Management of Children with newly Diagnosed ITP: the Toronto - PowerPoint PPT Presentation

Shared Decision Making in the Management of Children with newly Diagnosed ITP: the Toronto Experience Dr Victor Blanchette Professor of Pediatrics University of Toronto Medical Director, Pediatric Thrombosis and Hemostasis Program Division of Hematology/Oncology The Hospital for Sick Children Toronto, Canada

Presentation Outline • Definitions of ITP • Newly diagnosed ITP • Management of ITP - Background - Guidelines for the management of newly diagnosed ITP in children - The Toronto experience • Summary

Proposed New Definitions for the Different Phases of ITP Newly Diagnosed ITP ITP during the first 3 months of the illness replaces term acute ITP Persistent ITP ITP lasting between 3 to 12 months Chronic ITP ITP lasting for > 12 months Platelet “ threshold ” for definition of ITP < 100 x 10 9 /L Rodeghiero F et al Blood 2009 ;113 :2386-2393

Presentation Outline • Definitions of ITP • Newly diagnosed ITP • Management of ITP - Background - Guidelines for the management of newly diagnosed ITP in children - The Toronto experience • Summary

Newly Diagnosed ITP in Children Key Facts The typical child with newly diagnosed ITP is: • Young (average age 4-6 years) • Previously healthy with a negative family history of thrombocytopenia and has • A normal physical examination apart from bruising and/or a petechial rash • A normal blood count other than isolated thrombocytopenia

BONE MARROW ASPIRATE BLOOD SMEAR SHOWING A SHOWING INCREASED MEGATHROMBOCYTE NUMBERS OF MEGAKARYOCYTES

Grading of Bleeding Severity in Children With Newly Diagnosed Immune Thrombocytopenia N = 863 (2001-2004) Grading 1,2 Definition None or mild (76%) 3 no bleeding at all or bruising, petechiae, occasional mild epistaxis with little or no interference with daily living ( “ dry purpura ” ) Moderate (21%) more severe skin manifestations with some mucosal lesions and more tolerable epistaxis and menorrhagia ( “ wet purpura ” ) Severe (3%) bleeding episodes (epistaxis, melena, menorrhagia, and/or intracranial hemorrhage) requiring hospitalization and/or blood transfusions (1) Bolton-Maggs PH et al Lancet 1997;350:620-623 (2) Bolton-Maggs PH et al J Pediatr Hematol Oncol 2003;25(Suppl 1):S47-S51 (3) Neunert C et al Blood 2008;112:4003 - 4008

Presentation Outline • Definitions of ITP • Newly diagnosed ITP • Management of ITP - Background - Guidelines for the management of newly diagnosed ITP in children - The Toronto experience • Summary

Newly Diagnosed ITP in Children: Key Management Questions • To treat or not to treat? • To perform a bone marrow aspirate or not? • To hospitalize or not?

WHY TREAT ? “ FEAR OF INTRACRANIAL HEMORRHAGE ” Risk factors for intracranial hemorrhage (ICH) in children with acute ITP : • platelet count < 20,000/mL • head trauma • anti -platelet therapy e.g. Aspirin • vasculitis/vascular anomalies Incidence of ICH = approx. 2/500 cases ( 0.4% ) Neunert C et al J Thromb Haemost 2015;13:457-465

Immediate Responses to “ Front-Line ” Platelet Enhancing Therapies in Children with Newly Diagnosed ITP Percent (%) of children with platelet count > 20 x 10 9 /L at 72 hours following start of management strategy IVIG 0.8 g/kg x 1* 97% (34/35) IVIG 1.0g/kg x 2 94% (50/53) IV anti-D 82% (31/38) Oral prednisone** 79% (45/57) Observation ( “ no therapy ” ) 56% (9/16) *IVIG = Intravenous Immunoglobulin G **4mg/kg/day in divided doses (maximum dose = 150 mg/day) Blanchette V et al J Pediatr 1993;123:989-995 Blanchette V et al Lancet 1994;344:703-707

N = 25 Age 0.3 - 16 yr ( mean 6.4 ) Platelet count 1 - 14 x 10 9 / L ( mean 5 ) 65% Prednisone 4 mg/kg/ 42% day x 4 days without tapering 8% Acta Paediatrica Scandinavica 424 : 71 - 74 ; 1998

ACUTE LYMPHOBLASTIC LEUKEMIA ( ALL )

OUTCOME OF BONE MARROW ASPIRATION WITH “ TYPICAL ” AND “ ATYPICAL ” FEATURES OF ITP ITP Marrow Confirmed Leukemia Aplasia Typical 324 0 1 Atypical 135 3 7 Calpin C Arch Pediatric Adolescent Med 1998;152:345-347

Presentation Outline • Definitions of ITP • Newly diagnosed ITP • Management of ITP - Background - Guidelines for the management of newly diagnosed ITP in children - The Toronto experience • Summary

1. George J. N. et al. Blood 1996; 88:3-40 2. Provan D. et al. British Journal of Haematology 2003;120:574-596

Management of ITP in Children “ the majority of children with newly diagnosed ITP lack significant bleeding symptoms and may be managed without therapy directed at raising the platelet count at the discretion of the hematologist and the patient” and “it is necessary to treat all children with severe bleeding symptoms and treatment should also be considered in children with moderate bleeding or those at increased risk of bleeding” Provan D et al Blood 2010;115:168-186 (online publication October 21, 2009)

Management of ITP in Children “ children with no bleeding or mild bleeding (defined as skin manifestations only such as bruising and petechiae) be managed with observation alone regardless of platelet count” and “for pediatric patients requiring treatment a single dose of IVIG (0.8 to 1 g/kg) or a short course of corticosteroids be used as first-line treatment” Neunert C et al blood 2011;117(16):4190-4207 (first published on line February, 2011)

Presentation Outline • Definitions of ITP • Newly diagnosed ITP • Management of ITP - Background - Guidelines for the management of newly diagnosed ITP in children - The Toronto experience • Summary

Management of Children with Newly Diagnosed Immune Thrombocytopenia UK (1) Management Option Intercontinental ITP Hospital for Sick Children Study Group (2) Toronto (2007 - 2009)* (2007-2009) (3) Observation 84% 31% 6.3% } IVIG 29% 87.5% 16% Corticosteroids 33% 6.3% *data extracted from UK Childhood ITP Registry (1) Grainger JD et al Arch Dis Child 2012;97:8-11 (2) Kuhne T et al Lancet 2001;358-2122-2125 ISTH Definitions in Hemophilia Project Group : Personal communication V. Blanchette (2013) (3) Beck C Personal Communication

Shared Decision Making (SDM) • Refers to discussions between patients and/or their parents/guardians and their health care providers as they consider 2 or more clinically reasonable options • Discussions involve exchanging information about available medical evidence related to each option including potential benefits, risks and alternatives to the options presented GOAL OF SDM: identification of which course of action is most consistent with the preference of the patient and/or their parents/guardians Epstein RM et al JAMA 2009;3002:195-197 Charles C et al Soc Sci Med 1999; 49:651-661

Participants Number of Comment Participants Children with newly Median age 11 years diagnosed ITP* 7 (range 10-18 years) Parents of children Median age at diagnosis with newly diagnosed 3.25 years or persistent ITP 6 Parents of children with Median age at diagnosis chronic ITP 11 7.25 years Health care professionals 10 10 MD’s (4 trainees); 1 nurse * Onset of ITP ≤ 2 years before participation in the focus group Beck C. et al J Pediatr Hematol Oncol 2014;36:559-565

Responses: Children with ITP and their Parents/Guardians Decision-making Themes Quotations “so many things (were) running Anxiety, fear, confusion through my head” Understanding information Re explanation from doctors: “really big words”; “ scarry stuff” “… they basically said… this is what we do” Steroids were discussed as a Treatment choice treatment option but my parents said “no way” Beck CE J Pediatr Hematol Oncol 2014;36(7):559-565

Responses: Health Care Professionals Quotations Decision-making Themes “I would not take the risk, I would treat” Comfort level “Nobody wants steroids” Assumptions “It depends on how you say it. I Pending information can convince anybody to go on steroids” “The decision to treat with IVIG is Treatment choice easy but things need to change”

A Quality Improvement Bundle to Improve Informed Choice for Children with Typical Newly Diagnosed Immune Thrombocytopenia Child with newly diagnosed ITP Child and/or parents/guardians given ITP information sheet and evidence based protocol outlining 3 management options - observation - IVIG - oral corticosteroids Meeting between child and/or parents/guardians and a member of the hematology consult team and the general pediatric ward staff to discuss management options Beck CE, Personal Communication 2017

* Blood Cell and Components • Signs of ITP • What causes ITP • Important things to know about living with ITP • Treatment of ITP - Observation Petechiae and Bruises - IVIG - Corticosteroids (prednisone) • Follow up • Summary of key points * www.aboutkidshealth.ca

Patients with Newly Diagnosed, Typical ITP : 3 months - 18 years via Emergency Department or community hospital Assessment - history - physical examination - complete blood count (CBC) Treatment - observation - prednisone - IVIG Discharge - contact information for point of care hematology nurse - follow up appointment in hematology clinic www.aboutkidshealth.ca/EN/HealthAZ/ConditionsandDiseases/blooddisorders/Pages/ITP-what-happens-after-diagnosis.aspx