1. IMMUNE THROMBOCYTOPENIC PURPURA (ITP) Dr. Mohamed Haseen Basha Dr. Mohamed Haseen Basha Assistant professor ( Pediatrics) Faculty of Medicine Al Maarefa College of Science and Technology

2. Introduction Normal platelet count Newborn 84,000 – 4,78,000 cells/mm3 After 1 week-adults 1,50,000 – 4,00,000 cells/mm3 Average life span of platelets – 7-10 days Decrease in platelet count - Thrombocytopenia

3. Thrombocytopenia Platelet count < 1,50,000 cells/mm3 Causes Increased platelet sequestration Hypersplenism, hypothermia, burns Increased platelet destruction Immune, Non-immune Decreased platelet production

4. Cut-off values Neonates – 20,000 – 50,000 cells/mm3 (high risk for Intra Cranial Hemorrhage) Children – 10,000 – 20,000 cells/mm3 Spontaneous bleeding do not occur until counts are < 20,000 cells/mm3

5. Immune thrombocytopenic purpura Disorder characterized by accelerated destruction of antibody sensitized platelets by phagocytic cells, especially those of spleen usually 1-4 wk after exposure to a common viral infection. It is an acquired and most commonly benign disorder. Incidence – 1 in 20,000 children / yr. Peak age at diagnosis – 1-4 yrs. Male to female – 1:1 (children) A recent history of viral illness is described in 50-65% of cases of childhood ITP. ITP seems to occur more often in late winter and spring after the peak season of viral respiratory illness.

6. Pathogenesis In children with acute ITP, the acute presentation of an autoimmune disease is unknown. In chronic ITP, many patients demonstrate antibodies against the platelet glycoprotein complexes, αIIb-β3 and GPIb. After binding of the antibody to the platelet surface, circulating antibody-coated platelets are recognized by the Fc receptor on splenic macrophages, ingested, and destroyed. Most common viruses have been described in association with ITP, including Epstein-Barr virus and HIV. In some patients ITP appears to arise in children infected with Helicobacter pylori or rarely following vaccines.

7. Acute ITP Benign, self limited Young children (< 10 yrs) Often viral infection or vaccination precedes Resolves within weeks or a few months of original presentation Chronic ITP Approximately 20% of patients who present with acute ITP have persistent thrombocytopenia for >12 month and are said to have chronic ITP. Age > 10 yrs Insidious onset Female gender

9. Clinical features The classic presentation of ITP is a previously healthy 1-4 yr old child who has sudden onset of generalized petechiae and purpura. 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, lymphadenopathy, bone pain, and pallor are rare. Palpable spleen – 10% cases If malaise, bone pain, adenopathy is present – suspect malignancy

10. Severe bleeding is rare. 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 develop an intracranial hemorrhage. There is no evidence that therapy prevents serious bleeding. Approx 20% of children who present with acute ITP go on to chronic I The outcome/prognosis may be related more to age, as ITP in younger children is more likely to resolve whereas the development of chronic ITP in adolescents approaches 50%.

11. Classification system proposed 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 trouble some epistaxis and menorrhagia 4.Severe: bleeding episodes—menorrhagia, epistaxis, melena- requiring transfusion or hospitalization, symptoms interfering seriously with the quality of life

12. Investigations Severe thrombocytopenia (platelet count <20 × 10 9 /L) is common, and platelet size is normal or increased, reflective of increased platelet turnover Hb & WBC counts – normal Bleeding time prolonged, clotting time normal Bone marrow aspiration – Bone marrow examination shows normal granulocytic and erythrocytic series, with characteristically normal or increased megakaryocytes. This is indicated in children with atypical laboratory features and for those whom initial therapy fails

13. Investigations – Additional tests: (chronic cases) Screening for immunodeficiency Anti nuclear antibodies Direct coomb’s test Antiphospholipid antibody assay Thyroid function test Blood counts and peripheral smear for parents Serological testing for platelet auto antibody is unnecessary, because there is as yet no reliable test with sufficient specificity and sensitivity

14. Management Child’s activity should be limited Aspirin containing medications should be avoided Detailed education to family Careful follow up Observation only Platelet count > 20,000 cells/mm3 and only minor purpura

15. First line medical therapies Corticosteroids Intravenous immunoglobulin Anti D

16. Corticosteroids Inhibition of both phagocytosis & antibody production Improved platelet production and microvascular endothelial stability Traditional dose 2 mg/kg/day (60mg/day max) for approximately 21 days 4 mg/kg/day for 7 days then tapered to day 21 is equally effective Alternate – mega dose pulse therapy Methyl prednisolone 30 mg/kg/day IV or Oral for 3 days

17. Intravenous Immunoglobulin 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 down regulating Fc-mediated phagocytosis of antibody-coated platelets. IVIG therapy is both expensive and time-consuming Side effects: flu like symptoms, aseptic meningitis, anaphylaxis, hemolytic anemia, HCV transmission Duration of response is brief (2 – 4 weeks)

18. Anti D For Rh-positive patients, IV anti-D at a dose of 50-75 μg/kg causes a rise in platelet count to >20 × 10 9 /L in 80-90% of patients within 48-72 hr. 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. Therapeutic effects lasts for 1 – 5 weeks Side effects: headache, nausea, chills, dizziness, fever, hemolysis

19. Management of Chronic ITP Primary goal – prevent bleeding episodes & not to cure the disease 1/3 of these children – spontaneous remission in months or years later Observation alone is an approach for many patients, especially those with minimal symptoms. Role of splenectomy in ITP 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. Splenectomy is successful in inducing complete remission in 64-88% of children with chronic ITP.

20. Child can be managed using medical therapy, such as IVIG, corticosteroids, IV anti-D, or rituximab. Two effective agents that act to stimulate thrombopoiesis, romiplastin and eltrombopag are approved by the FDA to treat adults with chronic ITP. Preliminary data using thrombopoietic agents in children are encouraging.

21. Life threatening hemorrhage in ITP IV Ig 1g/kg Anti D 50 – 75 µg/kg High dose corticosteroid – methyl prednisolone 30mg/kg IV Platelet transfusion A combination of the above can be tried

22. Prognosis Excellent chance of recovery, irrespective of therapy Platelet count returns to normal in 4 – 8 weeks in ½ of the patients and in 2/3 of children by 3 months after diagnosis 5 % have recurrent ITP – characterized by intermittent episodes of thrombocytopenia followed by lengthy periods of remission

23. Thank you