HEPARIN INDUCED THROMBOCYTOPENIA

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HEPARIN INDUCED THROMBOCYTOPENIA

• GALILA ZAHER
• MBB ch, dip C Path,
• MRC Path

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Heparin induced thrombocytopenia(HIT)

• HIT is an immune mediated side effect which can
  be life threatening .
• Incidence 1-3of patient receiving heparin.

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Heparin induced thrombocytopenia

• Higher risk for HIT
  Therapeutic gt prophylactic doses .
  Bovine lung extract gt porcine heparin
  Unfractunated heparin gt LMWH.
• HIT
  IV , SC, hepsal flush , extra
  corporal blood circuit heparin coated
  materials.

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Pathogenesis

• Heparin treatment release platelet factor 4 .
• Heparin can bind to PF4 on platelet surface
  vascular endothelium.
• Antibodies are directed against heparin-PF4
  (H-PF4).
• Antibodies involved in HIT are usually IgG , but
  IgA IgM have been reported.

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Type 1 HIT

• The most common form of HIT.
• Early onset (3-5d).
• Mild thrombocytopenia(80-100x109/l).
• Direct effect of heparin .
• Reversible
• Asymptomatic .

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Type II HIT

• Less frequent than type I HIT
• Delayed onset (5-14d).
• Plt count is lt60x109/L
• Can be life threatening 29 mortality rate (HITT)
  .
• Immunological reaction .
• Requires clinical intervention immediate
  discontinuation of heparin.

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Ice burg model
Multiple thrombosis 0.01-0.1
Isolated thrombosis 30-80
Symptomatic thrombocytopenia 30-50-
HIT-IgG







HIT-IgG seroconversion 0-10
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Clinical presentation of type II HIT

• Males and females are equally affected.
• All ages.
• Venous thrombosis more common than arterial .
• Patient who develop skin lesions at heparin
  injection sites are at increased risk of
  thrombosis.
• CVD ?arterial .
• Post operative ?venous thrombosis .

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Clinical presentation

• Venous thrombosis
• DVTPE.
• Warfarin induced venous limb gangrene.
• Cerebral sinus thrombosis .
• Adrenal hemorrhagic infarction .
• Arterial thrombosis
• lower limb (distal aortic or iliofemoral).
• Stroke Myocardial infarction.
• Acute plt activation syndrome
• Skin lesions

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Laboratory diagnosis of HIT

• Existing lab methods do not distinguish between
  HIT HITTS.
• 14C Seratonin release assay .
  H-PF4 ELISA .
  
  The platelets aggregation assay.
  Flow-cytometric assay.
• Until improved laboratory diagnosis of HIT
  clinical impression are best used to direct
  therapy in patient with suspected HIT

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Flow cytometry in diagnosis of HIT

• Provides rapid diagnosis .
• 100 specificity and sensitivity .
• Reproducible .
• flow cytometric assay of CD62P can distinguish
  HIT from HITTS.

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Heparin therapy

• Regular platelets count .
• Type I HIT syndrome -?observation .
• Type II HIT syndrome
  D/C heparin
  no platelet concentrate
  no warfarin during the acute
  phase no LMWH
• Heparinoid

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Thrombin inhibitors

• HIRUIDIN
• Natural hiruidin
• The leech salivary extract (hirudo
  medicinalis).
• synthetic hirudin (argatroban).
• recombinant (r- hiruidin) .
• Danaparoid.
• Hirulogs.

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PLASMAPHERESIS

• Removal of plasma replacement with normal plasma
  or colloids.
• It has been done on 3 consecutive days.
• Early treatment (4 days) reduces the incidence of
  mortality
• It dose not affect the number of the thrombotic
  events .

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Extremity Arterial Thrombosis Stroke .

• Digits only
  
  Argatroban .
• Entire extremity
  Thrombolytic therapy, Continue
  argatroban,
  Plasmapharesis.
• Stroke with no evidence of hemorrhage
  Argatroban
• Stroke with evidence of hemorrhage
  Plasmapheresis.

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Laboratory diagnosis .ctd

• Combined results of the three assays enhances the
  positive response to 83of the total population
  with HIT.
• The combination of the three testing with
  multiple samples offers the best chance of
  confirming a positive diagnosis of HIT .
• Clinical event a positive reliable laboratory
  test confirms the diagnosis of HIT.

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14C serotonin release assay

• The gold standard for diagnosis.
• It is a biologic assay.
• It requires the use of radioactive materials.
• It has a sensitivity of 55.
• The complexity the slow turn around time of the
  assay compromise its practical usefulness for
  immediate treatment decisions.

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THANK YOU