR

NR

Prednisone
< placebo
(p < .05)
only at d 7
(bleeding
time and
clinical
score)

Increased
appetite,
weight gain

NR

77 percent
weight gain
or acne

Prednisone
> placebo
(p <.05)
only at d 7

Placebo

Imbach et al

Adverse
Effects

21 d

Placebo
Buchanan
and
Holtkamp

Bleeding
symptom
s

77 percent

remissions)
IVIg (0.4 g/kg/d x 5
d, follow-up protocol
for poor response/
remissions

Mazzucconi
et al

61

2-12
yr

>6
mo

Prednisone (0.5
mg/kg/d x 1 mo or
until platelet
normalization)

Proportion with platelet count

>150K

Prednisone (1.5
mg/kg/d x 1 mo or
until platelet
normalization)

83 percent
(no
difference)

NR

22 percent
with
headache,
fever,
vomiting,
vertigo

1 died on
day 6,
excluded
from
analysis

62 percent

NR

NR

NR

81 percent
(p <.05)

NR

NR

NR

4. NR: not reported.

5. Reproduced with permission from George, JN, Woolf, SH, Raskob, GE, et al.
Blood 1996; 88:3. Copyright 1996 American Society of Hematology.

6. Clinical trial evidence: effectiveness of

glucocorticoids, IVIg, and anti-D in initial treatment
of ITP in children-II (continued)
Authors
Belluci et
al

Study
N
160

Pop.
age
<15 yr

Followup
>12 mo

Randomized treatment
arms
Prednisone (0.25 mg/kg/d x
3 wk)

Outcome measure
Proportion with platelet
count >100K for >3 mo

Ozsoyle et
al

30

20

2 mo-15
yr

2 mo-11
yr

>6 mo

>6 mo

53

7 mo14 yr

180 d

146

6 mo18yr

6-32 mo

Deaths

NR

77 percent
(no difference)

NR

NR

NR

NR

Prednisone (2 mg/kg/d x 4
wk)

NR

NR

IVIg (0.4 g/kg/d x 5 d)

NR

NR

60 percent, 90
percent (no
difference)

None

NR

60 percent, 75
percent

NR

NR

2 d, 4d

NR

Weight gain,
behavioral
change 75
percent with
nausea,
vomiting,
headache, fever

M'prednisolone (IV, 10
mg/kg/d x 5 d)

M'prednisolone (po, 30
mg/kg/d x 3 d, then 20
mg/kg/d x 4 d)

Mean platelet count on

days 1-14

Proportion with platelet

count >150K in 3 d, 6
mo

Prednisone (4 mg/kg/d x 7
d, then tapered to d 21) IVIg
(1 g/kg/d x 2 d)

Median time to platelet

count >20K, >50K

No therapy

Blanchette

Adverse
Effects

NR

IVIg (0.4 g/kg/d x 5 d)

Blanchette
et al

Bleeding
symptoms

71 percent

Prednisone (1 mg/kg/d x 3
wk)
Khalifa et
al

Platelet
count

Prednisone (4 mg/kg/d x 7
d, then tapered to d 21)

1 d, 2 d (p< .
01 vs
prednisone) 4
d, 16 d (p
<0.1 vs either
treatment)
Median time to platelet
count >20K, >50K

2 d, 3 d

NR

None

IVIg (1 g/kg/d x 2 d)

2 d, 2 d

NR

16-18 percent
with fever,
nausea,
vomiting,
headache

IVIg (0.8 g/kg once)

1 d, 2 d (p
<.05 vs.
prednisone)

NR

Anti-D (25 g/kg/d x 2 d)

2 d, 2.5 d (p <
.05 vs. both

NR

24 percent with
hemoglobin

IVIg
regimens)

<10 g/dL

7. NR: not reported.

8. Reproduced with permission from George, JN, Woolf, SH, Raskob, GE, et al.
Blood 1996; 88:3. Copyright 1996 American Society of Hematology.

9. Clinical trial evidence: effectiveness of

glucocorticoids, IVIg, and anti-D in initial treatment
of ITP in children-III (continued)
Author
s

Stud
yN

Albayra
k et al

57

Pop.
age
2 mo17 yr

Follo
w-up
6 mo

Randomized
treatment arms

Outcome
measure

Platelet
count

M'prednisolone
(po, 30 mg/kg/d x
7d)

Mean platelet
count on
days 0-30

Mean
>100K by d
4. No
difference
among
groups

M'prednisolone
(po, 50 mg/kg/d x
7 d)

IVIg (0.5 g/kg/d x

5 d)

Bleeding
symptoms

Adverse
Effects

Deat
hs

NR

Increased
appetite and
Cushingoid
appearance

1 ICH

Increased
appetite and
Cushingoid
appearance

NR

1 pt with
aseptic
meningitis; 2
with
headache,
vomiting

10. NR: not reported; ICH: intracerebral hemorrhage.

11. Reproduced with permission from George, JN, Woolf, SH, Raskob, GE, et al.
Blood 1996; 88:3. Copyright 1996 American Society of Hematology.