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Idiopathic Thrombocytopenic Purpura
http://crisbertcualteros.page.tl
The most common cause of acute onset of thrombocytopenia in an otherwise well child is
(autoimmune) idiopathic thrombocytopenic purpura (ITP).
ETIOLOGY.
In a small number of children, 14 wk after exposure to a common viral infection, an
autoantibody directed against the platelet surface develops. The exact antigenic target for
most such antibodies in most cases of acute ITP remains undetermined. After binding of
the antibody to the platelet surface, circulating antibody-coated platelets are recognizedby the Fc receptor on the splenic macrophages, ingested, and destroyed. A recent history
of viral illness is described in 5065% of cases of childhood ITP. The reason why some
children respond to a common infection with an autoimmune disease remains unknown.Most common infectious viruses have been described in association with ITP, including
Epstein-Barr virus and HIV. Epstein-Barr virusrelated ITP is usually of short durationand follows the course of infectious mononucleosis. HIV-associated ITP is usuallychronic.
CLINICAL MANIFESTATIONS.
The classic presentation of ITP is that of a previously healthy 14 yr old child who hassudden onset of generalized petechiae and purpura. The parents often state that the child
was fine yesterday and now is covered with bruises and purple dots. Often there is
bleeding from the gums and mucous membranes, particularly with profoundthrombocytopenia (platelet count
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manifestation of a systemic illness, such as systemic lupus erythematosus (SLE), is more
likely.
In 7080% of children who present with acute ITP, spontaneous resolution occurs within6 mo. Therapy does not appear to affect the natural history of the illness. Fewer than 1%
of patients have intracranial hemorrhage. Those who favor interventional therapy arguethat the objective of early therapy is to raise the platelet count to >20 109/L and prevent
the rare development of intracranial hemorrhage. Approximately 20% of children whopresent with acute ITP go on to have chronic ITP.
LABORATORY FINDINGS.
Severe thrombocytopenia (platelet count
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to have low platelet counts, particularly if there is a history of eczema and recurrent
infection.
TREATMENT.
There are no data showing that treatment affects either short- or long-term clinical
outcome of ITP. Many patients with new-onset ITP have mild symptoms, with findingslimited to petechiae and purpura on the skin, despite severe thrombocytopenia. Comparedwith untreated control subjects, treatment appears to be capable of inducing a more rapid
rise in platelet count to the theoretically safe level of >20 109/L, although there are no
data indicating that early therapy prevents intracranial hemorrhage. Antiplateletantibodies bind to transfused platelets as well as they do to autologous platelets. Thus,
platelet transfusion in ITP is usually contraindicated unless life-threatening bleeding is
present. Initial approaches to the management of ITP include the following:
1. No therapy other than education and counseling of the family and patient for
patients with minimal, mild, and moderate symptoms, as defined earlier. This
approach emphasizes the usually benign nature of ITP and avoids the therapeuticroller coaster that ensues once interventional therapy is begun. This approach is far
less costly, and side effects are minimal.
2. Intravenous immunoglobulin (IVIG). IVIG at a dose of 0.81.0 g/kg/day for 12
days induces a rapid rise in platelet count (usually>20 109/L) in 95% of patients
within 48 hr. IVIG appears to induce a response by downregulating Fc-mediatedphagocytosis of antibody-coated platelets. IVIG therapy is both expensive and
time-consuming to administer. Additionally, after infusion, there is a high
frequency of headaches and vomiting, suggestive of IVIG-induced asepticmeningitis.
3. Intravenous anti-D therapy. For Rh positive patients, IV anti-D at a dose of 5075g/kg causes a rise in platelet count to>20 109/L in 8090% of patients within
4872 hr. When given to Rh positive individuals, IV anti-D induces mildhemolytic anemia. RBC-antibody complexes bind to macrophage Fc receptors and
interfere with platelet destruction, thereby causing a rise in platelet count. IV anti-
D is ineffective in Rh negative patients.
4. Prednisone. Corticosteroid therapy has been used for many years to treat acute and
chronic ITP in adults and children. Doses of prednisone of 14 mg/kg/24 hr appearto induce a more rapid rise in platelet count than in untreated patients with ITP.
Whether bone marrow examination should be performed to rule out other causes of
thrombocytopenia, especially acute lymphoblastic leukemia, before institution of
prednisone therapy in acute ITP is controversial. Corticosteroid therapy is usuallycontinued for 23 wk or until a rise in platelet count to>20 109/L has been
achieved, with a rapid taper to avoid the long-term side effects of corticosteroid
therapy, especially growth failure, diabetes mellitus, and osteoporosis.
Each of these medications may be used to treat exacerbations of ITP, which commonly
occur several wk after an initial course of therapy.
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In the special case of intracranial hemorrhage, multiple modalities should be used,
including platelet transfusion, IVIG, high-dose corticosteroids, and prompt surgical
consultation, with plans for emergency splenectomy.
Currently, there is no consensus regarding the management of acute childhood ITP. The
American Society of Hematology has published treatment guidelines for adults with ITP,but there is significant disagreement within the field. The only consensus is that patients
who are bleeding significantly should be treated, and these may represent only 5% ofchildren with ITP. Intracranial hemorrhage remains rare, and there are no data showing
that treatment actually reduces its incidence.
The role of splenectomy in ITP should be reserved for 1 of 2 circumstances. The olderchild (> 4 yr) with severe ITP that has lasted >1 yr (chronic ITP) and whose symptoms
are not easily controlled with therapy is a candidate for splenectomy. Splenectomy must
also be considered when life-threatening hemorrhage (intracranial hemorrhage)
complicates acute ITP, if the platelet count cannot be corrected rapidly with transfusion
of platelets and administration of IVIG and corticosteroids. Splenectomy is associatedwith a lifelong risk of overwhelming postsplenectomy infection caused by encapsulated
organisms.
CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA.
Approximately 20% of patients who present with acute ITP have persistent
thrombocytopenia for > 6 mo and are said to have chronic ITP. At that time, a careful re-evaluation for associated disorders should be performed, especially for autoimmune
disease, such as SLE; chronic infectious disorders, such as HIV; and nonimmune causes
of chronic thrombocytopenia, such as type 2B and platelet-type von Willebrand disease,X-linked thrombocytopenia, autoimmune lymphoproliferative syndrome, common
variable immunodeficiency syndrome, autosomal macrothrombocytopenia, and WAS(also X-linked). Therapy should be aimed at controlling symptoms and preventing serious
bleeding. In ITP, the spleen is the primary site of both antiplatelet antibody synthesis andplatelet destruction. Splenectomy is successful in inducing complete remission in 64
88% of children with chronic ITP. This must be balanced against the lifelong risk of
overwhelming postsplenectomy infection. This decision is often affected by lifestyleissues as well as the ease with which the child can be managed using medical therapy,
such as IVIG, corticosteroids, IV anti-D, or rituximab (see Chapter 464 ). AMG 531, a
thrombopoiesis-stimulating protein, has had some success in treating adults with chronicimmune thrombocytopenia. Before splenectomy, the child should receive pneumococcal
and meningococcal vaccines, and after splenectomy, he or she should receive penicillin
prophylaxis for a number of yr. Whether penicillin prophylaxis should be lifelong iscontroversial.
484.2 Drug-Induced Thrombocytopenia
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A number of drugs are associated with immune thrombocytopenia as the result of either
an immune process or megakaryocyte injury. Some common drugs used in pediatrics that
cause thrombocytopenia include valproic acid, phenytoin, sulfonamides, andtrimethoprim-sulfamethoxazole. Heparin-induced thrombocytopenia (and rarely,
thrombosis) is seldom seen in pediatrics, but it occurs when, after exposure to heparin,
the patient has an antibody directed against the heparin-platelet factor 4 complex.