SENIOR CASE PRESENTATION DEEPTHY DAMIEN 01/21/2010 Chief Complaint 4 y/o with spontaneous bruising x 1 month H/O Present Illness 4 y/o previously healthy female brought in by mother because multiple spontaneous bruising x 1 month. Mostly upper and lower extremities involved. Seen at another hospital and got referred to RCRMC No fever /chills/weight loss/bone pain /joint pain/nose bleed/head ache / blurry vision Positive h/o URI almost 1 month ago No similar problems in the past Past Medical History No prior hospitalizations Seen in the Ortho clinic for intoeing Surgical history : none Medications: none Allergies: none Family History: none Birth history: normal delivery ,no complications Social history: Lives with parents and brother Immunizations: up to date ROS HEENT:No headache /congestion/epistaxis Resp: No cough /wheeze Cardiac: No chest pain /cyanosis/palpitation Abdomen: No abd pain/diarrhea/constipation GU:neg Skin:pos for bruising Neuro:No weakness/seizure Physical Exam Vitals:T: 98.8 F,PR:90/min,RR:30/min,BP: 100/60,wt: 26.5 kg Gen: active ,talking Skin: ecchymosis R elbow, R knee, shin, L knee[3x4 cm], L ankle [3x1cm],purpura multiple around knee. ENT: normal Neck: NAD Heart: RRR, no murmur Abd: soft,non-tender,no organomegaly, BS+ Extremities: no swelling/effusion, normal ROM Neuro: no deficits Labs CBC:6.7/12.9/34.6/7 P/S: decreased platelets. Normal morphology of RBC,WBC Diagnosis ITP/ IMMUNE(IDIOPATHIC) THROMBOCYTOPENIC PURPURA Orders at Admission CBC with diff CMP,Uric acid,LDH,ESR,PS PT/INR/PTT NO NSAIDS NO STEROIDS Monitor for bleeding Restrict activities DAY 2 Patient stable No new lesions/ bleeding LABS: CBC:6.7/12.9/36.8/5 ESR:7 CRP: 0.3 PT:11.8/INR:1.1/PTT:26.6 CMP:142/3.5/104/27/11/0.5 ALP:170/AST:32/ALT:20/Bili:0.1 LDH:618 Uric acid:4.3 Orders IV IG 1 g /Kg IV x1 DAY 3 Patient stable No new lesions CBC:4.1/1.6/36.5/46 Discharged home with ,advised to f/u with PCP in 1 wk,CBC prior to clinic visit Take Home Message NO NSAIDS AS THEY INCREASE THE RISK OF BLEEDING DO NOT GIVE STEROIDS UNTILL OTHER DIAGNOSIS ARE EXCLUDED,AS THE STEROIDS CAN MASK EARLY LEUKEMIA. If the ITP is not resolved in 4-6 wks ,they may need a hematology referral/BM Bx If BM BX comes neg it is ok to treat with steroids Immune(idiopathic) Thrombocytopenic Purpura In Children Thrombocytopenia (usually <20,000/microL) that is acquired and generally benign Unknown cause Acute ITP is common in children Also known as autoimmune thrombocytopenic purpura/ isoimmune thrombocytopenic purpura Pathogenesis Auto antibodies (usually IgG) against platelet membrane antigens ,such as glycoprotein complex II b/III a. The antibody coated platelets have a shortened half-life because of the accelerated clearance by tissue macrophages in the spleen and other portions of RES.The net effect is a decrease in the platelet count. In chronic ITP, T cell mediated cytotoxicity may cause platelet destruction. Epidemiology ITP is one of the most common causes of symptomatic thrombocytopenia in children. Incidence 3-8 /100,000 children/ year Usual age 2-10 yrs ,peak 2-5yr Slightly boys>girls Clinical Presentation Sudden appearance of bruising and/or bleeding in an otherwise healthy child. History: in 60% , there is a history of prior infection. An increased risk of ITP is associated with MMR immunization. No systemic symptoms Presence of systemic symptoms like fever ,anorexia,joint pain,bone pain or weight loss usually points to other diagnosis Drug induced(heparin,quinidine,sulfonamides) thrombocytopenia is uncommon in kids Physical Findings: Signs of cutaneous bleeding(dry purpura) like petechiae,purpura and ecchymoses Less often mucosal bleeding(wet purpura) assoaciated with a platelet count <10,000/micro L Conjuctival and retinal hemorrhages are uncommon. No enlarged LN/spleen/liver Serious hemorrhages requiring blood transfusion and ICH are rare in children with ITP Disease course: 70% of children have the acute form of ITP, which is defined by recovery (platelet count >150,000/ micro L) in 6 months of presentation with or without treatment. Treatment do not affect the long term outcome,but minimize the risk of significant bleeding Diagnosis:2 criteria 1.Isolated thrombocytopenia,with otherwise normal blood counts and peripheral smear. 2.No clinically apparent associated conditions that may cause thrombocytopenia Exclude concurrent inf/autoimmune disorders/malignancy/drugs/genetic bleeding disorders/ marrow failure Most chldren:2-10 yrs ,with abrupt bruising in otherwise healthy child Labs: CBC: thrombocytopenia , usually the only abnormality detected,usually <20,000/microL Peripheral smear: no morphologic abnormalities in WBC/RBC.Platelet decreased in number,often large in size. Other studies : Coags,coombs’ test,retic count,HIV,studies for collagen vascular/rheumatoid disorders. Anti platelet ab testing-not routinely indicated in kids Bone marrow exam: increase number of megakaryocytes,may appear large and immature Routinely performed in the past to r/o marrow failure or malignancy(acute lymphoblastic leukemia).New guidelines –BM exam is unnecessary in the “typical” case of childhood ITP Indication for BM exam: -Atypical presentation -Persistent thrombocytopenia beyond 6 months -subsequent clinical course that is not consistent with ITP - Before Steroid treatment in typical ITP is recommended by some .(not by UpToDate) Differential Diagnosis Viral infection(IMN,Hepatitis,HIV- 1) Drug exposure(Heparin, Quinidine, Sulfonamide) Autoimmune Disorders(SLE) Leukemia (ALL) Acquired marrow failure syndrome (aplastic anemia) Inherited thrombocytopenic disorders(thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome,mutation of MYH 9 gene) Treatment Initial medical management: -Ideal management still unclear -observation alone vs observation with pharmacologic intervention -restrict contact sports/physical activity -avoid medications with antiplatelet or anticoagulant activities Pharmacologic Intervention Presence of severe life threatening bleeding,risk of significant bleeding (going for procedures/count <10,000/microL and cutaneous bleeding), concomitant / preexisting conditions(hemophilia) need intervention Corticosteroids: Reduce Ab production,RES phagocytosis of antibody coated platelets,improve vascular integrity, improve platelet production Prednisone 1-2 mg/kg/day(max 60 /day) in 3 divided doses x 2-4 wks, followed by a taper of 4mg / kg/day ,divided into 3 doses for 4 days OR Methylprednisolone( 30-50 mg /kg/day) for 3-7 days Some cases may need repeat courses IV IG: Mechanism of action is multi-factorial,inhibition of antibody adsorption to platelets,prevention of RES uptake of auto ab coated platelets, interaction of auto abs with idiotype abs in IV IG. Works better than steroids but higher cost Dose: 400mg /kg/day x 5 days OR Single dose of 1g/kg Anti-Rho(D) immune globulin: has been shown to be effective Platelet transfusion: used in case of life threatening bleeding(ICH) The therapy is targeted to increase count to >20,000.In risk of life threatening bleeding , IV IG could be repeated or combined with steroids Monitoring: the patients getting pharmacologic intervention the usual hospital stay is 2 days.In the ambulatory setting ,platelet count monitored 1-2 times /wk ,interval can increase as the platelet increase .monitoring is necessary until the count return to >150,000/microL(50% in 1 mont,70% in 3 months) Chronic ITP: persistent thrombocytopenia(<150,000/microL) for > 6 months 20-30% will have chronic ITP 1/3 rd of the cases will have spontaneous remission in months to years In chronic ITP the platelet count ranges between 20,000-75,000/microL.usually do not require any treatment Management: decrease the risk for bleeding. Pharmacologic therapy is used when they have significant bleeding/or need to go for procedures CORTICOSTEROIDS-short course/pulse course IV IG – 500 mg /kg/day x 2 days ,and may be repeated if the symptoms recur SPLENECTOMY- may be needed in patients needing repeated /continuous pharmacologic intervention even 12 months after diagnosis Rituximab,Danazol,Interferon,Cyclosporin,Cyclophosp hamide,Romiplostim,Eltombopag,Azathioprine Bibliography Up To Date, Treatment and prognosis of ITP in children, clinical manifestation and diagnosis of ITP in children, Evaluating purpura in children AAFP, August 1 ,2001, Evaluating the Child with Purpura.