Idiopathic Thrombocytopenic Purpura

ITP parthenogenesis, causes, investigations and treatment modalities

1. Idiopathic Thrombocytopenic Purpura Prepared by, Anish Dhakal (Aryan)

2. Abnormal bleeding Purpuric disorders (primary hemostasis) Disorders of Coagulation (secondary hemostasis) Vessel problem Platelet problem Abnormal function Decreased number Congenital Acquired Decreased production Increased destruction Sequestration ITP

3. Normal Platelet count : (1.5 -4.5) *10 5 /cu mm Thrombocytopenia : Reduced platelets < 1.5 * 10 5 / cu mm Causes of Thrombocytopenia : Decreased Production ( Congenital / Acquired) Sequestration of Platelets within enlarged spleen Increases destruction of normally synthesized platelets Non- Immune Immune Idiopathic thrombocytopenic Purpura

4. Acute (<6 months) Chronic (>6 months) Commonest bleeding disorder Presenting in children between 1-7 yrs age Etiology Cause is unknown Common viruses in association with ITP: Epstein Barr virus: usually of short duration follows Infectious mononucleosis Human Immuno Deficiency Virus: Chronic Introduction

5. Due to overactive immune system Exposure to common viral infection After 1-4 weeks Autoantibody against antigen: Platelet Glycoprotein IIb / IIIa complex Antibody coated Platelets circulate in blood Recognized by Fc receptor on Splenic macrophages Ingested Destroyed Pathogenesis

6. Depends on platelets count. Mild unless platelets drop below 20,000 /cu mm Petechiae & Ecchymoses following mild trauma :20,000- 50,000 /cu mm Antecedent history of febrile illness. On presentation afebrile & well. Apperance of bruises & mucosal bleeding ( Epistaxis /Oral oozing) Prolonged bleed on superficial trauma. Clinical manifestation

7. No symptoms Mild symptoms : Bruising & petechiae Occasional minor epistaxis Very little interference with daily living Moderate: More severe skin and mucosal lesions More troublesome epistaxis Menorrhagia Severe: Bleeding episodes- Menorrhagia Epistaxis Melena Classification of severity of bleeding:

8. Normal with Petechiae & Purpura . Splenomegaly, lymphadenopathy or pallor rare. Fanconi anaemia Hypoplasic / Absent thumb Short stature Hyperpigmentation Hemangiomas : By USG of abdomen Collagen vascular disorder or malignancy Splenomegaly & Lymphadenopathy Hypersplenism Physical exam

9. 1. Complete Blood Count: Acute ITP Hb , WBC & differential count=Normal Hb may be decreased 2. Peripheral Blood Smear: Abnormal blast cells Malarial parasites To know precise platelets count 3. LFT & RFT and blood level of lactic dehydrogenase R/O hepatitis, hemolysis, HUS, Occult malignancy Investigations

10. Bone marrow Aspiration: Normal granulocytes and erythrocytic series Indications: Abnormal WBC count Unexplained anaemia Findings suggestive of Bone failure syndrome/ Malignancy Hallmark: Increase in megakaryocyte number in the bone marrow.

11. Other tests Antinuclear antibody test: for SLE HIV test Platelet antibody test: Acute ITP Direct Antiglobulin test (Coombs) : R/O Evans syndrome Autoimmune hemolytic anemia and thrombocytopenia= Evans Syndrome

12. Management Goals of therapy Minimizing the risk of hemorrhage Decreasing long term side effects of treatment In minimal , mild, and moderate symptoms no therapy only counselling and close observation In bleeding child Intravenous immunoglobulin (IVIG) Intravenous anti-D therapy Corticosteroid therapy Splenectomy

13. IVIG dose of 0.8-1.0 g/kg/day for 1-2 days induces a rapid rise in platelet count 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 to administer. after infusion, there is a high frequency of headaches and vomiting, suggestive of IVIG-induced aseptic meningitis.

14. IV anti-D. For Rh positive patients, IV anti-D at a dose of 50-75  mg/kg causes a rise in platelet count in 80-90% of patients within 48-72 hr. RBC-antibody complexes bind to macrophage Fc receptors and interfere with platelet destruction, thereby causing a rise in platelet count But may induce mild hemolytic anemia IV anti-D is ineffective in Rh negative patients

15. C orticosteroids Steroids are presumed to reduce the risk of symptoms in ITP patients by: Reducing antibody production Reducing reticuloendothelial system phagocytosis of antibody-coated platelets Improving vascular integrity Prednisone — 1 to 2 mg/kg (maximum dose 60 mg) per day in 3 divided doses for 14 days followed by a week of tapering Methylprednisolone  — 30 mg/kg per day intravenously for 3 days

16. Splenectomy In child (≥4  yr ) with severe ITP for >1   yr (chronic ITP) with uncontrolled symptoms In life-threatening intracranial hemorrhage , if platelet count cannot be corrected rapidly with transfusion of platelets and administration of IVIG and corticosteroids High risk of post splenectomy infection caused by encapsulated organisms and pulmonary HTN in adulthood

17. Chronic ITP About 20% of patients with acute ITP have persistent thrombocytopenia for >12  mo and are said to have chronic ITP Splenectomy is successful in inducing complete remission in 64-88% of children with chronic ITP Alternate day low dose of steroids Various combinations of danazol , vincristine, cyclosporine, azathioprine, Anti CD20 monoclonal Ab To stimulate thrombopoiesis , romiplastin and eltrombopag

18. References: OP Ghai , GHAI ESSENTIAL PEDIATRICS, 8 th edition Nelson’s Pediatrics , 20 th edition

19. Thank you