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Heparin-induced Thrombocytopenia (HIT)

❓What❓

  • Type 1: non-immune platelet aggregation & thrombocytopenia results in nadir usually no deeper than 100k, with onset occurring within first 48 hours of heparin exposure & spontaneous resolution occurring through ongoing heparin exposure (i.e. benign)

  • Type 2*: heparin causes autoantibody production against PF4-platelet complexes (takes 5-10 days for antibody to form after exposure) → thrombocytopenia (due to platelet clumping; non-pathogenic) & ↑ thrombin (pathogenic) → ultrahypercoagulability in up to ~50% left untreated (venous > arterial)

  • Spontaneous: development of autoantibody without heparin exposure (i.e. monoclonal gammopathy of thrombotic significance)

*when people refer to “HIT,” they are generally referring to “type 2,” which is what the illness script below describes

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❓Epidemiology❓

  • Mortality ~20% if untreated (~2% if treated)

  • Occurs in ~1/5000 inpatients

❓Presentation❓

Timing = 🔑

  • Thrombocytopenia & thrombosis characteristically does not begin until 5 days after initial heparin exposure due to the time interval required for autoantibody production; however, there are a few major exceptions to this rule, which can be stratified into different populations:

  1. Chronic heparin exposure: notably, major surgery resets the clock in patients with chronic heparin exposure (e.g. hemodialysis patient who undergoes cardiac surgery), with the 5-10 day window resetting on the date of surgery

  1. Recent, “prior” heparin exposure: if patient has received heparin within the previous 90 days (especially <30 days), persistent circulating autoantibodies can result in immediate HIT upon heparin re-exposure, which can result in anaphylaxis within 30 minutes after a heparin bolus

  1. Spontaneous (i.e. no exposure): if clinical presentation fits, must be open to possibility of monoclonal gammopathy of thrombotic significance due to native autoantibody production. (Notably, this most often occurs after major surgery or infections. In theory, ELISA antibody & SRA testing should be ⊕, but there are reports of isolated MGTS requiring PF4-enhanced platelet-based testing for confirmation due to ELISA/SRA negativity.)

Thrombocytopenia, ↓ Depth ↓

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  • Platelet drop >50% from post-heparin peak highly suggestive

  • Platelet drop occurs rapidly, over period of 1-3 days

  • Platelet nadir typically 40-80k, but < 20k possible

Clinical: “Ultrahypercoagulability” (@CPSolvers)

  • Typical venous thrombosis (e.g. leg DVT)

  • Atypical venous thrombosis (i.e. portal vein, cerebral venous sinus, adrenal vein)

  • Arterial thrombosis (e.g. ischemic stroke)

❓Diagnosis❓

Pretest Probability = “4 Ts Score” 🥼

  • 0-3: low probability
  • 4-5: intermediate probability
  • 6-8: high probability

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Bayesian Reasoning 🩸

  • Step #1: PF4-heparin IgG immunoassay

⊖ → HIT unlikely

⊕ → assess strength of positivity (An optical density of less than 1.0 is rarely associated with clinically-relevant antibodies, whereas an optical density of greater than 1.0 is worrisome.)

  • Step #2: confirmation with functional platelet-activation test (e.g. serotonin release assay)

❓Treatment❓

  • Discontinue heparin products, including sneaky ones (e.g. heparinized saline flushes, hemodialysis membranes)

  • Initiate alternative therapeutic anticoagulant, even if no apparent thrombosis (e.g. argatroban, bivalirudin, fondaparinux)

📚 References 📚