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:6.7/12.9/36.8/5ESR:7CRP: 0.3PT:11.8/INR:1.1/PTT:26.6CMP:142/3.5/104/27/11/0.5ALP:170/AST:32/ALT:20/Bili:0.1LDH:618Uric 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 criteria1.Isolated thrombocytopenia,with otherwise normal blood counts and

peripheral smear.2.No clinically apparent associated conditions that may cause

thrombocytopeniaExclude concurrent inf/autoimmune disorders/malignancy/drugs/genetic

bleeding disorders/ marrow failureMost chldren:2-10 yrs ,with abrupt bruising in otherwise healthy child

Labs:CBC: thrombocytopenia , usually the only abnormality detected,usually <20,000/microLPeripheral 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 kidsBone marrow exam:increase number of megakaryocytes,may appear large and immatureRoutinely 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 productionPrednisone 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 daysORMethylprednisolone( 30-50 mg /kg/day) for 3-7 daysSome 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 costDose:400mg /kg/day x 5 daysORSingle 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,Cyclophosphamide,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.