• Two Types: Acute and Chronic

  • Diagnosis: Established by excluding known causes of thrombocytopenia

  • Treatment: Depends on the platelet count and the presence and severity of bleeding.

  • When therapy is indicated, the primary treatment options for the newly diagnosed patient are:

    • Corticosteroids

    • Intravenous immunoglobulin

    • Intravenous anti-D Ig

  • Immune thrombocytopenia purpura (ITP) of childhood is an acquired immune-mediated, and usually self-limiting, condition of low platelet counts.

  • Persistent ITP refers to ITP lasting between 3–12 months from diagnosis, which includes

    • Patients not achieving spontaneous remission or

    • Patients not maintaining their response after stopping treatment between 3–12 months from diagnosis

  • Chronic ITP is reserved for patients with ITP lasting >6 months.

  • Incidence

    • Estimated at 4–8 cases per 100,000 children annually

    • The rate is probably higher because of subclinical cases.

  • Age

    • Most common in children 2–10 years of age

    • Peak incidence at 2–4 years of age

  • Sex

    • In children, both sexes are equally affected.

    • Female predominance over male (2.3:1) is seen during adolescence and adulthood.

  • ITP is caused by antibodies (mostly immunoglobulin G [IgG]) directed against antigens normally present on platelet membranes such as glycoproteins IIb/IIa and Ib/IX.

  • The antibody-coated platelets are then recognized and destroyed by reticuloendothelial cells found mostly in the spleen.

  • History of a preceding infection, subsequently resolved

    • Elicited in the majority of patients

    • >70% of cases occur after viral infections.

  • In some cases, ITP is seen after measles-mumps-rubella immunization.

    • The best estimate of absolute risk is 1 in 24,000 doses.

    • Usually occurs within 6 weeks of vaccination

    • This number is considerably less than ITP that occurs after natural infections with measles, mumps, or rubella.

  • Typically, there is sudden onset of petechiae, purpura, and ecchymosis in the absence of other signs of illness.

  • Mucosal (nose, mouth, and gingival surfaces) bleeding may be present.

  • Usually, there are no significant abnormalities on history and physical examination.

    • No other systemic symptoms, such as fever, weight loss, bone pain, or joint pain

    • No significant enlargement of lymph nodes, liver, or spleen

    • If any of these symptoms or physical findings is present, the case is not typical of ITP and other diagnoses should be considered.

  • Infections with Epstein-Barr virus, hepatitis C virus, and HIVcan be ruled out by

    • History

    • Physical examination

    • Liver enzymes/function tests and viral studies, if needed

  • Drugs such as heparin and sulfonamides can be ruled out by history.

  • Other autoimmune diseases, such as systemic lupus erythematosus

    • May be difficult to diagnose

    • Are more likely to affect teenagers and adults than younger children

    • Common variable immunodeficiency and autoimmune lymphoproliferative syndrome should be considered in cases of multiple autoimmune cytopenias.

  • Acute leukemiaor bone marrow failure

    • Children with leukemiausually have symptoms and abnormal physical findings not seen in ITP.

      • Hepatosplenomegaly

      • Lymphadenopathy

      • Leukocytosis (white blood cell count >10,000/mcL)

      • Significant anemia(hemoglobin count < 10/dL)

  • Acquired aplastic anemia

    • Low platelet count is usually associated with other significant changes in peripheral blood, such as

      • Macrocytic anemia

      • Leukopenia

      • Neutropenia

  • Destructive thrombocytopenias, such as thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation(DIC)

    • Patients with these conditions present with other clinical and laboratory abnormalities and are usually sicker than ITP patients.

  • Inherited thrombocytopenia

    • Although thrombocytopenia in most children is either autoimmune or drug related, keep this category in mind.

    • Elicit a family history of thrombocytopenia, especially parent-child or maternal uncle–nephew.

    • Diagnostic features on peripheral smear that may point to inherited thrombocytopenia

      • Abnormal size of platelets (either small or giant)

      • Absence of platelet α-granules (gray platelets)

      • Döhle-like bodies

      • Microcytosis

    • Clinical features that suggest inherited thrombocytopenia

      • Bleeding out of proportion to the platelet count

      • Onset of thrombocytopenia early in life

    • Associated features, such as

  • Type 2B von Willebrand diseaseresults in increased spontaneous binding of the high-molecular-weight von Willebrand factor (VWF) multimers to platelets.

    • Can lead to increased clearance of platelets from circulation, resulting in variable thrombocytopenia

    • Usually of autosomal dominant inheritance, so important to obtain family history regarding mucocutaneous bleeding

    • If suspected, VWF studies including multimer analysis should be done in consultation with a hematologist.

  • ITP is a diagnosis of exclusion after considering other causes of isolated thrombocytopenia.

  • For patient with mucocutaneous signs of bleeding who is otherwise healthy, a reasonable workup includes

    • Complete blood count

    • Peripheral blood smear

    • Reticulocyte count

    • Blood typing

  • Complete blood count

    • Thrombocytopenia is usually the only laboratory abnormality.

    • Platelet count is usually < 20,000/mcL.

  • Peripheral blood smear

    • Will reveal morphologically normal leukocytes and erythrocytes

    • Large, freshly produced platelets are usually seen.

      • These young reticulated platelets contain messenger RNA and are metabolically active.

      • May explain why ITP patients do not bleed as severely as those with bone marrow failure and similarly low platelet counts

    • If other abnormalities are seen, obtaining additional tests may be indicated, such as

  • Reticulocyte count

    • Helpful when diagnosis of ITP is not straightforward (ie, in cases in which associated mild anemiaexists, which is not rare)

  • Blood typing

    • Determination of Rh status, which determines whether a patient is treatable with anti-D antibodies

  • Both reticulocyte count and blood typing are not strictly needed for evaluation.

    • However, drawing blood to keep aside for reticulocyte count and blood typing is preferable to performing multiple traumatic blood draws on a thrombocytopenic child.

  • Platelet antibodies tests

    • Although ITP is caused by platelet antibodies, these tests are sensitive but not specific.

    • Not indicated for the diagnosis of acute ITP in children

  • Assessment of bleeding time

    • Bleeding time is prolonged in ITP, but this test is unnecessary, traumatic, and inaccurate in children.

  • Tests for prothrombin time and activated partial thromboplastin time are unnecessary.

    • Results are typically normal in these patients.

  • Bone marrow biopsy

    • Performed in the past by many pediatric hematologists to rule out acute lymphocytic leukemiafor fear of partially treating and thus masking a leukemic process

    • Now, typically performed when patients have clinical or laboratory features atypical of ITP at presentation that suggest an alternate diagnosis, such as acute leukemiaor a bone marrow failure syndrome

    • Also indicated for patients in whom ITP is initially diagnosed but who do not respond to treatment

      • Timing of bone marrow evaluation is an individualized decision.

      • Most likely time is between 7–14 days after treatment begins, but response is poor

    • May be considered

      • In patients who have an atypical clinical course

      • In patients in whom splenectomy is contemplated for additional confirmation of diagnosis

      • To rule out a malignant process

    • Bone marrow in ITP

      • Is cellular, with normal erythroid and myeloid precursors

      • Usually shows increased numbers of megakaryocytes

  • Early treatment does not alter the natural course and does not affect the development of chronic ITP.

  • The same principles of treatment of acute ITP apply to a certain extent to management of chronic ITP.

  • Most ITP cases in children can be managed on an outpatient basis.

  • Consensus is that treatment is indicated for the patient with overt bleeding.

    • Treatment and management recommendations for patients who have different clinical manifestations remain a subject of debate.

    • Current therapy recommendations are based on expert consensus opinions.

  • American Society of Hematology guidelines

    • Children with ITP and platelet counts >30,000/mcL

      • Require no treatment if they have few or no symptoms, as is usually the case

    • Patients with platelet counts between 10,000 and 30,000/mcL

      • Treatment recommendations are based on the presence and severity of associated bleeding symptoms or the risk of bleeding.

      • The lower the platelet count, the more likely the patient is to receive treatment, even if symptoms are relatively mild.

    • Children who should be treated

      • Those with platelet counts < 10,000/mcL and purpura

      • Those with any concomitant or preexisting bleeding disorder

      • Those with extensive purpuraof the mucosal membranes may have a higher bleeding risk and should be treated more often than not.

  • Other important factors in treatment decision include

    • Child’s age

    • Child’s degree of activity

    • Social variables, such as reliability of caregivers and ease of access to emergency medical care

  • When therapy is indicated, the primary treatment options for the newly diagnosed patient are

    • Corticosteroids

    • Intravenous immunoglobulin (IVIG)

    • Intravenous anti-D Ig

  • Platelet transfusions

    • Ineffective because the transfused platelets are rapidly destroyed

  • Chronic ITP: the chance of spontaneous remission is still significant during this period, making deferral of more aggressive therapeutic approaches reasonable.

    • Other options include splenectomy, immunosuppressive therapy, rituximab, and thrombopoietin (TPO) receptor agonists.

  • General useful advice to families with an affected child includes

    • Avoid activities associated with increased likelihood of trauma, such as contact sports.

    • Make sure the child uses a helmet when riding a bicycle.

    • Avoid medications that interfere with platelet function, such as aspirin and nonsteroidal anti-inflammatory drugs.


  • Used for many years in all age groups

  • Reduce the risk of symptoms, most likely by reducing reticuloendothelial system phagocytosis of antibody-coated platelets

  • Most pediatric hematologists use prednisone for 2–3 weeks.

    • Shorter courses at higher doses are also effective.

    • Intravenous or oral methylprednisolone up to 3–7 days and dexamethasone for 4 days every 4 weeks have been given.

  • Most patients respond to steroids.

    • Response is faster with higher doses (seen after 72 hours of starting treatment).

    • Platelets usually decrease after steroids are discontinued if the titer of platelet antibodies remains elevated.

  • A second course of treatment may be necessary

    • If bleeding develops

    • If the platelet count decreases to < 10,000/mcL

  • Side effects of brief courses of corticosteroids include

    • Behavioral changes

    • Sleep disturbance

    • Increased appetite

    • Hyperglycemia

    • Weight gain

    • Side effects are more pronounced at higher doses.

    • Caution should be taken when using steroids in the setting of active infection, especially with varicellainfection.


  • Compared with patients receiving steroids

    • Rapid improvement in platelet count is seen, usually within 24 hours.

  • Probably interferes with Fc receptor activity, resulting in prolonged survival of antibody-coated platelets

    • Other mechanisms of action include

      • Regulatory properties of anti-idiotypic antibodies in IVIG

      • Effects on cytokine synthesis and on receptors for cytokines and complement

    • One intriguing proposal for mechanism of action

      • Concentration-dependent elimination of IgG is a known phenomenon and IVIG administration causes acceleration of the rate of IgG catabolism.

        • Such a process would eliminate individual IgG molecules in direct proportion to their relative concentration in plasma.

        • Thus elimination of antiplatelet antibodies is accelerated.

  • Far more expensive than steroids

  • Side effects

    • Chills

    • Fever

    • Headache

    • Nausea and vomiting

    • Tend to be more pronounced in older patients

    • Neutropenia (absolute neutrophil count < 1500/mcL) develops in ~30% of patients.

Anti-Rho (D) Ig

  • Binds to the D-antigen in Rh-positive individuals; the antibody-coated red cells block the Fc receptor of reticuloendothelial cells

    • Results in rapid increase in platelet count, usually in 1–2 days

  • A single dose of 50–75 mcg/kg is most commonly used.

    • Achieves a more rapid increase in platelet count that is similar to that seen with IVIG therapy

  • An average decrease in the hemoglobin level of ~1.3 g is seen as a result of the mild hemolysis of the patient’s Rho (D)-positive red cells.

    • Should be used with caution in children with preexisting anemia

    • Should probably be given only to children with a hemoglobin level >10 g/dL

    • With increased use, there have been a few cases of patients developing increased hemolysis leading to severe anemia, acute renal insufficiency, DIC, and multisystem organ failure.

      • It should always be used with caution.

      • It is recommended that patients treated with anti-Rho (D) receive intravenous fluids and be observed for the development of hematuriaand hemoglobinuria for at least 8 hours.

      • Signs and symptoms of intravascular hemolysis include back pain, shaking chills, fever, and discolored urine or hematuria.

        • Absence of the signs and symptoms of intravascular hemolysis within 8 hours does not indicate that intravascular hemolysis cannot occur subsequently.

Thrombopoietin receptor agonists

  • A number of studies with TPO receptor agonists have shown encouraging results in adults.

  • Some children have been successfully treated, and new information about safety and response is emerging.

  • Patients should have blood counts done once or twice weekly.

  • Blood counts should be less frequent when the platelet count is

    • Stable

    • >30,000 cells/mcL

    • Increasing with time


  • ~15–20% of pediatric patients will develop moderate or major hemorrhagic problems.

Intracranial hemorrhage

  • Intracranial hemorrhage (ICH) is rare; it occurs in 0.1–1% of acute ITP.

  • The most serious complication and most likely cause of death in ITP

  • Recognizing which patients are more likely to develop ICH is difficult.

    • A literature review of 62 reported pediatric and adolescent cases of ICH in the setting of ITP showed

      • Median time from the diagnosis of ITP to ICH was 32 days (range, 0 days–8 years).

      • 72% of cases occurred ≤6 months of diagnosis.

      • Platelet count was < 10,000/mcL in 71.4% of the cases.

      • Treatments before the ICH was primarily steroids but also included IVIG, splenectomy, and others.

      • A significant number of patients developed ICH despite having already initiated steroid treatment.

    • Many patients have other risk factors, including

  • Management is an emergency that requires

    • Immediate imaging (computed tomography) to determine location and extent of the bleeding

    • Immediate consultation with

      • Pediatric intensivist

      • Hematologist

      • Neurosurgeon

      • General surgeon

  • Treatment includes

    • Administration of IVIG, steroids, continuous platelet transfusions to rapidly increase the platelet count

    • Surgical intervention, if needed, including

      • Craniotomy (especially with posterior fossa hemorrhages that are more likely to cause herniation or brainstem compression)

      • Splenectomy

Chronic ITP

  • Defined as persistence of thrombocytopenia lasting for >6 months from the time of diagnosis

    • ~10% of patients with typical ITP develop chronic thrombocytopenia.

    • In a prospective Dutch study, variables that predicted development of chronic disease included

      • Platelet count >10,000/mcL at the onset

      • Absence of infection shortly before the onset of the disease

      • The 232I/T Fc gamma receptor IIB genotype

      • In another meta-analysis, female gender and older age (>11 years) at presentation, among other variables, correlated with increased likelihood of developing chronic ITP.

  • Given sufficient time (even years), a significant proportion of such patients will improve or remit.

    • Management should focus on

      • Minimizing risk for bleeding

      • Maintaining a safe platelet count

      • Many patients will require no treatment

  • If treatment is needed

    • Periodic short courses of steroids may be given.

    • In case of long-term need for steroids, alternate-day dosing may be effective in preventing bleeding while reducing side effects.

    • IVIG or anti-Rho(D) Ig has also been used, but these measures are only temporary.

    • Splenectomy

      • Effective in improving the platelet count and reducing the associated risk of bleeding in 60–90% of children

      • A small but real risk remains of overwhelming postsplenectomy sepsis, which may be life threatening.

        • Usually delayed until the child is >5 years because the risk of overwhelming sepsis decreases with age.

        • American Society of Hematology guidelines recommend waiting until ≥12 months after diagnosis, if possible.

      • Platelet counts following splenectomy

        • Generally monitored indefinitely

        • Any drop in platelet counts or increase in symptoms should prompt assessment for the presence of an accessory spleen.

      • If not previously done, bone marrow biopsy is recommended for patients being considered for splenectomy.

      • Presplenectomy immunizations and subsequent penicillin prophylaxis are necessary.

    • Rituximab for refractory chronic ITP

      • A chimeric murine-human anti-CD20 monoclonal antibody

      • Acts by destroying B-lymphocytes by activating complement-dependent and an antibody-dependent cellular toxicity

        • Therefore, mechanism of action is a slow but effective decrease in production of antibodies.

      • In a study of 24 patients 2–19 years of age who received 375 mg/m 2of rituximab in 4 weekly doses

        • 63% achieved complete remission for 4–30 months (platelet count of >150,000/mcL).

      • Although long-term remissions have been documented, use of rituximab in ITP is relatively recent.

      • Long-term follow-up may be needed for accurate prognostication.

      • Use may be associated with

        • Infusion-related reactions

        • Development of transient hypogammaglobulinemia

  • Treatment does not alter the course (ie, the incidence of patients who go on to develop chronic ITP).

    • It does shorten the duration of thrombocytopenia in some patients.

  • For typical cases of childhood ITP

    • 80% of patients will have platelet counts return to normal ≤2 months of presentation, with or without therapy.

    • Another 10% will recover normal platelet levels in the next few months.

    • ~10% will go on to have chronic thrombocytopenia (>6 months’ duration).

  • ~25% of children will have a relapse after initial treatment.

    • 10% have chronic ITP.

    • 10% have recurrence but resolution ≤6 months.

    • 5% have ITP recurrences and remissions throughout their lives.

  • Most neonatal thrombocytopenia is not immune in nature but is caused by

    • Sepsis

    • Congenital infections

    • Drugs

    • Asphyxia

    • Necrotizing enterocolitis

  • 2 conditions occur when immune thrombocytopenia is seen in neonates.

    • Neonatal alloimmune thrombocytopenia (NAIT)

      • A condition in which the mother develops antiplatelet antibodies directed against specific antigens found on fetal platelets but lacking on hers

      • Associated 20% risk of ICH

      • Treatment usually involves administration of maternal washed platelets and IVIG.

      • Importance of detection and accurate diagnosis of NAIT is in the ability to prevent complications in future pregnancies by

        • Treating the mother with IVIG and steroids

        • Performing in utero blood sampling and intervening in case of thrombocytopenia

      • Hematologist and high-risk fetal-maternal specialist should be involved in management.

    • Another less serious condition is that resulting from passive transfer of maternal platelet autoantibodies in a mother with ITP.

      • Only 4% of babies born to mothers with ITP have platelet counts < 20,000/mcL.

      • The risk of ICH is low (< 1%), and no proof exists that cesarean delivery alters that risk.

      • Usually resolves within a few weeks as the antibodies are used up

      • Physicians may choose to treat the babies with IVIG in case the platelet count decreases to < 30,000/mcL.

      • Maternal ITP is not a contraindication to breastfeeding.

  • Significant bleeding

  • Severe anemia

  • Significant concern for possible traumatic injury

  • Any neurologic change in the setting of thrombocytopenia

  • History of feveror bone pain

  • Hepatomegaly, splenomegaly, significant lymphadenopathy

  • Family history of thrombocytopenia

  • Platelet count < 20,000/mcL

  • Abnormal leukocyte count on peripheral smear or associated anemia

  • Lack of response to initial therapy

  • All children with refractory ITP

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Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology
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