AM Report 11/9/16: Heparin-Induced Thrombocytopenia

Remember the different types of HIT:


Type 1 Type 2
Mechanism Direct effect of heparin (non-immune) Immune (Ab)-mediated IgG against platlet factor 4-heparin complex
Incidence 10-20% 1-3% with UFH; 0-0.8% with LMWH


Onset After 1-4 day of heparin therapy


After 4-10 day; but can occur <24 h if prior exposure w/in 100 days (persistent Ab). Postop highest risk. Can occur after heparin d/c’d


Platelet nadir >100,000/μL


~60,000/μL, ê 50%


Sequelae None Thrombotic events (HITT) in 30-50%; rare hemorrhagic complications


Management Observe Cessation of heparin, alternative non-heparin anticoagulation to prevent thrombosis




  1. Autoantibodies (IgG) are formed to platelet factor 4 (PF4) complexed with heparin
  2. Platelet Fc receptors bind the antibody-heparin-PF4 immune complex
  • Thrombocytopenia occurs by two mechanisms:

1) Platelet removal by splenic macrophages
2) Platelet consumption due to thrombus formation

Clinical Variability:

  • 10 times higher incidence with UFH compared with LMWH
  • A metaanalysis of 15 studies (>7000 patients) that evaluated the risk of HIT with prophylactic UFH vs LWM found the following absolute risks of developing HIT
  • UFH – 2.6% (95% CI 1.5 – 3.8%)
  • LMH – 0.2 % (95% CI 0.1 – 0.4%)
  • Surgical > Medical patients; Incidence is particularly high after orthopedic surgery


Risk Factors:

  • There is no dose of heparin that is too low to cause HIT! Patients have developed HIT after exposure to as little as 250 U flush.
  • Female sex appears to be at a higher risk for unclear reasons – this was based on 7 trials comparing UFH vs LWH found approximately twice the risk.

Clinical Manifestations:

  • Thrombocytopenia (<150,000/microL ~ 85-90%)
  • Platelet drop of >50% is typical with mean nadir of 60,000/microL and RARELY <20,000/microL
  • Typical onset is 4-10 days after heparin therapy
  • Patients with exposure to heparin in the previous 100 days can develop a early onset (<24 hours) HIT
  • Thrombosis occurs in up to 50% of HIT patients (venous > arterial); presenting finding in up to 25%
  • Thrombotic sequelae – skin necrosis, limb gangrene, organ ischemia/infarction

4T Score:


  • A total score <4 points has a very high negative predictive value (97-99%); additional testing is not necessary

Assuming an intermediate/high risk score – what other labs can aid in the diagnosis:

  • Anti-PF4 heparin antibodies – excellent NPV (98-99%), but low PPV due to presence of clinically insignificant antibodies (IgM, IgA)
  • Our lab restricts the antibodies to only IgG – which increases the specificity
  • Also provides an optical density (magnitude of anti-PF4-heparin reactivity) ~ greater activity (>2.0) correlates to a greater likelihood of HIT
  • Serotonin-release assay – functional assay that measures heparin-dependent platelet activation; a negative result rules out HIT


Step 1: Immediate cessation of heparin

Step 2: : Initiation of an alternative anticoagulant at a therapeutic dose.

  • Vitamin K antagonists should NOT be given until HIT has resolved (i.e. platelets > 150,000 for >2 days) because they increase the risk of venous limb gangrene/limb loss by decreasing levels of protein C.
  • Argatroban (direct thrombin inhibitor) is the only currently FDA approved medication in the US.  Danaparoid (anti-factor Xa) is approved in Canada, EU, and Australia.  Other options include: Lepirudin and Bivalrudin.

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