3. Case
• A previously healthy 6-year-old boy is brought into the emergency
department (ED) from his family physician. He had a cold a few weeks ago,
although since that time he has been well with no fever or other
complaints. Yesterday, his parents noticed a rash on his legs, and today,
they noticed that he had multiple bruises. They went to his family physician
who diagnosed the rash as petechiae and recommended that he must be
taken immediately to the ED for blood work.
• A quick but thorough physical examination is remarkable only for
widespread petechiae and bruising on his trunk and extremities. He is
afebrile and has normal vital signs and is otherwise very well appearing.
Pertinent negatives include no blood blisters (“wet purpura”) in his oral
cavity, no lymphadenopathy, and no hepatosplenomegaly.
4. Introduction
• ITP was previously known as idiopathic thrombocytopenic purpura or
immune thrombocytopenic purpura.
• The current term Immune ThrombocytoPenia
• Not purpura because many cases do not present with purpura
• Immune thrombocytopenia (ITP) of childhood is characterized by:
• Isolated thrombocytopenia
• (platelet count <100,000/microL with normal white blood cell count and hemoglobin).
5. Terminology or Types
• Primary ITP – ITP in the absence of other causes. The main focus of this
Presentation.
• Categorized into three phases, depending on the duration of the disease course:
• Newly diagnosed ITP – ITP within three months from diagnosis
• Persistent ITP – Ongoing ITP between 3 and 12 months from the initial diagnosis
• Chronic ITP – ITP lasting for more than 12 months
• The clinical features are similar
• Secondary ITP –ITP with an underlying cause
6. Pathogenesis
• Autoantibodies (usually IgG) are directed against
• Platelet membrane antigens.
• Same antibodies may inhibit platelet production.
• In some patients with ITP, an alternative immunologic mechanism of
T-cell-mediated cytotoxicity may cause thrombocytopenia. These
cytotoxic T cells may act upon megakaryocytes in the bone marrow
rather than circulating platelets.
7. Epidemiology
• The annual incidence of ITP is estimated to be between 1 and 6.4 cases per 100,000 children.
• Present at any age, but there is a peak in incidence between two and five years
• There is a slight predominance of boys to girls, especially in infants. 1.7:1
• There is a female predominance in adolescents and younger adults.
• Seasonal fluctuations have been reported (Spring and early summer)
• An association with allergic diseases has also been reported.
8. Clinical Features
• ITP typically presents with the sudden appearance of a petechial rash,
bruising, and/or bleeding in an otherwise healthy child.
• ITP is occasionally detected incidentally without any clinical manifestation when
doing CBC for other reason.
9. Bleeding symptoms
Grade (international consensus report) Bleeding severity Clinical symptoms
Grade I Minor/minimal Few petechiae (≤100 total) and/or ≤5 small
bruises (≤3 cm in diameter)
Grade II Mild Many petechiae (>100 total) and/or >5 large
bruises (>3 cm in diameter)
Grade III Moderate Mucosal bleeding ("wet purpura") that does
not require immediate medical attention or
supervision, such as brief epistaxis,
intermittent gum bleeding
Grade IV Severe Mucosal bleeding or suspected internal
hemorrhage that requires immediate medical
attention (e.g. severe GI bleeding, severe
prolonged epistaxis, pulmonary
hemorrhage, muscle or joint hemorrhage)
Life-threatening Shock state Documented intracranial hemorrhage or life-
threatening or fatal hemorrhage in any site
Grading of severity of bleeding symptoms in children with immune thrombocytopenia (ITP)
10. Sites of Bleeding
• In a large registry study of children with newly
diagnosed ITP, the following bleeding manifestations
were reported:
• Cutaneous (petechiae, purpura, or bruising) – 86 percent
• Nasal – 20 percent
• Oral – 19 percent
• No bleeding – 9 percent
• Menstrual, gastrointestinal, or urinary bleeding – <3
percent
11. Serious hemorrhage
• Risk factors for serious bleeding include:
• Severe thrombocytopenia (platelet count <20,000/microL)
• Previous minor bleedings
• Chronic ITP
• Epistaxis >5 to 15 minutes duration
• Gastrointestinal bleeding,
• Other severe mucosal bleeding requiring hospital
admission and/or blood transfusions)
• Intracranial hemorrhage <1%
12. Intracranial Hemorrhage
• Signs and symptoms concerning for ICH
• Headache, persistent vomiting, altered mental status, seizures, focal
neurologic findings, recent head trauma)
• Require urgent evaluation including neuroimaging and management.
• Risk factors for ICH in children with ITP include:
• Head trauma
• Signs of severe bleeding (e.g. hematuria, prolonged epistaxis, GI bleeding)
• Platelet count <10,000/microL
13. Laboratory Findings
• Platelet count: A platelet count of <100,000/microL
• Other CBC findings: all are generally normal.
• Peripheral blood smear: platelets are usually decreased in number
but either normal in size or variably sized with large platelets present,
particularly when symptoms have been present for several days or
longer.
• Bone marrow examination — Bone marrow examination (aspirate
and biopsy) is not necessary for the great majority of children;
• It is performed in selected patients to exclude other causes of
thrombocytopenia, such as malignancy
14. Indications for bone marrow examination
• Atypical clinical or laboratory features at presentation
• Insufficient or no response to treatment
• glucocorticoids
• IVIG
• Anti-D immunoglobulin
• New findings that emerge during follow-up
• Loss of response to typical ITP therapies that had
previously been effective.
15. Evaluation
• Initial evaluation: Initial laboratory testing includes the following:
• Complete blood count (CBC), including platelet count, white blood cell
differential, and red blood cell indices
• Reticulocyte count
• Examination of the peripheral blood smear
• Blood type and direct antiglobulin test (DAT, formerly called the Coombs test)
16. Diagnosis
• ITP is a diagnosis of exclusion, so other causes of thrombocytopenia
must be ruled out
• For children with a typical presentation of ITP, presumptive diagnosis
may be established based upon the following criteria:
• Platelet count <100,000/microL.
• Otherwise normal CBC with normal differential white count, hemoglobin, and
reticulocyte count.
• No abnormalities on the peripheral blood smear after review by an
experienced practitioner
• Negative direct anti-globulin test (DAT).
• Absence of associated conditions that may cause thrombocytopenia
17. Findings that suggest a diagnosis other than ITP
• Enlargement of lymph nodes, liver, or spleen;
• Systemic symptoms (eg, fever, anorexia, bone or joint pain, or weight loss)
• long-standing history of atypical bleeding
• The presence of a clinically significant systemic disease.
18. Treatment Options in ITP
• Childhood ITP is usually acute and self-limited, with 75% to 80% of
children with ITP having a complete remission within 6 months.
• Close observation is often the only therapy needed because ITP is a
self-limiting condition and serious bleeding is rare, even with very low
counts.
• Medical treatment is often considered in patients with a platelet
count of less than 10 × 109/L or those with overt mucosal bleeding.
• Additional reasons to use pharmacologic therapy is to raise platelet
counts more rapidly, in patients who participate in high-risk activities
or upcoming invasive procedures.
19. Medical Treatment:
• First-line therapies include corticosteroids and intravenous
immunoglobulin (IVIG).
• Anti-D immunoglobulin is also an effective treatment option for
patients with ITP who are blood type Rh+
• Anti-D should be avoided in patients with any signs of hemolysis at baseline.
20. References
•Uptodate
• Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children:
report from an international working group. Blood 2009; 113:2386.
• Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
• D'Orazio JA, Neely J, Farhoudi N. ITP in children: pathophysiology and current treatment approaches. J Pediatr Hematol Oncol 2013; 35:1.
• Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol 2006; 133:364.
• British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic
purpura in adults, children and in pregnancy. Br J Haematol 2003; 120:574.
• Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol
2010; 85:174.
• Zeller B, Rajantie J, Hedlund-Treutiger I, et al. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease.
Acta Paediatr 2005; 94:178.
• Kühne T, Buchanan GR, Zimmerman S, et al. A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura
(ITP) from the Intercontinental Childhood ITP Study Group. J Pediatr 2003; 143:605.
• Kühne T, Imbach P, Bolton-Maggs PH, et al. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet 2001; 358:2122.
• Chiang MR, Wei CC, Muo CS, et al. Association of primary immune thrombocytopenia and common allergic diseases among children. Pediatr Res 2015; 77:597.
• Kühne T, Berchtold W, Michaels LA, et al. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the
Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica 2011; 96:1831.
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