Case Presentation

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Case Presentation

• Rashida Saif
• St. Josephs Regional Medical Center

2

• 1 year old boy with bruising and petechiae for
  one day

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History of Present Illness

• Epistaxis a day before admission
• Spontaneous bruising
• Bleeding from gums
• Rectal bleeding
• Fever 102 F

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Laboratory Tests
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Laboratory Tests
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Laboratory Tests U/A
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Laboratory Tests
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History of Present Illness

• No h/o upper respiratory illness
• No h/o hematuria, melena
• No h/o vomiting, diarrhea
• No h/o trauma
• No exposure to drugs and chemicals
• No h/o sick contact
• No h/o suggestive of abuse

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Birth History

• Full term normal delivery
• Birth weight 3.23 Kgs
• No history of resuscitation/jaundice

Developmental History

• Sat at 5 months
• Walked at 10 ½ months
• Speaks around 8 words

Past Medical History

• Febrile illness at 3 months of age (ER only)
• No previous hospital admissions

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Immunization

• MMR, Varicella and Prevnar 12 days before
  admission

Medication

• Fluoride vitamins with iron

Diet

• Regular Milk
• Table food

Social History

• Stays with father and paternal grandmother during
  the day Mom works
• No daycare

Travel

• Non contributory

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Family History
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Physical Exam

• Vitals
• Temperature 99.4F
• Pulse 114/min
• Respiratory rate 28/min
• BP 119/58 mm Hg
• Weight
• 10.7 kg (50th -75th)
• Height
• 79 cm (75th _ 90th)

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Physical Exam

• General
• Cranky
• Crying on exam
• HEENT
• Palpable bruises on head (at least 4)
• No scleral icterus, no papilledema, no hemorrhage
• Bleeding from lips and gums, clotted blood at
  nose
• Tympanic membrane intact
• Throat clear
• No dysmorphic features

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Physical Exam

• Neck
• Supple
• No lymphadenopathy
• Chest
• Air entry bilaterally equal
• No wheeze/No crackles
• CVS
• S1S2 normal
• No murmurs

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Physical Exam

• Abdomen
• Soft
• No hepatosplenomegaly
• No masses
• Bowel sounds present
• Extremities
• Full range of movement
• No swelling or tenderness at joints
• No abnormal thumb

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Physical Exam

• Genitourinary Exam
• Blood evident at anus
• Petechiae over shaft of penis
• Testes descended
• Skin
• Scattered bruises and petechiae over entire body
• Neurological
• Cranky but consolable
• No focal deficits
• Reflexes intact

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Differential Diagnoses

• Idiopathic Thrombocytopenic Purpura
• Leukemia
• Hemolytic Uremic Syndrome/Thrombotic
  Thrombocytopenic Purpura
• Disseminated Intravascular Coagulation
• Infection/Sepsis
• Evans Syndrome
• Wiskott-Aldrich syndrome

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Day 1 - Admission

• Hem/Onc consultation
• CBC with differential
• Peripheral smear
• Blood type
• Coombs test
• Ig levels IgG, IgA, IgM
• CT scan Brain (Non contrast)

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Lab results
CBC with Differential
Peripheral Smear
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Diagnosis

• Idiopathic Thrombocytopenic Purpura

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Medications

• IVIG - 11 gm to be infused over 6 hours (1
  gm/kg)
• Benadryl 10 mg IV before infusion followed by
  PO Q 6 hours (1 mg/kg per dose)
• Tylenol 150 mg PO X 1 before infusion followed
  by PO Q 4 hours (15 mg/kg per dose)

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45 minutes later

• Patient developed chills
• Vitals
• Temp 102 F
• HR 210
• RR 32
• BP 122/41
• Po2 98
• Patient transferred to PICU
• IVIG transfusion continued

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Day 2 - PICU

• No active bleeding
• Some new bruising
• Petechiae around diaper area

• IVIG 11 gms IV infusion over 6 hours
• Tylenol 150 mg PO Q 4 hrs
• Benadryl 10 mg PO Q 6 hrs

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Day 3

• Patient happy and playful
• Ecchymoses in various stages of healing
• Patient discharged home
• Follow up with Hem/Onc

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Idiopathic Thrombocytopenic Purpura
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Background

• Most common cause for acute onset of
  thrombocytopenia in an otherwise well child
• Patients fall broadly into two categories
• Acute ( 90) self limiting disease with
  spontaneous resolution within 6 months
• Chronic (10) Does not remit within 6 months
• Epidemiology
• 60-150 cases per 1 million children per year
• Distribution is equal between males and females
• Peak incidence 2-6 years

Pediatr Clin N Am 51 (2004) 1109-1140
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Pathogenesis

• Autoantibodies that interact with membrane
  glycoproteins on surface of platelets and
  megakaryocytes
• GPIIb-IIIa complex is the autoantigen implicated
  most often as the cause
• Others GPIb-IX-V, GPIa-IIa
• These antibodies result in accelerated platelet
  destruction
• Genetic factors Polymorphism in phagocyte
  Fcgamma receptor

Lin SY, Kinet JP, Immunology, 2001
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Clinical Features

• History
• Abrupt onset
• Bruising, petechiae and ecchymoses
• Epistaxis
• Gingival bleeding
• Hematuria, hematochezia, melena
• Menorrhagia in adolescent females
• Recent live virus immunization
• Recent viral illness

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Clinical Features

• Physical exam
• Non palpable petechiae
• Purpura
• Hemorrhagic Bullae on mucous membrane
• Retinal hemorrhages
• Neurologic symptoms (ICH)
• Spleen not enlarged
• Absence of significant lymphadenopathy,
  hepatosplenomegaly, joint swelling
• Spontaneous bleeding when platelet count lt
  20,000/mm3

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Lab Studies

• CBC
• Isolated Thrombocytopenia (Key finding)
• WBC usually normal
• RBC usually normal anemia can be seen in 15 of
  these children especially those with a
  significant h/o epistaxis, hematuria or GI
  bleeding
• Peripheral blood smear
• Large platelets

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Lab Studies

• Bone marrow exam
• Children with atypical features
• For those in whom initial therapy fails

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Additional Tests

• Coombs test
• Rh (D)
• Ig levels
• Coagulation studies
• ANA testing
• CTScan of head

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Management

• Benign, self limited disorder
• Requires minimal or no therapy in majority of
  cases
• No convincing evidence that medical treatment
  alters the natural history of disease
• Modalities
• Observation patients with platelets counts gt
  20,000 per microlitre and only minor purpura
• Medical Therapy
• IVIG
• Anti-D
• Corticosteroids
• Surgical Therapy
• Splenectomy

Nathan Oskis 6th Ed 1600
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Medical Therapy

• IVIG
• Mechanism of action Clearance of antibody coated
  blood cells from circulation by inhibiting
  phagocytic activity of cells of
  reticulo-endothelial system

Lin SY, Kinet JP, Immunology, 2001
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Medical Therapy

• IVIG
• Regimen
• Induction 400 mg/kg IV once daily X 5 days or
  1000 mg/kg IV once daily X 1-2 days
• Maintenance 400-1000 mg/kg IV intermittently as
  needed to maintain platelet count gt 30,000/mm3
• Side effects
• Flu like symptoms headache, nausea,
  lightheadedness, fever, chills, vomiting
• Aseptic meningitis
• Anaphylaxis

Micromedex
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Medical Therapy

• Anti D
• Can be used only in Rh(D) ve patients
• Mechanism of action phagocytic cell blockade
• Regimen 50-75 microgm/kg short IV infusion
• Side Effect Hemolysis

Lin SY, Kinet JP, Immunology, 2001
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Medical Therapy

• Corticosteroids (Methyl Prednisone)
• Mechanism of action
• Inhibition of phagocytosis and antibody synthesis
• Increased microvascular endothelial stability
• Regimen
• 2 mg/kg/day X 21 days
• 4 mg/kg/day X 7 days then tapered to day 21
• Megadose pulse therapy 30 mg/kg/day IV or orally
  X 3 days

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Role of splenectomy

• gt 4 year child with severe ITP that has lasted
  longer than 1 year and whose symptoms are not
  easily controlled with therapy
• Life threatening haemorrhage complicates acute
  ITP, if the platelet count cannot be rapidly
  corrected with transfusion of platelets and
  administration of IVIG and corticosteroids

Nelson, 17th ed
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Complications

• Intracranial Haemorrhage
• Rate 0.1-1
• Risk Factors
• Platelet count lt 10,000/L
• Retinal Haemorrhage
• Wet purpura ecchymoses in mouth
• Mucocutaneous bleeding hematuria/hematochezia
• Patients with underlying AV malformation,
  hemophilia, von Willebrand disease

Pediatr Clin N Am 51 (2004)
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ITP Treatment

• For serious bleeding (CNS, retroperitoneal, GI)
• Prednisone and IVIG
• Transfuse platelets
• Consider urgent splenectomy
• Provide other supportive/resuscitative care as
  needed

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Prognosis

• 80-90 of patients recover in few months with
  or without treatment
• lt5 patients develop recurrent acute
  thrombocytopenia
• 10 patients develop chronic ITP

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Chronic ITP

• Associated conditions
• Immunodeficiency
• Hypogammaglobulinemia
• Common variable immunodeficiency
• Lymphoproliferative disorders
• Autoimmune Lymphoproliferative disorders
• Hodgkin disease
• Collagen vascular disorders
• SLE
• Infection
• HIV

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Management

• First line medical therapies
• Corticosteroid
• IVIG
• Anti-D
• Splenectomy
• Second line medical therapies
• Azathioprine
• Cyclophosphamide
• Danazol
• Vinca Alkaloids
• Interferon Alpha
• Cyclosporine

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Recent Advances

• Rituximab
• Anti-CD20 monoclonal antibody
• Promising therapy for refractory ITP
• Mechanism of action Depletes B cells
• Regimen 375 mg/m2 weekly for 4 weeks
• Side effect Serum sickness

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Pros and Cons of Drug Therapy

• In favor of observation with drug treatment
• Treatment increases platelet count more rapidly
  than no treatment
• Severe hemorrhage more likely with platelet
  counts lt 10000 /mm3
• Drug treatment is cost effective if it prevents
  bleeding
• In favor of observation without drug treatment
• Severe hemorrhage is rare, 0.1 - 1
• Drug treatment may not prevent severe hemorrhage
• Drug treatment unnecessarily increases the cost
  of management
• Drug treatment may be harmful

Hematol Oncol Clin N Am 18 (2004) 1301-1314
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Thank You