case conference presentation tania kourtidou, md pgy-1 10/19/2011

Case Conference Presentation

Tania Kourtidou, MDPGY-1

10/19/2011

Case Description

14yo girl with c/o b/l lower leg rash x1d

Case Description

14yo girl with c/o b/l lower leg rash x1d

• Red spots, nontender, non-pruritic

• Applied Hydrocortisone cream ->no change

• Afebrile, no URI, GI, GU, musculoskeletal, visual disturbance

• On the 4th day of menstrual cycle

• 1st episode, no Hx of trauma, insect bite, pets, recent travel,

change in soaps, -sick contacts

Case description

PMHx: Tested for Marfan Syndrome – Negative

FH: Asthma, DM, HTN, Seizure disorder

Immunization status: Unknown

SHx: Denied smoking, sexual activity, illicit drug use, suicidal thoughts, both parents at home, attended high school.

Case Description

VS: T 98.2F, HR 98, BP 108/72, RR 20, SpO2 100%

Physical exam:

Skin: Flat, hemorrhagic, non-blanching, pinpoint, non tender, located only in lower extremities, ant>post

Rest of PE: wnl

Petechial - Porpuric rash

Petechea <3mm Porpura: 3-10mm

Glass test

Petechial - Porpuric rash

Differential diagnosis

Meningococcal infection

LeukemiaMalignancy

Viral infections

*Enterovirus

HSP

ITP

Pressure VomitingTraumaD.I.C.

*Simple porpura indicates a qualitative or quantitative PLTs disorder.!

Case Description

Lab tests:

1. CBC, RET count, Peripheral smear

2. PT, aPTT, INR

3. ERS, CRP

4. CMP

5. Blood Cx

6. *UA could not be evaluated for blood

Case Description

Lab results:

6.2 11840.5

13.7

140

4.6 29

106

0.6

10

7.5

4.7

13

21

0.9 94

0.9

9.6

94

11.6 1.1

25.7

ESR: 2Peripheral smear: (no schistocytes, blasts)

CRP, Blood Cx: Negative

Case Description

THROMBOCYTOPENIA

Production Destruction

Immune

Non-immune

CongenitalAplastic anemia

Infections (HIV,HCV,H.pylori)

Paroxysmal nocturnal hemoglobinuria

Von Willebrand’s IIBDrugs

DICTTP/HUS

Kassabach-Merrit syndrome

Hypersplenism

ITPAlloimune (neonate)

InfectionsDrugs

SLE, Antiphospholipid syndrome

Fleisher GA, LudwigS, et al., eds. Textbook of pediatric emergency medicine. 3d ed. Baltimore: Williams & Wilkins, 1993:430–8.

Case Description

Based on:

clinical presentation

PLTs

Normal CBC and peripheral smear

Pt d/c with the diagnosis of ITP

No indication for treatment

Recommended to f/u with hematology clinic

Idiopathic Thrombopenic Porpura

Porpura ~> Πορφύρα (porphyra)

Colouring substance produced with the treatment of shell Haustellum brandaris .Gives indelible deep red colour.

It was particularly precious because of its difficult production and the rarity of shells.

Therefore the use of clothing dyed with pupura represented a sign of wealth and power. Emperor’s cloak in the Empire of the Byzantium was always colored with porpura.

Justinian I

Idiopathic Thrombopenic Porpura

Outline

1. Introduction

2. Pathogenesis

3. Diagnosis

4. Clinical manifestations

5. Therapeutic principals

6. Latest treatment options

Idiopathic Thrombopenic Porpura

Isolated persistent thrombocytopenia: PLTs<100x109/L

Normal CBC

Normal peripheral smear

Idiopathic Thrombopenic Porpura

The most common cause of thrombocytopenia in children

Prevalence: 4.0-5.3/100.000, 3500 new cases per year

85% Acute and self-limited

Between 2 and 10 years (peak age: 5y)

Equal gender/ethnic distribution

>10y girlsInsidious presentation

Chronic ITP >6m

Idiopathic Thrombopenic Porpura

The etiology is still unknown.

Idiopathic Thrombopenic Porpura

*1-4week after exposure to common viral infection or immunization (varicella, MMR).

Theories

Antibody cross-reactivity H. pylori

bacterial lipopolysaccharide

s

Pathogenesis

Idiopathic Thrombopenic Porpura

Antibodies against viruses may x-react to PLT antigensimmune complexes on the PLT surfaceremoval by reticuloendothelial system

Some strains of H. pylori may induce PLT aggregation

Bacterial products (ex.LPS) once adhered to PLTs, may induce increased phagocytosis or “clearance” of PLTs

Pathogenesis

Pathophysiology

*B cells produce IgG autoantibodies against GP IIb/IIIa and Ib/IX.

Idiopathic Thrombopenic Porpura

Clinical manifestations

• Sudden onset

• Healthy child

• Mucocutaneous bleeding:

epistaxis, gum bleeding, menorrhagia

GI or CNS <1%

• 50% Minimal splenomegaly

Idiopathic Thrombopenic Porpura

Diagnosis (of exclusion)!!!PLTs<100x109 /L

Hb

Normal aPTT and PT

Prolonged BT

Peripheral smear: Megathrombocytes

Idiopathic Thrombopenic Porpura

Diagnosis

Bone Marrow aspiration

Anti-PLT antibody studies

+ANA (adolescents)

EBV, CMV, Mycoplasma, H.pylori (cITP)

Normal or Increased number of megakaryocytes

Sensitivity and specificity

Idiopathic Thrombopenic Porpura

These laboratory tests are NOT recommended by the ASH practice guidelines to patients with the typical ITP presentation.

(American Society of Hematology, 2011)

Diagnosis of ITP should be based on :

1. Infection history

2. Clinical features

3. Physical exam

4. Lab tests: CBC and peripheral blood smear

Idiopathic Thrombopenic Porpura

Treatment

Most of the cases can be managed at home

“Most patients and their parents can live quite comfortably with petechiae and low platelets awaiting spontaneous

remission providing their physicians can.”

Dickerhoff 1994, Thrombocytopenia in childhood.

Idiopathic Thrombopenic Porpura

Treatment guidelines

If skin manifestations only Observation regardless of the PLTcount

Hospitalize if

Close monitor of CBC once a week

Once PLT begin to increase, it takes 2-3 weeks to normalize.

Severe, life threatening bleeding regardless of the PLT count

Idiopathic Thrombopenic Porpura

Treatment guidelines

Consider treatment if PLTs<30x109/L

The goal is to raise PLT count hemostatically safe, not to cure

1st line treatment:

Single dose of IVIG (0.80.8-1g/kg x 2d or 400mg/kg/d x 5d)

Short course of corticosteroids(Methylprednisolone 20-30mg/kg x3d or Prednisone 1-2.g/kg/d x14d)

or

Idiopathic Thrombopenic Porpura

Treatment guidelines

IVIG:

Blocks Fc receptor on phagocytes PLT destruction

Rapid elevation of PLT count >20.000 within 48h Preferred to corticosteroids in severe disease

Expensive, long effusion time (6-8h), allergic reactions, aseptic meningitis

Idiopathic Thrombopenic Porpura

Treatment guidelines

Corticosteroids:

Reduce capillary fragility, inhibit PLT destruction and antibody production

No evidence supporting long course vs. brief course

Cheap and convenient but side effects of long term use

Idiopathic Thrombopenic Porpura

Treatment guidelines

IV Anti-D therapy:

1st line for Rh+ with functional spleen

Induces mild hemolytic anemia RBC-antibody complexes saturate the macrophage Fc receptors Increased survival of antibody-coated PLTsslow rise of PLTs

Less allergic reactions than IVIG, no aseptic meningitis

Hemolysis Transient Hb

Idiopathic Thrombopenic Porpura

Treatment guidelines

Splenectomy:

Reserved for children >4 years of age with

persistent symptoms (bleeding) lasted longer than 1 year and lack of response to therapy and/or who have a need for improved quality of life.

Idiopathic Thrombopenic Porpura

Treatment guidelines

Transfused PLTs

*Rapidly removed from the circulation only used in emergencies to control bleeding (PLT<3x109/L)

No role in the routine management of ITP

Idiopathic Thrombopenic Porpura

Life threatening hemorrhage:

1.PLT infusions (10ml/kg expect to PLT by 50.000/L)

2. IV Methyprednisolone 30mg/kg (max 1g) over 20min, repeat daily up to x3

2.IVIG (1g/kg over 4-6h, repeat daily up to x5)

3.Emergent splenectomy

4.Plasmapheresis, RBCs transfusion, antifibrinolytics

Idiopathic Thrombopenic Porpura

Special Considerations

TPO Mimetics and Receptor Agonists(Romiplostim, Eltrompobag)

No published data to guide the use of these agents in children

High-Dose Dexamethasone

Rituximab

A-Interferon

Adolescents with significant ongoing bleeding and/or need for improved quality of life despite conventional treatment.

Altenative to splenectomy or in those who have failed splenectomy.

Immunosuppression(AZA,CTX,VCR)

Multiple agents have been reported; however insufficient data for specific recommendations.

Idiopathic Thrombopenic Porpura

Follow up:

Spontaneous recovery:

10-20% chronic ITP adolescent girls

monitor platelet count and clinical status daily to weekly, depending on the severity and treatment

Once platelet count has normalized, recurrence is rare and follow-up platelet counts are unnecessary

-60% by 3months-80% by 6months-90% by 1year

Idiopathic Thrombopenic Porpura

Parent education.

Avoidance of contact sports, wearing protective headgear, lining the crib with protective padding

MMR should be given regardless PMHx of ITP

Discontinue medications that suppress platelet production

There should be a low threshold for prompt evaluation of child that has sustained blunt trauma with ITP.

Idiopathic Thrombopenic Porpura

ITP is often an acute and self-limiting disease in children

Most of the times no treatment is required

Goal = prevention of complications

Therapy needs to be tailored to the individual patient

Parent and patient education is very important

References:

2011 Clinical Practice Guideline on the Evaluation and Management of Immune Thrombocytopenia (ITP), The American Society of Hematology

Idiopathic Thrombocytopenic Purpura in Children: Diagnosis and ManagementP. D. McClure Pediatrics 1975;55;68

Evaluating the Child with Purpura, Leung et al., Am Fam Physician 2001;64:419-28

Childhood Immune Thrombocytopenic Purpura: Diagnosis and Management, Blanchette V., Bolton-Maggs P., DM, Pediatr Clin N Am 55 (2008) 393–420

www.uptodate.com

www.aap.org

www.hematology.org

www.pdsa.org

A 9-year-old boy presents to your office with purple spots on his legs and mild swelling of his scrotum of 1 day's duration. He has had no vomiting, diarrhea, or constipation. He is afebrile, alert, and active. On palpation, he reports mild abdominal discomfort. He has no edema of the lower extremities or presacral area. His weight is 1 kg more than his weight at his health supervision visit 6 months ago.

Of the following, the MOST likely abnormal laboratory finding to expect for this boy is:

A.anemia

B. hypoalbuminemia

C. microscopic hematuria

D.prolonged partial thromboplastin time

E. thrombocytopenia

A. anemia

B. hypoalbuminemia

C. microscopic hematuria

D. prolonged partial thromboplastin time

E. thrombocytopenia