Heparin-induced thrombocytopenia (HIT)

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Heparin-induced thrombocytopenia(HIT)
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• Two Forms
• HIT type I - non-immune, caused by direct effect
  of heparin on plt activation, lesser fall in
  platelet count that occurs within the first two
  days after heparin exposure, plts often
• return to normal with continued heparin use, no
  clinical consequence
• HIT type II - immune-mediated, antibodies to
  heparin-platelet factor 4 complex,
• often develop white-clot syndrome involving
  arterial thrombosis w/platelet-rich
• Clot

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• incidence
• 10-20 of pts on UFH have fall in plts to less
  than normal range, or 50 fall in plt within
  normal range (mostly type I nonimmune)
• 0.3-3of pts on UFH for gt4 days develop type II
  immune HIT
• Amount of heparin exposure minimal (250 U from
  heparin flush!)
• Studies show variable incidence w/different
  reason for use, prophylaxis vs treatment and UFH
  vs. LMWH

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• pathophysiology
• Usually gt 4 days exposure
• Antibodies provoked by heparin-PF4 antibody
  complex on plt surface leading to plt activation
  and further plt aggregation and thrombosis
• Clinical Manifestations
• Type II HIT occurs 4-10 days after exposure,
  onset after 2 weeks is unusual, Abs develop 5-8
  days after exposure and rarely later
• Type I is earlier onset though may be type II if
  prior heparin exposure in previous 3-4 months

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• Clinical Manifestations
• Type II HIT thrombocytopenia is rarely severe,
  plt stypcially gt20,000, spontaneous bleeding very
  unusual (in contrast to ITP)
• Can present as delayed onset HIT - occurs afer
  heparin withdrawn, avg 9 days after heparin,
  higher titer of plt-activating Abs
• Dx
• exposure to heparin and d/c after relatively
  benign course
• Re-presentation w/objectively proven venous
  and/or arterial thrombosis
• Thrombocytopenia after reexposure to heparin
• PF4 Abs
• Can be lethal if not recognized and heparin
  substitute initiated

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• Heparin substitutes
• Lepirudin
• Argatroban
• danaparoid
• Reexposure to heparin
• May be safe if PF4 Abs are negative, though if
  develops often does so sooner after reexposure
• Thrombosis
• Major clinical problem (venous and arterial)
• Precise mechanism unknown, likely due to
  procoagulant release from activated plts
• Incidences of thrombosis in HIT patients can be
  gt50

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• Arterial thrombosis
• MI
• CVA
• Limb ischemia
• Organ infarction
• Skin necrosis (w/subcutaneous admin)

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• Diagnosis
• Recognize the clinical syndrome
• New thrombocytopenia or drop in plt count
• Thrombosis associated w/thrombocytopenia or drop
  in plts
• Context of heparin within 5-10 days or prolonged
  LMWH Rx
• Assays
• PF4 relatively low sensitivity and must be
  repeated clinically
• 14 C-Serotonin release assay is the gold standard
  and is most sensitive (OR78), high cost, often
  delayed results necessitating empiric Rx if high
  clinical suspicion
• ELISA serotonin quantification w/100 sensitivity
  and 97 specificity
• Heparin-induced plt aggregation assay gt90
  specific, poorer sensitivity
• Solid phase immunoassay has high sensitivity 91
  but less specific for actual syndrome, may be
  improved by assaying only for heparin-PF4-IgG
  Abs

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• Prevention
• LMWH has lower incidence
• Judicious use of heparin products
• Early warfarin overlap, not until
  thrombocytopenia resolves if present (gt100,000)
• Treatment
• Stop all heparin immediately including heparin
  flushes
• Administration of argatroban or lepirudin, ?need
  for prophylaxis if no thrombosis observed until
  plts recover