Heparin-Induced Thrombocytopenia (HIT)

Snapshot

• 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.  

Introduction

• 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

Presentation

• 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

Evaluation

• 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 

Treatment

• 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