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INTRODUCTION
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Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. the number of circulating platelets decreases (thrombocytopenia), resulting in a characteristic bleeding tendency (purpura) . Immune thrombocytopenic purpura (ITP) is traditionally divided in acute and chronic forms based on the duration of the disease. A minority of children with idiopathic or immune thrombocytopenic purpura (ITP) have the refractory chronic form with bleeding problems (stage III or IV).
• Characters: • Immune (idiopathic) thrombocytopenic purpura (ITP) is a syndrome characterized by: • 1: Thrombocytopenia (platelet count less than 100 x 109 /L). • 2: Shortened platelet survival.(chromium -51 labeled platelets have a life span of a few minutes to 1-4 hours). • 3: Presence of antiplatelet antibody in the plasma. • 4: Increased megakaryocytes in the bone marrow.
Classification: This condition may be acute, chronic or recurrent. 1. Acute form, the platelet count return to normal (>150 x 109/L) within 6 months after diagnosis and relapse does not occur. 2. Chronic form, the platelet count remains low after 6 months. 3. Recurrent form, the platelet count decreases after having returned to normal levels. In adults, the chronic form is more common, whereas in children, the acute form is more common. ●A minority of children with idiopathic or immune thrombocytopenic purpura (ITP) have the refractory chronic form with bleeding problems (stage III or IV). Chronic refractory idiopathic thrombocytopenic purpura (ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with Prednisone and splenectomy
Pathophysiology •
Recent articles have revealed the dominance of a proinflammatory state in ITP following a relatively benign viral or environmental trigger
•
In addition, several articles have documented the persistence of inflammatory cytokines. and disturbed T cell apoptosis in childhood ITP. every child and adult has the potential to form autoantibodies to platelets. For unclear reasons, these self-reactive antiplatelet clones are not deleted during fetal development and persist in the antibody repertoire of the mature individual
Pathogenesis can be summarized in three steps: 1:Platelet Autoantibodies and Antigens: There are two types of mechanisms for the role of auto antibodies in ITP: A: Autoantibodies against Platelets: B: Autoantibodies against Megakaryocytes:
2: Platelets Clearance: 3: Infections
Diagnosis of ITP A. clinical Findings Typically, children with acute ITP appear healthy and the physical examination is unremarkable except for Skin Ecchymoses and petechiae Mucous membranes A small number of patients have ‘wet purpura’ with oral blood blisters or mucocutaneous or subconjunctival Bleeding from the nose gums, Mucous membranes, gastrointestinal tract, or kidneys is not uncommon, Menorrhagia may occur and may be severe. Hematemesis and melena are infrequent. Internal organs Bleeding may occur into the following organs: 1. Central nervous system a serious complication 2. Retinal hemorrhage 3. Middle ear: uncommon leading to hear impairment 4. Deep muscle hematoma and hemarthrosis: rare.
Signs With exception of hemorrhagic manifestation, the physical examination is not significant Usually, there is neither pallor nor hepatosplenomegaly. A palpable spleen is usually suggestive of a secondary cause (leukaemia, systemic lupus erythematosus, infectious mononucleosis, or hypersplenism) but the splenic tip may be palpable in 5–10% of patients with acute ITP. Cervical lymphadenopathy is not present unless the precipitating factor is viral illness
B. Laboratory Findings A complete blood count (CBC) and peripheral blood smear examination remain the most important laboratory tests The CBC should be within normal limits for age (normal hemoglobin levels, red blood cell count indices, and total and differential white blood cell counts) except for the low platelet count and mildly elevated platelet size. A peripheral smear should demonstrate normal morphology of all cell lines with a few large platelets.
Tests to consider when a patient does not meet the criteria forchildhood immune thrombocytopenic purpura or has persistent thrombocytopenia ---------------------------------------------------------------------------------Bone marrow aspiration Coagulation profile: prothrombin time, partial thromboplastin time Specific serum antibody assays for glycoprotein IIb/IIIa Viral serology (HIV, EBV, CMV, parvovirus B19, VZV, hepatitis A, B, C, roseola) Antinuclear antibodies, lupus anticoagulant Direct antiglobulin test Thyroid function studies Quantitative serum immunoglobulins with IgG subclasses Reticulated platelet count Platelet function tests ----------------------------------------------------------------------------------
Common laboratory tests obtained in the thrombocytopenic patient at presentation.
Complete blood count and differential review Rule out: Multilineage involvement leukemia or aplastic/myelodysplasia smear Evaluate platelet size (giant or "dust-like") Reticulocyte count
Hemolytic anemia or chronic blood loss
Blood type, Rh, antibody screen
Possible anti-D antibody treatment Autoimmune hemolytic disease
Chemistry panel
Eliminate systemic disease, i.e., hemolytic uremic syndrome, hepatitis, hemolysis, occult malignancy with elevated LDH or uric acid
DIC screen
Sepsis, Kasabach-Merritt syndrome
Quantitative immunoglobulin levels
Rule out: common variable immune deficiency, Wiscott-Aldrich
Viral titers/PCR
Cytomegalovirus, Epstein-Barr virus, human immundeficiency virus
Collagen vascular panel (ANA, anti-DNA)
Older patients, especially those with more chronic onset
History and physical findings not consistent with (ITP) of childhood. History/Findings
Alternative Diagnosis
Thrombocytopenia present from birth
Amegakaryocytosis Primary thrombocytopenia Giant platelet syndromes
Weight loss and recurrent fevers
Malignancy, immune deficiencies
Bloody diarrhea
Wiskott Aldrich Hemolytic uremic syndrome
Recurrent infections or failure to thrive
Primary immune disorder, HIV
History or presence of jaundice
Autoimmune hemolytic disease Hepatitis, cirrhosis with splenomegaly
Splenomegaly,lymphadenopathy
Autoimmune lymphoproliferative syndrome (ALPS), primary immune disorders, Gauchers malignancies, hypersplenism syndromes
Forearm or hand anomalies
Thrombocytopenia absent radii (TAR) Fanconi’s syndrome
Malar rash, dermatomyocytis, polymyocytis, eczema
Collagen vascular disease, Wiskott Aldrich
Cardiac malformation with or without DiGeorge Chromosome 22 microdeletions with large syndrome platelets, with or without Evans syndrome
C.Other Laboratory Tests Additional tests should be considered in children with persistent ITP of 3–6 months’ duration or in whom secondary thrombocytopenia is suspected . A-Specific serum antibody assays for glycoprotein IIb/IIIa have a role in distinguishing immune from non-immune thrombocytopenia in adults with ITP; their value in pediatric patients is limited , B- Assessment of platelet maturity by measuring reticulated platelets may be helpful in the diagnosis of ITP in children with atypical presentations. Elevated reticulated platelet
counts are indicative of increased production.
Differential diagnosis of childhood immune thrombocytopenic Purpura Congenital syndromes Fanconi anemia, thrombocytopenia-absent radii, Wiskott-Aldrich, Alport, and Bernard Soulier syndromes, May-Hegglin anomaly, gray platelet syndrome
Decreased platelet production Acute leukemia, lymphoma, aplastic anemia, amegakaryocytic thrombocytopenia, myelodysplastic syndrome, metastatic infiltration Of bone marrow
Increased platelet destruction Disseminated intravascular coagulation, thrombotic thrombocytopenic Purpura, hemolytic uremic syndrome, Evans syndrome.
• Criteria for the diagnosis : 1. Clinical examination: purpura with an otherwise essentially normal physical examination, with no significant splenomegaly and no lymphadenopathy
2. Platelet count and blood smears: thrombocytopenia only, with no evidence of red cell or white blood cell abnormalities
3.
Bone
marrow:
normal to increased number of megakaryocytes with normal myeloid and erythroid elements
4. Exclusion of secondary causes of thrombocytopenia, such as hypersplenism, microangiopathic hemolytic anaemia, disseminated intravascular coagulation, drug- induced thrombocytopenia, SLE, infections such as EBV, HIV, and parvovirus
Prognosis 1. Excellent; 50% recover usually within 1 month and 70-80% recover Within 6 months. 2. Spontaneous remission after 1 year is uncommon, although may occur even after several years. 3. When a demonstrable underlying cause of ITP exists, the prognosis is related to cause. 4. Age older than 10 years, insidious onset, and female gender are associated with the development of chronic ITP. 5. Of all chronic patients, 50-60% eventually stabilize without any therapy and without recourse to splenectomy
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• the recently published BSH (the British Committee for Standards in Hematology, 2003) practice guidelines for ITP in children clearly recommend that treatment be considered on the basis of clinical symptoms and cutaneous signs and not just platelet count alone. • The ASH (the American Society of Hematology ) practice guidelines published in 1996 differ from those of the BSH in that the triggers for initiating treatment for children with ITP are based on a low platelet count and the very small but definite risk of ICH, rather than symptoms. (George et al, 1996) and minor purpura do not require treatment or hospitalization. Children with platelet counts of
