Idiopathic Thrombocytopenic Purpura

1. 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, 1–4 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 recognized
by the Fc receptor on the splenic macrophages, ingested, and destroyed. A recent history
of viral illness is described in 50–65% 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 virus–related ITP is usually of short duration
and follows the course of infectious mononucleosis. HIV-associated ITP is usually
chronic.
CLINICAL MANIFESTATIONS.
The classic presentation of ITP is that of a previously healthy 1–4 yr old child who has
sudden 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 profound
thrombocytopenia (platelet count <10 × 109
/L). There is a history of a preceding viral
infection 1–4 wk before the onset of thrombocytopenia. Findings on physical
examination are normal, other than the finding of petechiae and purpura. Splenomegaly is
rare, as is lymphadenopathy or pallor. An easy to use classification system has been
proposed from the U.K. to characterize the severity of bleeding in ITP on the basis of
symptoms and signs, but not platelet count:
1. No symptoms
2. Mild symptoms: bruising and petechiae, occasional minor epistaxis, very little
interference with daily living
3. Moderate: more severe skin and mucosal lesions, more troublesome epistaxis and
menorrhagia
4. Severe: bleeding episodes—menorrhagia, epistaxis, melena—requiring transfusion
or hospitalization, symptoms interfering seriously with the quality of life
The presence of abnormal findings, such as hepatosplenomegaly or remarkable
lymphadenopathy, suggests other diagnoses (leukemia). When the onset is insidious,
especially in an adolescent, chronic ITP or the possibility that thrombocytopenia is a

2. manifestation of a systemic illness, such as systemic lupus erythematosus (SLE), is more
likely.
In 70–80% of children who present with acute ITP, spontaneous resolution occurs within
6 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 argue
that 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 who
present with acute ITP go on to have chronic ITP.
LABORATORY FINDINGS.
Severe thrombocytopenia (platelet count <20 × 109
/L) is common, and platelet size is
normal or increased, reflective of increased platelet turnover. In acute ITP, the
hemoglobin value, white blood cell (WBC) count, and differential count should be
normal. Hemoglobin may be decreased if there have been profuse nosebleeds or
menorrhagia. Bone marrow examination shows normal granulocytic and erythrocytic
series, with characteristically normal or increased numbers of megakaryocytes. Some of
the megakaryocytes may appear to be immature and are reflective of increased platelet
turnover. Indications for bone marrow aspiration include an abnormal WBC count or
differential or unexplained anemia as well as findings suggestive of bone marrow disease
on history and physical examination. Other laboratory tests should be done as indicated
by the history and physical examination. In adolescents with new-onset ITP, an
antinuclear antibody test should be done to evaluate for SLE. HIV studies should be done
in at-risk populations, especially sexually active teens. Platelet antibody testing is seldom
useful in acute ITP. A Coombs test should be done if there is unexplained anemia to rule
out Evans syndrome (autoimmune hemolytic anemia and thrombocytopenia) [see Chapter
464 ] or before instituting therapy with IV anti-D.
DIFFERENTIAL DIAGNOSIS.
The well-appearing child with moderate to severe thrombocytopenia, an otherwise
normal complete blood cell count (CBC), and normal findings on physical examination
has a limited differential diagnosis that includes exposure to medication that induces
drug-dependent antibodies, splenic sequestration due to previously unappreciated portal
hypertension, and rarely, early aplastic processes, such as Fanconi anemia. Other than
congenital syndromes, such as amegakaryocytic thrombocytopenia and
thrombocytopenia-absent radius (TAR) syndrome, most marrow processes that interfere
with platelet production also cause abnormal synthesis of red blood cells (RBCs) and
WBCs and therefore manifest diverse abnormalities on the CBC. Disorders that cause
increased platelet destruction on a nonimmune basis are usually serious systemic illnesses
with obvious clinical findings (e.g., hemolytic-uremic syndrome [HUS], disseminated
intravascular coagulation [DIC]). Isolated enlargement of the spleen suggests the
potential for hypersplenism owing to either liver disease or portal vein thrombosis.
Autoimmune thrombocytopenia may be an initial manifestation of SLE, HIV infection, or
rarely, lymphoma. Wiskott-Aldrich syndrome must be considered in young males found

3. 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 findings
limited to petechiae and purpura on the skin, despite severe thrombocytopenia. Compared
with 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. Antiplatelet
antibodies 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 therapeutic
roller 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 0.8–1.0 g/kg/day for 1–2
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-mediated
phagocytosis 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 aseptic
meningitis.
3. Intravenous anti-D therapy. For Rh positive patients, IV anti-D at a dose of 50–
75μg/kg causes a rise in platelet count to>20× 109
/L in 80–90% of patients within
48–72 hr. When given to Rh positive individuals, IV anti-D induces mild
hemolytic 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 1–4 mg/kg/24 hr appear
to 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 usually
continued for 2–3 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.

4. 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% of
children 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 older
child (> 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 associated
with 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 and
platelet 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 lifestyle
issues 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 chronic
immune 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 is
controversial.
484.2 Drug-Induced Thrombocytopenia

5. 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, and
trimethoprim-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.

6. 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, and
trimethoprim-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.