Updated: 8/9/2020

Heparin-Induced Thrombocytopenia (HIT)

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  • A 60-year-old woman presents after a 12 hour train ride with right-sided crampy leg pain. She is currently on hormone-replacement therapy for menopausal symptoms. On exam, the circumference on the right calf is larger than the left’s. An ultrasound shows a lower extremity DVT. She is started on heparin. Two days later, her platelets are measured at 30,000/mm3 which were previously at 150,000/mm3. On re-evaluation, her physician notes that she has several patches of purple/brown areas of skin necrosis. Concerned, he immediately stops the heparin and starts her on a direct thrombin inhibitor.  
  • Decreased platelets due to heparin exposure
  • Type I HIT
    • Two days after heparin exposure
    • not immune-mediated
    • platelet count normalizes spontaneously
    • no symptoms
  • Type II HIT
    • hypercoagulable state resulting from antibody-mediated destruction of platelets
    • 5-10 days after heparin
    • associated with significant risk of thrombosis
    • can be fatal
    • epidemiology
      • female > male (1.7x)
    • pathogenesis
      • heparin binds to platelet factor 4 (PF4)
      • IgG antibodies recognize the heparin-PF4 complex
        • type II hypersensitivity reaction 
      • complex-bound antibodies bind to platelets and cause platelet activation
        • thrombosis
        • thrombocytopenia
    • risk factors
      • more common with unfractionated heparin
  • Symptoms (type II HIT)
    • 5-10 days after heparin
    • > 30% drop in platelets
    • venous > arterial thrombosis
      • DVT/PE
      • skin necrosis
    • overt bleeding is rare
      • can see bleeding at injection sites
  • Complete blood count
    • drop in platelet count by > 30%
      • no matter what the absolute platelet count is
  • ↑ bleeding time
  • Normal PT/PTT
  • Presence of anti-PF4-heparin for type II HIT
    • serotonin release assay
    • enzyme immunoassay
Differential Diagnosis
  • DIC
  • ITP
  • TTP
  • HUS
  • Type II HIT
    • stop all heparin-containing products (including unfractionated and low molecular weight)
    • direct thrombin inhibitors
      • argatroban, lepirudin, and bivalirudin
    • transition to warfarin when platelets are back at baseline
    • PLT infusion
      • may be used if bleeding and platelets <50,000/mm^3 (<100,000/mm^3 for intracranial bleed)
      • not indicated if patient is not bleeding
      • may worsen thrombosis
Prognosis, Prevention, and Complications
  • Prognosis
    • mortality 5-10% in patients with type II HIT
      • from thrombosis
  • Complications
    • thrombosis
      • amputation of limb
      • stroke
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