3/21/2016. Immune Thrombocytopenia. My Background. Objectives. Case Study. Case Study. No disclosures. Rochelle Boote, MD 4/8/2016
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1 Immune Thrombocytopenia No disclosures Rochelle Boote, MD 4/8/2016 My Background From Lester, IA College: Augustana (now university) Medical School: Sanford School of Medicine at USD Residency: Omaha - UNMC/Children s Now: Pediatrician with Avera McGreevy Objectives What is ITP? How do we treat/manage ITP? Why is ITP important? What are the outcome of patients with ITP? 8yo female comes to clinic with a rash x1 days Pink/purple in color, started on upper back and had spread to legs/arms this morning Rash isn t itchy or painful 1 week ago had fever and cough Dx: viral URI Other than the rash, feels good Denies N/V/D, wt loss, fatigue, night sweats PMHx: seasonal allergies PSHx: none Meds: none Allergies: NKDA Immunizations: UTD Development: normal No recent travel, no sick contacts, has a pet fish 1
2 VS: T 37.2 P 102 R 22 BP 100/76 Wt: 39.7kg (94 percentile) Ht 140cm (88 percentile) Skin: petechiae present over cheeks, neck, arms, back, chest, legs, non-blanchable; ecchymoses on right shin and arms; palms and soles are clear, no pallor or jaundice Exam otherwise normal Differential normal What is ITP? ITP: Idiopathic Thrombocytopenic Purpura Immune Thrombocytopenic Purpura Immune ThrombocytoPenia Autoimmune disorder causing low platelet counts Discovered in 1951 by William Harrington and James Hollingsworth Injected plasma from pts with ITP to healthy volunteers Observed decrease platelet levels in volunteers Years later, antibodies directed against platelets were identified 2
3 May have a primary or secondary cause: SLE Medications Viruses: hepatitis C, HIV Bacteria: H. pylori, Rickettsia Leukemia, lymphomas Estimated fraction of the various forms of secondary ITP based on clinical experience of the authors. Pathogenesis: 1. Antibody-mediated destruction of platelets IgG targeting glycoprotein IIb/IIIa and/or Ib/IX on platelets Antibodies only documented in 75% of cases 2. Decreased production of platelets Increased clearance of thrombopoietin Damaged megakaryocytes Douglas B. Cines et al. Blood 2009;113: by American Society of Hematology Acute vs Chronic: Chronic have ITP for > 12 months 2009: Vicenza Consensus Conference Renamed to Immune ThrombocytoPenia Changed classification to newly diagnosed, persistent, and chronic Emphasized diagnosis of exclusion Stanton, Bonita F., Joseph W. St. Geme III, Nina F. Schor, and Richard E. Behrman. "Idiopathic Thrombocytopenic Purpura." Nelson's Textbook of Pediatrics. By Robert M. Kliegman. 19th ed. Philadelphia: Elsevier Saunders, Print. 3
4 Differential Diagnosis ID Tick-borne illnesses Meningococcemia Parvovirus Hematology ITP DIC Aplastic Anemia Evans Syndrome Autoimmune lymphoproliferative syndrome Oncology Leukemia Lymphoma Neuroblastoma Rhabdomyosarcoma Drug reaction SLE Lab error How to Treat ITP? Observation and education First Line Therapies IVIG Steroids IV Anti-D Therapy: Rh+, negative DAT, Hgb > 10 Second Line Therapies Rituximab Splenectomy Recombinant thrombopoietin IVIG Macrophage Flores, Adolfo, and George R. Buchanan. "Occult Hemorrhage in Immune Thrombocytopenia." Seminars in Hematology 50 (2013): S Web. IVIG Macrophage 4
5 Giving platelets is not effective but is needed for lifethreatening hemorrhages Primary reason for treatment: Prevent intracranial hemorrhages Treatment increases platelet levels > 20 more rapidly No data shows treatment effects outcomes of ITP Stanton, Bonita F., Joseph W. St. Geme III, Nina F. Schor, and Richard E. Behrman. "Idiopathic Thrombocytopenic Purpura." Nelson's Textbook of Pediatrics. By Robert M. Kliegman. 19th ed. Philadelphia: Elsevier Saunders, Print. Proven et al (2010, Blood): Attempt to provide consensus based recommendations for diagnosis/treatment of ITP Majority can avoid treatment must be counseled on risks of hemorrhages and life-style changes must have follow up Admit: clinically significant hemorrhages, social concerns Treat all children with severe hemorrhages and consider treating moderate hemorrhages/increased risk of hemorrhages IVIG, anti-rhesus, steroids Lo and Deane (2014, Autoimmunity Reviews): No bleeding or only mild bleeding: observe, follow plts level 5-7 days, avoid traumatic activities Moderate/Severe bleeding: first-line therapy Steroids, IVIG, anti-rhesus Goal: minimize risk of ICH until remission occurs Life-threatening bleeds: platelets + first-line txs Non-responders: Avoid trauma, minimize side effects of treatments Rituximab, splenectomy Provan, D., et al. "International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia." Blood (2010): Web. Lo, Ernest, and Seane Deane. "Diagnosis and Classification of Immune-mediated Thrombocytopenia." Autoimmunity Reviews 13 (2014): Web. Kime et al (2013, Pediatrics): use PHIS to examine patterns of inpatient care for newly diagnosed ITP from patients: 72.2% IVIG, 9.4% no treatment, 7.8% steroids Only 12% pts admitted had non-cutaneous bleeding Average cost: $8,984 (50% cost from pharmacy) Average length of stay: 2 days Kime, Courtney, Jennifer Klima, Melissa Rose, and Sarah O'Brien. "Patterns of Inpatient Care for Newly Diagnosed Immune Thrombocytopenia in US Children's Hospitals." Pediatrics (2013): Web. Kime, Courtney, Jennifer Klima, Melissa Rose, and Sarah O'Brien. "Patterns of Inpatient Care for Newly Diagnosed Immune Thrombocytopenia in US Children's Hospitals." Pediatrics (2013): Web. 5
6 Why is ITP Important? ITP is managed by primary care physicians Epidemiology: Most commonly affects ages 1-4 Affects 1/20,000 children 2/3 cases have history of a recent viral illness Occurs most often late winter and spring Affects males and females equally Increased risk after MMR immunization Stanton, Bonita F., Joseph W. St. Geme III, Nina F. Schor, and Richard E. Behrman. "Idiopathic Thrombocytopenic Purpura." Nelson's Textbook of Pediatrics. By Robert M. Kliegman. 19th ed. Philadelphia: Elsevier Saunders, Print. Platelets are important to prevent bleeding Low platelets cause or contribute to: Easy bruising Nose bleeds GI bleeds Bleeding gumlines Hematuria Intracranial hemorrhages Intracranial Hemorrhage Risk of intracranial hemorrhage is extremely low: 0.1-1% of patients 25% mortality rate 33% with neurologic sequelae Increased risk: Severe thrombocytopenia (< 10-20) Bleeding manifestations other than skin Head trauma Treatment does not decrease chance of developing ICH nor of developing chronic ITP Flores, Adolfo, and George R. Buchanan. "Occult Hemorrhage in Immune Thrombocytopenia." Seminars in Hematology 50 (2013): S Web. Intracranial Hemorrhage Psaila (2009, Blood): 40 pts with ITP and ICH (study group); 80 pts with ITP, no ICH (control) No difference in age, sex, or duration of ITP Median plt counts: study 5; control 8 4 with ICH had counts of 35 at time of bleed Half of control pts have counts < 10 45% had ICH w/in 7 days, 20% after 1 week, 25% 1wk-6 months, 30% > 6 months Risk factors: head trauma (33%), hematuria (22%), younger age, severe thrombocytopenia Effect of treatment: unknown Intracranial Hemorrhage Elalfy et al, 2010: reviewed medical records from patients with ITP from in Egypt Found 1840 patients 56% male, 44% female 10 developed ICH (0.54%) ICH occurred from 1 week from onset to over a year 4 had acute ITP, 2 persistent ITP, 4 chronic ITP Median plt count 12 < 10 in 7pts with ICH; in the other 3 7 received treatment 2 died, 3 residual seizures Psaila, B., A. Petrovic, L. K. Page, J. Menell, M. Schonholz, and J. B. Bussel. "Intracranial Hemorrhage (ICH) in Children with : Study of 40 Cases." Blood (2009): Web. Elalfy, Mohsen, et al. "Intracranial Hemorrhage in Acute and Chronic Childhood Immune Thrombocytopenic Purpura over a Ten-year Period: An Egyptian Multicenter Study." Acta Haematologica 123 (2010): Web. 6
7 Intracranial Hemorrhage Elalfy et al, 2010 ICH can neither be anticipated or prevented Steroids had limited effect in acute period Risk factors: plt count < 10, non-cutaneous bleeding, head trauma Counseling is essential Avoid situations causing head trauma ICH risk is present as long as patient has ITP Regular follow up is needed Outcomes of ITP Elalfy, Mohsen, et al. "Intracranial Hemorrhage in Acute and Chronic Childhood Immune Thrombocytopenic Purpura over a Ten-year Period: An Egyptian Multicenter Study." Acta Haematologica 123 (2010): Web. Outcomes: Self-limiting course, most resolve spontaneously by 6 months (70-85%) 12% later developed autoimmune disease SLE, CVID, autoimmune lymphoproliferative syndrome 20% develop chronic ITP More likely in teenagers (50%) 0.1-1% develop intracranial hemorrhage (ICH) 25% mortality 33% life-long neurologic sequelae Chronic ITP Managed by hematologist Lifestyle modifications Re-evaluate for secondary cause Treatment to prevent serious bleeding Usually chronic steroids Splenectomy: complete remission 64-88% Rituximab: complete remission 30-50% Flores, Adolfo, and George R. Buchanan. "Occult Hemorrhage in Immune Thrombocytopenia." Seminars in Hematology 50 (2013): S Web. Lo, Ernest, and Seane Deane. "Diagnosis and Classification of Immune-mediated Thrombocytopenia." Autoimmunity Reviews 13 (2014): Web. Stanton, Bonita F., Joseph W. St. Geme III, Nina F. Schor, and Richard E. Behrman. "Idiopathic Thrombocytopenic Purpura." Nelson's Textbook of Pediatrics. By Robert M. Kliegman. 19th ed. Philadelphia: Elsevier Saunders, Print. Treatment: Gave IVIG 1gram/kg over 6 hours Repeat CBC in AM Labs (after IVIG x1)
8 Summary Guidelines for treatment are unclear If treating, start with IVIG Be aware of potential risk factors for ICH Parental/Patient education Anticipatory guidance Close follow up Discussing risk of ICH and signs/symptoms When in doubt, call for guidance References Butros, Linda J., and James B. Bussel. "Intracranial Hemorrhage in Immune Thrombocytopenic Purpura: A Retrospective Analysis." Journal of Pediatric Hematology/Oncology 25.8 (2003): Web. Douglas B. Cines et al. Blood 2009;113: Elalfy, Mohsen, et al. "Intracranial Hemorrhage in Acute and Chronic Childhood Immune Thrombocytopenic Purpura over a Ten-year Period: An Egyptian Multicenter Study." Acta Haematologica 123 (2010): Web. Flores, Adolfo, and George R. Buchanan. "Occult Hemorrhage in Immune Thrombocytopenia." Seminars in Hematology 50 (2013): S Web. Kime, Courtney, Jennifer Klima, Melissa Rose, and Sarah O'Brien. "Patterns of Inpatient Care for Newly Diagnosed Immune Thrombocytopenia in US Children's Hospitals." Pediatrics (2013): Web. Labarque, Veerle, and Chris Geet. "Clinical Practice: Immune Thrombocytopenia in Paediatrics." European Journal of Pediatrics (2014): Web. Lo, Ernest, and Seane Deane. "Diagnosis and Classification of Immune-mediated Thrombocytopenia." Autoimmunity Reviews 13 (2014): Web. My, So, Li Ch, Lee Anslem, and Kwong NS. "Intracranial Hemorrhage among Chinese Children with Immune Thrombocytopenia in a Hong Kong Regional Hospital." Hong Kong Medical Journal 19 (2013): Web. Norton, Alice, and Irene Roberts. "Management of Evans Syndrome." British Journal of Haematology (2006): Web. Provan, D., et al. "International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia." Blood (2010): Web. Psaila, B., A. Petrovic, L. K. Page, J. Menell, M. Schonholz, and J. B. Bussel. "Intracranial Hemorrhage (ICH) in Children with Immune Thrombocytopenia (ITP): Study of 40 Cases." Blood (2009): Web. Stanton, Bonita F., Joseph W. St. Geme III, Nina F. Schor, and Richard E. Behrman. "Idiopathic Thrombocytopenic Purpura." Nelson's Textbook of Pediatrics. By Robert M. Kliegman. 19th ed. Philadelphia: Elsevier Saunders, Print. Thank You! Dr. Kara Bruning Dr. Stephanie Lowas (H/O Omaha) Dr. Nicholas Torbert Dr. Heidi Johnson Questions? 8
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