Itp seminar

immune thrombocytopenia purpura

1. IMMUNE THROMBOCYTOPENIC PURPURA ( ITP) R.Anusha, PharmD Intern, 170514882007. 1

2. IMMUNE THROMBOCYTOPENIC PURPURA ( ITP) The most common(4-8 /100,000) cause of thrombocytopenia in children and a result of immunologically mediated increased platelet destruction. Acute and self-limiting but may be recurrent or chronic disorder. Mainly affects children between 2 and 10 years of age. Boys and girls are equally affected. 2

3. Idiopathic thrombocytopenia purpura is a blood disorder affecting the platelets. It is a condition in, which there is bruising (purpura) because there are fewer platelets in the blood than usual (thrombocytopenia) and it is not known what causes it (idiopathic). 3

4. T he condition referred to as ‘immune’ thrombocytopenia purpura which means it could have been caused by something going wrong with the immune system (the body’s defence against infection) or an allergic reaction 4

5. Two Types of ITP Acute Immune Thrombocytopenic Purpura The course of disease is shorter or equal to than 6 months. Chronic Immune Thrombocytopenic Purpura The course of disease is longer than 6 months. 5

6. ETIOLOGY Idiopathic. Exact antigenic target for most such antibodies in most cases of childhood acute ITP remains undetermined. In chronic ITP May demonstrate antibodies against platelet glycoprotein. Most common viruses which are associated with ITP are EBV (short duration) & HIV (chronic).Rarely in children infected with H.pylori . These viral infections trigger the body to produce antibodies to destroy the virus. It is thought that these antibodies target platelets sothe spleen and liver see them as foreign and destroy them. 6

7. PATHOGENESIS 7 An autoantibody directed against the platelet surface develops with resultant sudden onset of thrombocytopenia. After binding of the antibody to the platelet surface, circulating antibody-coated platelets are recognised by the Fc receptors on splenic macrophages, ingested and destroyed.

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10. SIGNS AND SYMPTOMS Scattered petechiae Bleeding signs and symptoms Mucosal bleeding GI Bleeding Intracranial hemorrhage Hematuria Thrombocytopenia Purpura 10

11. Excessive bleeding with minor injuries Spontaneous bleeding from the mouth and nose Unexplainable or spontaneous bruising Excessive internal bleeding Disturbed sleep cycle/ Insomnia Irregular appetite Depression 11

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13. DIAGNOSTIC TESTS Coagulation test : PT and PTT are normal Bleeding time: Prolonged CBC: Low number of platelets Platelet associated Antibody may be detected Bone Marrow Examination: The bone marrow in patients with ITP contains normal or increased numbers of megakaryocytes, Indicating that platelet production is normal and that thrombocytopenia results from increased platelet destruction. NO SPECIFIC TEST THAT IS DIAGNOSTIC OF ACUTE OR CHRONIC ITP 13

14. TREATMENT There are NO DATA showing that treatment affects either short term or long term clinical outcome of ITP. SUPPORTIVE MEASURES: Reassurance. Restricting physical activity and avoiding trauma. Avoid medications that suppress platelet production or alter their function e.g , aspirin, heparin, valproic acid, digoxin etc. 14

15. INTRAVENOUS IMMUNOGLOBULIN(IVIG): MECHANISM:Blocking Fc receptor of the RE ( reticulo -endothelium) phagocytes. Preventing them from binding and destroying IgG antibody-coated platelets. DOSE:As per American Society of Hematology Guidelines: “A single dose of IVIG (0.8-1g/kg) or short course of corticosteroids should be used as first line treatment”. Dose of 0.8 – 1g/kg/day for 1-2 days induces a rapid rise in platelets usually > 20 ˣ10 9 /L in 95% patient within 48hours. MERIT: Results in faster elevation of the platelet count and may be indicated in severe disease. LIMITATION OF IVIG: Expensive, high frequency of headaches and vomiting suggestive of IVIG-induced aseptic meningitis. 15

16. CORTICOSTEROIDS: MECHANISM:Have a rapid, dose-dependent action that reduce RE destruction of antibody-coated platelets. Also more slowly reduces antibody production. DOSE:Oral prednisone 2 to 4 mg/kg/d tapered over 2 to 4 weeks. Children with chronic ITP who have mild or recurrent bleeding are sometimes treated with intermittent courses of IVIG or high dose corticosteroids(intravenous methylprednisolone 20~30mg/kg/d for 3 days, then decrement). MERIT:Cheap and convenient. DISADVANTAGE:Long - term use of corticosteroids should be avoided because of potential toxicity( moodiness,weight gain, etc) 16

17. IV ANTI-D THERAPY: For Rh + ve patients. Ineffective in Rh – ve patients. MECHANISM: Anti- Rh(D) immunoglobulin produces a mild hemolytic anemia that saturates the Fc receptors of the phagocytic elements of the RE system. Permitting increased survival of antibody-coated platelets. DOSE:50-75µg/kg causes rise in platelet count to > 20 ˣ10 9 /L in 80-90% of patients within 48-72hours. MERIT : less expensive than IVIG but more costly than steroids,lower rate of allergic side effects(10%) than IVIG and does not cause aseptic meningitis. DISADVANTAGE:Cause mild hemolysis with a transient hemoglobin decrease of 10 to 20g/L. 17

18. PLATELET TRANSFUSION: INDICATION: Platelets are less than 3 x 10 9 /L , intravenous platelet infusion is necessary to prevent severe hemorrhagic tendency. Platelet infusions have no role except in life - threatening emergencies. Because there are a lot of PAIgGs in circulation of patients, infusion platelets will be destroyed quickly. 18

19. SPLENECTOMY: Should be reserved for 1 of 2 circumstances. 1) The older child (≥4yr) with severe ITP that has lasted >1yr (chronic ITP). 2) 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 platelet count cannot be corrected rapidly with transfusion of platelets and administration of IVIG and corticosteroids. 19

20. ALTERNATIVE TO SPLENECTOMY: Rituximab used (off-label) in children to treat chronic ITP. In 30-40% it has induced a partial or complete remission. THROMBOPOIETIC AGENTS: Stimulate thrombopoiesis (in chronic ITP): 1) Romiplastin 2) Eltrombopag These have FDA approval in adults with chronic ITP who have insufficient response to corticosteroids,immunoglobulins,or splenectomy. 20

21. HIGH DOSE DEXAMETHASONE: Dexamethasone has FDA approval for treatment of ITP in adults. 21

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24. REFERENCE: 2011 Clinical Practice Guideline on the Evaluation and Management of Immune Thrombocytopenia(ITP);The American Society of Hematology. Raj AB (2017);Immune Thrombocytopenia:Pathogenesis and Treatment Approaches;Journal of Hematology and Transfusion,5(1):1056. 24