Dr. DeLoughery's Presentation

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Immune Thrombocytopenia

• 120,000
• Autoimmune destruction of platelets
• Patients present with very low platelet counts
• Clinical history is diagnostic test
• No other cause of thrombocytopenia
• Normal blood smear

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The Diagnosis ITP

• Low platelets in an otherwise healthy person
  without an obvious other cause

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Low Platelets

• Most patients with ITP have very low platelet
  counts
• Patient with moderate thrombocytopenia can be
  difficult to diagnosis
• Liver disease
• Congenital thrombocytopenia
• Bone marrow problems

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Otherwise Healthy

• Other blood counts normal
• Can be anemia due to blood loss
• No other new problems
• Kidney problems

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No Other Obvious Cause

• Drugs
• New drugs in last 2 weeks
• Infections
• Bone marrow diseases

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Fancy Tests

• There is no test that can directly diagnose ITP

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Testing

• Anti-platelet antibodies
• No helpful
• Lupus testing
• Thyroid testing

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Blood Smear

• Looking directly at the blood to see if anything
  is abnormal
• Also to verify platelet count

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www.pathy.med.nagoya-u.ac.jp/ atlas/doc/node114.ht
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Congenital Thrombocytopenia

• Platelet counts 10-100,000
• Clues
• Family history of "ITP"
• Very large platelets
• Bleeding out of proportion to platelet count

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www.pathy.med.nagoya-u.ac.jp/ atlas/doc/node114.ht
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Bone Marrow Testing

• Not indicated if everything else fits
• Indications
• Platelets dont respond
• Blood smear looks odd

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Ultimate Test

• If patient responds well to ITP therapy then they
  have ITP!

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Therapy of ITP
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Key Decisions in Treatment of ITP

• Acute or Chronic
• Bleeding or not bleeding
• Fast or slow

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Acute vs Chronic?

• Initial presentation treated more aggressively
• Long term patient therapy based on my experience
  with the patient

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Bleeding or Not Bleeding?

• Patients who are seriously bleeding get more
  aggressive treatment
• Major stomach bleeding
• Brain bleeding
• Blood blisters in mouth

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Fast or Slow?

• How fast do you want the platelets up?
• Fast
• lt 10,000
• Severe bleeding

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Overview of Therapy

• Prednisone
• Dexamethasone
• Methylprednisolone
• Immune Globulin
• Anti-D
• Splenectomy
• Rituximab
• Cyclophosphamide
• Azathioprine
• Mycophenolate
• Danazol
• Vincristine
• Dapsone
• Interferon
• Combined chemotherapy
• Stem cell transplant
• Neumega
• AMG 531
• Staph A column

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ITP New Diagnosis

• When to treat
• What to treat with

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When to treat

• Guided by counts and bleeding
• gt 50,000 - no therapy
• lt 20,000 - some therapy
• 20-50,000
• Treat if bleeding, older, etc..

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Initial Therapy

• Steroids for all
• IVIG or anti-D for very low counts or severe
  bleeding

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Steroids

• Decrease antibody production
• Decrease splenic uptake of platelets
• Increases platelet production
• First line therapy
• Prednisone 60 mg/day
• Dexamethasone 40 mg/day for 4 days
• May take up to a week to work
• Rarely "cures" people

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Steroids

• Good
• Cheap
• Effective initially in most patients
• Bad
• Numerous side effects

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Expected Response

• Initial response 80-90
• "Curative" response 10-30

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Fast Therapy

• Immune Globulin
• Anti-D

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Immune Globulin

• Lots of theories on how IVIG works
• 1 gram/kg x 2
• Very effective in inducing rapid rise in
  platelets counts (lt24 hours)
• Side effects
• Large amounts of volume and time
• Headaches
• Thrombosis

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Anti-D (WinRho)

• "D" (aka Rh) is protein found on red cells in 85
  of the population
• Spleen likes eating red cells more than platelets
• One dose can rise platelet counts in less than 24
  hours
• Cheaper, faster and safer than immune globulin
• WinRho 75 ug/kg
• Need spleen and to be Rh positive
• Can decrease red cell count in some patients

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Fast Therapy

• Good
• Fast
• Effective (gt90)
• Bad
• Expensive
• Anti-D cant be used in a lot of patients
• Temporizing measure

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Chronic ITP or Platelets are Low Again - Now What!

• Most adults will get chronic disease
• Absolutely no consensus on what to do

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Splenectomy

• Rates of splenectomy falling in USA
• Many patients options for medical therapy
• Acceptance of lower platelet counts as safe
• gt 20-30,000 ok

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Splenectomy

• Removes site of platelet destruction
• Removes site of antibody production
• Initial response 85 of patients
• "Cures" ITP 66 of time
• Mortality much less than 1
• Risk of overwhelming sepsis

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When and If to do Splenectomy

• Sooner
• Counts lt 5-10,000
• Patients desires
• Patient otherwise healthy
• Later
• Counts 10-30,000
• Patient desires
• Poor health

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Who Should do your Splenectomy

• Laparoscopic method of choice
• Surgeon should be experience with ITP patients

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Splenectomy

• Good
• Curative in most patients
• Bad
• Not 100
• Surgical complications
• Prone to odd but severe infections

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Infection

• Patients without spleens are more prone to
  overwhelming sepsis
• Risk is about 1500 and decreasing due to
  vaccinations
• However, patients must be concerned if high
  fevers occur

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Medical Therapy

• Some patients will resolve ITP over months to
  years
• Some patients may require minimal or infrequent
  therapy

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Medical Therapy

• IVIG or Anti-D
• Longer courses of Dexamethasone
• Danazol
• Rituximab

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Medical Therapy

• Good
• Some patients (30?) will avoid splenectomy or
  require infrequent therapy
• Bad
• Risk of bleeding if severely thrombocytopenic
• Expensive
• Side effects of therapy

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Splenectomy Failures

• Frustrating for all concerned
• No ideal therapy
• Treatments options are more aggressive as counts
  are lower

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Options

• Most patients
• Rituximab
• Danazol
• lt 10,000
• Azathioprine
• Mycophenolate
• lt 5,000
• Pulse cyclophosphamide

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Rituximab

• Binds protein on lymphocyte called CD-20
• Very effective in killing these cells
• Developed 10 years ago as lymphoma therapy

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Rituximab for ITP

• Best therapy for splenectomy failures
• Response rates of 60
• Long term in 30 or so
• May be higher?
• Why it works unknown

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Rituximab

• Given weekly for 4 weeks total
• Responses can take time
• 1/3 - first week
• 1/3 - first month
• 1/3 - up to 4 months
• Side effects
• Shakes, chills
• Rarely immune neutropenia

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Rituximab

• Good
• Seems to be safe
• Effective in most patients
• Bad
• No long term data
• Unknown long term side effects

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Why not Rituximab before Splenectomy

• Appealing concept and widely done
• However
• Lower response rate
• Spleen "sucks" up rituximab
• Unknown long term side effects

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Danazol

• Weak male hormone that may impair uptake of
  antibody coated platelets
• Need to use for up to 6 months to see effect
• Can lead to weight gain, liver problems
• Can be a effective and relatively safe therapy

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Azathioprine and Mycophenolate

• Weak immunosupressents
• Relatively safe (can see low blood counts)
• Takes time to work (4 months)

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Pulse Cyclophosphamide

• Large dose intravenous every month
• Higher risk of nausea/vomit and low blood counts
• Response rate is uncertain

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Counts Low - Now What

• Probably nothing works well
• Might be best to leave most patients alone
• "Therapy Roulette"
• Otherwise refer for studies

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Key Points

• No standard set of therapy for all patients
• Therapy tailored to patient
• Patient choice important!

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