❓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
❓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:
- 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
- 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
- No heparin 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.)
Thrombocytopenia, ↓ Depth ↓
- 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
Bayesian Reasoning 🩸
- Step #1: PF4-heparin IgG immunoassay. If ⊖, HIT unlikely. If ⊕, 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 📚
- Heparin-Induced Thrombocytopenia (NEJM)
